MDPI - Publisher of Open Access Journals

15 pages, 1224 KiB

Open AccessArticle

Development of a Pulmonary Nodule Service and Clinical Pathway: A Pragmatic Approach Addressing an Unmet Need

by Georgia Hardavella, Ioannis Karampinis, Nikolaos Anastasiou, Konstantinos Stefanidis, Kyriaki Tavernaraki, Styliani Arapostathi, Nektaria Sidiropoulou, Petros Filippousis, Alexandro Patirelis, Eugenio Pompeo, Panagiotis Demertzis and Stefano Elia

Diagnostics 2025, 15(9), 1162; https://doi.org/10.3390/diagnostics15091162 - 2 May 2025

Abstract

Background/Objectives: The surveillance of patients with incidental pulmonary nodules overloads existing respiratory and lung cancer clinics, as well as multidisciplinary team meetings. In our clinical setting, until 2018, we had numerous patients with incidental pulmonary nodules inundating our outpatient clinics; therefore, the need [...] Read more.

Background/Objectives: The surveillance of patients with incidental pulmonary nodules overloads existing respiratory and lung cancer clinics, as well as multidisciplinary team meetings. In our clinical setting, until 2018, we had numerous patients with incidental pulmonary nodules inundating our outpatient clinics; therefore, the need to develop a novel service and dedicated clinical pathway arose. The aims of this study are to 1. provide (a) a model of setting up a novel pulmonary nodule service, and (b) a pragmatic clinical pathway to address the increasing need for surveillance of patients with incidental pulmonary nodules. 2. share real-world data from a dedicated pulmonary nodule service running in a tertiary setting with existing resources. Methods: A retrospective review of established processes and referral mechanisms to our tertiary pulmonary nodule service was conducted. We have also performed a retrospective collection and review of data for patients reviewed and discussed in our tertiary pulmonary nodule service between April 2018 and April 2024. Results: Our tertiary pulmonary nodule service (PNS) comprises a dedicated pulmonary nodule clinic, a nodule multidisciplinary team (MDT) meeting and a dedicated proforma referral system. Due to the current national health system legislation and relevant processes, patients are required to physically attend clinic appointments. There are various sources of referral, including other departments within the hospital, other hospitals, various specialties in primary care and self-referrals. Between 15 April 2018 and 15 April 2024, 2203 patients were reviewed in the pulmonary nodule clinic (903 females, 1300 males, mean age 64 ± 19 years). Of those patients, 65% (1432/2203) were current smokers. A total of 1365 new patients and 838 follow-up patients were reviewed in total. Emphysema was radiologically present in 72% of patients, and 75% of those (1189/1586) already had a confirmed diagnosis of chronic obstructive pulmonary disease (COPD). Coronary calcification was identified in 32% (705/2203), and 78% of those (550/705) were already known to cardiology services. Interestingly, 27% (368/1365) of the new patients were discharged following their first MDT meeting discussion, and 67% of these were discharged as the reason for their referral was an intrapulmonary lymph node which did not warrant any further action. Among all patients, 11% (246/2203) were referred to the multidisciplinary thoracic oncology service (MTOS) due to suspicious appearances/changes in their nodules that warranted further investigation, and from those, 37% were discharged (92/246) from the MTOS. The lung cancer diagnosis rate was 7% (154/2203). Conclusions: The applied pathway offers a pragmatic approach in setting up a service that addresses an increasing patient need. Its application is feasible in a tertiary care setting, and admin support is of vital importance to ensure patients are appropriately tracked and not lost to follow-up. Real-world data from pulmonary nodules services provide a clear overview and contribute to understanding patients’ characteristics and improving service provision. Full article

(This article belongs to the Section Clinical Diagnosis and Prognosis)

► Show Figures

Figure 1

16 pages, 1198 KiB

Open AccessReview

Circulating Cell-Free DNA as an Epigenetic Biomarker for Early Diabetic Retinopathy: A Narrative Review

by Boaz Li, Megan M. Yim, Yu Xuan Jin, Brendan K. Tao, Jim S. Xie, Michael Balas, Haaris Khan, Wai-Ching Lam, Peng Yan and Eduardo V. Navajas

Diagnostics 2025, 15(9), 1161; https://doi.org/10.3390/diagnostics15091161 - 2 May 2025

Abstract

Diabetic retinopathy (DR), a complication of type 2 diabetes mellitus (T2DM), is typically asymptomatic in its early stages. Diagnosis typically relies on routine fundoscopy for the clinical detection of microvascular abnormalities. However, permanent retinal damage may occur well before clinical signs are appreciable. [...] Read more.

Diabetic retinopathy (DR), a complication of type 2 diabetes mellitus (T2DM), is typically asymptomatic in its early stages. Diagnosis typically relies on routine fundoscopy for the clinical detection of microvascular abnormalities. However, permanent retinal damage may occur well before clinical signs are appreciable. In the early stages of DR, the retina undergoes distinct epigenetic changes, including DNA methylation and histone modifications. Recent evidence supports unique epigenetic ‘signatures’ in patients with DR compared to non-diabetic controls. These DNA ‘signature’ sequences may be specific to the retina and may circulate in peripheral blood in the form of cell-free DNA (cfDNA). In this review, we explore the literature and clinical application of cfDNA sampling as an early, non-invasive, accessible assessment tool for early DR detection. First, we summarize the known epigenetic signatures of DR. Next, we review current sequencing technologies used for cfDNA detection, such as magnetic bead-based enrichment, next-generation sequencing, and bisulfite sequencing. Finally, we outline the current research limitations and emerging areas of study which aim to improve the clinical utility of cfDNA for DR evaluation. Full article

(This article belongs to the Special Issue New Insights into the Diagnosis and Prognosis of Eye Diseases)

► Show Figures

Figure 1

29 pages, 2144 KiB

Open AccessReview

Adipose Tissue-Derived Therapies for Osteoarthritis: Multifaceted Mechanisms and Clinical Prospects

by Hanwen Zhang, Oliver Felthaus and Lukas Prantl

Cells 2025, 14(9), 669; https://doi.org/10.3390/cells14090669 - 2 May 2025

Abstract

Osteoarthritis (OA) is a degenerative joint disease that significantly impacts quality of life and poses a growing economic burden. Adipose tissue-derived therapies, including both cell-based and cell-free products, have shown promising potential in promoting cartilage repair, modulating inflammation, and improving joint function. Recent [...] Read more.

Osteoarthritis (OA) is a degenerative joint disease that significantly impacts quality of life and poses a growing economic burden. Adipose tissue-derived therapies, including both cell-based and cell-free products, have shown promising potential in promoting cartilage repair, modulating inflammation, and improving joint function. Recent studies and clinical trials have demonstrated their regenerative effects, highlighting their feasibility as a novel treatment approach for OA. This review summarises the therapeutic mechanisms and latest advancements in adipose tissue-derived therapies, providing insights into their clinical applications and future prospects. Full article

(This article belongs to the Collection Research on Adipose Stem Cells)

► Show Figures

Figure 1

28 pages, 4599 KiB

Open AccessArticle

YOLO_SSP: An Auto-Algorithm to Detect Mature Soybean Stem Nodes Based on Keypoint Detection

by Qiong Wu, Hang Liu, Hongfei Zhu, Cong Wang, Haoyu Wang, Zhongzhi Han, Longgang Zhao and Fei Liu

Agronomy 2025, 15(5), 1128; https://doi.org/10.3390/agronomy15051128 - 2 May 2025

Abstract

The soybean stem node is a key part of soybean growth and development, and its numbers play a crucial role in soybean yield formation. Traditional manual methods are labor-intensive and error-prone. The keypoint detection method is an ideal choice for stem node detection [...] Read more.

