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Background: Many results suggested that chemotherapy cannot provide survival benefit for stage II nasopharyngeal carcinoma. It remained unclear whether the efficacy of chemotherapy differed in non-Asian populations., Objective: It was designed to analyze the effect of chemotherapy for Asian and non-Asian patients with stage II nasopharyngeal carcinoma., Method: Patients were collected using the SEER program. The variables included age, sex, race, marital status, survival time, survival status, TNM stage, radiation and chemotherapy. Utilizing the Rstudio (version: 2024.4.1.748) and R (version: 4.4.1), backward elimination method was employed to screen the variables and multivariate Cox regression analyses was conducted on the screened variables. Kaplan-Meier method was utilized to analyze the survival of sub-stages and different races with T1-2N1M0 stage. The log-rank test was used for statistical analysis., Result: 1539 patients were collected. Chemotherapy was statistically significant, with a hazard ratio (HR) of 0.64, P=0.003 in stage II patients. The HR for radiation was 0.33, P<0.001. Chemotherapy didn't improve cancer-specific survival for patients with T2N0M0 stage. Asian and non-Asian races showed no difference in cancer-specific survival in T2N0M0 stage with HR of 1.85, P=0.13. For patients with T1-2N1M0 stage, chemotherapy improved cancer-specific survival with a HR of 0.53, P<0.001. No significant difference was in the Kaplan-Meier analysis between the two sub-stages (P=0.065). In T1-2N1M0 stage, multivariate Cox regression analysis for Asian race indicated that chemotherapy didn't improve cancer-specific survival with a HR of 0.64, P=0.190. For non-Asian race, chemotherapy was found to improve cancer-specific survival, with a HR of 0.51, P<0.001. The Kaplan-Meier analysis of Asian and non-Asian patients with T1-2N1M0 stage exhibited significant differences (P<0.0001)., Conclusion: Chemotherapy is correlated with the cancer-specific survival in non-Asian patients with T1-2N1M0-stage nasopharyngeal carcinoma, but not in Asian patients at the same stage. For patients with the T2N0M0 stage, chemotherapy is not correlated with the cancer-specific survival rate, regardless of ethnicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Li, Zhong and Xu.)

Objectives: To systematically evaluate the efficacy of lateral unicompartmental knee arthroplasty (LUKA) and total knee arthroplasty (TKA) in the treatment of isolated lateral compartment knee osteoarthritis (LCKO), and to provide guidance and a basis for selecting surgery in clinical practice., Methods: Inclusion and exclusion criteria for literature were established, appropriate effect indicators were selected, and PubMed, Web of Science, Embase, Medline, Cochrane Library, and CNKI databases were searched using a computer. The Newcastle Ottawa scale (NOS) was used to evaluate the quality of the literature. After data extraction, Meta-analysis was performed using Revman5.4 software., Results: A total of 8 studies were included in this meta-analysis, involving 490 patients, with 204 in the TKA group and 286 in the LUKA group. Meta-analysis found that, there was no significant statistical difference in operation time between the LUKA group and the TKA group. Nevertheless, LUKA offers advantages such as reduced intraoperative blood loss and shorter hospitalization time. At the same time, the LUKA group also had advantages over the TKA group in postoperative visual analogue scale (VAS) score, knee joint range of motion, Oxford Knee Score (OKS)score and Hospital for Special Surgery (HSS) score., Conclusion: When LUKA and TKA are used to treat isolated LCKO, LUKA has the advantages of less intraoperative blood loss, shorter hospital stay, lower postoperative VAS score, and better knee function score and range of motion., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The conversion of alpha-linolenic acid (ALA) in feed to DHA in egg is inefficient, so there is a critical need for feed additives that can enhance the enrichment of docosahexaenoic acid (DHA) in egg yolk from ALA-rich feed. The present study evaluated the impact of dietary fucoxanthin on the conversion efficiency of ALA in feed to DHA in quail egg yolk. Results showed that the addition of 0.02 % fucoxanthin to the diet supplemented with 0.5 % ALA significantly enhanced the DHA conversion rate by 51.48 % and increased DHA content by 32.82 %, matching levels observed with 1 % ALA supplementation during the peak laying period. Importantly, fucoxanthin did not alter the proportion of phospholipid-bound DHA. These findings suggest that fucoxanthin, as a feed additive, has the potential to promote the accumulation of DHA in avian eggs when supplemented with ALA in feed., 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. Published by Elsevier Ltd.)

Background: As a broad-spectrum anti-tumour drug, the clinical application of DOX is often limited owing to its cardiotoxicity. Nerol is a naturally occurring compound with both anti-inflammatory and antioxidant properties. However, the ability of Nerol to improve DOX-induced heart failure and its underlying mechanisms remain unclear., Methods: Rat models of DOX-induced heart failure were established and rats were treated with various doses of Nerol. Apoptosis in cardiomyocytes was detected using TUNEL staining and the expression levels of apoptosis-related proteins were detected using western blotting and immunofluorescence. In addition, mitochondrial structure was observed using electron microscopy, mitochondrial membrane potential was detected using a JC-1 fluorescent probe, and superoxide dismutase were detected to comprehensively evaluate the regulatory effect of Nerol on mitochondrial function and oxidative stress., Results: Analysis showed that the number of apoptotic cardiomyocytes was significantly reduced after Nerol treatment, accompanied by the downregulation of Bax protein expression and upregulation of Bcl-2 protein expression, suggesting that Nerol may inhibit the apoptotic process of cardiomyocytes by regulating the balance of Bcl-2 family proteins. In addition, the mitochondrial function of Nerol-treated rats was protected, as indicated by the stability of the mitochondrial membrane potential, integrity of mitochondrial morphology. These changes suggest that Nerol may reduce the severity of heart failure by improving mitochondrial function., Conclusions: Nerol plays a positive role in alleviating DOX-induced heart failure in rats, possibly by inhibiting cardiomyocyte apoptosis. These findings provide novel evidence and potential targets for developing new cardioprotective drugs., 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 aim of this work was to study the lymphatic absorption characteristics of gastric hydrolysates and intestinal hydrolysates of eicosapentaenoic acid-enriched phosphoethanolamine plasmalogen (EPA-pPE) with focusing on the fate of EPA and vinyl ether bonds in the lymph fluid using lymphatic intubation and lipidomics. The results showed that the EPA peak occurred earlier in the gastric (1.5 h) and intestinal (1 h) hydrolysates than in the EPA-pPE group (3 h) with EPA peak content being 2.03 and 1.46 times higher, suggesting pre-hydrolysis contributed to lymphatic absorption. Further, duodenal injection of gastric hydrolysates sn2 EPA-lysoPE produced higher levels of EPA-LPC, PC, PE, and PG. Meanwhile, intestinal hydrolysates free EPA and sn1 lyso-pPE enriched the sn1 + 2 + 3 TG (20:5&#95;20:5&#95;20:5) and increased the vinyl ether bond-containing lipids, such as PE (18:0p&#95;18:0) and PE (18:0p&#95;20:4). This study provides insight into dietary molecular structures of EPA and plasmalogen., 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 Ltd.)

Pseudocontact shift (PCS) contains rich structural information of proteins in structural and chemical biology. 19 F-PCS is determined in live mammalian cells via dual labelling of the target protein with a paramagnetic tag and a 19 F-tag, which is achieved by varied reactivity of solvent exposed cysteines in selection of different types of tags. About 0.1 ppm 19 F-PCS can be observed over 20 Å from the paramagnetic center in the live cells.

Amyloidosis of the human islet amyloid polypeptide (hIAPP) is closely related to the pathogenesis of type 2 diabetes (T2D) and serves as both a diagnostic hallmark and a key therapeutic target for T2D. In this study, we discovered that oritavancin (Ori), a glycopeptide antibiotic primarily prescribed for Gram-positive bacterial infections, can dose-dependently inhibit recombinant hIAPP (rhIAPP) amyloid formation. Ori specifically inhibited rhIAPP amyloid formation at the initial nucleation stage but didn't affect mature rhIAPP fibrils. As a result, Ori reduced amyloidosis of rhIAPP induced pancreatic NIT-1 cell apoptosis and reactive oxygen species (ROS) release. Based on the results from studies involving antibiotic homologues of Ori and its acid hydrolysates, we demonstrated that both the N -(4-chlorobiphenyl) methyl group (CBP) and glycopeptide backbone were necessary for inhibiting rhIAPP amyloid formation. The mechanism behind Ori on rhIAPP amyloid formation lies in the direct interaction of the two molecules identified by ESI-MS and molecular docking assays. Consequently, this research not only lays the groundwork for developing novel therapeutic approaches for T2D but also presents the opportunity to repurpose Ori as a treatment option.

