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19 pages, 2750 KB  
Article
SORL1 as a Putative Candidate Gene for a Novel Recessive Form of Complicated Hereditary Spastic Paraplegia: Insights from a Deep Functional Study
by Ananthapadmanabha Kotambail, Yogananda Shamamandri Markandeya, Raghavendra Mahima, Ramya Sukrutha, Madhura Milind Nimonkar, Suravi Sasmita Dash, Chandrajit Prasad, Ghati Kasturirangan Chetan, Pooja Mailankody and Gautham Arunachal
Clin. Transl. Neurosci. 2025, 9(4), 46; https://doi.org/10.3390/ctn9040046 - 1 Oct 2025
Abstract
Introduction: Genes in the endolysosome and autophagy pathways are major contributors to hereditary spastic paraplegia (HSP). A pathogenetic link between HSP and Alzheimer disease (AD) involving macroautophagy is well established. Sortilin-related receptor 1 (SORL1), an endosomal trafficking protein, plays a [...] Read more.
Introduction: Genes in the endolysosome and autophagy pathways are major contributors to hereditary spastic paraplegia (HSP). A pathogenetic link between HSP and Alzheimer disease (AD) involving macroautophagy is well established. Sortilin-related receptor 1 (SORL1), an endosomal trafficking protein, plays a key role in glutamatergic neuron homeostasis and white matter tract integrity. Until now, SORL1 has only been associated with dominant AD and cerebral amyloid angiopathy. Methods: A case of HSP with cerebroretinal vasculopathy (CRV) negative on exome sequencing was further investigated using whole-genome sequencing. RNA-seq, Western blot, and immunofluorescence imaging were performed to explore a potential loss-of-function mechanism. Results: Sequencing revealed a biallelic SORL1 splice donor variant (c.1211 + 1G > A). Transcriptomics confirmed nonsense-mediated decay and aberrant splicing, predicting a disrupted reading frame. Reduced SORLA protein levels and significant enlargement of endolysosomes in patient-derived fibroblasts further cemented the pathogenicity of the variant. Conclusions: The probability that SORL1 acts as a recessive disease-causing gene gathers support from the following data: SORL1 genomic constraint score pRec = 1, high meiotic recombination rates on the locus, phenotype of Sorl1/ mice reminiscent of HSP with CRV, and endolysosomal enlargement in SORL1/ glutamatergic neurons in vitro. Taken together, SORL1 is probably a new candidate for a recessive form of complicated HSP. Full article
(This article belongs to the Section Neuroscience/translational neurology)
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14 pages, 6591 KB  
Article
One-Step Fe/N Co-Doping for Efficient Catalytic Oxidation and Selective Non-Radical Pathway Degradation in Sludge-Based Biochar
by Zupeng Gong, Shixuan Ding, Mingjie Huang, Wen-da Oh, Xiaohui Wu and Tao Zhou
Catalysts 2025, 15(10), 934; https://doi.org/10.3390/catal15100934 - 1 Oct 2025
Abstract
This study presents the preparation of iron and nitrogen co-doped sludge-based biochar (FeCN-MSBC) and iron oxide-doped biochar (FeO-MSBC) by ball milling municipal sludge with different iron precursors (K3Fe(CN)6 and Fe2O3), followed by pyrolysis. These biochars were [...] Read more.
This study presents the preparation of iron and nitrogen co-doped sludge-based biochar (FeCN-MSBC) and iron oxide-doped biochar (FeO-MSBC) by ball milling municipal sludge with different iron precursors (K3Fe(CN)6 and Fe2O3), followed by pyrolysis. These biochars were utilized to activate persulfate (PMS) for the degradation of phenolic pollutants. The results demonstrate that FeCN-MSBC, formed by the introduction of K3Fe(CN)6, contains Fe/N phases, with surface Fe sites exhibiting a lower oxidation state, which significantly enhances PMS activation efficiency. In contrast, FeO-MSBC, due to the aggregation of Fe2O3/Fe3O4, shows relatively lower catalytic activity. The FeCN-MSBC/PMS system degrades pollutants via a synergistic mechanism involving non-radical pathways mediated by 1O2 and electron transfer processes (ETP) catalyzed by surface Fe. Electrochemical oxidation and quenching experiments confirm that ETP is the dominant pathway. FeCN-MSBC, prepared at a pyrolysis temperature of 600 °C and an Fe loading of 3 mmol/g TSS, exhibited the best performance, achieving a phenol degradation rate constant (kobs) of 0.127 min−1, 4.5 times higher than that of undoped biochar (MSBC). FeCN-MSBC/PMS maintained high efficiency across a wide pH range and in complex water matrices, exhibiting excellent stability over multiple cycles, demonstrating strong potential for practical applications. This study provides an effective strategy for simultaneous Fe and N doping in sludge-derived biochar and offers mechanistic insights into Fe/N synergistic activation of PMS for practical water treatment. Full article
(This article belongs to the Special Issue Environmentally Friendly Catalysis for Green Future)
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17 pages, 5083 KB  
Article
Experimental Study on the Thermal Control Mechanism of Hydrogels Enhanced by Porous Framework
by Fajian Li, Yinwei Ma, Guangqi Dong, Xuyang Hu, Yian Wang, Sujun Dong, Junjian Wang and Xiaobo Liu
Appl. Sci. 2025, 15(19), 10578; https://doi.org/10.3390/app151910578 - 30 Sep 2025
Abstract
The enhancement effect and mechanism of porous frameworks on hydrogel thermal control performance are key factors in evaluating their engineering applications and performance improvements. This study investigates the enhancement mechanism of porous framework composite phase-change materials (CPCM) on hydrogel thermal control performance through [...] Read more.