The soybean stem node is a key part of soybean growth and development, and its numbers play a crucial role in soybean yield formation. Traditional manual methods are labor-intensive and error-prone. The keypoint detection method is an ideal choice for stem node detection due to its high accuracy and wide applicability. In this study, a new deep learning method, You Only Look Once _Soybean Stalk Pose (YOLO_SSP) was proposed, which innovatively applied the Small_Effective Low-Level Aggregation Network (S_ELAN) module and fused it with a smaller detection head for detecting stem nodes in mature soybeans. After optimization and iteration, the model achieved 88.1% accuracy on the dataset. Subsequently, by ablating the model, it was found that different improvements were effective in increasing the accuracy of the model. In addition, when comparing the classic YOLO series of keypoint detection models, the results show that YOLO_SSP achieved up to 87.7% of APs, which was higher than YOLOv7-w6-pose, YOLOv7-tiny-pose, YOLOv3s-pose, YOLOv5n-pose, YOLOv5s-pose, YOLOv5m- pose, YOLOv6n-pose, YOLOv8n-pose, and YOLOv10b-pose, which were 2.5%, 12.8%, 5.3%, 3.8%, 3.5%, 3.5%, 5.1%, 5.1%, 5.0%, and 4.5% higher, respectively. Finally, the proposed model was applied to the unique dataset with 85.3% precision and 82.6% accuracy, and the visualization of the model’s detection results proved its applicability and universality. This study provides an effective strategy for soybean stem node detection and significantly improves the accuracy of detection. Full article

(This article belongs to the Section Precision and Digital Agriculture)

26 pages, 1303 KiB

Open AccessReview

Expanding the Use of SGLT2 Inhibitors in T2D Patients Across Clinical Settings

by Alessandro Cuttone, Vittorio Cannavò, Raouf Mastan Sheik Abdullah, Pierluigi Fugazzotto, Giada Arena, Simona Brancati, Andrea Muscarà, Carmela Morace, Cristina Quartarone, Domenica Ruggeri, Giovanni Squadrito and Giuseppina Tiziana Russo

Cells 2025, 14(9), 668; https://doi.org/10.3390/cells14090668 - 2 May 2025

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are currently recommended in patients with type 2 diabetes (T2D) to reduce serum glucose levels. Moreover, robust evidence has clearly demonstrated their beneficial cardiovascular and renal effects, making this class of drugs pivotal for the treatment of T2D, especially [...] Read more.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are currently recommended in patients with type 2 diabetes (T2D) to reduce serum glucose levels. Moreover, robust evidence has clearly demonstrated their beneficial cardiovascular and renal effects, making this class of drugs pivotal for the treatment of T2D, especially when complicated by diabetic kidney disease or heart failure. However, several other comorbidities are frequently encountered in T2D patients beyond these long-term diabetes complications, especially in the internal medicine setting. For some of these comorbidities, such as MAFLD and cognitive impairment, the association with diabetes is increasingly recognized, with the hypothesis of a common pathophysiologic background, whereas, for others, a coincident epidemiology linked to the ageing of populations, including that of T2D subjects, may be advocated. In the effort of personalizing T2D treatment, evidence on the potential effects of SGLT2i in these different clinical conditions is accumulating. The purpose of this narrative review is to update current literature on the effects of SGLT2i for the treatment of T2D in different clinical settings beyond glycaemic control, and to elucidate potential molecular mechanisms by which they exert these effects. Full article

► Show Figures

Figure 1

18 pages, 3150 KiB

Open AccessArticle

Targeting ATF5, CEBPB, and CEBPD with Cell-Penetrating Dpep Sensitizes Tumor Cells to NK-92MI Cell Cytotoxicity

by Qing Zhou, Markus D. Siegelin and Lloyd A. Greene

Cells 2025, 14(9), 667; https://doi.org/10.3390/cells14090667 - 2 May 2025

Abstract

Natural killer (NK) cells are an important innate defense against malignancies, and exogenous sources of NK cells have been developed as anti-cancer agents. Nevertheless, the apparent limitations of NK cells in clearing cancers have suggested that their efficacy might be augmented by combination [...] Read more.

Natural killer (NK) cells are an important innate defense against malignancies, and exogenous sources of NK cells have been developed as anti-cancer agents. Nevertheless, the apparent limitations of NK cells in clearing cancers have suggested that their efficacy might be augmented by combination with other treatments. We have developed cell-penetrating peptides that target the transcription factors ATF5, CEBPB, and CEBPD and that promote apoptotic cancer cell death both in vitro and in vivo without apparent toxicity to non-transformed cells. We report here that one such peptide, Dpep, significantly sensitizes a variety of tumor cell types to the cytotoxic activity of the NK cell line, NK-92MI. Such sensitization requires pre-exposure of tumor cells to Dpep and does not appear due to effects of Dpep on NK cells themselves. Our findings suggest that Dpep acts in this context to lower the apoptotic threshold of tumor cells to NK cell toxicity. Additionally, while Dpep pre-treatment does not prevent tumor cells from causing NK cell “inactivation”, it sensitizes cancer cells to repeated rounds of exposure to fresh NK cells. These findings thus indicate that Dpep pre-treatment is an effective strategy to sensitize cancer cells to the cytotoxic actions of NK cells. Full article

► Show Figures

Figure 1

13 pages, 4773 KiB

Open AccessArticle

Microgliosis in the Spinal Dorsal Horn Early After Peripheral Nerve Injury Is Associated with Damage to Primary Afferent Aβ-Fibers

by Yuto Shibata, Yuki Matsumoto, Keita Kohno, Yasuharu Nakashima and Makoto Tsuda

Cells 2025, 14(9), 666; https://doi.org/10.3390/cells14090666 - 2 May 2025

Abstract

Neuropathic pain results from a lesion or disease affecting the somatosensory nervous system. Injury to primary afferent nerves leads to microgliosis in the spinal dorsal horn (SDH), which plays a crucial role in developing neuropathic pain. Within the SDH, primary afferent fibers broadly [...] Read more.

