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21 pages, 1558 KB  
Article
Inhibition of the HMGB1-RAGE Axis Attenuates Microglial Inflammation and Ameliorates Hypoxia-Induced Cognitive Impairment
by Chenlin Liu, Haowei Zhang, Ruili Guan, Yuankang Zou, Mengyu Chen, Mingrui Du, Wenjing Luo and Jianbin Zhang
Int. J. Mol. Sci. 2025, 26(18), 8782; https://doi.org/10.3390/ijms26188782 (registering DOI) - 9 Sep 2025
Abstract
The mechanisms underlying the abnormal activation of microglia affecting cognitive function under high-altitude hypobaric hypoxia (HAHH) have not been fully elucidated. This study aims to investigate the effects of HAHH on the expression of the receptor for advanced glycation end-products (RAGE) in hippocampal [...] Read more.
The mechanisms underlying the abnormal activation of microglia affecting cognitive function under high-altitude hypobaric hypoxia (HAHH) have not been fully elucidated. This study aims to investigate the effects of HAHH on the expression of the receptor for advanced glycation end-products (RAGE) in hippocampal microglia of mice and to explore the role of RAGE inhibitors in alleviating HAHH-induced microglial inflammation and cognitive impairment. Mice were exposed to HAHH via a multi-environment simulation chamber, and RNA sequencing, qPCR, WB, flow cytometry and immunohistochemistry showed that HAHH exposome significantly increased RAGE expression in hippocampal microglia of mice (p < 0.001 vs. normoxia), which was closely related to microglial neuroinflammatory responses. RAGE inhibitor (FPS-ZM1) alleviated HAHH-induced microglial inflammation (TNF-α decreased by 64%, p < 0.001; CD86+ cells decreased by 42%, p < 0.001) and improved cognitive function in mice (Y-maze novel arm time: 28.08 ± 5.14 s vs. hypoxia 19.67 ± 4.68 s, p = 0.016; NORT recognition index: 0.52 ± 0.05 vs. hypoxia 0.33 ± 0.07, p < 0.001). Mechanistic studies revealed that RAGE inhibitors reduced microglial inflammation by inhibiting the MAPK pathway and decreasing nuclear translocation of NF-κB p65. Furthermore, high-mobility group box 1 (HMGB1) expression increased under hypoxic conditions (p < 0.001 vs. normoxia) and positively regulated RAGE expression. HMGB1 inhibitors reduced RAGE expression and attenuated HAHH-induced microglial inflammation. Overall, the HAHH exposome induces microglial inflammation via the HMGB1-RAGE-NF-κB pathway. RAGE and HMGB1 inhibitors may serve as novel therapeutic strategies to mitigate HAHH-induced cognitive impairment, providing a theoretical basis for the treatment of cognitive impairment. Full article
(This article belongs to the Section Molecular Immunology)
16 pages, 2493 KB  
Article
Investigation of Insect Diversity in the Restoration Area of Yimin Surface Mine in Inner Mongolia
by Yuzhen Zhang, Yawen Yang, Rui Shi, Xintian Li, Haoran Yan, Xue Bai and Shaobo Gao
Diversity 2025, 17(9), 635; https://doi.org/10.3390/d17090635 (registering DOI) - 9 Sep 2025
Abstract
Elucidating the relationship between changes in insect assemblage structure and diversity and the number of years of ecological restoration will help us evaluate the effectiveness of ecological restoration. Our objective is to investigate the response of the structure and diversity of insect communities [...] Read more.
Elucidating the relationship between changes in insect assemblage structure and diversity and the number of years of ecological restoration will help us evaluate the effectiveness of ecological restoration. Our objective is to investigate the response of the structure and diversity of insect communities in the ecological restoration area of Yimin Surface Mine in Inner Mongolia to different restoration years (1 year, 4 years, 7 years) by monitoring in 2018, 2021, and 2024. A total of 1282 insect specimens were collected using sweep-netting methods, representing 70 species from 46 families across 8 orders. The results demonstrated that as restoration progressed, insect taxa significantly increased from 25 to 55 species (p < 0.01), with key functional groups (Coleoptera and Lepidoptera) showing marked richness enhancement. α-diversity indices (Shannon–Wiener and Margalef) significantly increased, while the Simpson dominance index decreased, indicating a more homogeneous species distribution. β-diversity analysis revealed reduced compositional dissimilarity among plots during later restoration stages, reflecting enhanced assemblage stability. The trophic structure shifted from phytophagous dominance to stabilized proportions across all feeding guilds, signaling food web maturation and ecosystem development. Overall, local ecological restoration projects had a significantly positive effect on insect survival and biodiversity development. Our research addresses a gap in faunal assemblage studies of coal mine rehabilitation zones. Full article
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20 pages, 4144 KB  
Article
Design and Evaluation of Modified Asphalt with Enhanced Stripping Resistance Based on Surface Free Energy
by Tomohiro Fujinaga, Tomohiro Miyasaka, Yousuke Kanou and Shouichi Akiba
Constr. Mater. 2025, 5(3), 64; https://doi.org/10.3390/constrmater5030064 (registering DOI) - 9 Sep 2025
Abstract
Latent stripping has become increasingly apparent in asphalt pavements, particularly in highway rehabilitation and international construction projects supported by Official Development Assistance (ODA) from the Government of Japan. Stripping accelerates structural deterioration, making countermeasures essential. However, in ODA projects, securing high-quality aggregates or [...] Read more.
