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Introduction: Depression with a history of trauma often responds poorly to conventional antidepressants and has a poor prognosis. Prazosin, an α1-adrenoceptor blocker, has shown promise in treating post-traumatic stress disorder symptoms, particularly nightmares. Its potential in treating depression with trauma history warrants investigation., Aims of the Study: This randomised, double-blind, placebo-controlled study aimed to investigate the efficacy and tolerability of low-dose prazosin (0.5-1 mg/day) as an augmentation strategy in patients with depression and a history of trauma. We sought to determine if prazosin could provide rapid symptom improvement and enhance overall treatment response compared to placebo in this difficult-to-treat patient population., Methods: This randomised, double-blind, placebo-controlled clinical study included 59 patients with first-episode or recurrent unipolar or bipolar depression. After basic antidepressant treatment, they were randomly assigned to a prazosin (0.5-1 mg/day) or placebo group for a 6-week double-blind controlled study. The Montgomery-Åsberg Depression Rating Scale, 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) were used to evaluate efficacy., Results: There were no significant differences in the results of the demographic and clinical symptom assessment between the two groups (p > 0.05). The difference between the HAMD-17 and HAMA scores was statistically significant after 3 days of treatment (p < 0.05). The difference in response rate between the two groups was statistically significant after week 4 of treatment (end of week 4, 56.7% vs. 24.1%, p = 0.011; end of week 6, 80.0% vs. 48.3%, p = 0.011). The incidence of adverse reactions in the prazosin and placebo groups was 20.0% and 24.1%, respectively, with no statistically significant differences (p > 0.05); however, the prazosin group had a lower incidence of sleeplessness or nightmares (3.3% vs. 20.7%, p = 0.039) but a higher incidence of orthostatic hypotension (16.7% vs. 0%, p = 0.007). The severity of orthostatic hypotension was mild to moderate., Conclusion: Low-dose prazosin can effectively improve the emotional symptoms of patients with depression and a history of trauma, and the common adverse reaction is mild-to-moderate orthostatic hypotension., Clinical Trial Registration: ChiCTR2200063642., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Neuroinflammatory reactions are crucial factors in secondary brain damage following intracerebral hemorrhage (ICH). Although previous studies have shown that IRAK3 is involved in immune responses, the potential effects of IRAK3 on ICH remain unclear., Methods: Collagenase IV-induced ICH mouse model. Western blotting was used to determine the expression of IRAK3 at different time points following ICH. Immunofluorescence was used to investigate the cellular localization of IRAK3. The ICH model was treated with recombinant human IRAK3 (rh-IRAK3) or IRAK3 siRNA via an intracerebroventricular injection. The effect of IRAK3 on ICH mice was assessed by Western blotting and short-term and long-term neurological function evaluation. RNA-seq was performed to explore the mechanism by which IRAK3 promotes inflammation after ICH. The mechanisms of IRAK3 and neuroinflammation will be further investigated by Western blotting, qRT-PCR and immunofluorescence. Recombinant IL-17A was used to investigate the connection between IRAK3 and the NF-κB/IL-17A signaling pathway in vivo and in vitro experiments., Results: The expression of IRAK3 increased, peaking at 24 h, followed by a subsequent decrease after ICH. IRAK3 is mainly expressed in the microglia. RNA-seq analysis revealed 1,797 differentially expressed genes around the perihematomal brain tissue after IRAK3 siRNA treatment, with multiple inflammatory pathways being downregulated. Rh-IRAK3 treatment resulted in upregulation of the levels of inflammatory cytokines around the perihematomal tissue and exacerbated neurological function deficits. Furthermore, IRAK3 siRNA treatment markedly decreased the expression of inflammatory cytokines and microglial activation via the NF-κB/IL-17A signaling pathway. Recombinant IL-17A exacerbated the inflammatory response in vivo and in vitro; however, IRAK3 knockdown reversed this process., Conclusion: IRAK3 aggravates neuroinflammation by activating the NF-κB/IL-17A signaling pathway, thereby exacerbating neurological deficits following ICH. Therefore, inhibition IRAK3 may be a promising approach for treating ICH., Competing Interests: The authors declare no conflicts of interest in this work., (© 2025 Wang et al.)

Cyanobacterial cytochrome c6 (Cyt c6) is crucial for electron transfer between the cytochrome b6f complex and photosystem I (PSI), playing a key role in photosynthesis and enhancing adaptation to extreme environments. This study investigates the high-resolution crystal structures of Cyt c6 from Synechococcus elongatus PCC 7942 and Synechocystis PCC 6803, focusing on its dimerization mechanisms and functional implications for photosynthesis. Cyt c6 was expressed in Escherichia coli using a dual-plasmid co-expression system and characterized in both oxidized and reduced states. X-ray crystallography revealed three distinct crystal forms, with asymmetric units containing 2, 4, or 12 molecules, all of which consist of repeating dimeric structures. Structural comparisons across species indicated that dimerization predominantly occurs through hydrophobic interactions within a conserved motif around the heme crevice, despite notable variations in dimer positioning. We propose that the dimerization of Cyt c6 enhances structural stability, optimizes electron transfer kinetics, and protects the protein from oxidative damage. Furthermore, we used AlphaFold3 to predict the structure of the PSI-Cyt c6 complex, revealing specific interactions that may facilitate efficient electron transfer. These findings provide new insights into the functional role of Cyt c6 dimerization and its contribution to improving cyanobacterial photosynthetic electron transport.

Achieving the ideal gel strength is essential for desired texture in minced chicken products. This study developed a rapid, non-destructive method using near-infrared (NIR) spectroscopy and nonlinear chemometric modeling to predict minced chicken gel strength under ultrasonic treatment. Initially, minced chicken samples were subjected to high-intensity ultrasound for 0-50 min. This was followed by heat-induced gelation. Gel strength was conventionally measured, and NIR spectra were collected. Nonlinearity between gel strength and spectral data was confirmed using augmented partial residual plots (APaRPs). Subsequently, nonlinear support vector machine (SVM) and extreme learning machine (ELM) models were developed using full NIR spectra and variable selection methods, including uninformative variable elimination (UVE), competitive adaptive reweighting (CARS), and genetic algorithms (GA). GA proved most effective for enhancing model performance, achieving the highest predicted coefficient of determination (Rp 2  = 0.8772) with the ELM model, demonstrating potential for rapid, non-destructive prediction of minced chicken gel strength quality., Competing Interests: Declaration of competing interest The authors disclose no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Developing dual-functional electrocatalysts for urea-water decomposition still faces significant challenges. In this study, the vanadium (V) and cerium (Ce) co-doped FeCoNi medium-entropy phosphide (VCe-FeCoNiP/NF) were effectively fabricated on nickel foam (NF) via "two-step method," which involved hydrothermal treatment followed by phosphorization. Experimental results indicate that, benefiting from dual-ion doping and medium-entropy configuration, VCe-FeCoNiP/NF demonstrates unique electronic effects among the multimetallic elements, thereby exhibited remarkable catalytic activity for both urea oxidation reaction (UOR) and hydrogen evolution reaction (HER). Under urea-water conditions (1 M KOH with 0.33 M urea), the VCe-FeCoNi/NF catalyst merely required 1.338 V (vs RHE) and an overpotential of 173 mV to attain a current density of 100 mA·cm -2 for UOR and HER, respectively. Moreover, it could stably operate at a current density of 20 mA·cm -2 for 225 h in overall urea-water decomposition. This work provides new insights for designing high-performance urea-water electrolysis catalysts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Prostate cancer (PCa) ranks as the second most common disease among men and the fourth most prevalent cancer worldwide. Enhanced glycolysis and excessive lactate secretion are recognized as critical factors driving the progression of various cancers. This study systematically investigated the research trends associated with glycolysis in PCa through bibliometric analysis., Method: In this study, we conducted a systematic search of the Web of Science and PubMed databases for literature pertaining to the glycolysis of PCa that was published between January 1, 2004, and June 30, 2024. To achieve this objective, we employed CiteSpace software to generate visualizations that illustrate countries/regions, institutions, journals, and keywords. Additionally, we extracted pertinent quantitative data. Furthermore, we utilized VOSviewer software to create a collaboration network map among various journals., Results: Between 2004 and 2024, a total of 408 research articles on glycolysis in PCa were published, indicating a consistent upward trend in the annual publication rate. In this field, the United States not only leads in the volume of research papers but also has the highest degree of centrality. The journal "Cancer Research" is recognized as the most influential in the field, whereas "Prostate and Cancer" serves as a significant platform for disseminating research related to glycolysis in PCa. Keyword analysis has identified four primary research directions that have dominated this field over the past two decades. The role of glycolysis and its associated enzymes in PCa underpins this research. Glycolysis has also demonstrated significant clinical value in the diagnosis and prognosis of PCa. Moreover, drugs targeting glycolytic inhibitors and natural products have exhibited therapeutic potential against this disease. By modulating glycolytic mechanisms, there is potential to increase resistance in PCa. Currently, leading research in this area encompasses the application of nanotechnology to PCa glycolysis, the roles of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) in this metabolic pathway, and the interactions between glycolysis and other biological processes in PCa., Conclusion: This study employs bibliometric analysis to provide a comprehensive overview of research on glycolysis in PCa over the past two decades. It highlights the current state of knowledge in this field, identifies key research hotspots, and explores emerging frontiers, particularly nanotechnology, lncRNA, and miRNA, which are driving innovative research directions., Competing Interests: Declarations. Ethics approval and consent to participate: The content of this article has no ethical implications. Consent for publication: All the authors have read and approved the final manuscript and agree with its submission to the Journal of Discover Oncology. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Cancer-associated fibroblasts (CAFs) are intrinsic components of the tumor microenvironment that promote cancer progression and metastasis. Through an unbiased integrated analysis of gastric tumor grade and stage, we identified a subset of proangiogenic CAFs characterized by high podoplanin (PDPN) expression, which are significantly enriched in metastatic lesions and secrete chemokine (CC-motif) ligand 2 (CCL2). Mechanistically, PDPN(+) CAFs enhance angiogenesis by activating the AKT/NF-κB signaling pathway. The canonical NF-κB signaling protein P65 binds to the promoter region of CCL2, inducing its expression. Additionally, we found that CCL2 interacts with its nonclassical receptor ACKR1 (expressed on endothelial cells) to exert its proangiogenic effects. Furthermore, the disruption of CCL2-ACKR1 communication via a CCL2 neutralizing antibody or the inhibition of AKT signaling transduction using AKT inhibitors effectively suppressed tumor growth. Together, this study elucidates the mechanism by which PDPN(+) CAFs promote angiogenesis, providing a deeper understanding of the molecular processes underlying CAF-mediated angiogenesis and suggesting potential therapeutic targets for gastric cancer treatment., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Objective: To reduce hip joint muscles' activation during walking with an active hip exoskeleton. Background: Few studies examine the optimal active assistance timing of the hip exoskeleton based on muscle activation characteristics. Methods: Sixteen gender-balanced healthy adults (mean age 28.8 years) performed four tasks (each over 20 min). Tasks were different in loading and assistance. Muscle activation was collected by surface electromyography. The collected oxygen consumption evaluated the performance of the proposed active assistance strategy. Results: Experimental results verified that lower muscle activation and metabolism could be achieved when the active assistance gait phase was 9-60% of the gait cycle than that of all-gait-cycle active assist. Conclusions: Regulating the exoskeleton's active assistance timing according to muscles' activation characteristics can improve functional assistance.