This study aimed to investigate the anti-fatigue efficacy and underlying mechanisms of Polygonatum cyrtonema Hua polysaccharide (PCP) in chronic sleep-deprived mice. Following three weeks of oral administration, PCP demonstrated significant efficacy in alleviating fatigue symptoms. This was evidenced by the prolonged swimming and rotarod time in the high-dose group of PCP, which increased by 73 % and 64 %, respectively. Additionally, serum activities of CAT, GSH-Px, and SOD enzymes rose by 53.56 %, 37.69 % and 53.67 %, respectively, while MDA, lactic acid and BUN levels decreased by 22.90 %, 17.48 % and 24.61 %. The crosstalk between bone and brain is crucial for maintaining energy homeostasis. Molecular docking studies indicated a spontaneous and strong mutual binding between PCP and the bone-promoting target protein BMPR1A. Furthermore, it was observed that PCP enhanced osteogenic differentiation via the BMP-2/Smad1 pathway, leading to an upregulation of osteocalcin expression, which in turn regulated neurotransmitter balance and improved central arousal capacity. Moreover, PCP treatment stimulated neurogenesis by activating the CREB/BDNF/Akt signaling cascade, exhibiting neurotrophic effects. Additionally, PCP increased AMPK phosphorylation and destabilized TXNIP, facilitating astrocyte glucose uptake, glycolysis, and lactate conversion to support neuronal activity. These findings suggested that PCP could effectively respond to energy demands through bone-brain crosstalk, ultimately exerting anti-fatigue properties., 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. Published by Elsevier B.V.)

Objective: To investigate whether there is mitochondrial transfer in dental mesenchymal stem cells (MSCs) and its significance for the odontogenic differentiation. Methods: Flow cytometry and immunohistochemical staining were used to isolate dental mesenchymal stem cells. Immunofluorescence staining and live cell imaging were applied to determine whether there is mitochondrial transfer in dental MSCs. Transcriptome sequencing data re-analysis of human dental pulp stem cells (DPSCs) and bone marrow mesenchymal stem cells (BMSCs) from gene expression omnibus (GEO) data base demonstrated the importance of mitochondrial transfer in dental MSCs. Cells were managed with mitochondrial transfer inhibitor ML141 with dimethyl sulfoxide as the control. Immunofluorescence staining, senescence-associated β-galactosidase (SA-β-gal) staining, reactive oxygen species (ROS) assay, 5-ethynyl-2'-deoxyuridine(EdU) labelling, cell counting kit-8 (CCK-8) assay, Western blotting, live cell imaging and transmission electron microscope were used to investigate cell morphology, ROS level, cellular senescence, cell proliferation, MSCs marker paired related homeobox 1 (Prrx1) and Sp7 transcription factor (Sp7) expression, mitochondrial transfer and mitochondrial morphology, respectively. Further, after using ML141 during the induction of odontogenic differentiation, alkaline phosphatase (ALP) chromogenic kit was used to detect ALP activity and real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression of odontogenic differentiation-related genes Alp, Sp7, dentin matrix protein 1 (Dmp1), and dentin salivary phosphoprotein (Dspp), which were applied to investigate the effect of mitochondrial transfer on odontogenic differentiation. Results: An ultrafine tunneling nanotubes (TNTs) structure labelled with F-actin existed between dental MSCs, and the presence of transferring mitochondria in this structure was also confirmed. Transcriptome sequencing data suggested that the gene expression profiles were significantly different between DPSCs and BMSCs. Genes related to mitochondrial transfer and mitochondrial dynamic were significantly increased in DPSCs compared to BMSCs. Compared with the control group, treatment with 1, 5, 10 μmol/L ML141, the mitochondrial transfer inhibitor, had little significant effects on the cell morphology, cytoskeleton and ROS level. SA-β-gal activity and the proportion of SA-β-gal positive cells in the ML141-treated groups [(3.93±0.21)%, (3.23±0.42)%, (4.06±0.84)%] had no significant differences with the control group [(3.83±0.28)%] (all P >0.05). In the cell proliferation assay, the proportion of EdU positive cells in the ML141-treated groups [(20.00±3.82)%, (19.48±1.96)%, (12.55±2.86)%] had no significant differences (all P >0.05) with the control group [(18.57±0.87)%], whereas the CCK-8 assay showed similar results in ML141-treated group of 1, 5 μmol/L (all P >0.05). Western blotting results showed that the protein expression levels of PRRX1 and SP7 in the ML141-treated group had no significant differences with the control group. Live cell imaging showed that compared with the control group [(31.42±4.01)%], the proportion of TNTs and mitochondrial transfer in the ML141-treated groups [(13.45±1.46)%, (10.36±3.47)%, (9.32±1.11)%] were significantly decreased in dental MSCs (all P <0.001). Scanning electron microscope showed that the mitochondrial morphology of dental MSCs in the ML141-treated group was similar to the control group, with globular and short-rod shape. After 7 days of odontogenic differentiation, the ALP staining intensity of the ML141-treated group was significantly lower than the control group. After 21 days of induction, RT-qPCR results showed that compared with control group, the relative mRNA expressions of Alp, Sp7, Dmp1 and Dspp were significantly decreased in the ML141-treated group (all P <0.05), indicating that the suppression of mitochondrial transfer in dental MSCs inhibited the odontogenic differentiation. Conclusions: Mitochondrial transfer exists between dental MSCs, and inhibition of mitochondrial transfer impairs the odontogenic differentiation.

Parkinson's disease (PD) and insomnia are prevalent neurological disorders, with emerging evidence implicating tryptophan (TRP) metabolism in their pathogenesis. However, the precise mechanisms by which TRP metabolism contributes to these conditions remain insufficiently elucidated. This study explores shared tryptophan metabolism-related genes (TMRGs) and molecular mechanisms underlying PD and insomnia, aiming to provide insights into their shared pathogenesis. We analyzed datasets for PD (GSE100054) and insomnia (GSE208668) obtained from the Gene Expression Omnibus (GEO) database. TMRGs were obtained from the Molecular Signatures Database (MSigDB) and the Genecards database. Tryptophan metabolism-related differentially expressed genes (TM-DEGs) were identified by intersecting TMRGs with shared differentially expressed genes (DEGs) from these datasets. Through Protein-Protein Interaction (PPI) network analysis, Support Vector Machine-Recursive Feature Elimination (SVM-RFE) , and Extreme Gradient Boosting (XGBoost) machine learning, we identified Cytochrome P4501B1 (CYP1B1) and Electron Transfer Flavoprotein Alpha (ETFA) as key hub genes. Subsequently, we employed CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) to further investigate the association between hub genes and peripheral immune activation and inflammatory response. Additionally, gene interaction, Drug-mRNA, Transcription Factor (TF)-mRNA, and competing endogenous RNA (ceRNA) networks centered on these hub genes were constructed to explore regulatory mechanisms and potential drug interactions. Finally, validation through bioinformatics and animal experiments identified CYP1B1 as a promising biomarker associated with both PD and insomnia., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: All experimental procedures were approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University (ZZU-LAC20240531[06])., (© 2025. The Author(s).)

Mine ecological restoration has experienced a long-term development process in China, in which various technologies have been constantly developing and integrating. Based on the related theoretical research and field program, the technical system of mine ecological restoration was constructed, and the characteristics of key technologies were specifically grasped. In this research, the environment, including natural elements and the spatial environment, is the object of mine ecological restoration, which requires further long-term investigation and monitoring. Therefore, natural element restoration technology, space environment restoration technology, and environmental survey and restoration monitoring technology should be considered when establishing technical systems. The research showed that： ① In mine natural element restoration, where soil and water are important, traditional technologies like pollution abatement with physical, chemical, and biological methods have been extensively used. Meanwhile, artificial soil reconstruction and multi-technology joint remediation became the main study focus in soil restoration and artificial wetlands have been gradually constructed as a new method in water restoration, covering water system restoration and pollution control. ② The two tasks of space environment restoration were geological disaster prevention and vegetation re-greening. Major technologies of the former were applied to surface mine slope treatment and mining subsidence area control, the latter of which could be divided into three technical links： vegetation selection, construction, and maintenance. Although many technologies are valid, a few frontiers need to be further pursued. ③ The mine environmental investigation and restoration monitoring were based on 3S technologies, containing GIS, GPS, and RS, all of which are developing rapidly but still have a large space for integration and innovation.