The enhancement effect and mechanism of porous frameworks on hydrogel thermal control performance are key factors in evaluating their engineering applications and performance improvements. This study investigates the enhancement mechanism of porous framework composite phase-change materials (CPCM) on hydrogel thermal control performance through multi-scale visualization comparison experiments. Results indicate that pure hydrogels, due to their dense internal structure, hinder water vapor escape, thereby impeding overall fluidity and mass transfer rates. The introduction of a porous framework significantly improves internal heat transfer and moisture transport pathways within the hydrogel, enabling smooth water vapor release during heating and preventing localized heat accumulation. Under 100 °C heating conditions, CPCM exhibited a 65% reduction in mass-specific dehydration rate compared to pure hydrogel, with a 25% lower temperature drop. Energy efficiency increased by 13.5% over hydrogel, while the coefficient of variation decreased by 34.1%, demonstrating superior thermal stability and temperature control capabilities. This study elucidates from a mechanistic perspective how porous frameworks regulate the thermal and mass transfer behaviors of hydrogels, providing a theoretical basis and experimental support for their advanced application and optimization in the thermal control systems of electronic devices. Full article
(This article belongs to the Section Applied Thermal Engineering)
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16 pages, 545 KB  
Review
Shared Immunopathogenic Mechanisms in Chronic Spontaneous Urticaria, Vitiligo, and Hashimoto’s Thyroiditis: The Role of Oxidative Stress and Vitamin D
by Rossella Casella, Federica Li Pomi, Francesco Borgia, Eustachio Nettis and Sebastiano Gangemi
Life 2025, 15(10), 1535; https://doi.org/10.3390/life15101535 - 29 Sep 2025
Abstract
Introduction: Chronic spontaneous urticaria (CSU), vitiligo, and Hashimoto’s thyroiditis (HT) frequently co-occur in the same patients, suggesting a shared autoimmune pathogenesis. These conditions are increasingly recognized as components of polyautoimmunity, with overlapping clinical, immunological, and pathogenetic features. Among the proposed common mechanisms, vitamin [...] Read more.
Introduction: Chronic spontaneous urticaria (CSU), vitiligo, and Hashimoto’s thyroiditis (HT) frequently co-occur in the same patients, suggesting a shared autoimmune pathogenesis. These conditions are increasingly recognized as components of polyautoimmunity, with overlapping clinical, immunological, and pathogenetic features. Among the proposed common mechanisms, vitamin D deficiency and oxidative stress (OS) have emerged as key contributors. We aimed to explore the shared immunopathogenic pathways linking these conditions, with a focus on the interplay between vitamin D status and redox imbalance. Methods: An extensive narrative review of the current literature regarding the associations among CSU, vitiligo, and HT, focusing on the role of vitamin D status, OS, and nitrosative stress, and shared immunological pathways was conducted. Discussion: Vitamin D deficiency was consistently observed across all three conditions and is associated with increased disease activity and poorer clinical outcomes. Several polymorphisms in the vitamin D receptor (VDR) and binding protein genes correlate with disease susceptibility. OS and nitrosative stress markers, such as malondialdehyde (MDA) and nitric oxide (NO) metabolites, are elevated in patients with CSU, vitiligo, and HT, and are linked to tissue-specific immune activation, apoptosis, and loss of self-tolerance. Evidence suggests that vitamin D and antioxidant supplementation may provide clinical benefit. In vitiligo, narrowband ultraviolet B (NB-UVB) phototherapy not only promotes repigmentation through melanocyte stimulation but also reduces ROS production and modulates local immune responses. Conclusions: The coexistence of CSU, vitiligo, and HT reflects a broader systemic autoimmune tendency, with vitamin D deficiency and redox imbalance serving as potential unifying mechanisms. Routine assessment of vitamin D levels and OS parameters may enhance diagnostic precision and inform therapeutic strategies. Antioxidant-based interventions represent promising avenues in the integrated management of autoimmune skin and endocrine disorders. Full article
(This article belongs to the Special Issue Innovative Approaches in Dermatological Therapies and Diagnostics)
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24 pages, 9143 KB  
Article
M2 Macrophage Polarization Mediated by Complement C3 from Hedgehog-Activated Fibroblasts Establishes an Immunosuppressive Niche in Gastric Cancer
by Jiaheng Lou, Jingcheng Zhang, Zhiyuan Song, Shuo Zhang, Sicheng Zhao, Yunhai Wei, Guiping Chen, Tao Jiang and Guangji Zhang
Cancers 2025, 17(19), 3164; https://doi.org/10.3390/cancers17193164 - 29 Sep 2025
Abstract
Introduction: The Hedgehog (Hh) signaling pathway is aberrantly activated in various types of cancer and plays a critical regulatory role. However, its biological significance in gastric cancer remains unclear. In this study, the mechanism underlying the role of Hh in gastric cancer [...] Read more.