Intervertebral disc degeneration (IDD) is a degenerative condition associated with impaired mitophagy. MANF has been shown to promote mitophagy in murine kidneys; however, its role in IDD remains unexplored. This study aimed to elucidate the mechanism by which MANF influences IDD development through the regulation of mitophagy. Human nucleus pulposus (NP) cells were exposed to tert-butyl hydroperoxide (TBHP) to establish an oxidative stress-induced cellular model. The expression levels of MANF in NP cells were quantified using quantitative real-time PCR (qPCR) and Western blotting. The impact of MANF on TBHP-induced NP cells was evaluated by assessing cell viability, apoptosis, and the levels of mitophagy-related proteins. The underlying mechanisms were further investigated using RNA-binding protein immunoprecipitation (RIP), dual-luciferase reporter assays, qPCR, and Western blotting. Results indicated that MANF expression was significantly downregulated in both IDD patients and TBHP-induced NP cells. Overexpression of MANF inhibited apoptosis, enhanced cell viability, and promoted mitophagy in TBHP-treated NP cells. MFN2 was identified as a downstream target of MANF, and MANF overexpression upregulated MFN2 expression in NP cells, whereas TBHP markedly suppressed MFN2 expression. Furthermore, knockdown of MFN2 partially reversed the effects of MANF overexpression on apoptosis, cell viability, and mitophagy in TBHP-treated NP cells. Collectively, these findings demonstrate that MANF overexpression enhances mitophagy by upregulating MFN2 expression, thereby mitigating oxidative stress-induced apoptosis in NP cells. These results provide novel insights into the pathogenesis of IDD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: This study was approved by the Ethics Committee of The Sixth Affiliated Hospital of Xinjiang Medical University. Informed consent was obtained from all individual participants included in the study. This study was performed in line with the principles of the Declaration of Helsinki. All methods were carried out in accordance with relevant guidelines and regulations. Consent for publication: Not applicable., (© 2024. The Author(s).)

Yeast β-glucan exhibits dramatic potential as wound healing regent owing to its various biological properties including immunomodulatory, anti-inflammatory, and antioxidant. But, the poor water solubility of yeast β-glucan limits its application. In this study, some carboxymethylated yeast β-glucans (CMGs) with different substitution degree was prepared. The effect of substitution degree on biological activities of carboxymethylated yeast β-glucan was investigated using zebrafish model. CMG 3 with substitution degree 0.55 showed anti-inflammatory, antioxidant, and immunomodulatory activities in zebrafish. CMG 3 also showed potential ability to promote angiogenesis and caudal fin regeneration. The cytotoxicity of CMG 3 was investigated on L929 cells and the effect of CMG 3 on cell migration was studied by scratch test. The hemolysis ratio of CMG 3 was determined, and the in vitro antioxidant activity was studied. Next, CMG 3 was used to prepare a sprayable hydrogel through a simple method, and the wound healing ability was studied using a streptozotocin-induced diabetic mice model. The results indicated that CMG 3 -based sprayable hydrogel could accelerate wound healing in a diabetic mice and influence the expression of biomarkers related to inflammatory, macrophage polarization, and angiogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The leaves of Elaeagnus angustifolia, belonging to the Elaeagnaceae Juss. family, are known for their medicinal properties for relieving cough and asthma, as well as treating dysentery and diarrhea., Objective: To establish a rapid qualitative method for the detection of secondary metabolites in leaves of Elaeagnus angustifolia, including the identification and analysis of various secondary metabolites in leaves of Elaeagnus angustifolia., Method: Samples were separated using a Waters ACQUITY H-Class ultra-performance liquid chromatography (UPLC) system (FTN autosampler, quaternary LC pump) and ACQUITY UPLC® BEH C18 column (1.7 μm, 2.1 mm × 100 mm). The flow rate was set to 0.4 mL/min, the injection volume was 1.0 μL, and the column temperature was set to 45°C. The mobile phase was methanol (A) with -0.1% formic acid in water (B). Samples were analyzed by quadrupole time-of-flight mass spectrometry (Q-TOF-MS)., Results: A total of 182 different secondary metabolites were detected from 10 varieties of leaves of Elaeagnus angustifolia, including 77 flavonoids, 20 steroids, 7 alkaloids, 15 amino acids, 18 organic acids, and 45 other compound types., Conclusions: A method for the rapid analysis of leaves of Elaeagnus angustifolia by UPLC-Q-TOF-MS was established, and the secondary metabolites in leaves of Elaeagnus angustifolia were identified. The enrichment of secondary metabolites in leaves of different varieties of Elaeagnus angustifolia was clarified., Highlights: The UPLC-Q-TOF-MS method is very fast and possesses a high degree of selectivity, precision, and sensitivity. These findings provide a reliable foundation for the development of medicinal resources derived from Elaeagnus angustifolia leaves., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Patients with hypertrophic cardiomyopathy (HCM) may develop concomitant advanced heart failure (HF). However, there is limited data on the clinical outcomes of HCM patients without sarcomere gene mutations who have advanced HF., Objectives: To identify prognostic factors for advanced HF in gene-negative patients within a large HCM cohort., Methods: A total of 1529 unrelated patients with HCM were enrolled between 1999 and 2018, and followed throughout the study period. All patients underwent genotyping through whole exome or panel sequencing. From this cohort, 735 patients without mutations were studied. We assessed the effects of family history, clinical findings, and echocardiographic parameters on the development of advanced HF. Multivariable Cox proportional hazards regression analysis was conducted to identify risk factors associated with advanced HF., Results: Of the 735 gene-negative patients studied, the mean age was 52.5±13.2 years, 69.5% were male, and the mean follow-up duration was 3.2±2.3 years. During this period, 97 patients (13.2%) developed advanced HF. Using multivariable analysis, we identified significant risk factors for advanced HF: female gender (adjusted hazard ratio [HR] 2.499, 95% confidence interval [CI] 1.531-4.081, P<0.001) and older age at enrollment (adjusted HR 1.298, 95% CI 1.00-1.682, P=0.049). These findings suggest that female patients and those enrolled at an older age are at a higher risk for developing advanced HF., Conclusion: Female gender and older age may predict a higher risk of advanced HF in gene-negative patients with HCM. Early detection and proactive treatment are crucial for managing and preventing complications in these patients., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests, (Copyright © 2024. Published by Elsevier Inc.)