Background: To construct a nomogram combining CT varices vein evaluation and clinical laboratory tests for predicting the risk of esophageal gastric variceal bleeding (EGVB) in patients with noncirrhotic portal hypertension (NCPH)., Methods: A total of 315 NCPH patients with non-EGVB and EGVB were retrospectively enrolled and randomly divided into training and testing cohorts. Thirteen collateral vessels were identified and evaluated after CT portal vein system reconstruction. Multivariate binary logistic regression analysis was used to choose CT images and clinical predictors of EGVB. The varices score of each patient was calculated. A nomogram was built by combining the varices score with the selected clinical predictors of EGVB. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the nomogram., Results: Platelet count and prothrombin time were selected as clinical predictors; the esophageal vein, gastroepiploic vein and omental vein were selected as CT image predictors for predicting EGVB. A reduced platelet count, prolonged prothrombin time, severe esophageal and gastroepiploic vein tortuosity and less omental vein tortuosity were predictors of EGVB in NCPH patients. The specificity, sensitivity, negative predictive value, positive predictive value and AUC of the ROC of the nomogram were 0.82, 0.81, 0.89, 0.70, and 0.88 (95% CI: 0.84-0.93) in the training cohort and 0.87, 0.86, 0.88, 0.84, and 0.91 (95% CI: 0.84-0.97) in the testing cohort, respectively., Conclusions: The nomogram combining CT images and clinical predictors could be useful to individualize and predict the risk of EGVB in NCPH patients., Clinical Relevance Statement: Results showed that the nomogram combining CT-evaluated collateral vessels (varices score) and clinical laboratory tests could be used to realize personalized prediction of first-time EGVB in NCPH patients., Competing Interests: Declarations. Ethics approval and consent to participate: This prospective study was reviewed and approved by the Institutional Review Board of Jinshan Hospital, Fudan University (JIEC 2023-S82). Written informed consent was obtained from all patients. The methods carried out in this study were in accordance with the relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, generally due to defects of insulin action or secretion. Inhibition of α-glucosidase, an enzyme responsible for carbohydrate degradation, is a promising strategy for managing postprandial hyperglycemia in diabetic patients. In this study, two new C-linked diarylheptanoid dimers, kaemgalanganols A (1) and B (2), were isolated from K. galanga, which showed obvious inhibitory activity on α-glucosidase but weak activity on protein tyrosine phosphatase 1B (PTP1B). Kaemgalanganol B had an IC 50 value of 35.1 μM against α-glucosidase, obviously more potent than kaemgalanganol A (IC 50  = 78.5 μM) and acarbose (IC 50  = 363.0 μM). Enzyme kinetic study indicated that 2 was a reversible mixed-type inhibitor of α-glucosidase via non-competitive and anti-competitive inhibition modes. Fluorescence quenching and UV-visible spectroscopic study revealed that fluorescence quenching mechanism of 2 on α-glucosidase is a combination of dynamic quenching and static quenching, accompanied by non-radiative energy transfer. Compound 2 formed complex with α-glucosidase closer to the Tyr residue, and induced changes in both the microenvironment and peptide backbone. Surface hydrophobicity and CD spectra measurement indicated that 2 affected the function of α-glucosidase by decreasing the surface hydrophobicity of α-glucosidase as well as altering the secondary structure instead of the overall three-dimensional framework, which is consistent with the results of fluorescence experiment. Molecular docking manifested that compound 2 had a strong binding affinity (-7.27 kcal/mol) with α-glucosidase, higher than 1 (-9.82 kcal/mol) and acarbose (-4.48 kcal/mol), consistent with the enzyme inhibitory assay. Besides hydrogen bonds, electrostatic interactions and hydrophobic interactions played important roles in the binding of 2 with α-glucosidase. This study disclosed the inhibitory activity and mechanism of 2 against α-glucosidase, which provides a theoretical basis for the development of new antidiabetic drugs form K. galanga., 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.)

Background: The purpose of this study was to investigate the effects of quality of sport friendships on mental health and the mediating role of sport motivation and exercise adherence in middle school students., Methods: A total of 1,083 middle school students were selected using a combination of cluster sampling and stratified sampling methods. The participants were assessed using the Sport Friendship Quality Scale, Mental Health Scale, Exercise Motivation Scale, and Physical Exercise Adherence Scale. Structural equation modeling was employed to examine the relationships among the four variables., Results: (1) The quality of sport friendships positively predicted mental health (β = 0.192, p < 0.01); (2) Sport motivation and exercise adherence act as independent mediators between the quality of sport friendships and mental health respectively; (3) Sport motivation and exercise adherence act as bi-directional chain mediators between the quality of sport friendships and mental health., Conclusion: (1) The quality of sports friendships can positively predict mental health, sport motivation, and exercise adherence. (2) The quality of sports friendships not only directly predicts mental health but also indirectly affects mental health through the mediating roles of sport motivation and exercise adherence, as well as the bidirectional chain mediation between the two. This further explains how the quality of sports friendships impacts the mental health of junior high school students, providing significant insights into improving their mental health levels., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki, and it has been approved by the Human Research Ethics Committee of Huaibei Normal University, and informed consent has been obtained from the parent or legal guardian of the participant under the age of 16. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The present study aims to summarize the current biomarker landscape in gynecological cancers (GCs) and incorporate bioinformatics analysis to highlight specific biological processes. The literature was retrieved from PubMed, Web of Science, Embase, Scopus, Ovid Medline, and Cochrane Library. The final search was conducted on December 7, 2022. Prospective registration was completed with the PROSPERO with registration number CRD42023477145. This systematic review covered proteomic research on biomarkers for cervical, endometrial, and ovarian cancers. The PANTHER classification system was used to classify the shortlisted candidate biomarkers (CBs), and the STRING database was utilized to visualize protein-protein interaction networks. A total of 23 articles were included in this systematic review. Consistently regulated CBs in the GCs include collagen alpha-2(I) chain, collagen alpha-1(III) chain, collagen alpha-2(V) chain, calreticulin, protein disulfide-isomerase A3, heat shock protein family A (Hsp70) member 5, prolyl 4-hydroxylase, beta polypeptide, fibrinogen alpha chain, fibrinogen gamma chain, apolipoprotein B-100, apolipoprotein C-IV, and apolipoprotein M. In conclusion, collagens, fibrinogens, chaperones, and apolipoproteins were revealed to be replicated in GCs and to be regulated consistently. These CBs contribute to GC etiology and physiology by participating in collagen fibril organization, blood coagulation, protein folding in endoplasmic reticulum, and lipid transporter activity.

Chinese coral snakes ( Sinomicrurus ) are highly neglected regarding their venom profiles and harm to humans, which impedes our ability to deeply understand their biological properties and explore their medicinal potential. In this study, we performed a comparative analysis to reveal the venom profiles of two Chinese coral snakes in terms of their venom yields, proteomic profiles, and immunorecognition by commercial antivenoms. The results showed that Sinomicrurus kelloggi expels more venom (lyophilized venom mass) than Sinomicrurus maccelellandi but possesses a similar solid venom content. These interspecific differences in venom yield were influenced by the snout-vent length. The venoms of these two species varied in their electrophoretic profiles, as well as in the presence or absence and relative abundance of protein families. They exhibited a 3-FTx-predominant phenotype, where the S. maccelellandi venom was dominated by 3-FTx (32.43%), SVMP (23.63%), PLA 2 (19.88%), and SVSP (12.61%), while the S. kelloggi venom was dominated by 3-FTx (65.81%), LAAO (11.35%), and AMP (10.09%). While both the commercial Naja atra and Bungarus multicinctus antivenoms could immunorecognize these two Chinese coral snake venoms, the N. atra antivenom possessed a higher neutralization capability than the B. multicinctus antivenom for both species of coral snakes. Our findings show significant interspecific variations in the venom profiles of these Sinomicrurus snakes for the first time. We suggest screening or preparing specific antivenoms with high efficiency for the clinical treatment of envenomation caused by these snakes.

Eriocraniidae (Lepidoptera) are widespread leaf miners and have unique adaptability to hypoxia and low temperatures, causing covert but devastating harm to Fagales (Betulaceae and Fagaceae) plants in the Holarctic. However, the lack of a high-quality genome of this most ancient family within the angiosperm-feeding group largely limits the studies on the phylogeny and environmental adaptation of the primitive Lepidoptera. In this study, utilizing Illumina sequencing, PacBio HiFi sequencing, and Hi-C technology, we constructed a chromosome-level genome assembly of E. semipurpurella alpina, representing the first high-quality genome in the Eriocraniidae family. The genome was 523.71 Mb in length, with a scaffold N50 of 17.55 Mb, and 95.56% of the assembly anchored onto 32 pseudochromosomes. BUSCO completeness values of 97.6%. 49.02% of the genome sequences were recognized as repetitive sequences, and a total of 22,581 protein-coding genes were annotated. This genome will greatly facilitate the phylogenomic studies of the most ancient lineages of Lepidoptera and provides insights into the genetic architectures underlying ecological adaptation., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

A 65-year-old male was admitted to Peking Union Medical College Hospital. The patient had intermittent fever for 2 months with a maximum body temperature of 39.3 ℃ and elevated serum creatinine levels for 1 week. He had no other suggestive symptoms or positive signs. Laboratory test results suggested acute kidney injury and a sharp elevation in serum lactic dehydrogenase levels. Abdominal enhanced computed tomography (CT) revealed multiple low-density lesions, and further biopsy pathology demonstrated chronic inflammation. Thereafter, positron emission tomography (PET)/CT showed abnormally elevated uptake value for the bones throughout the entire body, in addition to the liver and brain. Repeated bone marrow biopsy finally confirmed metastatic bone cancer, which possibly originated from the kidney according to immunohistochemical staining. In this rare case of fever of unknown origin, the primary lesion was a renal tumor with bone, liver, and brain metastases. Enhanced CT and PET/CT provided negative results, and the diagnosis was eventually confirmed by repeated bone marrow pathology.