Latent stripping has become increasingly apparent in asphalt pavements, particularly in highway rehabilitation and international construction projects supported by Official Development Assistance (ODA) from the Government of Japan. Stripping accelerates structural deterioration, making countermeasures essential. However, in ODA projects, securing high-quality aggregates or evaluating local materials is often difficult due to environmental and budgetary constraints. This study focused on Surface Free Energy (SFE) as a small-sample evaluation method and developed ten types of styrene–butadiene–styrene (SBS) polymers to enhance interfacial adhesion by targeting aggregate surface functional groups. The SFE of each Polymer-Modified Bitumen (PMB) and thirteen aggregates was measured, and the work of adhesion and moisture sensitivity index (MSI) were calculated for all combinations. Twenty-one Hot-Mix Asphalts (HMA) were then prepared and evaluated using the Hamburg Wheel Tracking Test (HWTT) based on load cycles to stripping initiation (LCSN) and to 12.5 mm rut depth (LCST). The developed PMBs showed a higher work of adhesion, a lower MSI, and substantially increased LCSN and LCST values. Strong negative correlations were observed between MSI and both HWTT indicators, confirming the utility of SFE-based MSI for material screening. This study demonstrates that interface-targeted PMBs can improve stripping resistance, thereby promoting the use of lower-quality aggregates in durable pavements. Full article
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15 pages, 957 KB  
Article
Effectiveness of a Nutritional Intervention in Patients with Chronic Heart Failure at Risk of Malnutrition: A Prespecified Subanalysis of the PACMAN-HF Trial
by Carolina Ortiz-Cortés, Purificación Rey-Sánchez, Paula Gómez-Turégano, Ramón Bover-Freire, Julián F. Calderón-García, Jose Javier Gómez-Barrado and Sergio Rico-Martín
Nutrients 2025, 17(17), 2899; https://doi.org/10.3390/nu17172899 - 8 Sep 2025
Abstract
Background and objectives: Nutritional disorders are common in patients with heart failure (HF) and are associated with reduced functional capacity and poor prognosis. In this study, we evaluated the prognostic, nutritional and functional impact of a structured nutritional intervention in patients with [...] Read more.
Background and objectives: Nutritional disorders are common in patients with heart failure (HF) and are associated with reduced functional capacity and poor prognosis. In this study, we evaluated the prognostic, nutritional and functional impact of a structured nutritional intervention in patients with chronic HF at risk of malnutrition. Methods: This is a prespecified subanalysis of the randomized controlled trial Prognostic And Clinical iMpAct of a Nutritional intervention in patients with chronic HF (PACMAN-HF). Ambulatory patients with chronic HF at risk of malnutrition were identified using the Mini Nutritional Assessment (MNA) questionnaire and randomized to receive either an individualised nutritional intervention (intervention group) or standard care (control group). We evaluated the frequency of malnutrition risk and the impact of the intervention on clinical outcomes, defined as a composite of all-cause mortality or time to first HF hospitalisation, as well as nutritional status and functional capacity at 3- and 12-month follow-ups. Results: A total of 225 patients were screened. Of these, 72 (32%) were identified as being at risk of malnutrition and 64 (28.4%) met the inclusion criteria and were randomized (31 in the intervention group and 33 in the control group). There were no significant differences between the groups in terms of all-cause mortality or time to first HF hospitalisation (HR = 0.34 [0.11–1.09]; p = 0.072). At 12 months, the intervention group demonstrated a significant improvement in functional capacity, with an increase of 31.3 metres in the 6-minute walk test (6MWT) (p = 0.002), whereas no significant change was observed in the control group. Nutritional status improved significantly in the intervention group (MNA score +4.12, p < 0.001) and declined in the control group (−1.15, p = 0.029). At 12 months, body mass index, tricipital skinfold thickness, arm circumference, and serum albumin levels increased in the intervention group. Conclusions: A structured and individualised nutritional intervention significantly improved nutritional status and functional capacity over 12 months, although it did not impact major clinical outcomes. Full article
(This article belongs to the Section Clinical Nutrition)
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25 pages, 9121 KB  
Article
Integrative Multi-Omics Reveals the Anti-Colitis Mechanisms of Polygonatum kingianum Collett & Hemsl Polysaccharides in a Mouse DSS Model
by Siyu Li, Xingrui Xu, Yuezhi Pan, Yu Chen, Zihuan Wu and Shengbao Cai
Nutrients 2025, 17(17), 2895; https://doi.org/10.3390/nu17172895 - 8 Sep 2025
Abstract
Background/Objectives: Ulcerative colitis (UC) incidence has risen alarmingly worldwide, posing significant clinical challenges due to limitations of therapeutic efficacy and side effects of current drugs. While Polygonatum kingianum polysaccharides (PKPs) exhibit anti-inflammatory and antioxidant properties, their anti-colitis potential remains unexplored. This study [...] Read more.