Introduction: The Hedgehog (Hh) signaling pathway is aberrantly activated in various types of cancer and plays a critical regulatory role. However, its biological significance in gastric cancer remains unclear. In this study, the mechanism underlying the role of Hh in gastric cancer progression and prognosis was investigated through bioinformatics analysis as well as in vitro and in vivo experiments. Methods: In this study, a systematic analysis of scRNA-seq datasets and bulk RNA-seq datasets from gastric cancer patients derived from the GEO database and TCGA database was performed by us, which revealed the activation characteristics of Hh in different cell types within the gastric cancer tumor microenvironment (TME). Furthermore, through conducting multiplex immunofluorescence staining experiments on clinical gastric cancer samples, we clarified the association mechanism between fibroblasts with highly activated Hh and the gastric cancer tumor immunosuppressive microenvironment. Finally, by means of in vitro and in vivo experiments, we elucidated the key molecular mechanism by which fibroblasts with highly activated Hh remodel the gastric cancer tumor immunosuppressive microenvironment. Results: We identified a distinct subpopulation of fibroblasts, designated MMP1 + FIB, in the gastric cancer tumor microenvironment. Studies revealed that this subpopulation can significantly activate Hh, suggesting it may play a crucial role in the regulation of the TME. Subsequent mechanistic investigations further confirmed that MMP1 + FIB exhibits a significant correlation with the immunosuppressive state of the TME (R = 0.29, p = 2.5 × 10−0.8). In terms of the specific functions, the complement system in this fibroblast subpopulation is significantly activated (p < 0.05); further studies demonstrated that MMP1 + FIB can induce the polarization of macrophages toward the M2 subtype (an immunosuppressive phenotype) by specifically secreting complement C3 protein. Collectively, these processes contribute to the establishment of an immunosuppressive TME and ultimately promote the proliferation and metastasis of gastric cancer cells. Discussion: Aberrant activation of the Hh signaling pathway promotes gastric cancer progression via the MMP1 + FIB–C3–macrophage axis, providing a potential therapeutic strategy for targeting the tumor microenvironment. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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11 pages, 538 KB  
Article
Real-Life Use Patterns of Androgen Receptor Pathway Inhibitors (ARPIs): A Nationwide Register-Based Study in Finland During 2012–2023
by Terhi Kurko, Pekka Heino, Pirkko-Liisa Kellokumpu-Lehtinen, Kati Sarnola, Hanna Koskinen and Maarit Bärlund
Cancers 2025, 17(19), 3162; https://doi.org/10.3390/cancers17193162 - 29 Sep 2025
Abstract
Background and Objective: Prostate cancer (PC) is the most common cancer among males in the Western World. Androgens are key growth regulators both in normal and malignant prostate growth. Several new types of androgen pathway inhibitors (ARPIs) have been developed for the treatment [...] Read more.
Background and Objective: Prostate cancer (PC) is the most common cancer among males in the Western World. Androgens are key growth regulators both in normal and malignant prostate growth. Several new types of androgen pathway inhibitors (ARPIs) have been developed for the treatment of PC. Despite the lack of evidence, sequential use of ARPIs has been adopted into everyday clinical practice. This study aimed to assess real-life ARPI use patterns, especially sequential use and treatment costs, in Finland. Methods: Nationwide register data on all ARPI (enzalutamide, apalutamide, darolutamide, abiraterone) purchases recorded in the National Health Insurance scheme register maintained by the Social Insurance Institution of Finland from January 2012 to December 2023 were used. The data included patient demographics and medicine purchase details, which were descriptively analysed. Results: During the study period, 8369 patients initiated ARPIs. The median age of the users was 75.1 years. Of these, 32.1% (n = 2685) used at least two ARPIs sequentially. The proportion of treatment initiations leading to sequential use increased from 36% in 2012 to 56% in 2017, then decreased to 14% in 2022. The total cost of sequential use was €43.8 million. Limitations include the unrecorded phase of PC. The study’s strength is its inclusion of all reimbursed ARPI purchases nationwide. Conclusions: Despite the lack of evidence, sequential ARPI use was initially prevalent but declined after the introduction of new guidelines. Randomised trials are needed to guide the sequential use of these medicines. Patient summary: Androgen pathway inhibitors (ARPIs) are widely used in prostate cancer in Finland. One-third of patients use at least two ARPIs sequentially to inhibit testosterone effect. However, there are no large clinical trials published demonstrating the benefits of sequential treatment. More evidence is needed to justify sequential use. Full article
(This article belongs to the Section Clinical Research of Cancer)
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19 pages, 1897 KB  
Systematic Review
Unveiling the Mechanisms for the Development of Cardiotoxicity Following Chemotherapy Regimens Administration for Primary Colorectal Cancer: A Systematic Review
by Sophia Tsokkou, Ioannis Konstantinidis, Paraskevi Chatzikomnitsa, Menelaos Papakonstantinou, Evdokia Toutziari, Dimitrios Giakoustidis, Theodora Papamitsou, Vasileios Papadopoulos and Alexandros Giakoustidis
Cancers 2025, 17(19), 3129; https://doi.org/10.3390/cancers17193129 - 26 Sep 2025
Abstract
Background/Introduction: Colorectal carcinoma (CRC) belongs to the most commonly diagnosed malignancies to this date, ranking as third across the globe. In addition, CRC remains a leading cause of cancer-related deaths as it is ranked as the second most common cause of mortality. [...] Read more.