Cancer poses a significant global public health challenge, with commonly used adjuvant or neoadjuvant chemotherapy often leading to adverse side effects and drug resistance. Therefore, advancing cancer treatment necessitates the ongoing development of novel anticancer agents with diverse structures and mechanisms of action. Natural products remain crucial in the process of drug discovery, serving as a primary source for pharmaceutical leads and therapeutic advancements. Triterpenoids are particularly compelling due to their complex structures and wide array of biological activities. Recent research has demonstrated that naturally occurring triterpenes and their derivatives have the potential to serve as promising candidates for new drug development. This review aims to comprehensively explore the anticancer properties of triterpenoids and their synthetic analogs, with a focus on recent advancements. Various aspects, such as synthesis, phytochemistry, and molecular simulation for structure-activity relationship analyses, are summarized. It is anticipated that triterpenoid derivatives will emerge as notable anticancer agents following further investigation into their mechanisms of action and in vivo studies., 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.)

Background: Dementia with Lewy bodies (DLB) commonly exhibits a complex neuropathology, sharing characteristics with Alzheimer's disease (AD), including tau aggregates. However, studies using the 18 F-AV-1451 tau tracer have shown inconsistent findings regarding both the extent and topographical distribution of tau pathology in DLB., Objectives: Our aim was to elucidate the topographical patterns of tau deposition in DLB and to investigate the in vivo pathological distinction between DLB and AD in virtue of the 18 F-Florzolotau positron emission tomography (PET) imaging., Methods: This cross-sectional study enrolled patients with DLB (n = 24), AD (n = 43), and cognitively healthy controls (n = 18). Clinical assessments and 18 F-Florzolotau PET imaging were performed. 18 F-Florzolotau binding was quantitatively assessed on PET images using standardized uptake value ratios and voxel-wise analysis., Results: 18 F-Florzolotau PET imaging revealed widespread tau deposition across various cortical regions in DLB, uncovering heterogeneous topographical patterns. Among patients, 54.17% showed patterns similar to AD, whereas 16.67% exhibited distinct patterns. Compared to AD, DLB exhibited a unique in vivo neuropathological profile, characterized by a lower tau protein burden, heterogeneous topographical distributions, and a specific role of the medial temporal lobe in tau pathology., Conclusions: 18 F-Florzolotau PET imaging elucidated tau pathology patterns in DLB, providing valuable insights for future in vivo pathological differentiation and potential disease-modifying therapies. © 2024 International Parkinson and Movement Disorder Society., (© 2024 International Parkinson and Movement Disorder Society.)

Dysbiosis of the gut microbiota is closely associated with neurodegenerative diseases, including Huntington's disease (HD). Gut microbiome-derived metabolites are key factors in host-microbiome interactions. This study aimed to investigate the crucial gut microbiome and metabolites in HD and their correlations. Fecal and serum samples from 11 to 26 patients with HD, respectively, and 16 and 23 healthy controls, respectively, were collected. The fecal samples were used for shotgun metagenomics while the serum samples for metabolomics analysis. Integrated analysis of the metagenomics and metabolomics data was also conducted. Firmicutes, Bacteroidota, Proteobacteria, Uroviricota, Actinobacteria, and Verrucomicrobia were the dominant phyla. At the genus level, the presence of Bacteroides, Faecalibacterium, Parabacteroides, Alistipes, Dialister, and Christensenella was higher in HD patients, while the abundance of Lachnospira, Roseburia, Clostridium, Ruminococcus, Blautia, Butyricicoccus, Agathobaculum, Phocaeicola, Coprococcus, and Fusicatenibacter decreased. A total of 244 differential metabolites were identified and found to be enriched in the glycerophospholipid, nucleotide, biotin, galactose, and alpha-linolenic acid metabolic pathways. The AUC value from the integrated analysis (1) was higher than that from the analysis of the gut microbiota (0.8632). No significant differences were found in the ACE, Simpson, Shannon, Sobs, and Chao indexes between HD patients and controls. Our study determined crucial functional gut microbiota and potential biomarkers associated with HD pathogenesis, providing new insights into the role of the gut microbiota-brain axis in HD occurrence and development., Competing Interests: Declarations. Ethics Approval and Consent to Participate: This study was approved by the Ethics Committees of the Second Affiliated Hospital of Zhejiang University (approval no. 2015-048) and the Second Affiliated Hospital of Jiaxing University (approval no. 2022SW064-02). Written informed consents were obtained from all participants. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Wide-bandgap perovskite sub-cells (WPSCs), one of the most crucial components of perovskite-based tandem solar cells (PTSCs), play a critical role in determining the performance of tandem devices. However, confined by the compromised crystallization properties of wide-bandgap perovskites, WPSCs exhibit significantly lower efficiency than their theoretical limit. In particular, for n-i-p structured all-inorganic WPSCs (AIWPSCs), severe nonradiative recombination due to the buried interface defects severely decreases the photovoltaic performance. Herein, an efficient propionate group (PA - ) based ionic liquid, methylamine propionate (MAPA), is introduced into the perovskite/electron-transport layer (ETL) interface to passivate the buried interface of AIWPSCs. The intense interaction between the PA - and Pb-Pb dimer effectively heals the defects at the buried interface and facilitates a more homogeneous elemental distribution in the perovskite film. As a result, CsPbI 2.2 Br 0.8 -based AIWPSCs with a high power conversion efficiency (PCE) of 18.29% and open-circuit voltage (V OC ) of 1.33 V are obtained, which illustrates the superiority of MAPA in optimizing the performance of AIWPSCs. Moreover, by integrating these AIWPSCs with small-bandgap organic solar cells (SOSCs), high performance n-i-p structured all-inorganic perovskite/organic tandem solar cells (AIPOTSCs) with a high PCE of 23.19% and V OC of 2.08 V are also achieved., (© 2024 Wiley‐VCH GmbH.)

Purpose: The identification of tau accumulation within living brains holds significant potential in facilitating accurate diagnosis of progressive supranuclear palsy (PSP). While visual assessment is frequently employed, standardized methods for tau positron emission tomography (PET) specifically in PSP are absent. We aimed to develop a visual reading algorithm dedicated to the evaluation of [ 18 F]Florzolotau PET in PSP., Methods: 148 PSP and 30 healthy volunteers were divided into a development set (for the establishment of the reading rules; n = 89) and a testing set (for the validation of the reading rules; n = 89). For differential diagnosis, 55 α-synucleinopathies were additionally included into the testing set. The visual reading method was established by an experienced assessor (Reader 0) and was then validated by Reader 0 and two additional readers on regional and overall binary manners. A positive binding in both midbrain and globus pallidus/putamen regions was characterized as a PSP-like pattern, whereas any other pattern was classified as non-PSP-like., Results: Reader 1 (94.4%) and Reader 2 (93.8%) showed excellent agreement for the overall binary determination against Reader 0. The regional binary determinations of midbrain and globus pallidus/putamen showed excellent agreement among readers (kappa > 0.80). The overall binary evaluation demonstrated reproducibility of 86.1%, 94.4% and 77.8% for three readers. The visual reading algorithm showed high agreement with regional standardized uptake value ratios and clinical diagnoses., Conclusion: Through the application of the suggested visual reading algorithm, [ 18 F]Florzorotau PET imaging demonstrated a robust performance for the imaging diagnosis of PSP., Competing Interests: Declarations. Ethics approval: The Institutional Review Board of Huashan Hospital granted approval for this study. Consent to participate: All participants or their legally appointed guardians provided their written informed consent. Consent to publish: Not applicable. Competing interests: Tzu-Chen Yen is an employee of APRINOIA Therapeutics Co., Ltd. Matthias Brendel is a member of the Neuroimaging Committee of the EANM and the SNMMI Brain Imaging Council. Matthias Brendel received speaker honoraria from Roche, GE healthcare and Life Molecular Imaging and is an advisor of Life Molecular Imaging. Axel Rominger, Kuangyu Shi and Xiao-Li Lan are editors of this journal. Other authors report no financial interests or potential conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As naturally essential biomacromolecule, HSA has become diagnostic indicators for various diseases and universal carriers for anticancer drug delivery, therefore, fluorescence detection and labeling for HSA possess significant application value in the biomedical field. In this paper, hydrazide Schiff base fluorescent probe NDQC was designed and synthesized, which self-assembled into nanoparticles in aqueous solution system and demonstrated excellent selectivity and sensitivity towards HSA. Through displacement assay and molecular docking simulation, the binding of NDQC with HSA in FA1 site was demonstrated, thereby no obvious fluorescence signal presented for homologous protein BSA due to their structural differences in binding site. Non-toxic probe NDQC is suitable for the fluorescence imaging of HSA in cells, and colocalization fluorescence images showed that NDQC-HSA could illuminate mitochondria. Based on the pH sensitivity of fluorescence emission for NDQC-HSA, discrimination of cancer cells and normal cells could be achieved. For practical applications, NDQC-HSA can be employed to measure the content of hemin. More importantly, NDQC could fluorescently label HSA and therefore NDQC-HSA complex act as the carrier for loading cisplatin. The present findings demonstrate that the probe NDQC has potential in exploring HSA at cellular levels and hold great promise in application of tracking drug-loading nanoparticles., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bo-Wen Ding, Ruo-Xi Sang, Xiao-Yu Li, Jing Fan, Cheng-Zhi Xie, Jing-Yuan Xu has patent #CN PAT:202411331340.2 pending to Licensee. If there are other authors, they 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.)