Neuropathic pain results from a lesion or disease affecting the somatosensory nervous system. Injury to primary afferent nerves leads to microgliosis in the spinal dorsal horn (SDH), which plays a crucial role in developing neuropathic pain. Within the SDH, primary afferent fibers broadly project, and microglia are nearly ubiquitously distributed under normal conditions. However, not all microglia react to injuries affecting primary afferent fibers, resulting in spatially heterogeneous microgliosis within the SDH. The mechanisms underlying this phenomenon remain elusive. In this study, the spatial relationship between microgliosis and the projections of injured nerves was investigated by generating mice that had expressed tdTomato in the fourth lumbar dorsal root ganglion (L4-DRG) neurons via intra-L4-spinal nerve (SpN) injection of adeno-associated viral vectors. After transection of the L4-SpN, we found that microgliosis in the SDH selectively occurred in the innervation territories of the injured primary afferent fibers. However, denervating transient receptor potential vanilloid 1 (TRPV1)-expressing primary afferent fibers in the SDH through intrathecal injection of capsaicin did not trigger microgliosis, nor did it influence the microgliosis induced by L4-SpN injury. Conversely, pharmacological damage to myelinated DRG neurons, including Aβ-fibers, was sufficient to induce microgliosis. Furthermore, L4-SpN injury also induced microgliosis in the gracile nucleus, which primarily receives innervation from Aβ-fibers. These findings suggest that microgliosis in the SDH shortly after peripheral nerve injury is predominantly associated with damage to primary afferent Aβ-fibers. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Neuropathic Pain)

► Show Figures

Figure 1

11 pages, 4941 KiB

Open AccessArticle

Consistent Killers: Conservation of Thrombin-Like Action on Fibrinogen by Bushmaster (Lachesis Species) Venoms Underpins Broad Antivenom Cross-Reactivities

by Lee Jones and Bryan G. Fry

Toxins 2025, 17(5), 224; https://doi.org/10.3390/toxins17050224 - 2 May 2025

Abstract

Snakebite represents a significant public health challenge in Central and South America, with Lachesis (Bushmaster) species posing unique clinical challenges due to their severe envenomation effects arising from a combination of potent venom and copious venom yields. Using in vitro coagulation assays, we [...] Read more.

Snakebite represents a significant public health challenge in Central and South America, with Lachesis (Bushmaster) species posing unique clinical challenges due to their severe envenomation effects arising from a combination of potent venom and copious venom yields. Using in vitro coagulation assays, we analyzed the coagulotoxic venom effects from four distinct localities: L. muta from Surinam and French Guiana and L. stenophrys from Costa Rica and Panama. This study examined the venom’s impact on human plasma and fibrinogen and evaluated the efficacy of two regionally available antivenoms (PoliVal-ICP and Antivipmyn-Tri) in neutralizing the pathophysiological effects. Our results demonstrated a remarkable consistency in the pseudo-procoagulant venom activity (also known as: thrombin-like) across different species and localities. Antivenom efficacy testing revealed that both the PoliVal-ICP and Antivipmyn-Tri antivenoms effectively neutralized the venom effects across localities for both species, with the ICP antivenom showing the highest neutralization capacity. These toxicology findings highlight the biochemical conservation of venom composition across Lachesis species which underpins effective cross-neutralization in antivenom treatment. Full article

(This article belongs to the Section Animal Venoms)

► Show Figures

Graphical abstract

20 pages, 5467 KiB

Open AccessArticle

Bongkrekic Acid and Its Novel Isomers: Separation, Identification, and Determination in Food Matrices

by Suhe Dong, Danli Liu, Runfeng Lin, Yingjie Zhu, Peihong Zhu, Xin Jiang, Jie Mao, Yanqing Cao, Jing Peng, Tianyue Zhao, Danning Shen, Tao Li, Kun He and Na Wang

Toxins 2025, 17(5), 223; https://doi.org/10.3390/toxins17050223 - 2 May 2025

Abstract

The toxicity associated with bongkrekic acid (BKA) is severe due to its chemical structure, which also facilitates high mortality rates; however, its isomer, isobongkrekic acid (iBKA), with only minor structural variance, demonstrates marked differences in toxicity. This discrepancy in structural properties and toxicity [...] Read more.

The toxicity associated with bongkrekic acid (BKA) is severe due to its chemical structure, which also facilitates high mortality rates; however, its isomer, isobongkrekic acid (iBKA), with only minor structural variance, demonstrates marked differences in toxicity. This discrepancy in structural properties and toxicity highlights that risks have been potentially underestimated within current detection standards for BKAs. In this study, a novel BKA trans isomer at the C8 and C9 double carbon bonds (E-configuration), termed iBKA-neo, was successfully separated and identified. Subsequently, the multiple reaction monitoring parameters and chromatographic conditions for three BKA isomers were optimized, enabling effective separation within 15 min via UHPLC-MS/MS, among which the ammonium positive adduct ions yielded significantly higher response intensities for all BKA isomers than traditional deprotonated molecules. Additionally, distinct differences in the ion ratios between iBKA-neo and BKA were utilized for preliminary screening. On this basis, the extraction and enrichment strategies for BKAs were optimized in food matrices and validated comprehensively with good linearity (0.25–500 μg/kg), a superior limit of quantification (0.25 μg/kg), acceptable recoveries (82.32–114.84%), and stable intraday and interday precision (an RSD less than 12.67%). These findings significantly contribute to ecotoxicology and the formulation of safety standards concerning BKAs. Full article

(This article belongs to the Special Issue Novel Technologies for the Detection and Identification of Natural Toxins)

► Show Figures

Graphical abstract

31 pages, 6396 KiB

Open AccessSystematic Review

Pharmacological and Non-Pharmacological Interventions for Polycystic Ovary Syndrome (PCOS) in Indian Women: A Systematic Review and Meta-Analysis

by Pratibha Maan, Rohit Gautam, Sudharsan Vasudevan, Geetha R. Menon, Amit Arora, Abilash Nair, Puthiyaveettil Khadar Jabbar and Taruna Arora

Pharmaceuticals 2025, 18(5), 680; https://doi.org/10.3390/ph18050680 - 2 May 2025

Abstract

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age. Treatment or management of this syndrome includes several pharmacological and non-pharmacological treatment approaches for different manifestations of the disease that vary with the patient’s age, symptoms, requirements, and [...] Read more.

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age. Treatment or management of this syndrome includes several pharmacological and non-pharmacological treatment approaches for different manifestations of the disease that vary with the patient’s age, symptoms, requirements, and geographical location. Objective: This systematic review aims to conduct a comprehensive and evidence-based analysis of the various available treatment options and identify knowledge gaps in PCOS management in India. Methods: A comprehensive search was conducted in PubMed, Scopus, and Embase databases from January 2010 till February 2024. We included randomized control trials (RCTs) using any pharmacological drugs (e.g., insulin sensitizers, anti-androgens, anti-obesity drugs, oral contraceptive pills, ovulation induction drugs, etc.) or non-pharmacological intervention (e.g., yoga, diet, herbal supplements, etc.) with Indian PCOS patients for improving common manifestations of PCOS and written in the English language. Studies were screened by two authors independently in a two-level process. Data extraction was also performed by two authors. Risk of bias was performed using the RoB 2 Tool. Subgroup analysis and meta-analysis were performed using the RevMan tool. Results: Thirty RCTs on pharmacological and eight on non-pharmacological interventions were included in the study. However, all the RCTs were so heterogeneous in terms of intervention used, subject recruited, and outcomes measured that meta-analysis was possible for only three subgroups (metformin vs. inositol, metformin vs. metformin+ inositol, and letrozole vs. clomiphene citrate), with only two or three studies per analysis. Most studies were single-centric and small-sized and had a high risk of bias, limiting their generalizability. Conclusions: This systematic review synthesized existing research and evaluated the effectiveness and safety of existing treatments. Limitations and gaps in the current research were identified, which may inform future research for better understanding and management of PCOS in the Indian context. Full article

(This article belongs to the Special Issue NeuroImmunoEndocrinology)

► Show Figures

Graphical abstract

19 pages, 670 KiB

Open AccessArticle

Relationship Between Perceived Stress, Midwife Support and Exclusive Breastfeeding Among Polish Mothers

by Agnieszka Czerwińska-Osipiak, Anna Weronika Szablewska, Wiktoria Karasek, Aleksandra Krawczyk and Krzysztof Jurek

Nutrients 2025, 17(9), 1573; https://doi.org/10.3390/nu17091573 - 2 May 2025

Abstract

Background/Objectives: Breastfeeding is a cornerstone of infant nutrition, promoting optimal development and health benefits for both mother and child. Despite high initiation rates in Poland (97%), exclusive breastfeeding (EBF) drops sharply, reaching only 4% by six months postpartum. The aim of this study [...] Read more.