Background/Introduction: Colorectal carcinoma (CRC) belongs to the most commonly diagnosed malignancies to this date, ranking as third across the globe. In addition, CRC remains a leading cause of cancer-related deaths as it is ranked as the second most common cause of mortality. Therapeutic strategies for the management and treatment of CRC have made significant progress in the last two decades, with both adjuvant and neoadjuvant approaches playing critical roles in enhancing favorable outcomes with regimens like FOLFOX, CAPOX, and 5-FU-based therapies demonstrating effectiveness. Nevertheless, growing evidence indicates that these therapies may pose a risk of cardiotoxicity development. A systematic review will be conducted to map the mechanistic pathways of chemotherapy-induced in CRC in order to bridge oncology and cardiology perspectives, highlighting emerging diagnostic tools and long-term surveillance gaps. Purpose: The objective of this study is the investigation of the prevalence and characteristics of cardiovascular problems linked to frequently employed chemotherapy regimens, as well as to evaluate existing diagnostic and therapeutic approaches. Methodology: A thorough search across databases, including PubMed (MEDLINE), Embase, and Cochrane Library, was performed to locate articles published up to 2025. The final studies included in the review underwent quality assessment. Results: Fourteen qualifying studies, comprising both prospective trials and case reports from diverse geographies, were included. Cardiovascular outcomes including myocardial strain, arrhythmias, angina, heart failure, and Takotsubo cardiomyopathy were evaluated. The diagnostic methods assessed comprised echocardiography, cardiac biomarkers, and electrocardiograms. In the reviewed trials, chemotherapy-induced cardiotoxicity varied from asymptomatic ventricular strain to serious cardiac complications. The FOLFOX and 5-FU regimens were predominantly linked to adverse cardiac outcomes. Prompt identification by echocardiographic strain imaging and biomarker monitoring facilitated timely intervention. Case studies revealed that, given proper cardiological support, certain patients could safely recommence chemotherapy following recovery. No standardized cardiac screening protocol was identified among the trials. Conclusions: Chemotherapy for colorectal cancer may present considerable cardiovascular hazards, highlighting the necessity for routine cardiac monitoring prior to and throughout treatment. This systematic review promotes collaborative cardio-oncology strategies to reduce risk and enhance therapeutic safety. Full article
(This article belongs to the Special Issue Cardio-Oncology: An Emerging Paradigm in Modern Medicine: 2nd Edition)
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16 pages, 1915 KB  
Article
Effects of Mn Deficiency on Hepatic Oxidative Stress, Lipid Metabolism, Inflammatory Response, and Transcriptomic Profile in Mice
by Yaodong Hu, Shi Tang, Silu Wang, Caiyun Sun, Binlong Chen, Binjian Cai and Heng Yin
Nutrients 2025, 17(19), 3030; https://doi.org/10.3390/nu17193030 - 23 Sep 2025
Viewed by 127
Abstract
Introduction: Mn is a trace element essential for growth and development in organisms, and adequate Mn levels are crucial for maintaining normal liver function. This study aimed to investigate the effects of Mn deficiency on the liver and elucidate the underlying mechanisms using [...] Read more.