Osteoarthritis (OA) stands as a prevalent chronic joint pathology, emerging as a leading cause of disability on a global scale. However, the current therapeutic efficacy in OA treatment remains unsatisfactory. Chondrocyte ferroptosis has become to a critical target for OA treatment, while the fabrication of nanomedicines emerges as a promising strategy for OA treatment. Nevertheless, there exists a paucity of reported nanomedicine systems designed to combat chondrocyte ferroptosis for OA alleviation. In light of this, our study introduced a reactive oxygen species (ROS)-sensitive fenofibrate-loaded targeted nanoparticle (FN-CNPs) as a means of alleviating OA by suppressing chondrocyte ferroptosis. In vitro investigations demonstrated the FN-CNPs can achieve this through the reduction of lipid peroxidation and ROS levels, as well as the elevation of anti-ferroptosis markers (GPX4, FSP1, and ACSL3). Consequently, FN-CNPs exhibited significant anti-inflammatory effects and downregulated the expression of key catabolic mediators in vitro. Furthermore, in vivo studies underscored the ability of FN-CNPs to alleviate OA progression and protect cartilage. Collectively, these findings highlight the efficacy of FN-CNPs in mitigating OA progression by suppressing chondrocyte ferroptosis via regulating ROS levels, antioxidant systems and lipid metabolism of chondrocytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Exploring single-atom (SA) catalysts in hybrid urea-assisted water electrolysis offers a viable alternative to both Hydrogen (H 2 ) generation and polluted water treatment. However, the unfavorable electronic stabilization, low SA content, intrinsically slow kinetics, and imbalanced adsorption-desorption steps are the bottleneck for its scale-up implementation. Herein, a rare-earth Terbium single atom (Tb SA ) is topologically stabilized on defect-rich Co 3 O 4 (Tb SA @d-Co 3 O 4 ) by Tb─O co-ordination for urea oxidation reaction (UOR) and H 2 evolution reaction (HER). Benefitting from the strong Tb SA interaction with the d-Co 3 O 4, the Tb SA @d-Co 3 O 4 achieves a 10 mA cm -2 current density at 1.27 V and -35 mV for UOR and HER, respectively. Remarkably, when Tb SA @d-Co 3 O 4 is applied as a bi-functional catalyst in a two-electrode system, it merely requires 1.22 V to acquire 10 mA cm -2 with excellent operational stability for 100 h. The hybrid electrolyzer can be successfully empowered by the triboelectric nanogenerator, AA battery, and solar panel with a nominal potential of 1.5 V. The mechanistic investigation predicts "Tb SA " insertion in d-Co 3 O 4 lowered the potential determining step, attributed to balanced reaction energetics for adsorption-desorption of intermediates and favorable charge transfer characteristics for UOR. This work offers a new paradigm to explore the catalytic properties of rare-earth "f-block" elements to create advanced electrocatalysts via structural modulation., (© 2024 Wiley‐VCH GmbH.)

Background: Transcription factors (TFs) fulfill a critical role in the formation and maintenance of different cell types during the developmental process as well as disease. It is believed that cancer-associated fibroblasts (CAFs) are activation status of tissue-resident fibroblasts or derived from form other cell types via transdifferentiation or dedifferentiation. Despite a subgroup of CAFs exhibit anti-cancer effects, most of them are reported to exert effects on tumor progression, further indicating their heterogeneous origin., Aim of Review: This review aimed to summarize and review the roles of TFs in the reciprocal crosstalk between CAFs and tumor cells, discuss the emerging mechanisms, and their roles in cell-fate decision, cellular reprogramming and advancing our understanding of the gene regulatory networks over the period of cancer initiation and progression., Key Scientific Concepts of Review: This manuscript delves into the key contributory factors of TFs that are involved in activating CAFs and maintaining their unique states. Additionally, it explores how TFs play a pivotal and multifaceted role in the reciprocal crosstalk between CAFs and tumor cells. This includes their involvement in processes such as epithelial-mesenchymal transition (EMT), proliferation, invasion, and metastasis, as well as metabolic reprogramming. TFs also have a role in constructing an immunosuppressive microenvironment, inducing resistance to radiation and chemotherapy, facilitating angiogenesis, and even 'educating' CAFs to support the malignancies of tumor cells. Furthermore, this manuscript delves into the current status of TF-targeted therapy and considers the future directions of TFs in conjunction with anti-CAFs therapies to address the challenges in clinical cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Intracranial aneurysms (IAs) are pathological dilations occurring at major branch points of cerebral arteries, which can lead to aneurysmal subarachnoid hemorrhage (aSAH) upon rupture. Recent studies have identified developmental endothelial locus-1 (DEL1) as closely associated with IA, though its role remains not fully understood. This study aimed to investigate serum DEL1 level differences in IA patients and explore its function in vascular endothelial cells., Methods: We enrolled 32 IA patients and 32 healthy controls at our hospital between February 2024 and August 2024. Clinical data were collected from electronic medical records. Peripheral blood samples were taken preoperatively to measure serum DEL1 concentrations using enzyme-linked immunosorbent assay (ELISA). Functional assays were conducted on human umbilical vein endothelial cells (HUVECs) in vitro., Results: Serum DEL1 levels were significantly lower in IA patients compared to healthy controls. Subgroup analysis showed that DEL1 levels were lower in patients with ruptured IAs and multiple IAs. Serum DEL1 level exhibits good performance as a biomarker for IA and aSHA. Additionally, in vitro experiments demonstrated that DEL1 knockdown (siDEL1) in HUVECs significantly enhanced cell proliferation, migration, and tube formation, while abnormal shear stress reduced endothelial DEL1 gene expression and disrupted endothelial barrier, suggesting a role in IA formation and progression., Conclusion: Our findings suggest that decreased serum DEL1 levels may serve as a potential biomarker for the formation and progression of IAs. DEL1 could be a key target for future studies investigating the pathogenesis of IA and aSAH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

As a heavy metal contaminant, mercury ion (Hg 2+ ) has caused great harm to environment and life. Mercury ions will migrate and transform in the environment and eventually accumulate in the human body, thus causing human poisoning. Therefore, it is of great significance to detect Hg 2+ in the environment and living bodies. Based on this, we constructed an example of reactive near-infrared ratiometric fluorescent probe NIRPC-Hg based on the ICT-ESIPT mechanism. The probe could not only effectively overcome the effects of environmental changes, thus realizing the accurate detection of Hg 2+ in the environment, but also possessed the advantages of large emission wavelength shift (130 nm red shift). In addition, the probe NIRPC-Hg was constructed with the classical recognition structure of Hg 2+ and NIR fluorophore, which could detect Hg 2+ sensitively with a low detection limit (9.21 nM). The satisfactory experimental results of environmental water samples proved that the probe had high application potential in the environment. At the same time, the probe NIRPC-Hg had the characteristics of smaller photo-toxicity and lower autofluorescence interference in the bioimaging applications, which could conveniently realize the sensitive detection of Hg 2+ in cells and zebrafish. Therefore, the construction of probe NIRPC-Hg provided an effective tool to detect Hg 2+ in the environment and living organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The denatured bovine serum albumin (dBSA) is coupled with the CdTe/CdS quantum dot and the resulting CdTe/CdS@dBSA complex is assembled and retained in the poly(n-isopropyl acrylamide) (PNIPAM) hydrogel via regulating temperature and pH to form the CdTe/CdS@dBSA-PNIPAM fluorescence hydrogel substrate, which is able to adsorb and sense cadmium ions (Cd 2+ ). Based on this fluorescence hydrogel, a fluorescence and colorimetric dual-mode detection system is established to quantitatively detect Cd 2+ with a limit of detection (LOD) of 2.88 nM for fluorescence detection and 11.66 nM for colorimetric detection. Here, the fluorescence and colorimetric detection mode can obtain the dual test signal including the fluorescence signal and visual orange-red color signal. Therein, the utilization of smartphone can achieve the conversion of visual color signals into RGB digital signals, facilitating the interconnection of data among the communication devices. This research provides a novel and advanced strategy for the accurate and real-time detection of Cd 2+ ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence-based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk. Additionally, recommendations for digital rectal examination and DNA polymerase epsilon (POLE)/ DNA polymerase delta 1 (POLD1) gene mutation testing have been strengthened. The 2024 CSCO Guidelines are based on both Chinese and international clinical research, as well as expert consensus, ensuring their relevance and applicability in clinical practice, while maintaining a commitment to scientific rigor, impartiality, and timely updates., (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat‐sen University Cancer Center.)