Background/Objectives: Breastfeeding is a cornerstone of infant nutrition, promoting optimal development and health benefits for both mother and child. Despite high initiation rates in Poland (97%), exclusive breastfeeding (EBF) drops sharply, reaching only 4% by six months postpartum. The aim of this study is to identify factors associated with breastfeeding practices and barriers to exclusive breastfeeding (EBF) among Polish women during the postpartum period, with particular emphasis on the role of medical personnel support and maternal stress levels. Methods: A cross-sectional observational study, adhering to STROBE guidelines, was conducted from January to May 2023. The study included 1092 Polish women, surveyed using the Computer-Assisted Web Interview (CAWI) methodology. The women exclusively breastfeeding accounted for 79% (n = 863) of the study group. The remaining women supplemented their child with modified milk (n = 229; 21%). Statistical analyses were performed using IBM SPSS Statistics (Version 26.0), and logistic regression to assess associations between variables and breastfeeding outcomes. Results: Logistic regression analysis indicated that in the women experiencing low or medium stress, none of the analysed support factors significantly influenced the likelihood of exclusive breastfeeding discontinuation. However, women experiencing high stress, receiving counselling for effective breastfeeding (OR = 0.467; 95% CI: 0.232–0.941; p = 0.033) and assistance with proper breastfeeding (OR = 0.424; 95% CI: 0.220–0.819; p = 0.011) were associated with a lower likelihood of introducing formula feeding. The main reported reasons for early breastfeeding cessation included breast health issues, mental exhaustion, lack of medical support and infant-related difficulties. Conclusions: The findings allow us to underscore the urgent need for targeted interventions to improve breastfeeding rates in Poland. New evidence indicates that women experiencing higher levels of stress require increased support from medical personnel in order to breastfeed exclusively. Full article

(This article belongs to the Special Issue Own or Donated Human Milk: Its Role in Today's Society)

19 pages, 2212 KiB

Open AccessArticle

Highlighting the Potential of LyeTx I, a Peptide Derived from the Venom of the Spider Lycosa erythrognatha, as a Potential Prototype for the Development of a New Antimicrobial Against Carbapenem-Resistant Klebsiella pneumoniae

by William Gustavo Lima, Amanda Souza Félix, Felipe Rocha da Silva Santos, Fernanda de Lima Tana, Amanda Neves de Souza, Rodrigo Moreira Verly and Maria Elena de Lima

Pharmaceuticals 2025, 18(5), 679; https://doi.org/10.3390/ph18050679 - 2 May 2025

Abstract

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a multidrug-resistant (MDR) gram-negative bacterium frequently involved in hospital-acquired pneumonia. The infection caused by this superbug has spread quickly in health centers worldwide, leading to high mortality rates. Due to this emerging scenario, the World Health [...] Read more.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a multidrug-resistant (MDR) gram-negative bacterium frequently involved in hospital-acquired pneumonia. The infection caused by this superbug has spread quickly in health centers worldwide, leading to high mortality rates. Due to this emerging scenario, the World Health Organization has categorized CRKP as the highest-priority species for the development of new compounds. In this context, antimicrobial peptides (AMPs) stand out as prototypes for alternative antimicrobials against superbugs, including CRKP. Objectives: We aimed to describe the antibacterial effect of an AMP (LyeTx I), derived from the venom of the spider Lycosa erythrognatha, against CRKP in vitro and in a murine pneumonia model. Results: LyeTx I showed antibacterial effects against all the CRKP clinical isolates tested, with a minimum inhibitory concentration (MIC) range of 2–8 µM and a minimum bactericidal concentration (MBC) range of 2–16 µM. The microbial anionic membrane was the primary target of LyeTx I, which acts by displacing divalent cations bound to this structure in a manner similar to that of polymyxins. Notably, LyeTx I displayed significant lytic activity against mimetic membranes, indicating its potential to disrupt bacterial cell integrity. In in vivo assays, the LyeTx I peptide proved to be safe at a dose of 10 mg/kg. In addition, intraperitoneal use of LyeTx I reduced the bacterial load and inflammation in the lungs of animals infected with a hypervirulent strain of CRKP. Conclusions: These results indicate that LyeTx I is a potential prototype for the development of new antibacterials against MDR species, such as CRKP. Full article

(This article belongs to the Special Issue Development of Antibacterial Drugs to Combat Drug-Resistant Bacteria)

18 pages, 3075 KiB

Open AccessArticle

Snake Venom Peptide Fractions from Bothrops jararaca and Daboia siamensis Exhibit Differential Neuroprotective Effects in Oxidative Stress-Induced Zebrafish Models

by Felipe Assumpção da Cunha e Silva, Brenda Rufino da Silva, Leticia Ribeiro de Barros, Emidio Beraldo-Neto, Adolfo Luis Almeida Maleski and Carlos Alberto-Silva

Pharmaceuticals 2025, 18(5), 678; https://doi.org/10.3390/ph18050678 - 2 May 2025

Abstract

Introduction: Snake venoms are rich sources of bioactive peptides with therapeutic potential, particularly against neurodegenerative diseases linked to oxidative stress. While the peptide fraction (<10 kDa) from Bothrops jararaca venom has shown in vitro neuroprotection, analogous fractions from related species remain unexplored in vivo. [...] Read more.

Introduction: Snake venoms are rich sources of bioactive peptides with therapeutic potential, particularly against neurodegenerative diseases linked to oxidative stress. While the peptide fraction (<10 kDa) from Bothrops jararaca venom has shown in vitro neuroprotection, analogous fractions from related species remain unexplored in vivo. Methods: This study comparatively evaluated the neuroprotective effects of two peptide fractions (pf) from Daboia siamensis (pf-Ds) and B. jararaca (pf-Bj) against H₂O₂-induced oxidative stress using in vitro (PC12 cells) and in vivo (zebrafish, Danio rerio) models. Results: In vitro, pf-Ds (1 µg mL⁻¹) did not protect PC12 cells against H₂O₂-induced cytotoxicity, unlike previously reported effects of pf-Bj. In vivo, neither pf-Ds nor pf-Bj (1–20 µg mL⁻¹) induced significant developmental toxicity in zebrafish larvae up to 120 h post-fertilization (hpf). The neuroprotective effects of both pf were evaluated using two experimental models: (I) Larvae at 96 hpf were exposed to either pf-Ds or pf-Bj (10 µg mL⁻¹) for 4 h, followed by co-exposure to H₂O₂ (0.2 mmol L⁻¹) for an additional 10 h to induce oxidative stress (4–20 h model); (II) Embryos at 4 hpf were treated with pf-Ds or pf-Bj (10 µg mL⁻¹) continuously until 96 hpf, after which they were exposed to H₂O₂ (0.2 mmol L⁻¹) for another 24 h (96–120 h model). In a short-term treatment model, neither fraction reversed H₂O₂-induced deficits in metabolism or locomotor activity. However, in a prolonged treatment model, pf-Bj significantly reversed the H₂O₂-induced locomotor impairment, whereas pf-Ds did not confer protection. Conclusions: These findings demonstrate, for the first time, the in vivo neuroprotective potential of pf-Bj against oxidative stress-induced behavioral deficits in zebrafish, contingent on the treatment regimen. The differential effects between pf-Ds and pf-Bj highlight species-specific venom composition and underscore the value of zebrafish for evaluating venom-derived peptides. Full article