Objectives: This systematic review aims to (1) summarize the clinical, laboratory, and imaging characteristics of Palmar Fasciitis and Polyarthritis Syndrome (PFPAS) patients and (2) evaluate the effectiveness of different treatments., Methods: We conducted a systematic search of three electronic databases (Scopus, Embase, and PubMed) from inception to December 31, 2023. We presented demographic and clinical features, along with laboratory factors and imaging examinations of PFPAS patients. Additionally, we outline main treatments and evaluate therapeutic effectiveness., Results: A total of 121 patients were included in the analysis, with a mean onset age of 61.4 years. Swelling or thickening (49.6%, n=60/121) and pain (41.3%, n=50/121) were characteristic musculoskeletal symptoms of the hands. The median time between onset of PFPAS symptoms and detection of malignancy was 4 months, with a median survival of 13.0 months (range=2 to 69). The abnormal rate of ultrasound, magnetic resonance imaging, and bone scan of the musculoskeletal system was more than 80%. Effective therapeutic responses were observed in 66.0% (n=33/50) of cases treated with chemotherapies and 79.2% (n=19/24) with operations. Two patients who received biologics achieved partial remission., Conclusion: PFPAS is a rare paraneoplastic condition, and early recognition of its distinctive symptoms may lead to the detection of underlying malignancy and timely treatments, potentially saving lives., (Copyright © 2024 Sociýtý Franýaise de Rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Vibegron functions as a potent and selective β 3 -adrenergic receptor agonist, with its chiral precursor (2S,3R)-aminohydroxy ester (1b) being crucial to its synthesis. In this study, loop engineering was applied to the carbonyl reductase (EaSDR6) from Exiguobacterium algae to achieve an asymmetric reduction of the (rac)-aminoketone ester 1a. The variant M5 (A138L/A190V/S193A/Y201F/N204A) was obtained and demonstrated an 868-fold increase in catalytic efficiency (k cat /K m  = 260.3 s -1  mM -1 ) and a desirable stereoselectivity (>99% enantiomeric excess, e.e.; >99% diastereomeric excess, d.e.) for the target product 1b in contrast to the wild-type EaSDR6 (WT). Structural alignment with WT indicated that loops 137-154 and 182-210 potentially play vital roles in facilitating catalysis and substrate binding. Moreover, molecular dynamics (MD) simulations of WT-1a and M5-1a complex illustrated that M5-1a exhibits a more effective nucleophilic attack distance and more readily adopts a pre-reaction state. The interaction analysis unveiled that M5 enhanced hydrophobic interactions with substrate 1a on cavities A and B while diminishing unfavorable hydrophilic interactions on cavity C. Computational analysis of binding free energies indicated that M5 displayed heightened affinity towards substrate 1a compared to the WT, aligning with its decreased K m value. Under organic-aqueous biphasic conditions, the M5 mutant showed >99% conversion within 12 h with 300 g/L substrate 1a (highest substrate loading as reported). This study enhanced the catalytic performance of carbonyl reductase through functional loops engineering and established a robust framework for the large-scale biosynthesis of the vibegron intermediate., (© 2024 Wiley Periodicals LLC.)

Three new cyclopentanoid monoterpenes, neopiscrocins A-C ( 1 - 3 ), together with 14 known compounds ( 4 - 17 ), were isolated from the roots of Picrorhiza scrophulariiflora . The structres of these compounds were elucidated on the basis of their spectroscopic data. All compounds were evaluated for cytotoxicity against six human tumor cell lines (PC9, PANC1, HCT-116, Hep-G2, BGC-823, and MCF-7), hepatoprotective activity and anti-inflammatory activity.

Objective: We aimed to assess the effects of olanzapine in the improvement of body weight and appetite in patients with cancer or receiving chemotherapy through a systematic review and meta-analysis., Methods: We searched the following databases from their inception to April 23, 2024: Embase, PubMed, Web of Science, and the Cochrane Library. The mean difference (MD) and risk ratios were used to calculate by random effects models. The primary outcome was the proportion of patients with > 5% weight gain., Results: Seventeen studies with 3457 participants were included. For primary outcomes, 1 study with 124 participants showed olanzapine increased the proportion of patients with > 5% weight gain compared with placebo (60% vs. 9%, P < 0.001). Versus active controls (3 studies, 439 participants), no significant difference in the proportion of patients with > 5% weight gain (RR = 1.69, 95%CI: 0.91 to 3.13, I 2  = 27%, P = 0.10), with moderate-quality evidence. Olanzapine increased appetite scores compared to both placebo (1 study, 112 participants; MD = 3, 95%CI: 2.3 to 3.7, P < 0.001) and active controls (2 studies, 106 participants; MD = 4.96, 95%CI: 4.61 to 5.30, I 2  = 0%, P < 0.01). For mean weight change, olanzapine showed no significant differences versus placebo (2 studies, 164 participants, MD = 2.78 kg, 95%CI: - 1.60 to 7.17, I 2  = 48%, P = 0.21) or active controls (2 studies, 480 participants, MD = 0.44 kg, 95%CI: - 1.04 to 1.91, I 2  = 58%, P = 0.56)., Conclusions: Olanzapine appears to be a potential option for improving appetite and weight gain in cancer patients. Future trials need to focus on the optimal target dose and use durations of olanzapine. Registered: https://archive.org/details/osf-registrations-kpv4h-v ., Competing Interests: Declarations. Ethical approval: Our study was a systematic review and meta-analysis and was exempt from review and approval by the research ethics committee. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intermittent hypoxia (IH), a major pathophysiologic alteration in obstructive sleep apnea syndrome (OSAS), is an important contributor to cognitive impairment. Increasing research suggests that melatonin has anti-inflammatory properties and improves functions related to synaptic plasticity. However, it is unclear whether melatonin has a protective effect against OSAS-induced cognitive dysfunction in aged individuals and the involved mechanisms are also unclear. Therefore, in the study, the effects of exposure to IH alone and IH in combination with daily melatonin treatment were investigated in C57BL/6 J mice aged 18 months. Assessment of the cognitive ability of mice in a Morris water maze showed that melatonin attenuated IH-induced impairment of learning and memory in aged mice. Enzyme-linked immunosorbent assay, polymerase chain reaction, and western blotting molecular techniques showed that melatonin treatment reduced the levels of the proinflammatory cytokines, interleukin-1β, interleukin-6, and tumor necrosis factor-α, decreased the levels of NOD-like receptor thermal protein domain associated protein 3 and nuclear factor kappa-B, lowered the levels of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, and increased the levels of the synaptic proteins, activity-regulated cytoskeleton-associated protein, growth-associated protein-43, postsynaptic density protein 95, and synaptophysin in IH-exposed mice. Moreover, electrophysiological results showed that melatonin ameliorated the decline in long-term potentiation induced by IH. The results suggest that melatonin can ameliorate IH-induced cognitive deficits by inhibiting neuroinflammation and improving synaptic plasticity in aged mice., Competing Interests: Declaration of Competing Interest All authors declare no competing financial interests or potential conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Changes in postmenopausal hormone levels are associated with a variety of disorders. This study elucidated the mechanism by which follicle-stimulating hormone (FSH) increases cortisol production involved in development of menopause-related diseases., Methods: The expression of FSH receptors (FSHRs) in murine adrenal zona fasciculata (AZF) cells and ATC7 cells was verified by immunofluorescence, western blotting and RT-PCR. The function of FSHR in promoting cortisol production was analyzed by cell culture and molecular biological methods. FSHR signaling pathways in ATC7 cells were analyzed by ELISA, qRT-PCR, and western blotting. Further, a mouse model was established by ovariectomy. Ovariectomized mice were treated with GnRHa. Ovariectomized mice initially received physiological doses of estrogen and were then injected with recombinant FSH. Then serum FSH, luteinizing hormone (LH), estradiol, and cortisol, and bone mineral density (BMD), blood pressure (BP) and heart rate (HR) were determined., Results: FSHRs were expressed in murine AZF cells and ATC7 cells. FSH accelerated cortisol production through activated protein kinase A (PKA), cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), protein kinase B (PKB/AKT) and 5' AMP-activated protein kinase (MAPK) signaling pathways by Gsα-coupled FSHRs in ATC7 cells. Serum FSH levels ( P< 0.001) were elevated in ovariectomized mice with concurrent increases in cortisol ( P< 0.01), areal BMD (aBMD) ( P< 0.05), volumetric BMD (vBMD) ( P< 0.05), systolic BP (SBP) ( P< 0.05), diastolic BP (DBP) ( P< 0.05), and HR ( P< 0.05). However, the administration of GnRHa suppressed the increase in FSH levels and the elevation of cortisol, aBMD, vBMD, SBP, DBP, and HR induced by ovariectomy, even in the presence of normal serum estradiol levels., Conclusion: The study findings indicate that elevated FSH levels stimulate cortisol secretion, through a mechanism related to FSHRs expression in AZF cells., Competing Interests: The authors declare that there is no conflict of interest., (Thieme. All rights reserved.)