Objectives: This study compared the clinical outcomes of minimally invasive surgery (MIS) and open surgery (OS) for patients with intraspinal tumors., Methods: A systematic search of PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases was conducted to identify relevant studies. Continuous variables, including estimated blood loss, surgery duration, time to mobilization, length of hospitalization, visual analog scale (VAS) score, and incision length, were reported as mean differences (MD) with 95% confidence intervals (95% CIs). Dichotomous variables, such as gross total resection, blood transfusion, cerebrospinal fluid (CSF) leakage, and overall complications, were presented as risk ratios (RR) with 95% CIs. Meta-analyses were performed using RevMan 5.3., Results: Fifteen studies, comprising a total of 943 patients (488 in the MIS group and 455 in the OS group), met the inclusion criteria. The meta-analysis indicated that MIS significantly reduced estimated blood loss (MD = -76.73, 95% CI -102.56 to -50.91, P < 0.01), incision length (MD = -4.09, 95% CI -5.20 to -2.97, P < 0.01), VAS score (MD = -0.79, 95% CI -1.48 to -0.11, P = 0.02), time to mobilization (MD = -4.27, 95% CI -5.12 to -3.43, P < 0.01), length of hospitalization, (MD = -3.94, 95% CI -5.05 to -2.84, P < 0.01), and overall complications (RR = 0.40, 95% CI 0.25 to 0.64, P < 0.01) compared with OS. No significant differences were observed in surgery duration (MD = -28.67, 95% CI -58.58 to 1.23, P = 0.06), gross total resection (RR = 1.00, 95% CI 0.94 to 1.07, P = 0.92), blood transfusion (RR = 0.23, 95% CI 0.05 to 1.04, P = 0.06), or CSF leakage (RR = 0.50, 95% CI 0.24 to 1.04, P = 0.07)., Conclusion: Findings from this analysis suggest that MIS offers clinical advantages over OS in reducing blood loss, incision length, pain, time to mobilization, length of hospitalization, and overall complication rates., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Precursor solution aging process can cause significant influence on the photovoltaic performance of perovskite solar cells (PVSCs). Notably, we first observe that the aging phenomenon is more severe in the precursor of two-step sequential method compared to that in one-step method due to that the protic solvent isopropanol facilitates amine-cation side reaction and iodide ions oxidation. Herein, we report a novel approach for selectively stabilizing both organic amine salt and lead iodide (PbI 2 ) precursor solutions in two-step method. The introduction of benzene-1,3-dithiol into organic amine salt solution can mitigate amine-cation side reactions due to the formation of an acidic and reducing environment. Simultaneously, decamethylferrocene (FcMe 10 /FcMe + 10 ) pair can act as a redox shuttle in PbI 2 solution to concurrently oxidize Pb 0 and reduce I 2 in cyclic manner. Consequently, the PVSCs device fabricated from ameliorative precursor solutions demonstrates superior power conversion efficiency of 25.31 %, retaining 95 % of its efficiency after 21 days of solution aging. Moreover, the unencapsulated devices maintain 85 % of primitive efficiency for 1500 h at maximum power point tracking under continuous illumination. This work establishes a fundamental guidance and scientific direction for the stabilization of two-step perovskite precursor solutions., (© 2024 Wiley-VCH GmbH.)

Background: Oxidative stress (OS) is involved in low female fertility by altering multi-omics such as the transcriptome, miRome, and lncRNome in follicular cells and follicular fluid. However, the mechanism by which OS affects multi-omics dynamics remains largely unknown. Here, we report that OS induces lncRNome dynamics in sow granulosa cells (sGCs), which is partially dependent on the transcription factor activity of its effector, FoxO1., Results: A total of 2,283 putative FoxO recognition elements (FREs) were identified in the promoters of 394 lncRNAs, accounting for 91.20% (394/432) of the lncRNAs regulated by OS. ChIP and reporter assays showed that the effector FoxO1 mediated OS regulation of lncRNA transcription in a transcription factor activity-dependent manner. In sGCs, OS induces the transcription and function (e.g., apoptosis) of NORSF (non-coding RNA involved in sow fertility), a nuclear lncRNA involved in sGC function via FoxO1. Furthermore, FoxO1 has been identified as a transcriptional activator of NORSF in sGCs that interacts with the FRE motif of its promoter. Meanwhile, OS downregulates the transcription of CYP19A1, which encodes an essential enzyme for estrogen synthesis and 17β-estradiol (E2) release by sGCs via the FoxO1 and NORSF axis. Phenotypically, dysregulation of NORSF transcription caused by 2 novel adjacent transitions in the promoter leads to decreased sow fertility., Conclusion: These results suggest a model of OS-stimulated lncRNome dynamics in sGCs and a new signaling pathway of OS that influences sGC function and sow fertility., Competing Interests: Declarations. Ethics approval and consent to participate: All sow experiments were approved by the Animal Ethics Committee at Nanjing Agriculture University, China. Consent for publication: Not applicable. Competing interests: The authors declare no conflict of interest., (© 2024. The Author(s).)

Pork batter quality significantly affects its product. Herein, this study explored the use of Raman spectroscopy combined with deep learning algorithms for rapidly detecting pork batter quality and revealing the mechanisms of quality changes during heating. Results showed that heating increased β-sheet content (from 26.38 to 41.42%) and exposed hidden hydrophobic groups, which formed aggregates through chemical bonds. Dominant hydrophobic interactions further cross-linked these aggregates, establishing a more homogeneous and denser network at 80 °C. Subsequently, convolutional neural networks (CNN), long short-term memory neural networks (LSTM), and CNN-LSTM were comparatively used to predict gel strength and whiteness in batters based on the Raman spectrum. Thereinto, CNN-LSTM provided the optimal results for gel strength (Rp = 0.9515, RPD = 3.1513) and whiteness (Rp = 0.9383, RPD = 3.0152). Therefore, this study demonstrated the potential of Raman spectroscopy combined with deep learning algorithms as non-destructive tools for predicting pork batter quality and elucidating quality change mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Treatment of bacterial infected full-thickness wounds remains a great challenge in clinic. Herein, a HYP hydrogel was prepared using carboxymethyl chitosan, dialdehyde carboxymethyl cellulose, and marine snail peptide (Tyr-Ile-Ala-Glu-Asp-Ala-Glu-Arg) as starting materials. The marine snail peptide with good antioxidant activity could remove the reactive oxygen species in wound sites, thereby alleviating the excessive inflammatory response. The dynamic Schiff-base bonds endowed HYP with good injectable and self-healing abilities. HYP exhibited suitable gelation time, good rheological properties, and unique porosity structure, which were conducive to wound healing. In vitro biological studies indicated that HYP showed good biocompatibility, low hemolysis ratio, and improved antibacterial and antioxidant activities. In vivo study revealed that HYP could promote wound healing in a bacterial infected full-thickness skin defect rat model. The wound tissues showed reduced number of inflammatory cells, newly formed hair follicles, and obvious collagen deposition. The expression of inflammatory and angiogenesis related biomarkers (IL-6, IL-10, CD31, and α-SMA) significantly improved. Therefore, HYP hydrogel showed great application prospect as a wound dressing for bacterial infected wound., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The objectives of this study are to analyse the effect and safety of procalcitonin (PCT)-guided antibiotic therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD)., Methods: We conducted a multicentre, open-label, randomized controlled trial amongst patients hospitalized for AECOPD in six hospitals in China. Enrolled patients were randomly assigned to either the PCT-guided group or the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy-guided group. The co-primary endpoints were antibiotic prescription rate for AECOPD within 30 days after randomization (to demonstrate superiority) and treatment success rate at day 30 after randomization (to demonstrate non-inferiority). For primary outcomes, χ 2 test, corrected χ 2 test, or Fisher's exact test was used to evaluate the differences between the intervention and control groups. 95% CIs were calculated for all the outcomes. Secondary outcomes, including days of antibiotic use during hospitalization, length of hospital stay, and change in modified Medical Research Council dyspnoea scale and COPD Assessment Test score, were compared using the Student's t-test, with corresponding differences and 95% CIs calculated. Intention-to-treat (ITT) population were those who were randomly assigned, and per-protocol population were those who strictly adhered to the treatment plan., Results: A total of 455 patients were randomly assigned, with 229 in the PCT-guided group and 226 in the GOLD-guided group. The rate of antibiotic prescription for AECOPD by day 30 was significantly lower in the PCT-guided group than that in the GOLD-guided group (38% [88/229] vs. 59% [134/226]; difference -21%; 95% CI: -30% to -12%; p < 0.0001) in the ITT analysis. There was no significant difference in the clinical treatment success rate by day 30 between the 2 groups (97% [223/229] vs. 94% [212/229]; difference 4%, 95% CI: 0-7%; p 0.06). Compared with the GOLD strategy, PCT-guided antibiotic therapy was significantly associated with lower antibiotic prescription rate during hospitalization (37% vs. 59%, difference -22%, 95% CI: -31 to -13; p < 0.0001), and fewer days of antibiotic use during hospitalization (2.63 ± 4.66 vs. 4.86 ± 4.83, difference -2.23 days, 95% CI: -1.35 to -3.11; p < 0.0001). There were no significant differences between the two groups in length of hospital stay, subsequent exacerbation rate, hospital readmission rate, intensive care unit admission, and 30-day mortality in the ITT analysis. The results in the per-protocol analysis were consistent with that in the ITT analysis., Discussion: Compared with the GOLD strategy, PCT-guided antibiotic therapy significantly reduced the rate of antibiotic prescription for patients with AECOPD, without negatively affecting the treatment success rate., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