Background/Objectives: Ulcerative colitis (UC) incidence has risen alarmingly worldwide, posing significant clinical challenges due to limitations of therapeutic efficacy and side effects of current drugs. While Polygonatum kingianum polysaccharides (PKPs) exhibit anti-inflammatory and antioxidant properties, their anti-colitis potential remains unexplored. This study aimed to validate the protective effects of PKPs against dextran sulfate sodium (DSS)-induced colitis and elucidate its mechanisms. Methods: Acute UC was induced in C57BL/6J mice by 3% DSS. PKPs (125 mg/kg) were administered via gavage for 10 days. Integrated approaches included histopathology, tight junction protein (ZO-1/Occludin/Claudin-1) immunohistochemistry, inflammatory/oxidative markers (ELISA), Nrf2 pathway proteins (Western blot), 16S rRNA gut microbiota sequencing, fecal untargeted metabolomics (UHPLC-MS), short-chain fatty acids (SCFAs) analysis and combined analysis. Results: PKPs significantly alleviated colitis phenotypes: reduced weight loss, lowered disease activity index (DAI), and attenuated colon shortening. They restored intestinal barrier integrity by upregulating tight junction proteins and reducing plasma Diamine Oxidase (DAO)/D-lactate (D-Lac)/Endotoxin (ET). PKPs suppressed pro-inflammatory cytokines (TNF-α/IL-1β/IL-6) while elevating IL-10, activated the Nrf2/HO-1/NQO1 antioxidant pathway, and reduced oxidative stress (MDA decreased, SOD/GSH increased). Multi-omics revealed PKPs enriched beneficial bacteria (Blautia, Odoribacter, Rikenellaceae_RC9_gut_group), restored SCFAs (acetate/propionate/butyrate), and modulated metabolic pathways (sphingolipid/linoleic acid metabolism). Conclusions: PKPs ameliorate DSS-induced colitis through multi-target mechanisms: (1) preserving intestinal barrier function, (2) suppressing inflammation and oxidative stress via Nrf2 activation, (3) restoring gut microbiota balance and SCFA production, and (4) regulating host-microbiota metabolic interactions. These findings support PKPs as a promising dietary supplement for UC management. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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20 pages, 577 KB  
Article
Novel 3-Dehydroteasterone Derivatives with 23,24-Dinorcholanic Side Chain and Benzoate Groups at C-22: Synthesis and Activity Evaluation by Rice Lamina Inclination Test and Bean Second-Internode Bioassay
by Ernesto Valdés, Katy Díaz, María Núñez, Andrés F. Olea, José F. Quilez del Moral, Rodrigo Carvajal, Mauricio A. Cuellar and Luis Espinoza-Catalán
Int. J. Mol. Sci. 2025, 26(17), 8710; https://doi.org/10.3390/ijms26178710 (registering DOI) - 6 Sep 2025
Viewed by 446
Abstract
Herein, a new series of 3-DT analogs with benzoylated groups at C-23 are synthesized and characterized. The benzoylated groups carry the same substituents in the ortho- or para-positions. Thus, the effect of structure on activity, measured using the rice lamina inclination [...] Read more.
Herein, a new series of 3-DT analogs with benzoylated groups at C-23 are synthesized and characterized. The benzoylated groups carry the same substituents in the ortho- or para-positions. Thus, the effect of structure on activity, measured using the rice lamina inclination test (RLIT) and the bean second-internode assay (BSI), is evaluated. The RLIT results indicate that a benzoylate function at C-22 induces a strong increase in activity that depends on the position and nature of the substituent in the phenyl ring. For example, an analog with an -OAc group in the ortho-position is the most active derivative, and its activity is like that of brassinolide. A relative index is calculated using brassinolide as a positive control to compare the RLIT results with those reported previously. This analysis allows for the conclusion that benzoylated derivatives with a hydroxyl group at C-3 are much more active than the corresponding analogs with a carbonyl group in this position, and one extra alcohol group in the alkyl chain decreases RLIT activity. Finally, the results obtained with the BSI are clearly different to those obtained in the RLIT bioassay. Therefore, the application of any activity–structure relationship will always be dependent on the bioassay used to determine activity. Full article
(This article belongs to the Special Issue Molecular Research in Natural Products)
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12 pages, 1214 KB  
Article
The Reliability and Validity of a New Laryngeal Palpation Tool for Static and Dynamic Examination
by Isabelle Bargar, Melina Maria Ippers, Katrin Neumann, Philipp Mathmann and Ben Barsties v. Latoszek
J. Clin. Med. 2025, 14(17), 6309; https://doi.org/10.3390/jcm14176309 - 6 Sep 2025
Viewed by 232
Abstract
Background/Objectives: Voice disorders caused by laryngeal hypertension can impact volume, quality, pitch, resonance, flexibility, and stamina. The laryngeal palpation is a tactile-perceptual assessment, which is one of a few examination methods to evaluate laryngeal hypertension. Laryngeal palpation is a manual examination of [...] Read more.