Objective: To investigate the role of N-glycosylation modification of proteins in adipocyte differentiation during the adipogenic process., Methods: SVF cells and adipocytes were analyzed for proteomics and intact N-glycopeptide modificationomics.Differential expression of proteins, glycoforms, and sites between the two groups was screened and subjected to Gene Ontology (GO) functional enrichment analysis, KEGG pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. The top 20 most significantly differentially expressed adipogenic differentiation-related proteins were identified, and the most pronouncedly altered proteins were analyzed for glycoforms, glycan chains, and sites., Results: Proteomics analysis identified 39,392 peptides and 5208 proteins, while intact N-glycopeptide modification profiling identified 3293 intact glycopeptides, 426 proteins, and 161 glycan chains. Proteomics identified 2510 differentially expressed proteins, with CD36 (Cluster of Differentiation 36, CD36) significantly upregulated. In adipocytes, CD36 had 4 N-glycosylation sites: N79, N220, N320, N417, with N320 being a newly identified site. GO enrichment results indicated that CD36 is associated with fatty acid oxidation, lipid oxidation, and fatty acid uptake into cells., Conclusion: Multiple proteins undergo N-glycosylation modification during adipocyte differentiation, with CD36, a fatty acid translocase, being significantly expressed in adipocytes. This suggests that N-glycosylation modification of CD36 may play a crucial role in adipocyte differentiation, providing a foundation for further investigation into the function of CD36 N-glycosylation in adipocyte differentiation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Using the e^{+}e^{-} collision data collected with the BESIII detector operating at the BEPCII collider, at center-of-mass energies from the threshold to 4.95 GeV, we present precise measurements of the cross section for the process e^{+}e^{-}→D&#95;{s}^{+}D&#95;{s}^{-} using a single-tag method. The resulting cross section line shape exhibits several new structures, thereby offering an input for a future coupled-channel analysis and model tests, which are critical to understand vector charmonium-like states with masses between 4 and 5 GeV.

One of the most important characteristics of ornamental plants is leaf color, which enhances the color of plant landscapes and attracts pollinators for reproduction. The leaves of Impatiens hawkeri 'Sakimp005' are initially green, then the middle part appears yellow, then gradually become white, while the edge remains green. In the study, leaves of I. hawkeri 'Sakimp005', in four developmental stages (S1-G, S2-C, S3-C, and S4-C), were selected for the determination of pigment content, chromaticity values, integrative metabolomics, and transcriptomics analyses. The carotenoid content of leaves varied significantly and regularly at four stages, and the colorimetric values corroborated the phenotypic observations. The results of integrative metabolomics and transcriptomics analysis show that the accumulation of two carotenoids (lutein and zeaxanthin), to different degrees in the leaves of I. hawkeri 'Sakimp005' at four stages, led to the vary yellowing phenomenon. We speculated that the carotenoid biosynthesis (containing two branches: α-branch and β-branch) in leaves by IhLUT1 and IhLUT5 in the α-branch and IhBCH2 genes in the β-branch differed. These findings provide a molecular basis for Impatiens plants' leaf color breeding and improve the knowledge of the leaf color mechanism.

Background: Wireless capsule endoscopy (WCE) has become an important noninvasive and portable tool for diagnosing digestive tract diseases and has been propelled by advancements in medical imaging technology. However, the complexity of the digestive tract structure, and the diversity of lesion types, results in different sites and types of lesions distinctly appearing in the images, posing a challenge for the accurate identification of digestive tract diseases., Aim: To propose a deep learning-based lesion detection model to automatically identify and accurately label digestive tract lesions, thereby improving the diagnostic efficiency of doctors, and creating significant clinical application value., Methods: In this paper, we propose a neural network model, WCE&#95;Detection, for the accurate detection and classification of 23 classes of digestive tract lesion images. First, since multicategory lesion images exhibit various shapes and scales, a multidetection head strategy is adopted in the object detection network to increase the model's robustness for multiscale lesion detection. Moreover, a bidirectional feature pyramid network (BiFPN) is introduced, which effectively fuses shallow semantic features by adding skip connections, significantly reducing the detection error rate. On the basis of the above, we utilize the Swin Transformer with its unique self-attention mechanism and hierarchical structure in conjunction with the BiFPN feature fusion technique to enhance the feature representation of multicategory lesion images., Results: The model constructed in this study achieved an mAP50 of 91.5% for detecting 23 lesions. More than eleven single-category lesions achieved an mAP50 of over 99.4%, and more than twenty lesions had an mAP50 value of over 80%. These results indicate that the model outperforms other state-of-the-art models in the end-to-end integrated detection of human digestive tract lesion images., Conclusion: The deep learning-based object detection network detects multiple digestive tract lesions in WCE images with high accuracy, improving the diagnostic efficiency of doctors, and demonstrating significant clinical application value., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Nowadays, cognitive impairment has been characterized as one of the most vital clinical symptoms in progressive supranuclear palsy (PSP)., Objectives: Based on a relatively large cohort, we aimed to show the cognitive deterioration in different PSP subtypes during 1-year follow-up and investigate potential contributors for disease prognosis., Methods: One hundred seventeen patients from Progressive Supranuclear Palsy Neuroimage Initiative (PSPNI) cohort underwent neuropsychological tests and 1-year follow-up, with 73 diagnosed as PSP-Richardson syndrome (PSP-RS) and 44 as PSP-non-RS. Patients were divided into normal cognition (PSP-NC), mild cognitive impairment (PSP-MCI), and PSP-dementia. Cognitive impairment and progression rates were compared between PSP-RS and PSP-non-RS, and determinants for MCI conversion to dementia were calculated by multiple cox regression., Results: At baseline, 30.8% of PSP patients were diagnosed as dementia, 53.0% as MCI, and only 16.2% as NC. Compared to PSP-non-RS, PSP-RS suffered more from motor symptoms and cognitive impairment. During follow-up, PSP-RS also exhibited faster disease progression in Mini-Mental State Examination and visuospatial function, with cognitive deterioration in attention and executive function, but retained in language and memory subdomains. Twenty-seven of 62 PSP-MCI patients converted to dementia during follow-up, with the diagnosis of RS subtype as the most significant contributor to conversion (hazard ration = 2.993, 95% confidence interval = 1.451, 5.232, P = 0.009)., Conclusions: Patients with PSP-RS showed more severe cognitive impairment and faster decline longitudinally than patients with PSP-non-RS. Additionally, the diagnosis of RS subtype appears to be the most contributed factor for MCI conversion to dementia within just 1-year follow-up period., (© 2024 International Parkinson and Movement Disorder Society.)

Human pathogen Streptococcus pneumoniae forms multiple epigenetically and phenotypically distinct intra-populations by invertase PsrA-driven inversions of DNA methyltransferase hsdS genes in the colony opacity-determinant (cod) locus. As manifested by phase switch between opaque and transparent colonies, different genome methylation patterns or epigenomes confer pathogenesis-associated traits, but it is unknown how the pathogen controls the hsdS inversion orientations. Here, we report our finding of the SpxA1-TenA toxin-antitoxin (TA) system that regulates the orientations of hsdS inversions, and thereby bacterial epigenome and associated traits (e.g., colony opacity) by targeting pneumococcal protein synthesis. SpxA1 and TenA were found to constitute a highly conserved type II TA system in S. pneumoniae, primarily based on the observation that overexpressing toxin TenA led to growth arrest in E. coli and enhanced autolysis in S. pneumoniae, and the antitoxin SpxA1 repressed the transcription of the spxA1-tenA operon. When the transcription of tenA was de-repressed by a spontaneous AT di-nucleotide insertion/deletion in the promoter region of the spxA1-tenA operon, TenA bound to the ribosome maturation factor RimM, and thereby reduced the cellular level of alternative sigma factor ComX (known for the activation of natural transformation-associated genes). Attenuation of ComX expression in turn enhanced the transcription of the invertase gene psrA, which favored the formation of the transparent colony phase-associated hsdS allelic configurations in the cod locus. Phenotypically, moderate expression of TenA dramatically reshaped pneumococcal epigenome and colony opacity. Because spontaneous variations frequently occur during bacterial growth in the number of the AT di-nucleotides in the promoter region of the spxA1-tenA operon, this locus acts as a programmed genetic switch that generates pneumococcal subpopulations with epigenetic and phenotypic diversity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Elucidating biodegradation mechanisms and predicting pollutant reactivities are essential for advancing the application of biodegradation engineering to address the challenge of thousands of emerging contaminants. Molecular biology and computational chemistry are powerful tools for this purpose, enabling the investigation of biochemical reactions at both the gene and atomic levels. This study employs the biodegradation of ten sulfonamide antibiotics as a case study to demonstrate the integration of genomics and quantum chemistry approaches in exploring the biodegradation behavior of emerging contaminants. The isolated functional strain, Paenarthrobacter sp., could completely degrade all ten model sulfonamides under aerobic conditions. These compounds share a 4-aminobenzenesulfonamide core but differ in N 1 -substituent rings. Despite structural variations, all sulfonamides follow a consistent degradation pathway, yielding aminated heterocycles as end products. This pathway involves key steps such as dehydrogenation activation, ipso-hydroxylation, and the cleavage of S-N and S-C bonds, with the latter being particularly influenced by the N 1 -substituents. Heterocyclic structures affect biodegradation rates by altering the electronic density at the C 3 and N 1 atoms of sulfonamides. Substituents with higher electron-donating potential and lower Gibbs free energy barriers for S-C and C-N bond cleavage significantly enhance biodegradation efficiency. This work not only deciphers the universal biodegradation mechanism of sulfonamides but also offers theoretical insights for predicting the biodegradation behavior and pattern of emerging contaminants. These findings contribute to the effective removal of emerging contaminants from aquatic environments, advancing the practical application of biotreatment technologies., 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.)