One important target for anion exchange membrane fuel cells (AEMFCs) is to enable the application of anode non-precious metal hydrogen oxidation reaction (HOR) catalyst. Nickel presents a promising candidate for alkaline HOR; yet, its practical application is hampered by the intrinsically sluggish activity and poor stability. Herein, a series of Ni-based metals (Ni 5 Mo, Ni 25 Co, Ni 14 W and Ni) are electrodeposited as model catalysts to systematically explore the alkaline HOR by considering the role of adsorbed hydroxyl (OH ad ). Spectroscopic studies together with density functional theory calculations shed light on the beneficial effect of transition metal M (M=Mo, Co, W) alloying/doping on HOR by introducing the charge transfer from M to Ni and down shifting Ni 3d band center. The HOR specific activities on Ni-based catalysts reveal a volcano-type relationship with the hydrogen binding energy (HBE). The strongly adsorbed OH ad is proven to induce deactivation for Ni active sites, and the deactivation potential is OH ad binding energy (OHBE) dependent. This study adds new insight into the HOR mechanism and stability of Ni-based electrocatalysts, providing a new avenue for the rational design of highly efficient and robust alkaline HOR catalysts., (© 2024 Wiley-VCH GmbH.)

Alkali stress is one of the most serious abiotic stresses limiting crop yield and it has become an increasingly serious global problem in recent years. Alkalinity tolerance (AT) at the seedling stage is one of the determinant factors for establishment of rice population under alkaline stress condition. Here, we evaluated and measured seven traits related to AT of 528 diverse rice accessions at the seedling stage. Xian accessions were generally more alkali-tolerant than Geng accessions. GJ-tmp accessions showed the most alkali tolerance in the Geng subgroups and XI-1B accessions had the weakest alkali tolerance in the Xian subgroups. A total of 121 QTLs were identified for AT by genome-wide association study (GWAS), and five important candidate genes, LOC&#95;Os01g19800, LOC&#95;Os01g20160, LOC&#95;Os01g52500, LOC&#95;Os01g67370 and LOC&#95;Os03g03900, were selected by gene function annotation, haplotype analysis, and qRT-PCR. Pyramiding of multiple AT advanced candidate genes is a favorable strategy for improving AT of rice varieties. Our study has screened alkali-tolerant germplasm resources and provided valuable genetic information for alkali-tolerant rice breeding., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The two-step deposition method effectively mitigates the efficiency decline observed in tin-based perovskite solar cells (TPVSCs) with increasing cell area, stemming from film in-homogeneity. However, the high solubility of SnI 2 in the conventionally used solvent isopropyl alcohol, coupled with the absence of effective modulation of reaction-diffusion process, results in inadequate film coverage and conversion. In this study, we introduce formic acid as the second-step solvent and introduce dithiothreitol (DTT) to regulate reaction-diffusion/crystallization kinetics meticulously. Moreover, this research underscores a fundamental principle that the suitable binding energy ranging from -1.38 to -10.10 kcal mol -1 between ligands and Sn 2+ significantly enhances the effectiveness of two-step crystallization control. Notably, a uniform perovskite film is achieved on large-scale substrate, and TPVSCs processed with DTT exhibit the highest efficiencies of 12.68 % for 0.04 cm 2 device and 11.30 % for 1 cm 2 device among tin-based perovskite devices in two-step sequential deposition method, even in the absence of dimethyl sulfoxide. This study lays the groundwork for the potential scale-up development of lead-free perovskite solar cells., (© 2024 Wiley-VCH GmbH.)

An oxidising and substituting one-pot reaction strategy has been developed to synthesise dihydromyricetin derivatives with the aim of enhancing the inhibitory activity of dihydromyricetin against SARS-CoV-2. Different ω -methoxy- ω -oxeylkyl was introduced in C 7 -OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CL pro with IC 50 values ranging from 0.72 to 2.36 μM. In the Vero E6-cell, compound 3 has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC 50 of 15.84 μM, and so do compound 10 in the therapeutic model, with an EC 50 of 11.52 μM. The results suggest that the introduction of long chain ω -oxeylkyl at C 7 -OH facilitate the inhibition of viral replication in the therapeutic model, which is consistent with the binding energies predicted from molecular docking conclusions. It implies that dihydromyricetin derivatives have the potential to become effective inhibitors of SARS-CoV-2 Omicron and other viruses.

Cadmium (Cd) pollution poses a significant threat to wetland ecosystems. Phragmites australis, a species with intraspecific ploidy diversity, is commonly used in constructed wetlands for pollution remediation. However, little is known about how the ploidy variation of P. australis influences the phytoremediation processes via physiological and rhizosphere regulations. Here, we used P. australis from two major lineages in China (i.e., tetraploid lineage O and octoploid lineage P) and applied three Cd treatments (control, low Cd concentration, and high Cd concentration). We found that the lineage O had a bioconcentration factor of Cd approximately 40% higher than that of the lineage P. The translocation factor of the lineage P was about 300% higher than that of the lineage O. These suggest that the lower ploidy lineage exhibited a greater capacity to absorb Cd from the environment into the underground part compared to the higher ploidy lineage, and the higher ploidy lineage demonstrated a superior ability in transferring Cd from the underground to the aboveground part. The advanced transpiration system in the higher ploidy lineage can contribute to its enhanced ability to translocate Cd, as the translocation factor of Cd was significantly correlated with the base shoot diameter and the transpiration rate, both notably higher in the lineage P. The rhizobacterial community associated with the lineage P displayed a more intense response to Cd, characterized by an increase in both the diversity of the community and the number of varied bacterial functions following the addition of Cd. Our study offers profound insights into the ecological consequences of intraspecific polyploidization and the application of intraspecific ploidy variation in environmental management and wetland restoration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