Background/Objectives: Voice disorders caused by laryngeal hypertension can impact volume, quality, pitch, resonance, flexibility, and stamina. The laryngeal palpation is a tactile-perceptual assessment, which is one of a few examination methods to evaluate laryngeal hypertension. Laryngeal palpation is a manual examination of the extrinsic and paralaryngeal tissues of the larynx (e.g., lateral laryngeal mobility, thyrohyoid and cricothyroid spaces, vertical laryngeal position/mobility, and pain) through the examiner’s fingers. It can be performed during rest (static assessment) or during phonation (dynamic assessment) of the individual being evaluated. This study aimed to validate a novel laryngeal palpation tool with quantitative ordinal scores by assessing its reliability and diagnostic accuracy establishing preliminary clinical cut-off values, and examining its correlations with self-reported voice disorder symptoms. Methods: In a prospective, controlled validation study, 33 participants were selected to assess the validity and reliability of the novel diagnostic tool in a clinical sample and healthy controls. The clinical sample (n = 19) comprised individuals diagnosed with voice disorders, whereas the healthy control group (n = 14) included participants with no history or symptoms of voice pathology. The novel laryngeal palpation tool was employed by two independent examiners to assess both static and dynamic laryngeal function in all participants. In addition, each participant completed the following questionnaires: Voice Handicap Index (VHI-30) with the 30-item, Vocal Fatigue Index (VFI), and the Vocal Tract Discomfort Scale (VTD). Results: Static palpatory assessment of laryngeal tension demonstrated excellent discriminatory power between groups and tension levels (AROC = 0.979), along with high intra-rater (ICC = 0.966) and inter-rater reliability (ICC = 0.866). Significant correlations were revealed between the static palpation results and the VHI scores (r = 0.496; p < 0.01) and VFI (r = 0.514; p < 0.01). For the dynamic evaluation of the palpation tool, comparable results for the validity (AROC = 0.840) and reliability (inter-rater: ICC = 0.800, and intra-rater: ICC = 0.840) were revealed. However, no significant correlations were found between dynamic palpation and self-perceived questionnaires, although some were likely found with static palpation. The validity of the total score was found to be AROC = 0.992. Conclusions: The static and dynamic assessments using the novel laryngeal palpation tool demonstrated promising reliability and diagnostic accuracy, providing initial evidence to support its clinical utility. Further studies are needed to establish broader validation. Full article
(This article belongs to the Special Issue New Advances in the Management of Voice Disorders: 2nd Edition)
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11 pages, 949 KB  
Article
Patient-Reported Outcomes of Microfracture, Nanofracture, and K-Wire Drilling in Talus Osteochondral Lesions
by Ahmet Görkem Kasapoğlu, Mehmet Arıcan, Yıldıray Tekçe, Giray Tekçe and İlyas Kaban
Diagnostics 2025, 15(17), 2255; https://doi.org/10.3390/diagnostics15172255 - 6 Sep 2025
Viewed by 286
Abstract
Background/Objectives: Different patient-reported outcomes and radiological results are reported depending on whether microfracture, drilling, or nanofracture is utilized in the arthroscopic treatment of talus osteochondral lesions, but the first-line treatment is still controversial. The aim of this study is to evaluate the early [...] Read more.
Background/Objectives: Different patient-reported outcomes and radiological results are reported depending on whether microfracture, drilling, or nanofracture is utilized in the arthroscopic treatment of talus osteochondral lesions, but the first-line treatment is still controversial. The aim of this study is to evaluate the early patient-reported outcomes of microfracture, nanofracture, and antegrade drilling methods in talus anteromedial osteochondral lesions. Methods: A total of 77 patients who presented with ankle pain between October 2016 and June 2022, were diagnosed with talus osteochondral lesions, and underwent microfracture (n: 27), nanofracture (n: 25), and K-wire drilling (n: 25) were included. Demographic data of the patients were evaluated, such as age, gender, lesion side, dominant extremity, body mass index (BMI), smoking status, smoking (pack/day-year), and symptom duration. Patient-reported outcomes of the patients were evaluated with VAS (visual analog scale) and AOFAS (American Orthopedic Foot & Ankle Society) scores measured before surgery and at 6 and 12 months after surgery. The results were evaluated at the significance level of p < 0.05. Results: There were no statistically significant differences among the microfracture, nanofracture, and drilling groups in terms of age, gender, lesion side, dominant extremity, BMI, smoking, or daily cigarette use (p = 0.121, p = 0.852, p = 0.956, p = 0.731, p = 0.881, p = 0.769, p = 0.124). Similarly, the mean duration of symptoms did not differ significantly between the groups (p = 0.336). Although AOFAS and VAS scores significantly improved in all groups (p = 0.0001), there were no statistically significant differences between the microfracture, nanofracture, and drilling groups at preoperative, 6th-, and 12th-month measuring points. The microfracture group showed a significantly higher AOFAS improvement from preop to 6 months compared to the other groups (p = 0.012), though no differences were found between nanofracture and drilling or in 12-month changes. VAS percentage changes showed no significant differences among groups at either time point. Conclusions: All treatment groups had similar baseline characteristics and outcomes, with the microfracture group showing a greater functional improvement at 6 months. Full article
(This article belongs to the Special Issue Recent Advances in Bone and Joint Imaging—3rd Edition)
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11 pages, 562 KB  
Article
Reconstructive Arthroplasty for Malignant Bone Tumors of the Knee—A Single-Center Experience of Functionality and Quality of Life
by Thilo Khakzad, Michael Putzier, Leonard Thielscher, Nima Taheri, Silvan Wittenberg, Alp Paksoy, Daniel Rau and Sven Märdian
J. Clin. Med. 2025, 14(17), 6287; https://doi.org/10.3390/jcm14176287 - 5 Sep 2025
Viewed by 183
Abstract
Background/Objectives: Resection arthroplasty is well established in treating bone defects following tumor resection, with the distal femur and proximal tibia being its most common localizations. The aim of this study was to analyze the functional outcomes and quality of life following endoprosthetic reconstruction [...] Read more.