Objective: To evaluate the safety, effectiveness, and long-term efficacy of the Jinling procedure for management of refractory mixed constipation. Methods: We prospectively collected clinical data of patients with refractory mixed constipation treated by the Jinling procedure in the Institute of General Surgery of our hospital from January 2007 to August 2023. Perioperative complications, effectiveness within 1 year of surgery (as assessed by the Wexner constipation score, gastrointestinal quality of life index, frequency of spontaneous defecation, rate of satisfactory defecation, body composition, serological indicators, defecography, anorectal manometry) and 10 years after surgery (as assessed by the Wexner constipation score, patient assessment of constipation symptom, SF-36 quality of life score, and questionnaire concerning satisfaction with defecation). Results: The study cohort comprised 3310 patients of mean age 44±15 years, including 653 men and 2657 women. The duration of constipation was 141±114 months. The 1-month, 3-month, 6-month, and 12-month follow-up rates were 98.07% (3246/3310), 95.11% (3148/3310), 93.38% (3091/3310), and 92.81% (3072/3310), respectively. Overall, 1100 patients had undergone surgery at least 10 years previously, 683 of whom completed the questionnaire, making the 10-year follow-up rate 62.09%. The overall incidence of postoperative complications was 21.99% (728/3310), mortality 0.45% (15/3310), and duration of postoperative hospital stay 12.5±5.4 days. Compared with preoperative values, Wexner scores decreased significantly from 1 to 12 months after surgery, whereas the gastrointestinal quality of life index scores had gradually increased by 3 months after surgery; both changes were statistically significant (both P < 0.001). The frequency of spontaneous defecation increased significantly to > five times/day 1 month after surgery, following which it decreased gradually with time, falling to two to five times/day by 6 months after surgery. All nutritional indicators returned to preoperative levels within 1 year except for that of inorganic salt, which did not change significantly. By 6-12 months after surgery, the proportions of rectocele, mucosal prolapse, internal rectal intussusception, visceral ptosis, perineal descent, pelvic floor spasm, and puborectalis syndrome assessed by defecography were all significantly lower than before surgery (all P < 0.05). By 3 months after surgery, the anal resting pressure, anal maximum systolic pressure, and anorectal depression had all returned to preoperative levels. Twelve months after surgery, the rectoanal inhibition reflex was stronger than that before surgery, whereas anal relaxation was less pronounced than that before surgery; these differences are statistically significant (both P < 0.05). The Wexner scores (7±2 vs. 21±6) and patient assessment of constipation symptoms scores (13±5 vs. 39±5) were significantly lower 10 years after the Jinling procedure than they had been before surgery. The eight dimensions of the SF-36 quality of life scores for physical functioning (90±5 vs. 78±8), role limitations in physical functioning (89±12 vs. 50±24), bodily pain (67±18 vs. 33±22), emotional well-being (63±23 vs. 48±30), vitality (71±11 vs. 31±13), mental health (71±10 vs. 30±10), social functioning (69±17 vs. 26±15) and general health (79±9 vs. 35±12) had all improved significantly (all P < 0.001). The total rates of satisfaction with defecation were 95.02% (2919/3072) and 87.56% (598/683) 1 year and 10 years after surgery, respectively. Conclusion: The Jinling procedure is a safe and effective means of treating refractory mixed constipation, achieving improvement in long-term defecation function and gastrointestinal quality of life.

Objective: To explore clinical efficacy of unilateral and bilateral nail-rod system fixation in single-level intervertebral fusion fixation of lumbar disc herniation (LDH) and instability with unilateral dual-channel spinal endoscopy., Methods: The clinical data of 63 patients with LDH complicated with instability treated by unilateral double-channel spinal endoscopy from March 2021 to June 2022 were retrospectively analyzed. According to intraoperative fixation methods, the patients were divided into two groups, included unilateral nail rod system fixation group(unilateral group) and bilateral nail rod system fixation group(bilateral group). There were 31 patients in unilateral group, including 15 males and 16 females; aged from 40 to 67 years old with an average of (54.65±7.32) years old; 3 patients with L 3,4 , 15 patients with L 4,5 , 13 patients with L 5 S 1 . There were 32 patients in bilateral group, including 18 males and 14 females, aged from 43 to 68 years old with an average of (56.19±6.63) years old;4 patients with L 3,4 , 17 patients with L 4,5 , 11 patients with L 5 S 1 . The time of operation, length of incision, operation time, length of hospital stay, cost of treatment, occurrence of complications and adverse events were recorded and compared between two groups. Visual analogue scale (VAS) of lumbar and leg pain, Japanese Orthopaedic Association (JOA) and Oswestry disability index (ODI) were compared before operation, 3 and 12 months after operation. MacNab standard was used to evaluate clinical effect., Results: Both of two groups were successfully completed operation and followed up. In unilateral fixation group, follow-up time, operation time, incision length, postoperative ambulation time, hospital stay and treatment cost were (11.81±1.08) months, (122.48±13.86) min, (3.15±0.45) cm, (3.06±0.73) d, (6.87±1.09) d, and (3.49±0.09) ten thousand yuan;while (11.47±1.16) months, (134.94±10.94) min, (6.45±0.83) cm, (3.19±0.86) d, (7.03±1.03) d, (3.77±0.12) ten thousand yuan in bilateral fixation group, respectively;there were significant differences in operation time, incision length and treatment cost between two groups ( P <0.05), no significant difference in follow-up time, postoperative ambulation time and hospital stay ( P >0.05). There were no significant difference in VAS of low back pain, JOA score, ODI and MacNab grade between two groups before and after operation ( P >0.05). No significant complications and adverse events were observed between two groups after operation., Conclusion: Both of unilateral and bilateral nail rod system for the treatment of LDH with instability could achieve the expected results. Unilateral fixation has more advantageous than bilateral fixation in terms of operation time, incision length and treatment cost. For patients with osteoporosis before operation or insufficient fixation strength of unilateral pedicle nails during surgery, bilateral fixation is feasible to enhance reliability of fixation.

Objectives: Associations of ABO blood group specifying transferases A/B (ABO) and fucosyltransferase 2 (FUT2) with CP remain inconclusive. We aimed to comprehensively investigate the associations by Chinese sequencing cohorts and external cohorts., Methods: First, we analyzed the distributions of ABO blood groups and FUT2 status, along with lead single nucleotide polymorphisms (SNPs) at ABO (rs8176693 C/T) and FUT2 (rs632111 A/G) gene loci in Chinese low-coverage whole-genome sequencing discovery cohort. Subsequently, we investigated the associations of CP with ABO and FUT2 SNPs in Chinese whole-exome sequencing validation cohort and three public biobanks (FinnGen, UK Biobank, and BioBank Japan). Finally, comprehensive meta-analysis was performed by integrating data from two Chinese cohorts, reported cohorts and public biobanks., Results: Firstly, in Chinese discovery cohort, the distribution of blood types in CP patients showed no significant difference compared to healthy controls, and similar results were observed in subgroup analyses and in meta-analysis with the reported cohorts. Secondly, results indicated no association between rs8176693 or rs632111 and CP in Chinese cohorts and meta-analysis of three biobanks, though ABO SNP was found to be significantly associated with CP in UK Biobank (odds ratio [OR] = 1.27, P = 0.04). Finally, no association was observed between rs8176693 (OR = 1.03, P = 0.29) or rs632111 (OR = 1.04, P = 0.10) and CP in comprehensive meta-analysis., Conclusions: No association was found between lead SNPs of ABO or FUT2 and CP in meta-analysis, nor was there an association between ABO blood group or FUT2 secretor status and CP in Chinese cohort. ABO and FUT2 might play limited role in CP development., Competing Interests: Declaration of competing interest None., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Lumbar disc degeneration (LDD) is a ubiquitous finding in low back pain. Many different etiology factors may explain the LDD process, such as bone morphogenetic proteins (BMPs), DNA methylation, and gut microbiota. Until recently the mechanisms underlying the LDD process have been elusive., Methods: BMP-related genes were extracted from the GeneCards database. The LDD transcriptome dataset was obtained from the Gene Expression Omnibus. We used linear regression and meta-analysis to screen and integrate the differentially expressed genes associated with BMPs in LDD. Genome-wide association studies (GWASs) of LDD were from FinnGen and UKBB. The expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci from the blood were identified via the summary data-based Mendelian randomization (SMR) method, and the possible blood BMP genes and their regulatory elements associated with the risk of LDD were prioritized. Intestinal eQTLs and fecal microbial QTLs (mbQTLs) were integrated, and the potential interactions between BMP gene expression in host intestinal tissue and the gut microbiota were revealed through SMR and colocalization analysis. The GWAS catalog (GCST90246169) was used to validate SMR results., Results: A meta-analysis of five datasets revealed that 113 BMP genes were differentially expressed between LDD and control tissues. Seven genes were selected as candidate pathogenic genes of LDD via the three-step SMR method: CREB1 , BMP6 , PTCH1 , GLI1 , MEG3 , GALNS , and NF1 . SMR analysis also revealed five possible gut genes: HFE , MET , MAPK3 , NPC1 , and GDF5 . The correlation between the gut microbiota and BMP gene expression in intestinal tissues was verified by eQTL-mbQTL colocalization., Conclusion: This multi-omics study revealed that the BMP genes associated with LDD are regulated by DNA methylation. There are genetic differences between gut gene expression and the gut microbiota. These findings provide evidence for new therapeutic targets in the future., Competing Interests: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 The Author(s). JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Utilizing enzymes as biocatalysts, an alternative strategy has been developed for the highly enantioselective synthesis of chiral 2,3-dihydrobenzofuran (2,3-DHB) esters via the dynamic kinetic resolution of 2,3-dihydro-3-benzofuranols, which are generated from an intramolecular Aldol reaction. This protocol provides easy access to a series of 2,3-DHB ester derivatives, prodrugs, and allows for functional group transformations. Biological evaluation also indicates that some of the products exhibit potent anti-inflammatory activity.