ATP6V1B2 encodes the subunit of the vacuolar H + -ATPase, which is an enzyme responsible for the acidification of intracellular organelles and essential for cell signaling and neurotransmitter release. The aim of the study is to identify the correlation between ATP6V1B2 and epilepsy. Trio-exome sequencing was performed. Reverse Transcription-PCR and Quantitative real-time PCR analyses were carried out to determine whether this variant leads to nonsense-mediated mRNA decay (NMD). Drosophila models with knocked-down homologous genes of ATP6V1B2 were generated to study the causal relationship between the ATP6V1B2 and the phenotype of epilepsy. We described a 5-year-old male with a novel variant c.1163delT(p.Tyr389IlefsTer13) in ATP6V1B2, who presented with epilepsy. The expression level of the premature termination codon (PTC) transcript was normal in the patient, which indicated that NMD evasion existed in the PTC transcript. We generated an animal model using Drosophila to study the knock down effects of Vha55, which is the ATP6V1B2 ortholog in fly. The Vha55 knockdown flies show seizure-like behaviors and climbing defects. This study expands the variation spectrum of the ATP6V1B2 gene. Cross-species animal model demonstrates the causal relationship between ATP6V1B2 defect and epilepsy, and shed new insights into the disease mechanism caused by ATP6V1B2 LOF variants., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The κ-carrageenan/microbial-originated dextran-based multifunctional intelligent packaging films, integrated with natural anthocyanins as a colorant and ZnO as an antibacterial agent, were successfully developed using a casting method. Their applicability and functionality were systematically assessed through various analytical techniques. The addition of dextran, anthocyanins, and ZnO in the films resulted in an increased tensile strength (from 13.66 ± 0.53 to 29.70 ± 1.29 MPa) and elongation at break (from 16.69 ± 1.05 % to 39.49 ± 0.73 %), and decreased water solubility (from 64.94 ± 0.34 % to 32.84 ± 1.55 %) and water vapor barrier property (from 8.29 ± 0.12 × 10 -10  g/m•s•Pa to 6.92 ± 0.1 × 10 -10  g/m•s•Pa). Spectroscopic analysis revealed that the dextran, ZnO and anthocyanins were uniformly dispersed within the film-forming substrates, achieved through hydrogen bonds and electrostatic interactions. The addition of anthocyanins and ZnO not only enhanced the antibacterial and antioxidant properties of the film but also provided it with good pH sensitivity and color stability, making it highly promising for use in shrimp freshness monitoring. All the films were shown to be biodegradable, decomposing completely in soil within 30 days. Overall, these results suggest that the films could serve as a potential replacement for plastic food packaging and additionally monitor the freshness of food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Single-nucleotide polymorphism (SNP) allele frequencies, dietary habits, and folate status and their associations vary across ethnic populations. Little is known about the SNPs accounting for variations of folate-related biomarkers for Chinese preparing-for-pregnant females., Objectives: We aimed to identify SNPs contributing to RBC and serum folate, vitamin B-12, and homocysteine concentrations in Chinese female preconception population., Methods: A genome-wide association study was conducted on 1000 randomly selected preconception Chinese women from the Shanghai Preconception Cohort. SNPs were genotyped using Illumina chips, and associations with biomarkers were assessed using simple linear regression models under the assumption of an additive genetic model. Genome-wide significance was considered at P < 10 -7 ., Results: The MTHFR rs1801133 was the major genetic coding variant contributing to RBC folate, serum folate, and homocysteine concentrations (P = 2.28 × 10 -16 ; P = 8.85 × 10 -8 , and P = 2.46 × 10 -13 , repsectively). It is associated with increased RBC folate (β: 0.154 per additional risk allele after log transform), decreased serum folate (β: -0.951 per additional risk allele), and increased serum homocysteine concentrations (β: 1.153 per additional risk allele). The predominant SNP associated with serum folate was rs147162222 in NTRK2 (P = 2.55 × 10 -8 ), although that associated with homocysteine was rs77025184 located between PDE7B and LINC00271 (P = 4.91 × 10 -17 ). For vitamin B-12, FUT2 rs1047781 was the dominant genetic variant (P = 1.59 × 10 -10 ). The numbers of signals with a P value of <10 -7 for RBC folate, serum folate, vitamin B-12, and homocysteine were 12, 18, 8, and 614, respectively., Conclusions: This study represents the first genome-wide association study focusing on folate-related biomarkers in a Chinese preparing-for-pregnant female population. The contributions of dominent SNPs to each biomarker are partly different from other populations. The rs1801133 (C677T) in MTHFR is the predominant genetic variant contributing to RBC folate and rs1047781 (A385T) in FUT2 as the primary one explaining vitamin B-12. Notably, the intronic rs147162222 and noncoding rs77025184 are the predominant SNPs for serum folate and homocysteine, respectively., Competing Interests: Conflict of interest GH reports financial support was provided by the National Key Research and Development Program of China (grant numbers 2021YFC2701000 and 2016YFC1000500); CAMS Innovation Fund for Medical Sciences (grant number 2019-I2M-5-002); and National Natural Science Foundation of China (grant number 82270312). The other authors report no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Moving object detection in satellite videos (SVMOD) is a challenging task due to the extremely dim and small target characteristics. Current learning-based methods extract spatio-temporal information from multi-frame dense representation with labor-intensive manual labels to tackle SVMOD, which needs high annotation costs and contains tremendous computational redundancy due to the severe imbalance between foreground and background regions. In this paper, we propose a highly efficient unsupervised framework for SVMOD. Specifically, we propose a generic unsupervised framework for SVMOD, in which pseudo labels generated by a traditional method can evolve with the training process to promote detection performance. Furthermore, we propose a highly efficient and effective sparse convolutional anchor-free detection network by sampling the dense multi-frame image form into a sparse spatio-temporal point cloud representation and skipping the redundant computation on background regions. Coping these two designs, we can achieve both high efficiency (label and computation efficiency) and effectiveness. Extensive experiments demonstrate that our method can not only process 98.8 frames per second on 1024 ×1024 images but also achieve state-of-the-art performance.

Introduction: Autosomal recessive polycystic kidney disease (ARPKD) ranks among the most severe chronic kidney diseases (CKD). Its primary cause is variants in the Polycystic Kidney and Hepatic Disease 1 gene (PKHD1). The clinical spectrum of ARPKD varies widely, ranging from mild late-onset symptoms to severe perinatal mortality. However, achieving an early genetic diagnosis in ARPKD patients before clinical symptoms appear proves challenging., Case Presentation: This case is a 4-year-old boy who experienced a convulsion characterized by a generalized tonic attack lasting approximately 3-5 minutes and later sought treatment to our hospital. However, routine abdominal ultrasound examination accidentally detected that he had diffuse liver lesions, splenomegaly, and bilateral renal enlargement with renal pelvis dilation. Given the uncertainty regarding the underlying cause of the patient's structural abnormalities and convulsions, karyotyping, whole exome sequencing (WES), structural variant analysis (SV analysis) of whole genome sequencing (WGS) were recommended. The result of SV analysis revealed that he has an RBT impacting PKHD1 and the precise location of breakpoints was confirmed through Long-Range Polymerase Chain Reaction (LR-PCR). However, WES did not screen out pathogenic variants initially, the WES data was reviewed subsequently based on SV analysis results., Conclusion: We identified an infrequent variant combination, c.2507T>C (p.V836A) in PKHD1 and an RBT with broken PKHD1, which extends the genetic spectrum of ARPKD, and provide a basis for further genetic counselling to the family., (© 2024 Asian Pacific Society of Nephrology.)

Background: Spinal cord injury (SCI) is a debilitating condition with profound implications on patients' quality of life. Recent advancements in brain-computer interface (BCI) technology have provided novel opportunities for individuals with paralysis due to SCI. Consequently, research on the application of BCI for treating SCI has received increasing attention from scholars worldwide. However, there is a lack of rigorous bibliometric studies on the evolution and trends in this field. Hence, the present study aimed to use bibliometric methods to investigate the current status and emerging trends in the field of applying BCI for treating SCI and thus identify novel therapeutic options for SCI., Methods: We conducted a comprehensive review of the relevant literature on BCI applications for treating SCI published between 2005 and 2024 by using the Web of Science Core Collection database. To facilitate visualization and quantitative analysis of the published literature, we used VOSviewer and CiteSpace software tools. These tools enabled the assessment of co-authorships, co-occurrences, citations, and co-citations in the selected literature, thereby providing an overview of the current trends and predictive insights into the field., Results: The literature search yielded 714 publications from the Web of Science Core Collection database. The findings indicated a significant upward trend in the number of publications, yielding a total of 24,804 citations, with an average citation rate of 34.74 per publication and an H-index of 75. Research contributions were identified from 54 countries/regions, and the United States, China, and Germany emerged as the predominant contributors. A total of 1114 research institutions contributed to the retrieved literature, with Harvard Medical School, Brown University, and Northwestern University producing the highest number of publications. The published literature was predominantly distributed across 258 academic journals, and the Journal of Neural Engineering was the most frequently utilized publication source. Hochberg, Leigh, Henderson, Jaimie, and Collinger were the prominent authors in this field., Conclusions: In recent years, there has been a steep increase in research on the use of BCI for treating SCI. Existing research focuses on the application of BCI for improving rehabilitation and quality of life of patients with SCI. Interdisciplinary collaboration is the current trend in this field., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Correctly diagnosing neuroendocrine neoplasm (NEN) has become increasingly challenging, given that more histomorphologic and immunophenotypic NEN mimics have been identified in recent years. A systemic review was conducted on the 4795 consult cases submitted with initial diagnoses of NEN to a national reference center in China from 2013 to 2021. Among them, 443 cases were misdiagnosed as epithelial NENs after reevaluation with the help of immunohistochemical and/or molecular tests, ranging from 7.1 to 13.2%, with yearly increases. The misdiagnoses varied among age groups and tumor sites. Exocrine carcinoma was the most common (63.2%), followed by mesenchymal tumors. Other common tumors that were misdiagnosed included hepatocellular carcinoma, salivary gland tumor, and gastrointestinal stromal tumor. Aberrant expression of neuroendocrine markers was frequent (218/408, 53.4%), with diffuse positivity ranging from 8.2 to 51.7% for synaptophysin, chromogranin A, and INSM1 stains in all non-NEN cases. Selecting appropriate immunohistochemical stains based on H&E morphology is the key to avoiding diagnostic pitfalls. Medical history and molecular genomic information greatly assist in correctly diagnosing NENs and their mimics., Competing Interests: Declarations. Ethics approval: This study was conducted following the Declaration of Helsinki and approved by the Ethical Committee for Clinical Research at Fudan University Shanghai Cancer Center. Consent for publication: Consent was obtained directly from patients. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