Introduction: Mn is a trace element essential for growth and development in organisms, and adequate Mn levels are crucial for maintaining normal liver function. This study aimed to investigate the effects of Mn deficiency on the liver and elucidate the underlying mechanisms using transcriptomics. Methods: Weanling mice were fed a Mn-deficient diet, and Mn chloride (MnCl2) was administered intraperitoneally to correct the deficiency. Liver pathological changes were evaluated through histological examination. Liver function and key lipid metabolism markers were assessed using biochemical assays, while hepatic oxidative stress levels were measured via flow cytometry and biochemical kits. Alterations in inflammatory factors were detected using ELISA and qPCR. The mechanisms underlying Mn’s effects on liver function were further explored through Western blot, qPCR, and transcriptome sequencing. Results: Mn deficiency impaired liver morphology and structure. Serum levels of ALT, AST, and ALP were significantly elevated, while ALB decreased, confirming hepatic dysfunction. This dysfunction led to oxidative stress, characterized by increased hepatic ROS and MDA levels, alongside reduced Mn-SOD, GSH-Px, and T-AOC activities. Additionally, Mn deficiency elevated serum TG, TC, and LDL-C levels, indicating abnormal lipid metabolism. Hepatic pro-inflammatory factors (IL-6, IL-1β, and TNF-α) were significantly upregulated. Transcriptomic analysis revealed distinct gene expression patterns under different Mn conditions, with KEGG pathway analysis identifying the PPAR signaling pathway as a key regulatory target. Conclusions: Our findings suggest a potential pathogenic cascade in which manganese deficiency may initially induce hepatic oxidative stress, potentially leading to suppression of the PPAR signaling pathway. This inhibition of PPARα/γ could subsequently orchestrate downstream manifestations of aberrant lipid metabolism and inflammatory responses. Thus, the PPAR signaling pathway is proposed as a plausible central hub for translating oxidative damage into metabolic and inflammatory dysfunction in the manganese-deficient liver. Full article
(This article belongs to the Special Issue A New Perspective: The Effect of Trace Elements on Human Health)
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30 pages, 4224 KB  
Article
Tracing Five Decades of Psoriasis Pharmacotherapy: A Large-Scale Bibliometric Investigation with AI-Guided Terminology Normalization
by Ada Radu, Andrei-Flavius Radu, Gabriela S. Bungau, Delia Mirela Tit and Paul Andrei Negru
Pharmaceuticals 2025, 18(9), 1422; https://doi.org/10.3390/ph18091422 - 21 Sep 2025
Viewed by 347
Abstract
Background/Objectives: Large-scale bibliometric assessments of psoriasis pharmacotherapy research remain limited despite significant research output in this rapidly evolving field. This study aimed to map the evolution of systemic psoriasis therapy research over five decades and demonstrate how systematic analysis of research trajectories [...] Read more.
Background/Objectives: Large-scale bibliometric assessments of psoriasis pharmacotherapy research remain limited despite significant research output in this rapidly evolving field. This study aimed to map the evolution of systemic psoriasis therapy research over five decades and demonstrate how systematic analysis of research trajectories can illuminate the transformation of specialized medical fields into central components of precision medicine. Methods: A comprehensive bibliometric analysis was conducted using Web of Science Core Collection as the single data source, examining 19,284 publications spanning 1975–2025. The methodology employed AI-enhanced terminology normalization for standardizing pharmaceutical nomenclature, VOSviewer version 1.6.20 for network visualization, and Bibliometrix package for temporal trend analysis and thematic evolution mapping. International collaboration networks, thematic evolution across three distinct periods (1975–2000, 2001–2010, 2011–2025), and citation impact patterns were systematically analyzed. Results: Four distinct developmental phases were identified, with publications growing from 9 articles in 1975 to 1638 in 2024. The United States dominated research output with 5959 documents, while Canada achieved the highest citation efficiency at 62.65 citations per document. Global collaboration encompassed 70 countries organized into four regional clusters, with a 28-nation Asia–Pacific–Africa–Middle East alliance representing the largest collaborative group. Citation impact peaked during 2001–2008, coinciding with revolutionary biological therapy introduction. Thematic evolution demonstrated systematic transformation from two foundational themes to nine specialized domains, ultimately consolidating into four core areas focused on targeted therapeutics and evidence-based methodologies. Keyword analysis demonstrated progression from basic immunological studies to sophisticated targeted interventions, evolving from tumor necrosis factor alpha inhibitors to contemporary interleukin-17/interleukin-23 pathway targeting and Janus kinase inhibitors. Conclusions: Over five decades, psoriasis therapeutics research has shifted from a niche dermatological discipline to a central model for innovation in immune-mediated diseases. This evolution illustrates how bibliometric approaches can capture the dynamics of scientific transformation, offering strategic insights for guiding pharmaceutical innovation, shaping research priorities, and informing precision medicine strategies across inflammatory conditions. Full article
(This article belongs to the Section Pharmacology)
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19 pages, 20956 KB  
Article
Analysis of Potential Q-Markers for Salt-Processed Alismatis Rhizoma in Diuresis Based on Fingerprinting Technology and Network Analysis
by Lin Yan, Zemin Ou, Yun Wang, Yan Tong, Jinyu Wang and Dewen Liu
Curr. Issues Mol. Biol. 2025, 47(9), 783; https://doi.org/10.3390/cimb47090783 - 21 Sep 2025
Viewed by 153
Abstract
Introduction: The ability of salt-processed Alismatis Rhizoma (SAR) (Alisma plantago-aquqtica L.) to nourish Yin and promote urination is stronger than that of Alismatis Rhizoma (AR). However, there are few studies focused on evaluating the quality of its medicinal materials. Objectives: This study [...] Read more.