Hyperzrones A ( 1 ) and B ( 2 ), two unprecedented nor -polycyclic polyprenylated acylphloroglucinols with a characteristic cyclobutane moiety, were discovered from Hypericum beanii . Their structures were determined by extensive spectroscopic analysis, X-ray crystallography, and quantum chemical calculation methods. A bioinspired semisynthesis of 1 and 2 was achieved from the natural precursor hypercalin B ( 3 ), featuring a Favorskii-type rearrangement and a visible-light-mediated [2 + 2] photocycloaddition. Several diverse derivatives were also obtained, providing a compound library for biological studies.

A growing number of studies show that the diabetes drug Semaglutide is neuroprotective in Alzheimer's disease (AD) animal models, but its mode of action is not fully understood. In order to explore the mechanism of Semaglutide, 7-month-old APP/PS1/tau transgenic (3xTg) mice and wild-type (WT) mice were randomly divided into four groups: control group (WT + PBS), AD model group (3xTg + PBS), Semaglutide control group (WT + Semaglutide) and Semaglutide treatment group (3xTg + Semaglutide). Semaglutide (25 nmol/kg) or PBS was administered intraperitoneally once every two days for 30 days, followed by behavioral and molecular experiments. The results show that Semaglutide can improve working memory and spatial reference memory of 3xTg-AD mice, promote the release of anti-inflammatory factors and inhibit the production of pro-inflammatory factors in the cortex and hippocampus, and reduce Aβ deposition in the hippocampal CA1 region of 3xTg mice. Semaglutide can inhibit the apoptosis of BV2 cells induced by Aβ1-42 in a dose-dependent manner and promote the transformation of microglia from M1 to M2, thereby exerting anti-inflammatory and neuroprotective effects. Therefore, we speculate that Semaglutide shows an anti-inflammatory effect by promoting the transformation of microglia from M1 to M2 type in the brain of 3xTg mice, and thus exerts a neuroprotective effect., 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 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Hypobaric hypoxia exposure occurs at high altitudes, including plateaus, and affects normal intestinal function and microbiota composition. Exposure induces an intestinal inflammatory response and oxidative stress injury, ultimately disrupting intestinal homeostasis and causing barrier damage. Thus, due to its anti-inflammatory, antioxidative, and intestinal microbiota-regulating properties, Bifidobacterium longum is a potentially effective probiotic intervention to protect the intestinal barrier during low-pressure hypoxia on plateaus. However, its mechanism of action is not fully defined. In this study, we investigate the mechanism by which B. longum intervenes in intestinal barrier damage caused by plateau low-pressure hypoxia. To this end, an in vivo model is established by exposing rats to a simulated low-pressure hypoxic plateau environment. The experimental rats were subsequently supplemented with a B. longum strain (JBLC-141) extracted from the feces of healthy adults in Bama, Guangxi. B. longum JBLC-141 mitigates the effects of plateau low-pressure hypoxia on the rat intestinal barrier. This is achieved by activating the intestinal Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway, alleviating plateau hypoxia-induced intestinal oxidative stress injury. B. longum JBLC-141 also attenuates the inflammatory response and upregulates the expression of the tight junction proteins claudin-1, occludin, and zonula occludens-1. Furthermore, it reduces intestinal permeability, effectively ameliorating and repairing the barrier histological damage induced by the plateau low-pressure hypoxic environment. In addition, B. longum JBLC-141 positively regulates the intestinal microbiota, increasing the relative abundance of beneficial bacteria while reducing that of pathogenic bacteria and maintaining intestinal flora homeostasis in rats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Shang, Wang, Ma, Ren and Zhang.)

Climate warming affects antibiotic resistance genes (ARGs) in soil and the plant microbiome, including seed endophytes. Seeds act as vectors for ARG dissemination in the soil-plant system, but the impact of elevated CO 2 on seed resistomes remains poorly understood. Here, a free-air CO 2 enrichment system was used to examine the impact of elevated CO 2 on seed-associated ARGs and seed endophytic bacteria and fungi. Results indicated that elevated CO 2 levels significantly increased the relative abundance of seed ARGs and mobile genetic elements (MGEs), especially those related to beta-lactam resistance and MGEs. Increased CO 2 levels also influenced the composition of seed bacterial and fungal communities and the complexity of bacteria-fungi interactions. Fungi were more sensitive to changes in the CO 2 level than bacteria, with deterministic processes playing a greater role in fungal community assembly. Co-occurrence network analysis revealed a stronger correlation between fungi and ARGs compared to bacteria. The structure equation model (SEM) showed that elevated CO 2 directly influenced seed resistomes by altering bacterial composition and indirectly through bacteria-fungi interactions. Together, our work offers new insights into the effects of elevated CO 2 on antibiotic resistomes in the seed endosphere, highlighting their increased dissemination potential within soil-plant systems and the associated health risks in a changing environment.

Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus, which is an efficient anti-inflammatory agent that functions both in vivo and in vitro. However, it is not clear whether anisomycin can exert neuroprotective effect in AD. In the present study, anisomycin was intragastrically administrated to female triple-transgenic AD (3xTg-AD) model mice, then Morris water maze test was used to observe the long-term spatial memory of mice, the in vivo hippocampal field potential recording was performed to evaluate the synaptic plasticity, the Western blot and immunofluorescence were employed to detect pathological changes, and the bioinformatics analysis was used to predict the potential target of anisomycin exerting effects in AD. The results showed that anisomycin ameliorated the long-term spatial memory deficits, improved LTP depression and increased the expression of PSD-95, reduced the Aβ and tau pathologies, and alleviated the activation of microglia and astrocytes in the brains of 3xTg-AD mice. In addition, the results from bioinformatics analysis showed that the potential target of anisomycin focused on inflammatory pathway. These results indicated that anisomycin exerts neuroprotective effects in 3xTg-AD mice by alleviating neuroinflammation, but the potential mechanism of anisomycin exerting neuroprotective effects needs to be further investigated., 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.)

Background: Colorectal cancer (CRC) is characterized by high heterogeneity, aggressiveness, and high morbidity and mortality rates. With machine learning (ML) algorithms, patient, tumor, and treatment features can be used to develop and validate models for predicting survival. In addition, important variables can be screened and different applications can be provided that could serve as vital references when making clinical decisions and potentially improving patient outcomes in clinical settings., Aim: To construct prognostic prediction models and screen important variables for patients with stage I to III CRC., Methods: More than 1000 postoperative CRC patients were grouped according to survival time (with cutoff values of 3 years and 5 years) and assigned to training and testing cohorts (7:3). For each 3-category survival time, predictions were made by 4 ML algorithms (all-variable and important variable-only datasets), each of which was validated via 5-fold cross-validation and bootstrap validation. Important variables were screened with multivariable regression methods. Model performance was evaluated and compared before and after variable screening with the area under the curve (AUC). SHapley Additive exPlanations (SHAP) further demonstrated the impact of important variables on model decision-making. Nomograms were constructed for practical model application., Results: Our ML models performed well; the model performance before and after important parameter identification was consistent, and variable screening was effective. The highest pre- and postscreening model AUCs 95% confidence intervals in the testing set were 0.87 (0.81-0.92) and 0.89 (0.84-0.93) for overall survival, 0.75 (0.69-0.82) and 0.73 (0.64-0.81) for disease-free survival, 0.95 (0.88-1.00) and 0.88 (0.75-0.97) for recurrence-free survival, and 0.76 (0.47-0.95) and 0.80 (0.53-0.94) for distant metastasis-free survival. Repeated cross-validation and bootstrap validation were performed in both the training and testing datasets. The SHAP values of the important variables were consistent with the clinicopathological characteristics of patients with tumors. The nomograms were created., Conclusion: We constructed a comprehensive, high-accuracy, important variable-based ML architecture for predicting the 3-category survival times. This architecture could serve as a vital reference for managing CRC patients., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)