Background/Objectives: Resection arthroplasty is well established in treating bone defects following tumor resection, with the distal femur and proximal tibia being its most common localizations. The aim of this study was to analyze the functional outcomes and quality of life following endoprosthetic reconstruction for malignant bone tumors of the knee joint. Methods: We retrospectively included all patients treated with an endoprosthetic reconstruction following resection of a malignant bone tumor of the knee at our institution. Functional outcomes (KOOS, OKS, MSTS, and KSS) and health-related quality of life scores [QoL] (SF-36, Karnofsky Index) were evaluated. Chi-square and Fisher’s exact test was used for categorical variables, T-test and Whitney U-Mann tests for continuous variables. Survival was calculated using the Kaplan–Meier curves. Results: 32 patients were included. A total of 12 patients had died at the time of follow-up. Among the remaining 20 patients (m:w 17:3), mean follow-up was 8.1 years (range, 8.12 ± 6.8). Mean age at the time of tumor diagnosis was 50 ± 23.3 (10–83) years. According to age, patients were divided into two groups (group C1: <29 years, group C2: >29 years). Group C1 showed significantly better results regarding functional outcome (p < 0.05). The anatomic location of the replacement and a revision surgery did not influence the functional outcome (p > 0.05). QoL showed no significant differences in subgroup analysis (p > 0.05). Primary bone tumors had a significantly better survival (primary tumor: 216.90 months [168.42–265.83]; secondary tumor: 37.03 months [11.71–62.35] p = 0.01). Furthermore, pathologic fractures were associated with significantly worse survival (pathologic fracture: 50.24 months [0.00–102.43]; pathologic fracture 190.63 moths [139.28–241.45]; p = 0.007). Conclusions: Knee resection arthroplasty can offer meaningful long-term functional outcomes and acceptable quality of life in selected patients with musculoskeletal tumors. While the rarity and heterogeneity of such cases remain a challenge, our findings contribute to the growing evidence supporting this complex but limb-sparing surgical option. Full article
(This article belongs to the Section Orthopedics)
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24 pages, 603 KB  
Review
Dexamethasone Suppression Testing in Patients with Adrenal Incidentalomas with/Without Mild Autonomous Cortisol Secretion: Spectrum of Cortisol Cutoffs and Additional Assays (An Updated Analysis)
by Alexandra-Ioana Trandafir and Mara Carsote
Biomedicines 2025, 13(9), 2169; https://doi.org/10.3390/biomedicines13092169 - 5 Sep 2025
Viewed by 329
Abstract
Background/Objective: The overnight 1-mg dexamethasone suppression test (DST) represents the conventional/standard tool for endogenous hypercortisolemia screening, typically in relationship with adrenal and pituitary masses. Nevertheless, an associated spectrum of challenges and pitfalls is found in daily practice. This analysis aimed to evaluate: [...] Read more.
Background/Objective: The overnight 1-mg dexamethasone suppression test (DST) represents the conventional/standard tool for endogenous hypercortisolemia screening, typically in relationship with adrenal and pituitary masses. Nevertheless, an associated spectrum of challenges and pitfalls is found in daily practice. This analysis aimed to evaluate: (I.) the diagnosis relevance of 1-mg DST in patients with adrenal incidentalomas (AIs) with/without mild autonomous cortisol secretion (MACS) exploring different cutoffs of the second-day plasma cortisol after dexamethasone administration (cs-DST) with respect to cardio-metabolic outcomes; (II.) the potential utility of adding other biomarkers to DST [plasma morning adrenocorticotropic hormone (ACTH), 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), dehydroepiandrosterone sulfate (DHEAS)]; and (III.) DST variability in time. Methods: This narrative analysis was based on searching full-text, English articles in PubMed (between January 2023 and April 2025) via using different term combinations: “dexamethasone suppression test” (n = 239), “diagnosis test for autonomous cortisol secretion” (n = 22), “diagnosis test for mild autonomous cortisol secretion” (n = 13) and “diagnosis test for Cushing