Introduction: The ability of salt-processed Alismatis Rhizoma (SAR) (Alisma plantago-aquqtica L.) to nourish Yin and promote urination is stronger than that of Alismatis Rhizoma (AR). However, there are few studies focused on evaluating the quality of its medicinal materials. Objectives: This study aimed to identify potential quality markers (Q-markers) for SAR, thereby providing a more reliable basis for its quality control and clinical application. Methods: Q-markers were identified through fingerprinting and chemical pattern recognition analysis of 15 batches of SAR. The diuretic effects of these markers were then verified by network analysis and molecular docking. Results: HPLC fingerprints of 15 SAR batches were established, with similarity analysis showing values > 0.85 (0.852–0.990). Chemical pattern recognition identified six critical compounds contributing to SAR quality: alisol F, alisol C 23-acetate, alisol A, alisol A 24-acetate, alisol B 23-acetate, and an alisol O isomer (VIP > 1.0). Network analysis revealed 76 overlapping targets between these compounds and diuretic-related diseases, with core targets including non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), which were identified through protein–protein interaction (PPI) network analysis, with degrees of 27, 24, and 22, respectively. Key pathways involved were the EGFR tyrosine kinase inhibitor resistance pathway, calcium signaling pathway, tumor necrosis factor signaling pathway, etc. Molecular docking confirmed strong binding interactions between the Q-markers and the hub targets, particularly alisol B 23-acetate with MAPK1 (−60.10 kcal·mol−1) and alisol A 24-acetate with EGFR (−46.14 kcal·mol−1) and SRC (−48.86 kcal·mol−1). The diuretic effects of SAR are likely mediated through anti-inflammatory actions and regulation of water–sodium balance via multi-target and multi-pathway mechanisms. Conclusion: This study provides a robust foundation for quality control and clinical application of SAR, though further in vivo validation is warranted. Full article
(This article belongs to the Section Molecular Pharmacology)
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31 pages, 5583 KB  
Article
Leguminous Cover Crops Promote Microbial Community Diversity in the Rhizosphere Soil of Tea Plants: Insights from 16S rRNA Microbiome Analysis
by Sabin Saurav Pokharel, Zahid Ali, Changyu Wang, Xingfu Jiang and Fajun Chen
Agronomy 2025, 15(9), 2217; https://doi.org/10.3390/agronomy15092217 - 19 Sep 2025
Viewed by 326
Abstract
The integration of leguminous cover cropping systems (LCR), particularly soybean (LC-S) and cowpea (LC-C), into tea agroecosystem provides a sustainable strategy to enhance soil ecosystem services by promoting beneficial soil microbial communities through the modulation of the rhizosphere microbiome in the tea rhizosphere [...] Read more.
The integration of leguminous cover cropping systems (LCR), particularly soybean (LC-S) and cowpea (LC-C), into tea agroecosystem provides a sustainable strategy to enhance soil ecosystem services by promoting beneficial soil microbial communities through the modulation of the rhizosphere microbiome in the tea rhizosphere soil. This study employs 16S rRNA gene sequencing to assess how these leguminous cover crops, when incorporated as green manure within the tea row spaces, influence the microbial community diversity in the rhizosphere soil of tea plants. Compared to conventional monoculture tea plantations (CK), the introduction of LC-S and LC-C significantly reshape the microbial communities in the tea rhizosphere soil. They promote the abundance of copiotrophic and specialized taxa such as Proteobacteria, Actinobacteria, and Mycobacterium, which are crucial for nutrient cycling and organic matter decomposition. Additionally, LC-S and LC-C enrich beneficial microbes including Chloroflexi, Bradyrhizobium, Acidothermus, and Cyanobacteria, supporting processes like nitrogen fixation and pathogen suppression. The metagenomic analysis confirms that leguminous cover crops consistently increase bacterial diversity and enrich beneficial phyla vital for soil nutrient dynamics, organic matter breakdown, and environmental stress resilience. Furthermore, microbial genera linked to nitrogen mobilization and complex organic matter degradation are promoted, underpinning the synthesis of nitrogenous compounds (such as theanine, amino acids), polyphenolic secondary metabolites (like flavonoids), and volatile organic compounds essential for tea quality. Functional pathway analyses revealed that LC-S enhances degradation pathways involved in carbohydrate and aromatic compound metabolism, augmenting precursors for key bioactive constituents such as theanine and catechins. Conversely, LC-C favors glycan biosynthesis and degradation pathways, likely improving root–microbe interactions and micronutrient uptake, both critical for polyphenol biosynthesis. Collectively, these microbiome-driven changes improve tea’s sensory qualities, including flavor, aroma, and antioxidant capacity, by enriching bioactive compounds. This microbiome-mediated agro-ecological approach offers a sustainable alternative to conventional monoculture, enhancing soil functionality, ecological resilience, and the economic viability of tea production systems. Full article
(This article belongs to the Section Innovative Cropping Systems)
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28 pages, 4839 KB  
Review
Advancing Zinc–Manganese Oxide Batteries: Mechanistic Insights, Anode Engineering, and Cathode Regulation
by Chuang Zhao, Yiheng Zhou, Yudong Liu, Bo Li, Zhaoqiang Li, Yu Zhang, Deqiang Wang, Ruilin Qiu, Qilin Shuai, Yuan Xue, Haoqi Wang, Xiaojuan Shen, Wu Wen, Di Wu and Qingsong Hua
Nanomaterials 2025, 15(18), 1439; https://doi.org/10.3390/nano15181439 - 18 Sep 2025
Viewed by 385
Abstract
Rechargeable aqueous Zn-MnO2 batteries are positioned as a highly promising candidate for next-generation energy storage, owing to their compelling combination of economic viability, inherent safety, exceptional capacity (with a theoretical value of ≈308 mAh·g−1), and eco-sustainability. However, this system still [...] Read more.