(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals: Advances in Peptide Drug Design and Development: From Sequences to Drug Candidates)

► Show Figures

Graphical abstract

11 pages, 1084 KiB

Open AccessCommunication

A Successful Experience of Individualized Vancomycin Dosing in Critically Ill Patients by Using a Loading Dose and Maintenance Dose

by Jorge S. Amador, Álvaro Vega, Patricio Araos, Luis A. Quiñones and Cristián A. Amador

Pharmaceuticals 2025, 18(5), 677; https://doi.org/10.3390/ph18050677 - 2 May 2025

Abstract

Background/Objective: Vancomycin, a hydrophilic glycopeptide antibiotic with bactericidal activity against Gram-positive microorganisms, is one of the most commonly used antibiotics un the intensive care unit (ICU). Different efforts have been made to achieve a therapeutically effective plasma concentration of vancomycin by using loading [...] Read more.

Background/Objective: Vancomycin, a hydrophilic glycopeptide antibiotic with bactericidal activity against Gram-positive microorganisms, is one of the most commonly used antibiotics un the intensive care unit (ICU). Different efforts have been made to achieve a therapeutically effective plasma concentration of vancomycin by using loading and subsequent maintenance doses on an individual basis, but this remains subject to debate. Our objective was to individualize a dosage regimen in a Chilean ICU to optimize the pharmacological treatment of vancomycin by using a population pharmacokinetic model. Methods: A quantitative descriptive study was carried out in 51 patients at the adult ICU, San Borja Arriarán Clinical Hospital in Santiago, Chile. The dose of vancomycin was calculated by using a population pharmacokinetic software, the Antibiotic Kinetics^®, and was subsequently validated with plasma trough levels of the drug through a patient sample. Results: The most commonly prescribed loading dose was 1500 mg and the most commonly used maintenance dose was 1000 mg, three times a day. The measured blood plasma concentrations of each patient (16.98 ± 5.423 μg/mL) were compared with the concentrations calculated through the population pharmacokinetic model (14.33 ± 4.630 μg/mL, p < 0.05). In addition, a correlation was found between the software-calculated trough concentration versus the measured trough concentration for vancomycin, with a positive correlation between both variables established (R² = 0.65; p < 0.0001). No renal side effects were observed in the treated patient group. Conclusions: In the present study, a vancomycin dosing model for critically ill patients, based on a population pharmacokinetic model, was successfully implemented for routine clinical practice. Full article

(This article belongs to the Special Issue Population Pharmacokinetics and Pharmacogenetics)

► Show Figures

Figure 1

19 pages, 1070 KiB

Open AccessReview

The Application of Glycolipid-Type Microbial Biosurfactants as Active Pharmaceutical Ingredients for the Treatment and Prevention of Cancer

by Aileen M. B. McMahon, Matthew S. Twigg, Roger Marchant and Ibrahim M. Banat

Pharmaceuticals 2025, 18(5), 676; https://doi.org/10.3390/ph18050676 - 2 May 2025

Abstract

Pharmaceutical scientists have researched the potential of secondary metabolites biosynthesized by microorganisms as active pharmaceutical ingredients (APIs) for the treatment of cancer. Ideally, these APIs should possess anticancer bioactivity that specifically targets tumor cells while having little cytotoxic effect on healthy tissue. Biosurfactants [...] Read more.

Pharmaceutical scientists have researched the potential of secondary metabolites biosynthesized by microorganisms as active pharmaceutical ingredients (APIs) for the treatment of cancer. Ideally, these APIs should possess anticancer bioactivity that specifically targets tumor cells while having little cytotoxic effect on healthy tissue. Biosurfactants are microbial secondary metabolites with surface-active properties and individual bioactivities that have the potential to either destroy cancer cells in a targeted fashion or prevent tumor cell formation. Currently, the best-studied class of microbial biosurfactants for the purpose of anticancer bioactivity is glycolipids, which contain a hydrophilic sugar moiety bonded to a hydrophobic fatty acid. Anticancer investigations are mainly carried out using in vitro models that show that compounds belonging to each of the four sub-classes of microbial glycolipid have significant anticancer bioactivity. The targeted action of this activity appears to be highly dependent on a specific congener molecular structure with nuanced alterations in structure leading to the killing of both tumor and healthy cells. This review compiles the current literature relating to glycolipid anticancer activity and provides a critical appraisal of exploiting the bioactivity of these compounds as novel anticancer agents. Finally, we propose several suggestions on how this research could be improved moving forward via method standardization. Full article

(This article belongs to the Section Biopharmaceuticals)

► Show Figures

Figure 1

29 pages, 4528 KiB

Open AccessArticle

Performance Evaluation of Inherent Optical Property Algorithms and Identification of Potential Water Quality Indicators Using GCOM-C Data in Eutrophic Lake Kasumigaura, Japan

by Misganaw Choto, Hiroto HIGA, Salem Ibrahim Salem, Eko Siswanto, Takayuki Suzuki and Martin Mäll

Remote Sens. 2025, 17(9), 1621; https://doi.org/10.3390/rs17091621 - 2 May 2025

Abstract

Lake Kasumigaura, one of Japan’s largest lakes, presents significant challenges for remote sensing due to its eutrophic conditions and complex optical properties. Although the Global Change Observation Mission-Climate (GCOM-C)/Second-generation Global Imager (SGLI)-derived inherent optical properties (IOPs) offer water quality monitoring potential, their performance [...] Read more.

Lake Kasumigaura, one of Japan’s largest lakes, presents significant challenges for remote sensing due to its eutrophic conditions and complex optical properties. Although the Global Change Observation Mission-Climate (GCOM-C)/Second-generation Global Imager (SGLI)-derived inherent optical properties (IOPs) offer water quality monitoring potential, their performance in such turbid inland waters remains inadequately validated. This study evaluated five established IOP retrieval algorithms, including the quasi-analytical algorithm (QAA_V6), Garver–Siegel–Maritorena (GSM), generalized IOP (GIOP-DC), Plymouth Marine Laboratory (PML), and linear matrix inversion (LMI), using measured remote sensing reflectance (Rrs) and corresponding IOPs between 2017–2018. The results demonstrated that the QAA had the highest performance for retrieving absorption of particles (a_p) with a Pearson correlation (r) = 0.98, phytoplankton (a_ph) with r = 0.97, and non-algal particles (a_nap) with r = 0.85. In contrast, the GSM algorithm exhibited the best accuracy for estimating absorption by colored dissolved organic matter (a_CDOM), with r = 0.87, along with the lowest mean absolute percentage error (MAPE) and root mean square error (RMSE). Additionally, a strong correlation (r = 0.81) was observed between SGLI satellite-derived remote-sensing reflectance (R_rs) and in situ measurements. Notably, a high correlation was observed between the a_ph (443 nm) and the chlorophyll a (Chl-a) concentration (r = 0.84), as well as between the backscattering coefficient (b_bp) at 443 nm and inorganic suspended solids (r = 0.64), confirming that IOPs are reliable water quality assessment indicators. Furthermore, the use of IOPs as variables for estimating water quality parameters such as Chl-a and suspended solids showed better performance compared to empirical methods. Full article

(This article belongs to the Special Issue Remote Sensing Band Ratios for the Assessment of Water Quality)

20 pages, 9767 KiB

Open AccessArticle

Ecological Value Measurement Assessment and Forecasting in Chengdu City, Sichuan Province, China

by Ran Li, Wende Chen, Kening Xu, Xuan Qi and Jiali Zhou

Sustainability 2025, 17(9), 4138; https://doi.org/10.3390/su17094138 - 2 May 2025

Abstract

This study employs an accounting approach to quantitatively assess Chengdu’s ecological value, focusing on agriculture, forestry, animal husbandry, fisheries, climate regulation, water conservation, water quality purification, and air quality improvement. The value of each indicator is calculated and visualized using ArcGIS 10.8, with [...] Read more.