Syndrome” (n = 61). We manually checked the title and abstract and finally included only the studies that provided hormonal testing results in adults with non-functional adenomas (NFAs) ± MACS. We excluded: reviews, meta-analyses, editorials, conference abstracts, case reports, and case series; non-human research; studies that did not provide clear criteria for distinguishing between Cushing syndrome and MACS; primary aldosteronism. Results: The sample-focused analysis (n = 13 studies) involved various designs: cross-sectional (n = 4), prospective (n = 1), retrospective (n = 7), and cohort (n = 1); a total of 4203 patients (female-to-male ratio = 1.45), mean age of 59.92 years. I. Cs-DST cutoffs varied among the studies (n = 6), specifically, 0.87, 0.9, 1.2, and 1.4 µg/dL in relationship with the cardio-metabolic outcomes. After adjusting for age (n = 1), only the prevalence of cardiovascular disease remained significantly higher in >0.9 µg/dL vs. ≤0.9 group (OR = 2.23). Multivariate analysis (n = 1) found cs-DST between 1.2 and 1.79 µg/dL was independently associated with hypertension (OR = 1.55, 95%CI: 1.08–2.23, p = 0.018), diabetes (OR = 1.60, 95%CI: 1.01–2.57, p = 0.045), and their combination (OR = 1.96, 95%CI:1.12–3.41, p = 0.018) after adjusting for age, gender, obesity, and dyslipidemia. A higher cs-DST was associated with a lower estimated glomerular filtration rate (eGFR), independently of traditional cardiovascular risk factors. Post-adrenalectomy eGFR improvement was more pronounced in younger individuals, those with lower eGFR before surgery, and with a longer post-operative follow-up. Cs-DST (n = 1) was strongly associated with AIs size and weakly associated with age, body mass index and eGFR. Cortisol level increased by 9% (95% CI: 6–11%) for each 10 mL/min/1.73 m2 decrease in eGFR. A lower cs-DST was associated with a faster post-adrenalectomy function recovery; the co-diagnosis of diabetes reduced the likelihood of this recovery (OR = 24.55, p = 0.036). II. Additional biomarkers assays (n = 5) showed effectiveness only for lower DHEAS to pinpoint MACS amid AIs (n = 2, cutoffs of <49.31 µg/dL, respectively, <75 µg/dL), and lower ACTH (n = 1, <12.6 pmol/L). III. Longitudinal analysis of DST’s results (n = 3): 22% of NFAS switch to MACS after a median of 35.7 months (n = 1), respectively, 29% (n = 1) after 48.6 ± 12.5 months, 11.8% (n = 1) after 40.4 ± 51.17 months. A multifactorial model of prediction showed the lowest risk of switch (2.4%) in individuals < 50 years with unilateral tumor and cs-DST < 0.45 µg/dL. In the subgroup of subjects without cardio-metabolic comorbidities at presentation, 25.6% developed ≥1 comorbidities during surveillance. Conclusions: The importance of exploring the domain of AIs/NFAs/MACS relates to an increasing detection in aging population, hence, the importance of their optimum hormonal characterization and identifying/forestalling cardio-metabolic consequences. The spectrum of additional biomarkers in MACS (other than DST) remains heterogeneous and still controversial, noting the importance of their cost-effectiveness, and availability in daily practice. Cs-DST serves as an independent predictor of cardio-metabolic outcomes, kidney dysfunction, while adrenalectomy may correct them in both MACS and NFAs, especially in younger population. Moreover, it serves as a predictor of switching the NFA into MACS category during surveillance. Changing the hormonal behavior over time implies awareness, since it increases the overall disease burden. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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13 pages, 1415 KB  
Article
The Impact of Sarcopenia, Myosteatosis, and Visceral Adiposity on Renal Transplantation Outcomes
by Esin Olcucuoglu, Utku Eren Ozkaya, Muhammed Emin Polat, Mehmet Yılmaz, Sedat Tastemur, Rıza Sarper Okten and Erkan Olcucuoglu
Medicina 2025, 61(9), 1608; https://doi.org/10.3390/medicina61091608 - 5 Sep 2025
Viewed by 184
Abstract
Background and Objectives: The impact of sarcopenia and myosteatosis on renal transplantation (RT) outcomes has yet to be explained, certainly due to differences in assessment methods. The role of visceral adiposity is also not clearly defined. This retrospective study aimed to evaluate [...] Read more.