Rechargeable aqueous Zn-MnO2 batteries are positioned as a highly promising candidate for next-generation energy storage, owing to their compelling combination of economic viability, inherent safety, exceptional capacity (with a theoretical value of ≈308 mAh·g−1), and eco-sustainability. However, this system still faces multiple critical challenges that hinder its practical application, primarily including the ambiguous energy storage reaction mechanism (e.g., unresolved debates on core issues such as ion transport pathways and phase transition kinetics), dendrite growth and side reactions (e.g., the hydrogen evolution reaction and corrosion reaction) on the metallic Zn anode, inadequate intrinsic electrical conductivity of MnO2 cathodes (≈10−5 S·cm−1), active material dissolution, and structural collapse. This review begins by systematically summarizing the prevailing theoretical models that describe the energy storage reactions in Zn-Mn batteries, categorizing them into the Zn2+ insertion/extraction model, the conversion reaction involving MnOx dissolution–deposition, and the hybrid mechanism of H+/Zn2+ co-intercalation. Subsequently, we present a comprehensive discussion on Zn anode protection strategies, such as surface protective layer construction, 3D structure design, and electrolyte additive regulation. Furthermore, we focus on analyzing the performance optimization strategies for MnO2 cathodes, covering key pathways including metal ion doping (e.g., introduction of heteroions such as Al3+ and Ni2+), defect engineering (oxygen vacancy/cation vacancy regulation), structural topology optimization (layered/tunnel-type structure design), and composite modification with high-conductivity substrates (e.g., carbon nanotubes and graphene). Therefore, this review aims to establish a theoretical foundation and offer practical guidance for advancing both fundamental research and practical engineering of Zn-manganese oxide secondary batteries. Full article
(This article belongs to the Section Nanoelectronics, Nanosensors and Devices)
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17 pages, 7817 KB  
Article
French Maritime Pine Bark Extract Alleviates Lung Injury by Regulating Inflammatory–Oxidative–Apoptotic Pathway and P2X7 Receptor Expression in LPS-Induced Sepsis
by Nergis Ulas, Seckin Ozkanlar, Serkan Yildirim, Omer Aydin and Yunusemre Ozkanlar
Curr. Issues Mol. Biol. 2025, 47(9), 770; https://doi.org/10.3390/cimb47090770 - 18 Sep 2025
Viewed by 269
Abstract
Introduction: Sepsis is a dysregulated systemic immune response to infection which may result in mortality. It may also lead to organ injury, including injury to the lung. French maritime pine bark extract (MPBE) has been proposed to prevent/treat various inflammatory diseases due to [...] Read more.
Introduction: Sepsis is a dysregulated systemic immune response to infection which may result in mortality. It may also lead to organ injury, including injury to the lung. French maritime pine bark extract (MPBE) has been proposed to prevent/treat various inflammatory diseases due to its strong anti-inflammatory and antioxidant effects. This study evaluates the protective and therapeutic effects of MPBE on lung injury induced by intraperitoneal E. coli lipopolysaccharide (LPS) in rats. Materials and Methods: The study design was as follows: Control, MPBE20, MPBE50, LPS, LPS+MPBE20 and LPS+MPBE50. Blood and lung tissue samples were collected 6 h after the LPS induction following a 10-day administration of MPBE. Results: LPS-induced sepsis was confirmed by the overproduction of IL-1β and TNF-α in bloodstream compared to the Control (p < 0.001). Lung injury was determined by severe histopathological changes and neutrophil infiltration in the lung tissue following intraperitoneal LPS injection. In lung tissue, MPBE improved the levels of P2X7R, TLR4, NLRP3, IL-1β, TNF-α, JNK, H2AX, 8-OHdG, MDA, GSH, Caspase-1 and Caspase-3, and pathological changes in MPBE+LPS groups compared to the LPS group. Conclusions: MPBE appears to regulate P2X7R signaling and the inflammatory–apoptotic pathway by protecting the lung from oxidative cell damage in LPS-induced sepsis in vivo. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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14 pages, 344 KB  
Review
The Potential Risk of Bactrocera dorsalis (Tephritidae) Invasion into the Fruit Industry in the Iberian Peninsula: A Review
by Chandana Dammika Wijekoon, Amílcar Duarte and Luís Neto
Insects 2025, 16(9), 969; https://doi.org/10.3390/insects16090969 - 16 Sep 2025
Viewed by 666
Abstract
Bactrocera dorsalis (Hendel, 1912) (Diptera: Tephritidae) is considered a highly invasive fruit fly species already widespread in Indo-Asia and sub-Saharan Africa. In recent years, this species has extended its range into new regions previously considered unsuitable, posing an alarming new risk for the [...] Read more.