This study employs an accounting approach to quantitatively assess Chengdu’s ecological value, focusing on agriculture, forestry, animal husbandry, fisheries, climate regulation, water conservation, water quality purification, and air quality improvement. The value of each indicator is calculated and visualized using ArcGIS 10.8, with predictions made for four future time intervals. The analysis reveals the spatial distribution patterns of ecological value across Chengdu. The results indicate the following: (1) From 2015 to 2019, Chengdu’s ecological value indicators demonstrated a positive growth trend, with notable increases in recreation services (CNY 178.5 billion), agriculture, forestry, animal husbandry, and fisheries (CNY 32.88 billion), and water conservation (CNY 9.26 billion). Values exhibited a general decrease from the city center outward. (2) Water quality purification, air quality improvement, and pest control values exhibited slight declines in 2015, 2017, and 2019 compared to 2015. (3) Ecological values demonstrate spatial diversity, with lower values in central areas for categories such as soil conservation and a “high-low-high” pattern for water conservation. Recreation services exhibit a “high in the center, low around the edges” pattern. (4) The gray prediction model forecasts that by 2027, the values for agriculture, forestry, animal husbandry and fisheries, water conservation, and soil conservation will double relative to 2015. Climate regulation and air quality improvement values are predicted to triple, while water quality purification exhibits minimal change. Pest control is expected to decline to 67% of its 2015 value, while the value of recreation services will increase to 12 times its 2015 value. The results of this study reveal the evolutionary characteristics of the ecological value volume index in Chengdu, fill a gap in the field of ecological value volume measurement and prediction in the region, and provide scientific support for understanding the evolutionary trajectory of Chengdu’s ecological environment. Full article

20 pages, 2421 KiB

Open AccessArticle

Socioeconomic Profile of Agricultural Producers and Production Systems in Municipalities of Piauí, Brazil

by Creusa Carvalho da Costa, Ana Cristina Alves Rodrigues, Caroline Chaves Arantes, Graciliano Galdino Alves dos Santos and Emil José Hernández Ruz

Sustainability 2025, 17(9), 4137; https://doi.org/10.3390/su17094137 - 2 May 2025

Abstract

Floodplain agriculture is a practice that involves cultivating arable soils along riverbanks and reservoirs, which become submerged during the rainy season. This study aimed to analyze the socioeconomic aspects of floodplain farmers in the municipalities of Amarante, Floriano, and Uruçuí along the banks [...] Read more.

Floodplain agriculture is a practice that involves cultivating arable soils along riverbanks and reservoirs, which become submerged during the rainy season. This study aimed to analyze the socioeconomic aspects of floodplain farmers in the municipalities of Amarante, Floriano, and Uruçuí along the banks of the Parnaíba River in northeastern Brazil. We conducted semi-structured interviews using the rapport technique. Data were analyzed using generalized linear models with four distributions (gamma, inverse Gaussian, exponential, and Gaussian), with the aim of identifying patterns and relationships between socioeconomic variables and production system profiles. The average age of respondents was 49 years across the three communities, with a predominance of male farmers. Regarding the length of residence, communities in Uruçuí had lived in the area the longest. In terms of monthly income, 80% of farmers earned up to one minimum wage. Land size analysis indicated that properties in Amarante had the highest average land area in hectares. We conclude that agriculture in the region studied is dominated by manual planting, low adoption of technologies, and scarce use of soil conservation techniques, suggesting more sustainable agricultural practices, the development of management plans, and rural extension practices. Full article

► Show Figures

Figure 1

20 pages, 7021 KiB

Open AccessArticle

Construction of Knowledge Graphs for the Constituent Elements and Mineralization Process of Urban Minerals: A Case of Iron and Steel Resources

by Youliang Chen, Lifen Zhang, Lin Chen and Yan Shi

Sustainability 2025, 17(9), 4136; https://doi.org/10.3390/su17094136 - 2 May 2025

Abstract

Urban minerals are secondary resources with economic value that can be recycled and utilized, including iron and steel, non-ferrous metals, rubber, and others. Accurately estimating the quantities of various components is a critical element in the urban mining operations that support sustainable resource [...] Read more.

Urban minerals are secondary resources with economic value that can be recycled and utilized, including iron and steel, non-ferrous metals, rubber, and others. Accurately estimating the quantities of various components is a critical element in the urban mining operations that support sustainable resource management. To achieve this, ontology construction was employed to systematically define and structure the relationships among different entities in the domain. Knowledge graphs were developed to identify the constituent elements and mineralization process of iron and steel, contributing to improved sustainability in urban resource utilization. The knowledge graphs were constructed using a top-down approach and stored in a Neo4j database. When a knowledge graph of iron and steel components is constructed, the iron and steel products are classified into 5 major categories and 14 subcategories. The knowledge graph of the iron and steel mineralization process is divided into five iron and steel mineralization stages and combines industrialization and urbanization to represent the factors that play a role in the iron and steel mineralization process. By leveraging ontology construction, the knowledge graph can improve the efficiency of refining and analyzing data in urban mineral-related fields. This, in turn, provides an essential data basis for establishing a circular economic system for iron and steel industry resources and advancing sustainability-oriented urban mining practices. Full article

(This article belongs to the Section Sustainable Management)

38 pages, 8552 KiB

Open AccessReview

Enzyme-Based Anti-Inflammatory Therapeutics for Inflammatory Diseases

by Kannan Badri Narayanan

Pharmaceutics 2025, 17(5), 606; https://doi.org/10.3390/pharmaceutics17050606 - 2 May 2025

Abstract

Inflammation is a multifaceted biological response of the immune system against various harmful stimuli, including pathogens (such as bacteria and viruses), cellular damage, toxins, and natural/synthetic irritants. This protective mechanism is essential for eliminating the cause of injury, removing damaged cells, and initiating [...] Read more.