Background and Objectives: The impact of sarcopenia and myosteatosis on renal transplantation (RT) outcomes has yet to be explained, certainly due to differences in assessment methods. The role of visceral adiposity is also not clearly defined. This retrospective study aimed to evaluate pretransplant body composition—including sarcopenia, myosteatosis, and visceral adiposity ratio (VSR)—using computed tomography (CT) and analyze their relationship with short- and long-term graft outcomes. Materials and Methods: A total of 94 patients who underwent RT between 2019 and 2023 and had pretransplant non-contrast abdominal CT scans were included. Skeletal muscle area (SMA) was assessed at the L3 vertebral level, including multiple muscle groups. Sarcopenia was defined by a low skeletal muscle index (SMI), while myosteatosis was defined by high intramuscular adipose tissue content (IMAC). Visceral adiposity was evaluated by the visceral-to-subcutaneous adipose tissue ratio (VSR). These parameters were compared with post-transplant outcomes. Results: The mean age was 42.69 ± 12.47 years, with 54.3% male patients. High IMAC was significantly associated with early graft failure (p = 0.026), delayed graft function (p = 0.005), death-censored graft failure (p = 0.036), and overall graft failure (p = 0.047). One-year mortality was also higher in the high IMAC group (14.8% vs. 0.0%, p = 0.012). SMI and VSR were not significantly associated with outcomes. Myosteatosis emerged as a significant risk factor in univariate analysis but was not independently predictive in multivariate analysis. Among the established risk factors identified in the study, recipient age was found to be a significant predictor for overall graft failure, donation type (cadaveric vs. living) for death-censored graft failure, and cold ischemia time for delayed graft function (OR: 1.068, 95% CI: 1.001–1.141, p = 0.049; OR: 147.7, 95% CI: 2.1—10,427.0, p = 0.021; OR: 1.003, 95% CI: 1.001–1.006, p = 0.023). Conclusions: Myosteatosis correlates with worse graft outcomes and higher mortality, but its independent prognostic value requires further investigation. Full article
(This article belongs to the Section Urology & Nephrology)
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15 pages, 840 KB  
Article
Long-Term Prospective Follow-Up of Spinal Interventional Pain Procedures and Physical Therapy Compliance on Outcomes in Chronic Pain Patients
by Wael Saleem, Jo Ann LeQuang, Muntaha Elayyan, Mustafa Rezk, Zeineb Fourati, Ahmad Hajaj, Mohammed Orompurath, Shaif Jarallah, Flaminia Coluzzi and Joseph V. Pergolizzi
J. Clin. Med. 2025, 14(17), 6271; https://doi.org/10.3390/jcm14176271 - 5 Sep 2025
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Abstract
Background/Objective: The long-term implications of spinal interventional pain procedures (IPPs) remain underexplored. This study aimed to evaluate pain intensity, overall health quality, and disability over a four-year period following an IPP, while also assessing physical therapy (PT) compliance, the need for repeated procedures, [...] Read more.
Background/Objective: The long-term implications of spinal interventional pain procedures (IPPs) remain underexplored. This study aimed to evaluate pain intensity, overall health quality, and disability over a four-year period following an IPP, while also assessing physical therapy (PT) compliance, the need for repeated procedures, and analgesic consumption. Methods: A prospective observational study with retrospective registration was conducted on patients with chronic spinal pain at Hamad Medical Corporation (HMC), Qatar. Patients were assessed using the Numeric Rating Scale (NRS), the Oswestry Disability Index (ODI), and the EuroQol 5-Dimension Index (EQ-5D). Additional tools included the EQ-Health Visual Analog Scale and the Patient Global Impression of Change (PGIC). Follow-ups were performed at 6, 12, 24, 36, and 48 months. Results: A total of 766 patients were initially recruited, of whom 174 met the inclusion criteria. All patients demonstrated significant improvement across all outcome measures compared to the baseline. No significant differences were observed in pain or functional outcomes between PT-compliant and non-compliant groups. By the end of this study, 56.9% of patients reported reduced analgesic use, while 43.1% reported increased use. The patient satisfaction data showed that 55% (62/113) of those receiving a single IPP were satisfied, compared to 54% (33/61) in the multiple IPP group. The PGIC satisfaction scores revealed no statistically significant differences (p = 1). Overall health status, as measured by the EQ-5D Health scale, also showed no meaningful differences between groups. Conclusions: Despite several limitations, patients reported sustained improvement and satisfaction four years post-IPP. PT compliance did not appear to significantly influence long-term outcomes. Further research is needed to identify factors affecting post-IPP recovery and medication usage. Full article
(This article belongs to the Special Issue Clinical Advances in Pain Management)
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17 pages, 5764 KB  
Article
Effects of Different Agricultural Wastes on the Growth of Photinia × fraseri Under Natural Low-Temperature Conditions
by Xiaoye Li, Jie Li, Airong Liu, Yuanbing Zhang and Kunkun Zhao
Horticulturae 2025, 11(9), 1055; https://doi.org/10.3390/horticulturae11091055 - 3 Sep 2025
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Abstract
As low temperature is a key factor affecting the growth and development of plants and the utilization of agricultural waste has significant research value, this study explores the effects of 16 agricultural wastes on the growth of P. fraseri under natural low-temperature conditions [...] Read more.
As low temperature is a key factor affecting the growth and development of plants and the utilization of agricultural waste has significant research value, this study explores the effects of 16 agricultural wastes on the growth of P. fraseri under natural low-temperature conditions and evaluates its cold resistance capacity. Soil chemical properties were analyzed and all the wastes were found to exhibit alkalinity. The highest total nitrogen content was found in group A (garden soil/coir/municipal sludge = 7:1:2). In this group, the branch number, branch length, and branch diameter were the largest. Interestingly, the plants in group E (garden soil/coir/pig manure = 7:1:2) had the highest average number of new shoots, with 5.72. Analysis of the physiological indexes of leaves revealed that the proline content, superoxide dismutase activity, fresh weight, and dry weight of plants in group L (garden soil/coir/pear residue = 7:1:2) were the highest. The stomatal conductance and transpiration rate of the leaves of plants in group L were the largest, at 86.23 mmol∙m−2∙s−1 and 1.67 mmol∙m−2∙s−1, respectively. Furthermore, combined with morphological and physiological indicators for membership function analysis, the results show that plants in group A exhibited optimal growth under natural low temperature. Correlation analysis indicated varying degrees of correlation between 38 pairs of indicators, including branch number and branch length, intercellular CO2 concentration and stomatal conductance, and leaf fresh weight and dry weight. Heatmap analysis showed that branch number, branch length, and branch diameter were highest in group A plants, while the highest levels of proline occurred in group L plants. In this study, groups A and L are recommended for growth under naturally low-temperature conditions. Full article
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13 pages, 325 KB  
Article
Predicting Sleep Quality Based on Metabolic, Body Composition, and Physical Fitness Variables in Aged People: Exploratory Analysis with a Conventional Machine Learning Model
by Pedro Forte, Samuel G. Encarnação, José E. Teixeira, Luís Branquinho, Tiago M. Barbosa, António M. Monteiro and Daniel Pecos-Martín
J. Funct. Morphol. Kinesiol. 2025, 10(3), 337; https://doi.org/10.3390/jfmk10030337 - 2 Sep 2025
Viewed by 544
Abstract
Background: Sleep plays a crucial role in the health of older adults, and its quality is influenced by multiple physiological and functional factors. However, the relationship between sleep quality and physical fitness, body composition, and metabolic markers remains unclear. This exploratory study [...] Read more.