DNA walkers have emerged as a powerful tool in various biosensors, enabling the detection of low-abundance analytes with their precise programmability and efficient signal amplification capacity. However, many existing approaches are hampered by limited reaction kinetics. Herein, we designed a stochastic bipedal dual-DNA walkers (SBDW) that can traverse at high speed on AuNP-based three-dimensional (3D) tracks powered by Exo III. The SBDW exhibited superior reaction kinetics and are up to least 2.25 times faster than traditional DNA walkers, reaching a plateau within 40 min. This advancement allows for rapid and highly sensitive fluorescence detection of a significant base excision repair enzyme of APE1 with a detection limit of 0.001 U/mL. In comparison to traditional DNA walkers, this platform enables highly sensitive and specific APE1 assays in cell lysate and facilitates rapid and accurate screening of APE1 inhibitors. Given its rapid, sensitive, specific, and reliable analysis features, the strategy shows great promise in drug discovery and clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The progression of diabetic nephropathy (DN) is closely associated with lipid accumulation. Diosgenin (Dio) plays a beneficial role in the lipid metabolism associated with multiple diseases. Thus, the mechanism underlying Dio's function in DN associated with aberrant lipid accumulation warrants further investigation., Methods: To model DN in vitro, HK-2 cells were treated with high glucose (HG) and palmitic acid. Cell viability was evaluated using MTT assay. The triglyceride (TG) content in HK-2 cells was measured using a commercial assay kit. The formation of lipid droplets in HK-2 cells was observed using Oil Red O staining. The expression levels of mRNA and protein were detected using RT-qPCR and Western blot, respectively. The DNA methylation of FOXO1 was assessed using MSP. The interaction between DNMT1 and the FOXO1 promoter was confirmed by ChIP assay., Results: Dio treatment reduced TG levels and lipid droplet formation in HK-2 cells co-treated with HG and palmitic acid. Simultaneously, the levels of miR-148b-3p and FOXO1 were increased by Dio, while Dio decreased the expression levels of DNMT1 and SREBP-2. Meanwhile, miR-148b-3p can bind to DNMT1, which in turn inhibits the expression of FOXO1 by mediating the DNA methylation of FOXO1. In addition, FOXO1 negatively regulates the expression of SREBP-2 by interacting with the SREBP-2 promoter. MiR-148b-3p inhibition or silencing of FOXO1 abolished the inhibitory effect of Dio on TG production and lipid droplet formation. This effect was further exacerbated by the downregulation of DNMT1. FOXO1 overexpression may counteract the promotive effects of miR-148b-3p inhibitor on lipid accumulation., Conclusions: Dio treatment reduced TG production and lipid droplet formation in HK-2 cells during the progression of DN by modulating the miR-148b-3p/DNMT1/FOXO1/SREBP-2 axis. This finding provides new evidence supporting the therapeutic potential of Dio for DN., (© 2025 S. Karger AG, Basel.)

Introduction: This study investigates the differences between early-onset gastric carcinoma (EOGC) and late-onset gastric carcinoma (LOGC) by examining trends, demographics, clinical and molecular features, treatments, and outcomes at a leading cancer center in China., Objectives: To delineate the distinctions between EOGC and LOGC in terms of patient characteristics, disease progression, and treatment outcomes, and to suggest appropriate screening strategies., Methods: We analyzed 18,877 gastric carcinoma cases treated at Fudan University Shanghai Cancer Center (FUSCC) from 2000 to 2022. Descriptive statistics were performed using IBM SPSS. Survival rates were assessed via the Kaplan-Meier method and log-rank test, while COX regression analysis identified factors affecting disease-free survival (DFS) and overall survival (OS)., Results: The average age of gastric cancer diagnosis has increased slightly since 2000, with a steady rise in both EOGC and LOGC cases, though EOGC's proportion has slightly decreased. EOGC had a higher proportion of female patients and was more common in the gastric body and antrum pylorus. EOGC cases showed lower levels of cancer biomarkers, HER2 expression, vascular and lymphatic invasion, and lower differentiation and invasion depth. They also exhibited more advanced N and TNM staging, Borrmann IV type, and low adhesive carcinoma. EOGC underwent more extensive D2 lymphadenectomy and neoadjuvant chemotherapy. There were no significant differences in Claudin18.2 and MMR protein status between EOGC and LOGC. EOGC had higher rates of ovarian and peritoneal metastases, with a better early prognosis but faster late-stage progression., Conclusion: EOGC and LOGC cases have increased over the past two decades. EOGC presents unique clinical and pathological features, requiring thorough surgical treatment and has a better early prognosis but more rapid late-stage progression. Enhanced screening for younger adults is recommended to address the rising EOGC trend., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

A visible-light-induced radical cascade reaction for the synthesis of structurally diverse sulfonated chromanes is described. The protocol involves the addition of sulfonyl radicals to ortho -allyloxy chalcones and intramolecular Michael addition reactions in the presence of eosin Y as a photocatalyst. Additionally, this protocol shows that it is also an effective method to construct seven-membered oxygen-containing heterocycles. The method features a wide substrate scope, the use of easily accessible materials and excellent functional group tolerance with high to excellent yields. Control experiments and mechanistic studies indicate that a visible light-induced radical cascade process is involved in the transformation.

To evaluate different Lynch syndrome (LS) screening approaches and establish an efficient and sensitive strategy are critical for clinical practice. In total, 583 patients with colorectal carcinoma (CRC) at Fudan University Shanghai Cancer Center were enrolled. Patient samples were examined by immunohistochemistry (IHC) and next-generation sequencing (NGS), and MLH1 promoter hypermethylation (MPH) was detected in MLH1-deficient cases. Germline genetic testing was performed in cases with deleterious variants and large genomic rearrangements (LGRs) of tumor MMR genes were detected in cases with dMMR or MSI-H cases with no MMR germline variants. Our results showed that triage with IHC and followed by BRAF/MLH1 methylation testing (Strategy 1) identified 93.3% (70/75) of LS cases. IHC followed by germline NGS (Strategy 2) or direct tumor NGS (Strategy 3) both identified 98.7% (74/75) of LS cases. The proportion of LGRs in LS cases was 16.0% (12/75), while 84.0% (63/75) showed SNV/Indel. The average cost per patient was ¥6010.81, ¥6058.48, and ¥8029.98 for Strategy 1, Strategy 2 and Strategy 3, respectively. The average time spent on different strategies was 4.74 days (Strategy 1), 4.89 days (Strategy 2), and 14.50 days (Strategy 3) per patient, respectively. LS and Lynch-like syndrome (LLS) were associated with an earlier onset age than MPH. In conclusion, we compared different workflows for LS screening and IHC plus germline NGS is recommended for LS screening when taking sensitivity, time, and cost into account. Moreover, multiplex ligation-dependent probe amplification made up for the shortcoming of NGS and should be incorporated into routine screening., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The aim of the present study was to examine the effects of Astragalus polysaccharide (APS) on gut microbiota and serum metabolites in asthmatic mice. For this purpose, a total of 36 BALB/c female mice were selected and randomly classified into the following groups: i) The normal control group sensitized with phosphate-buffered saline; ii) the asthma group sensitized and challenged with ovalbumin (OVA); iii) the OVA + APS (2.5 g/kg) treatment group; iv) the OVA + APS (5.0 g/kg) treatment group; v) the OVA + APS (10 g/kg) treatment group; and vi) the OVA + dexamethasone (2 mg/kg) treatment group, with 6 mice in each group. OVA was used to establish the mouse model of asthma. In the APS group, the asthmatic mice were intragastrically administered APS at various doses at 1 h prior to each OVA stimulation. The airway hyperreactivity (AHR) was measured, and hematoxylin and eosin staining was employed to evaluate pulmonary inflammatory infiltration. In addition, 16S rRNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry were used to detect the changes in the mouse gut microbiota and serum metabolites. The results revealed that compared with the asthma model group, APS improved airway inflammation and eosinophil infiltration in asthmatic mice. In asthmatic mice, the gut microbial imbalance mainly manifested as a low abundance of Bacteroidetes and a high abundance of Firmicutes, yielding an increased F/B ratio. In the high-dose APS group, the abundance of Firmicutes was reduced, and the abundance of Bacteroidetes was increased, which thereby decreased the F/B ratio and corrected the gut microbial imbalance. Through blood metabolomics, 145 and 105 significantly differential metabolites were detected in the medium- and high-dose APS groups, respectively. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that the metabolic pathways in the medium-dose APS group included the biosynthesis of unsaturated fatty acids and the biosynthesis of arginine. On the other hand, the metabolic pathways enriched in high-dose APS group were the biosynthesis of unsaturated fatty acids, and pyrimidine metabolism. On the whole, the present study demonstrates that APS may regulate the gut microbiota and the metabolites to improve airway inflammation and AHR in asthmatic mice., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Zhang et al.)