Inflammation is a multifaceted biological response of the immune system against various harmful stimuli, including pathogens (such as bacteria and viruses), cellular damage, toxins, and natural/synthetic irritants. This protective mechanism is essential for eliminating the cause of injury, removing damaged cells, and initiating the repair process. While inflammation is a fundamental component of the body’s defense and healing process, its dysregulation can lead to pathological consequences, contributing to various acute and chronic diseases, such as autoimmune disorders, cancer, metabolic syndromes, cardiovascular diseases, neurodegenerative conditions, and other systemic complications. Generally, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs), antihistamines, biologics, and colchicine are used as pharmacological agents in the management of inflammatory diseases. However, these conventional treatments often have limitations, including adverse side effects, long-term toxicity, and drug resistance. In contrast, enzyme-based therapeutics have emerged as a promising alternative due to their high specificity, catalytic efficiency, and ability to modulate inflammatory pathways with reduced side effects. These enzymes function by scavenging reactive oxygen species (ROS), inhibiting cytokine transcription, degrading circulating cytokines, and blocking cytokine release by targeting exocytosis-related receptors. Additionally, their role in tissue repair and regeneration further enhances their therapeutic potential. Most natural anti-inflammatory enzymes belong to the oxidoreductase class, including catalase and superoxide dismutase, as well as hydrolases such as trypsin, chymotrypsin, nattokinase, bromelain, papain, serratiopeptidase, collagenase, hyaluronidase, and lysozyme. Engineered enzymes, such as Tobacco Etch Virus (TEV) protease and botulinum neurotoxin type A (BoNT/A), have also demonstrated significant potential in targeted anti-inflammatory therapies. Recent advancements in enzyme engineering, nanotechnology-based enzyme delivery, and biopharmaceutical formulations have further expanded their applicability in treating inflammatory diseases. This review provides a comprehensive overview of both natural and engineered enzymes, along with their formulations, used as anti-inflammatory therapeutics. It highlights improvements in stability, efficacy, and specificity, as well as minimized immunogenicity, while discussing their mechanisms of action and clinical applications and potential future developments in enzyme-based biomedical therapeutics. Full article

(This article belongs to the Special Issue Medical Applications of Biologic Drugs)

► Show Figures

Figure 1

9 pages, 400 KiB

Open AccessArticle

Diabetic Macular Edema in Maintenance Intravitreal Scheduling

by Enzo Maria Vingolo, Mattia Calabro, Simona Mascolo, Filippo Miccichè, Lorenzo Casillo, Stefano Lupo and Feliciana Menna

Pharmaceutics 2025, 17(5), 605; https://doi.org/10.3390/pharmaceutics17050605 - 2 May 2025

Abstract

Objectives: This study aimed to assess the impact of an oral formulation combining bromelain (250 mg) derived from Ananas comosus (L.) Merr. Jambs and diosmin mcgSMIN Plus (250 mg) on visual acuity and central retinal thickness (CRT) in patients undergoing anti-VEGF intravitreal maintenance [...] Read more.

Objectives: This study aimed to assess the impact of an oral formulation combining bromelain (250 mg) derived from Ananas comosus (L.) Merr. Jambs and diosmin mcgSMIN Plus (250 mg) on visual acuity and central retinal thickness (CRT) in patients undergoing anti-VEGF intravitreal maintenance therapy (IVT) for cystoid, center-involving diabetic macular edema (DME). Methods: A total of forty patients with type 2 diabetes and center-involving DME, all receiving anti-VEGF maintenance therapy, were prospectively enrolled in a case-control study. Group A (20 eyes) was administered one tablet containing 250 mg of bromelain and 250 mg of diosmin mcgSMIN Plus twice daily for a period of two months. Group B (20 eyes) was monitored without drug administration until the next IVT. After two months and IVT administration, the groups were switched. At the end of the study, the collected data were divided into two groups. The treatment group included data from patients who received the dietary supplement, and the control group consisted of data from patients who were only observed during anti-VEGF therapy. Best-corrected visual acuity (BCVA) and CRT measurements were assessed at baseline, after two months, and after four months. Results: A statistically significant improvement in CRT was observed in the treatment group compared to the control group during follow-up (p < 0.05). However, the improvement in BCVA was not statistically significant. Conclusions: Orally administered combination of bromelain 250 mg and 250 mg diosmin mcgSMIN Plus has positive impact on central retinal thickness in patients treated for cystoid center-involving diabetic macular edema (DME) with anti-VEGF intravitreal maintenance therapy. Full article

(This article belongs to the Section Drug Delivery and Controlled Release)

► Show Figures

Figure 1

16 pages, 2598 KiB

Open AccessArticle

Noncanonical Poly(A) Polymerase TENT4 Drives Expression of Subgenomic Hepatitis A Virus RNAs in Infected Cells

by You Li, Ankit Gupta, Brian N. Papas, David Aponte-Diaz, Jayden M. Harris, Ichiro Misumi, Jason K. Whitmire, Craig E. Cameron, Marcos Morgan and Stanley M. Lemon

Viruses 2025, 17(5), 665; https://doi.org/10.3390/v17050665 - 2 May 2025

Abstract

Both hepatitis B virus (HBV), an hepadnavirus with a DNA genome, and hepatitis A virus (HAV), a picornavirus, require the TRAMP-like host ZCCHC14-TENT4 complex for efficient replication. However, whereas HBV requires the nucleotidyltransferase activity of TENT4 to extend and stabilize the 3′ poly(A) [...] Read more.

Both hepatitis B virus (HBV), an hepadnavirus with a DNA genome, and hepatitis A virus (HAV), a picornavirus, require the TRAMP-like host ZCCHC14-TENT4 complex for efficient replication. However, whereas HBV requires the nucleotidyltransferase activity of TENT4 to extend and stabilize the 3′ poly(A) tails of mRNA transcribed from its genome, the role played by TENT4 in HAV replication is uncertain. HAV proteins are synthesized directly from its genomic RNA, which possesses a 3′ poly(A) tail, with its length and composition presumably maintained by 3D^pol-catalyzed RNA transcription during its replicative cycle. Using nanopore long-read sequencing of RNA from infected cells, we confirm here that the length of the HAV 3′ poly(A) tail is not altered by treating infected cells with RG7834, a small molecule TENT4 inhibitor with potent anti-HAV activity. Despite this, TENT4 catalytic activity is essential for HAV replication. Surprisingly, nanopore sequencing revealed a low abundance of HAV subgenomic RNAs (hsRNAs) that extend from the 5′ end of the genome to a site within the 5′ untranslated RNA (5′UTR) immediately downstream of a stem-loop to which the ZCCHC14-TENT4 complex is recruited. These hsRNAs are polyadenylated, and their abundance is sharply reduced by RG7834 treatment, implying they are likely products of TENT4. Similar subgenomic RNAs were not identified in poliovirus-infected cells. hsRNAs are present not only in HAV-infected cell culture but also in the liver of HAV-infected mice, where they represent 1–3% of all HAV transcripts, suggesting their physiological relevance. However, transfecting exogenous hsRNA into TENT4-depleted cells failed to rescue HAV replication, leaving the functional role of hsRNA unresolved. These findings reveal a novel picornaviral subgenomic RNA species while highlighting mechanistic differences in the manner in which HAV and HBV exploit the host ZCCHC4-TENT4 complex for their replication. Full article

(This article belongs to the Special Issue 15-Year Anniversary of Viruses)

► Show Figures

Figure 1

23 pages, 6791 KiB

Open AccessArticle

Modeling Ecological Risk in Bottom Sediments Using Predictive Data Analytics: Implications for Energy Systems

by Bartosz Przysucha, Monika Kulisz, Justyna Kujawska, Michał Cioch, Adam Gawryluk and Rafał Garbacz

Energies 2025, 18(9), 2329; https://doi.org/10.3390/en18092329 - 2 May 2025

Abstract

Sediment accumulation in dam reservoirs significantly impacts hydropower efficiency and infrastructure sustainability. Bottom sediments often contain heavy metals such as Cr, Ni, Cu, Zn, Cd, and Pb, which can pose ecological risks and affect water quality. Moreover, excessive sedimentation reduces reservoir capacity, increases [...] Read more.