Background: Sleep plays a crucial role in the health of older adults, and its quality is influenced by multiple physiological and functional factors. However, the relationship between sleep quality and physical fitness, body composition, and metabolic markers remains unclear. This exploratory study aimed to investigate the associations between sleep quality and physical, metabolic, and body composition variables in older adults, and to evaluate the preliminary performance of a logistic regression model in classifying sleep quality. Methods: A total of 32 subjects participated in this study, with a mean age of 69. The resting arterial pressure (systolic and diastolic), resting heart rate, anthropometrics (high waist girth), body composition (by bioimpedance), and physical fitness (Functional Fitness Test) and sleep quality (Pitsburg sleep-quality index) were evaluated. Group comparisons, associative analysis and logistic regression with 5-fold stratified cross-validation was used to classify sleep quality based on selected non-sleep-related predictors. Results: Individuals with good sleep quality showed significantly better back stretch (t = 2.592; p = 0.015; η2 = 0.239), lower limb strength (5TSTS; t = 2.564; p = 0.016; η2 = 0.476), and longer total sleep time (t = 6.882; p < 0.001; η2 = 0.675). Exploratory correlations showed that poor sleep quality was moderately associated with reduced lower-limb strength and mobility. The logistic regression model including 5TSTS and TUG achieved a mean accuracy of 0.76 ± 0.15, precision of 0.79 ± 0.18, recall of 0.83 ± 0.21, and AUC of 0.74 ± 0.16 across cross-validation folds. Conclusions: These preliminary findings suggest that physical fitness and clinical variables significantly influence sleep quality in older adults. Sleep-quality-dependent patterns suggest that interventions to improve lower limb strength may promote better sleep outcomes. Full article
14 pages, 2327 KB  
Article
Sex-Associated Indels and Candidate Gene Identification in Fujian Oyster (Magallana angulata)
by Yi Han, Yue Ning, Ling Li, Qijuan Wan, Shuqiong Li, Ying Yao, Chaonan Tang, Qisheng Wu, Xiang Guo, Jianfei Qi, Yizhou Ke, Hui Ge and Mingyi Cai
Fishes 2025, 10(9), 438; https://doi.org/10.3390/fishes10090438 - 2 Sep 2025
Viewed by 631
Abstract
Sex determination is a fundamental biological process governing animal reproduction. Although substantial progress has been made in elucidating its genetic basis, the genetic architecture underlying complex sex determination systems remains poorly understood. In this study, we identify sex-associated insertion–deletion (indel) variants, screen candidate [...] Read more.
Sex determination is a fundamental biological process governing animal reproduction. Although substantial progress has been made in elucidating its genetic basis, the genetic architecture underlying complex sex determination systems remains poorly understood. In this study, we identify sex-associated insertion–deletion (indel) variants, screen candidate genes, and compare sex-associated variation across populations with different genetic backgrounds in the Fujian oyster (Magallana angulata). Based on whole-genome resequencing data of a culture strain (designated FL), a total of 299,774 high-quality indels were identified. By integrating genome-wide association analysis (GWAS), fixation index (FST) analysis, and sex-biased genotype frequency comparisons, 77 overlapping sex-associated indels were identified, predominantly clustered within a 1.8 Mb (8.3–10.1 Mb) region on chromosome 9. Principal component analysis (PCA) based on the sex-associated markers and their subsets consistently separated male and female individuals in the FL strain. For two representative sex-associated indels, PCR-based genotyping methods were developed and validated. Functional annotation identified putative candidate genes for sex determination, including PKD1L1, 5-HTRL, SCP, and CCKRa. Comparative analysis of variants within PKD1L1 across wild, farmed, and selectively bred populations revealed a progressive enrichment of male-linked alleles in domesticated and selectively bred groups, particularly in male individuals. This study provides direct evidence that sex in the Fujian oyster is genetically determined and reveals that domestication and artificial selection may drive the emergence of major sex-determining loci, offering important insights into the genetic basis of sex determination in the Fujian oyster, and establishing a theoretical and practical foundation for molecular marker-assisted breeding of monosex lines for this species. Full article
(This article belongs to the Section Genetics and Biotechnology)
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