Bactrocera dorsalis (Hendel, 1912) (Diptera: Tephritidae) is considered a highly invasive fruit fly species already widespread in Indo-Asia and sub-Saharan Africa. In recent years, this species has extended its range into new regions previously considered unsuitable, posing an alarming new risk for the subtropical regions of Europe. This review aimed to assess the potential risk of B. dorsalis invasion into the fruit industry in the Iberian Peninsula, the southwesternmost tip of Europe. With the collected information from published scientific knowledge on B. dorsalis’s distribution, biology, climatic tolerance, host plant diversity, and recent invasion pathways, we have provided an assessment of the possibilities of introducing this alarming fruit fly species to the Iberian Peninsula. In this review, we found that B. dorsalis has been recently reported in several adjacent European countries such as France, Italy, and Austria, and it serves as a warning signal to the Iberian Peninsula for the possible risks that this species poses in the future. Considering this persistent threat posed by B. dorsalis, we reviewed its potential future threat by considering the status of the fruit industry and Mediterranean climate in the Iberian Peninsula. We also considered the findings of recent climatic forecasting models. This review provides a theoretical basis for the prospective intrusion of B. dorsalis into the Iberian Peninsula’s fruit industry, as well as the potential impact following its establishment, together with recommendations for restricting the introduction and spread. Full article
(This article belongs to the Section Insect Pest and Vector Management)
21 pages, 1335 KB  
Review
Machine Learning in Stroke Lesion Segmentation and Recovery Forecasting: A Review
by Simi Meledathu Sasidharan, Sibusiso Mdletshe and Alan Wang
Appl. Sci. 2025, 15(18), 10082; https://doi.org/10.3390/app151810082 - 15 Sep 2025
Viewed by 360
Abstract
Introduction: Stroke remains a major cause of disability worldwide, and precise identification of stroke lesions is essential for prognosis and rehabilitation planning. Machine learning has emerged as a powerful tool for automating stroke lesion segmentation and outcome prediction; however, these tasks are often [...] Read more.
Introduction: Stroke remains a major cause of disability worldwide, and precise identification of stroke lesions is essential for prognosis and rehabilitation planning. Machine learning has emerged as a powerful tool for automating stroke lesion segmentation and outcome prediction; however, these tasks are often studied in isolation. The two strategies are inherently interdependent since segmentation provides lesion-based features that directly inform prediction models. Methods: This narrative review synthesises studies published between 2010 and 2024 on the application of machine learning in stroke lesion segmentation and recovery forecasting. A total of 23 relevant studies were reviewed, including 10 focused on lesion segmentation and 13 on recovery prediction. Results: Convolutional Neural Networks (CNNs), including architectures such as U-Net, have improved segmentation accuracy on the Anatomical Tracings of Lesions After Stroke (ATLAS) V2 dataset; however, dataset bias and inconsistent evaluation metrics limit comparability. Integrating imaging-derived lesion characteristics with clinical features improves predictive accuracy at a higher level. Furthermore, semi-supervised and self-supervised methods enhanced performance where annotated datasets are scarce. Discussion: The review highlights the interdependence between segmentation and outcome prediction. Reliable segmentation provides biologically meaningful features that underpin recovery forecasting, while prediction tasks validate the clinical relevance of segmentation outputs. This bidirectional relationship underlines the need for unified pipelines integrating lesion segmentation with outcome prediction. Future research can improve generalisability and foster clinically robust models by advancing semi-supervised and self-supervised learning, bridging the gap between automated image analysis and patient-centred prognosis. Conclusion: Accurate lesion segmentation and outcome prediction should be viewed not as separate goals but as mutually reinforcing components of a single pipeline. Progress in segmentation strengthens recovery forecasting, while predictive modelling emphasises the clinical importance of segmentation outputs. This interdependence provides a pathway for developing more effective, generalisable, and relevant AI-driven stroke care tools. Full article
(This article belongs to the Special Issue Advances in Medical Imaging: Techniques and Applications)
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