Sediment accumulation in dam reservoirs significantly impacts hydropower efficiency and infrastructure sustainability. Bottom sediments often contain heavy metals such as Cr, Ni, Cu, Zn, Cd, and Pb, which can pose ecological risks and affect water quality. Moreover, excessive sedimentation reduces reservoir capacity, increases turbine wear, and raises operational costs, ultimately hindering energy production. This study examined the ecological risk of heavy metals in bottom sediments and explored predictive approaches to support sediment management. Using 27 sediment samples from Zemborzyce Lake, the concentrations of selected heavy metals were measured at two depths (5 cm and 30 cm). Ecological risk index (ERI) values for the deep layer were predicted based on surface data using artificial neural networks (ANNs) and multiple linear regression (MLR). Both models showed a high predictive accuracy, demonstrating the potential of data-driven methods in sediment quality assessment. The early identification of high-risk areas allows for targeted dredging and optimized maintenance planning, minimizing disruption to dam operations. Integrating predictive analytics into hydropower management enhances system resilience, environmental protection, and long-term energy efficiency. Full article

(This article belongs to the Special Issue Sustainable Energy, Environment and Low-Carbon Development)

► Show Figures

Figure 1

15 pages, 2018 KiB

Open AccessArticle

Shear Wave Elastography of the Sciatic Nerve and Its Relationship with Posterior Chain Flexibility in Healthy Participants: An Observational Study

by Charles Cotteret, Jaime Almazán-Polo and Ángel González-de-la-Flor

Sensors 2025, 25(9), 2885; https://doi.org/10.3390/s25092885 - 2 May 2025

Abstract

Introduction: Shear wave elastography (SWE) has been widely used to assess the mechanical properties of peripheral nerves, including the sciatic nerve. However, the relationship between sciatic nerve stiffness and posterior chain flexibility remains unclear. Therefore, we aimed to examine differences in sciatic nerve [...] Read more.

Introduction: Shear wave elastography (SWE) has been widely used to assess the mechanical properties of peripheral nerves, including the sciatic nerve. However, the relationship between sciatic nerve stiffness and posterior chain flexibility remains unclear. Therefore, we aimed to examine differences in sciatic nerve stiffness and shear wave speed (SWS) based on limb dominance and hamstring flexibility, and to explore their association with posterior chain mobility assessed through AKE and ASLR tests in healthy individuals. Methods: An observational study was conducted on 25 healthy, physically active participants (49 lower limbs). Sciatic nerve stiffness was measured using SWE at a standardized location in the posterior thigh. Posterior chain flexibility was assessed using the Active Knee Extension (AKE) and Active Straight Leg Raise (ASLR) tests. Participants were categorized based on hamstring flexibility, and comparisons were made between dominant and non-dominant limbs. Results: Participants with limited hamstring flexibility exhibited significantly higher AKE and ASLR values (p < 0.001) and showed an increased stiffness and SWS towards greater sciatic nerve (p = 0.05), although correlations between SWE values and flexibility tests were not significant. No significant differences were found between dominant and non-dominant limbs in AKE (p = 0.28), ASLR (p = 0.47), SWE (p = 0.38), or SWS (p = 0.34) values. Conclusion: Although no significant correlations were found between SWE parameters and flexibility tests, individuals with limited posterior chain mobility exhibited higher sciatic nerve stiffness in healthy participants. Full article

(This article belongs to the Section Physical Sensors)

12 pages, 5190 KiB

Open AccessArticle

Flexible Stretchable Strain Sensor Based on LIG/PDMS for Real-Time Health Monitoring of Test Pilots

by Shouqing Li, Zhanghui Wu, Hongyun Fan, Mian Zhong, Xiaoqing Xing, Yongzheng Wang, Huaxiao Yang, Qijian Liu and Deyin Zhang

Sensors 2025, 25(9), 2884; https://doi.org/10.3390/s25092884 - 2 May 2025

Abstract

In the rapidly advancing era of intelligent technology, flexible strain sensors are emerging as a key component in wearable electronics. Laser-induced graphene (LIG) stands out as a promising fabrication method due to its rapid processing, environmental sustainability, low cost, and superior physicochemical properties. [...] Read more.

In the rapidly advancing era of intelligent technology, flexible strain sensors are emerging as a key component in wearable electronics. Laser-induced graphene (LIG) stands out as a promising fabrication method due to its rapid processing, environmental sustainability, low cost, and superior physicochemical properties. However, the stretchability and conformability of LIG are often limited by the substrate material, hindering its application in scenarios requiring high deformation. To address this issue, we propose a high-performance flexible and stretchable strain sensor fabricated by generating graphene on a polyimide (PI) substrate using laser induction and subsequently transferred onto a polydimethylsiloxane (PDMS). The resultant sensor demonstrates an ultra-low detection limit (0.1%), a rapid response time (150 ms), a wide strain range (40%), and retains stable performance after 1000 stretching cycles. Notably, this sensor has been successfully applied to the real-time monitoring of civil aviation test pilots during flight for the first time, enabling the accurate detection of physiological signals such as pulse, hand movements, and blink frequency. This study introduces a unique and innovative solution for the real-time health monitoring of civil aviation test pilots, with significant implications for enhancing flight safety. Full article

(This article belongs to the Special Issue Smart Wearable Health Monitoring Systems: Materials, Sensors, Nanogenerators and Self-Powered Applications)

► Show Figures

Figure 1

26 pages, 744 KiB

Open AccessArticle

Novel Gain-Optimized Two-Step Fusion Filtering Method for Ranging-Based Localization Using Predicted Residuals

by Bo Chang, Xinrong Zhang, Na Sun and Hao Ni

Sensors 2025, 25(9), 2883; https://doi.org/10.3390/s25092883 - 2 May 2025

Abstract

A two-stage fusion filtering positioning algorithm based on prediction residuals and gain adaptation is proposed to address the problems of disturbance and modeling errors in the application of distance-based positioning algorithms in wireless sensor networks, as well as inaccurate initial filtering values leading [...] Read more.

A two-stage fusion filtering positioning algorithm based on prediction residuals and gain adaptation is proposed to address the problems of disturbance and modeling errors in the application of distance-based positioning algorithms in wireless sensor networks, as well as inaccurate initial filtering values leading to large estimation errors or even divergence. Firstly, based on parameterization methods, a pseudo linear equation is constructed from the time of arrival (TOA) and multipath delay. The weighted least squares (WLS) method is applied to obtain the initial value of target position resolution, and its performance approaches the Cramér–Rao lower bound (CRLB). Secondly, the exact position of the target is obtained using the reconstructed Gaussian white noise statistics and the Kalman filtering algorithm. The simulation results show that compared with other initial positioning algorithms, the average positioning accuracy of the proposed algorithm is improved by 28.57%, and it has a better filtering performance. Full article

(This article belongs to the Section Sensor Networks)

Recent Articles

Open Access Journals

Highly Accessed Articles

Latest Books

News

Blog Posts

Topics

Selected Special Issues

Selected Collections

Journals by Subject

Further Information

Guidelines

MDPI Initiatives

Follow MDPI