Osteoarthritis (OA) is the most prevalent degenerative joint disease, marked by cartilage degeneration, synovitis, and subchondral bone changes. The absence of effective drugs and treatments to decelerate OA's progression highlights a significant gap in clinical practice. Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, has emerged as a research focus in osteoarthritic chondrocytes. This form of cell death is characterized by imbalances in iron and increased lipid peroxidation within osteoarthritic chondrocytes. Key antioxidant mechanisms, such as Glutathione Peroxidase 4 (GPX4) and the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) pathway, are vital in countering ferroptosis in osteoarthritic chondrocytes. This review collates recent findings on ferroptosis in osteoarthritic chondrocytes, emphasizing iron regulation, lipid peroxidation, and antioxidative responses. It also explores emerging therapeutics aimed at mitigating OA by targeting ferroptosis in chondrocytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

A flexible pressure sensor, capable of effectively detecting forces exerted on soft or deformable surfaces, has demonstrated broad application in diverse fields, including human motion tracking, health monitoring, electronic skin, and artificial intelligence systems. However, the design of convenient sensors with high sensitivity and excellent stability is still a great challenge. Herein, we present a multi-scale 3D graphene pressure sensor composed of two types of 3D graphene foam. The sensor exhibits a high sensitivity of 0.42 kPa -1 within the low-pressure range of 0-390 Pa and 0.012 kPa -1 within the higher-pressure range of 0.4 to 42 kPa, a rapid response time of 62 ms, and exceptional repeatability and stability exceeding 10,000 cycles. These characteristics empower the sensor to realize the sensation of a drop of water, the speed of airflow, and human movements.

Herein, we present a straightforward CuBr-mediated surface-initiated controlled radical polymerization (SI-CRP) method for fabricating polymer brushes using microliter volumes of reaction solution in air and at room temperature. The key advantage of this method is its ability to rapidly grow polymer brushes with oxygen tolerance, driven by the controlled disproportionation of Cu I into Cu II and Cu 0 by CuBr and ligand. We demonstrate the successful preparation of homo-, block, patterned, and wafer-scale polymer brushes. Additionally, the catalyst in CuBr-mediated SI-CRP is reusable, long-lasting, and compatible with various monomers. This work broadens the potential of CuBr for polymer brush growth, making it accessible to both experts and non-experts., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: This study aimed to investigate the associations of 2 preoperative muscle-related parameters, the third lumbar vertebra skeletal muscle index (L3 SMI) for muscle mass and the Hounsfield unit average calculation (HUAC) for muscle density, with the occurrence of postoperative complications among patients undergoing colorectal tumor resection surgery under general anesthesia. We hypothesized that muscle-related parameters are associated with the occurrence of postoperative complications., Methods: This was a single-center, retrospective observational study. Adult patients who underwent colorectal tumor resection surgery under general anesthesia between 2018.09.01 and 2021.09.01 were enrolled. The last abdominal computed tomography (CT) scan images obtained within 3 months before surgery were used to calculate the L3 SMI and HUAC. The primary outcome was defined as the occurrence of any postoperative complications corresponding to Clavien-Dindo classification before discharge. The secondary outcome was defined as the occurrence of any severe postoperative complications (Clavien-Dindo grade ≥3) before discharge. Multivariable logistic regression analyses were used to estimate the association between muscle-related parameters and incidence of postoperative complications. Patients' baseline demographics, past medical history and intraoperative parameters were adjusted in the multivariable logistic regression analysis., Results: A total of 317 patients with a median age of 66 (58-72) years were included. Sarcopenia (muscle mass reduction) patients in our cohort and myosteatosis (muscle density decline) were present in 254 (80.1 %) and 79 (24.9%) patients, respectively. A total of 135 patients (42.6 %) developed postoperative complications. According to the multivariable logistic regression, myosteatosis (odds ratio [OR], 1.8, 95% confidence interval [CI], 1.0-3.3, P = .039) was significantly associated with postoperative complications., Conclusions: A significant association was observed between myosteatosis and postoperative complications (corresponding to Clavien-Dindo classification before discharge), especially severe postoperative complications (Clavien-Dindo grade ≥3) in patients undergoing colorectal tumor resection. Screening for myosteatosis with HUAC using the CT before surgery may help clinicians identify high-risk perioperative patients early., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

The abuse of antibiotics has caused gradually increases drug-resistant bacterial strains that pose health risks. Herein, a sensitive SERS sensor coupled multivariate calibration was proposed for quantification of antibiotics in milk. Initially, octahedral gold-silver nanocages (Au@Ag MCs) were synthesized by Cu 2 O template etching method as SERS substrates, which enhanced the plasmonic effect through sharp edges and hollow nanostructures. Afterwards, five chemometric algorithms, like partial least square (PLS), uninformative variable elimination-PLS (UVE-PLS), competitive adaptive reweighted sampling-PLS (CARS-PLS), random frog-PLS (RF-PLS), and convolutional neural network (CNN) were applied for TTC and CAP. RF-PLS performed optimally for TTC and CAP (Rc = 0.9686, Rp = 0.9648, RPD = 3.79 for TTC and Rc = 0.9893, Rp = 0.9878, RPD = 5.88 for CAP). Furthermore, the detection limit of 0.0001 µg/mL for both TTC and CAP was obtained. Finally, satisfactory (p > 0.05) results were obtained with the standard HPLC method. Therefore, SERS combined RF-PLS could be applied for fast, nondestructive sensing of TTC and CAP in milk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

NORSF is a nuclear long noncoding RNA (lncRNA) that contributes to the follicular atresia and restrains 17β-estradiol (E 2 ) release by granulosa cells (GCs). Importantly, it is also a potential candidate gene in the quantitative trait locus (QTLs) for sow fertility traits. We identified NORSF as a candidate (causal) gene affecting sow fertility traits. A novel G-A variant was discovered at -478 nt of the NORSF promoter and termed as g.-478G>A. Association analysis revealed that this variant was associated with sow fertility traits (e.g., the total number of piglets born, the total number of piglets born alive, and the number of healthy piglets). Mechanistically, the g.-478G>A variant reduced the binding activity of the NORSF promoter to its transcription activator regulatory factor X7 (RFX7), leading to decreased NORSF promoter activity and transcription levels in sow GCs (sGCs), and weakened inhibitory effects on the transcription of CYP19A1, which encodes a rate-limiting enzyme for E 2 synthesis and E 2 release by sGCs. In addition, RFX7 is transcriptionally activated by P53, which restrains E 2 release from sGCs via the RFX7/NORSF/CYP19A1 pathway. These findings indicate that the lncRNA NORSF is a causal gene in QTLs for sow fertility traits and define the P53/NORSF/CYP19A1 pathway as a new signaling pathway affecting sow reproduction, which provides a new target for improving female fertility., (© 2024 Wiley Periodicals LLC.)