The role of HnrnpF/H as a driver of oligoteratozoospermia.

Male subfertility or infertility is a common condition often characterized by men producing a low number of sperm with poor quality. To gain insight into this condition, we performed a quantitative proteomic analysis of semen samples obtained from infertile and fertile men. At least 6 proteins showed significant differences in regulation of alternatively spliced isoforms. To investigate this link between aberrant alternative splicing and production of poor-quality spermatozoa, we overexpressed the hnrnpH/F-orthologue Glorund (Glo) in Drosophila, which was also found to be abundant in poor quality human sperm. Transgenic animals produced low numbers of morphologically defective spermatozoa and aberrant formation of the "dense body," an organelle akin to the mammalian manchette. Furthermore, fertility trials demonstrated that transgenic flies were either completely infertile or highly subfertile. These findings suggest that dysregulation of hnrnpH/F is likely to result in the production of low-quality semen, leading to subfertility or infertility in men.

Development and validation of a prognostic nomogram to predict 30-day all-cause mortality in patients with CRO infection treated with colistin sulfate.

Background: Carbapenem-resistant Gram-negative organism (CRO) infection is a critical clinical disease with high mortality rates. The 30-day mortality rate following antibiotic treatment serves as a benchmark for assessing the quality of care. Colistin sulfate is currently considered the last resort therapy against infections caused by CRO. Nevertheless, there is a scarcity of reliable tools for personalized prognosis of CRO infections. This study aimed to develop and validate a nomogram to predict the 30-day all-cause mortality in patients with CRO infection who underwent colistin sulfate treatment. Methods: A prediction model was developed and preliminarily validated using CRO-infected patients treated with colistin sulfate at Tongji Hospital in Wuhan, China, who were hospitalized between May 2018 and May 2023, forming the study cohort. Patients admitted to Xianning Central Hospital in Xianning, China, between May 2018 and May 2023 were considered for external validation. Multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of 30-day all-cause mortality. The receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and the calibration curve were used to evaluate model performance. The decision curve analysis (DCA) was used to assess the model clinical utility. Results: A total of 170 patients in the study cohort and 65 patients in the external validation cohort were included. Factors such as age, duration of combination therapy, nasogastric tube placement, history of previous surgery, presence of polymicrobial infections, and occurrence of septic shock were independently associated with 30-day all-cause mortality and were used to construct the nomogram. The AUC of the nomogram constructed from the above six factors was 0.888 in the training set. The Hosmer-Lemeshow test showed that the model was a good fit (p = 0.944). The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, the decision curve analysis demonstrated significantly better net benefit in the model. The external validation proved the reliability of the prediction nomogram. Conclusion: A nomogram was developed and validated to predict the occurrence of 30-day all-cause mortality in patients with CRO infection treated with colistin sulfate. This nomogram offers healthcare providers a precise and efficient means for early prediction, treatment management, and patient notification in cases of CRO infection treated with colistin sulfate.

Changes of cerebral structure and perfusion in subtypes of systemic sclerosis: a brain magnetic resonance imaging study.

OBJECTIVES: The characteristics of brain impairment in different subtypes of systemic sclerosis (SSc) (dcSSc, diffuse cutaneous SSc; lcSSc, limited cutaneous SSc) remain unclear. This study aimed to characterize cerebral structure and perfusion changes in different subtype of SSc patients using magnetic resonance (MR) imaging. METHODS: Seventy SSc patients (46.0 ± 11.7 years, 62 females) and 30 healthy volunteers (44.8 ± 13.7 years, 24 females) were recruited and underwent brain MR imaging and Montreal Cognitive Assessment (MoCA) test. Gray matter (GM) volumes were measured using voxel-based morphometry analysis on T1-weighted images. Voxel-based and regional cerebral blood flow (CBF) was calculated on arterial spin labelling images. The cerebral structural and perfusion measurements by MR imaging were compared among dcSSc, lcSSc and healthy subjects using one-way ANOVA. The correlations between clinical characteristics and MR imaging measurements were also analyzed. RESULTS: The dcSSc patients exhibited a significant reduction in GM volume in the para-hippocampal region (cluster p < 0.01, FWE corrected) compared with healthy volunteers. Whereas, SSc patients, particularly lcSSc patients, showed elevated CBF in cerebellum, insula, cerebral cortex, and subcortical structures (regional analyses: all p < 0.05; voxel-based analyses: cluster p < 0.01, FWE corrected). Furthermore, clinical characteristics of modified Rodnan skin score (mRSS) (r value ranged from -0.29 to -0.45), MoCA scores (r = 0.40) and antinuclear antibody (ANA) positivity (r=-0.33) were significantly associated with CBF in some regions (all p < 0.05). CONCLUSION: The manifestations of brain involvement vary among different subtypes of SSc. In addition, severe skin sclerosis may indicate higher risk of brain involvement in SSc patients.

[Influence of gingival biotype width on the health of peri-implant bone and soft tissues and the aesthetic outcome of the gingival papilla for single maxillary posterior implants].

PURPOSE: To explore the influence of gingival biotype and width of keratinized gingiva on peri-implant bone tissue, soft tissue health, and esthetic outcome of the papilla surrounding single posterior maxillary implants. METHODS: Seventy-eight patients who underwent single posterior maxillary implant surgery from May 2019 to September 2022 were selected, involving the placement of 78 implants. Based on periodontal probing outcomes one month post-restoration, the patients were divided into thin gingival biotype group(n=32) and thick gingival biotype group(n=46). Comparisons were made six months after implant restoration regarding buccal keratinized mucosa width(KMW), peri-implant bone tissue [implant bone loss(IBL)], soft tissue health [modified plaque index (mPLI), modified bleeding index for implants (mBLI), probing pocket depth (PPD)], and esthetic effect of the papilla [papilla index score (PIS), food impaction, gingival margin color satisfaction index (GMCS)]. Statistical analysis was performed with SPSS 27.0 software package. RESULTS: The thick gingival biotype group showed significantly greater keratinized gingival width compared to the thin gingival biotype group (P＜0.05). Spearman correlation analysis revealed a positive correlation between gingival biotype and keratinized gingival width(r=-0.416, P=0.000). For peri-implant bone tissue, bone loss in the thin gingival biotype group was significantly higher than that in the thick gingival biotype group. In soft tissue health, the probing pocket depth for implants in the thin gingival biotype group was significantly less than that in the thick gingival biotype group. In terms of esthetic effect of the papilla, PES score in the thin gingival biotype group was significantly lower than in the thick gingival biotype group(P＜0.05). Pearson correlation analysis showed a negative correlation between gingival biotype and papilla index score, GMCS, bleeding on probing, and PPD, but a positive correlation with food impaction, bone loss and mPLI(P＜0.05). The width of keratinized gingiva was positively correlated with papilla index score, GMCS, bleeding on probing and PPD, but negatively correlated with food impaction, bone loss and mPLI(P＜0.05). There was significantly difference between thin and thick gingival biotype groups for KMW >2 mm(P＜0.05). A significant difference was showed in thick gingival biotype group when KMW ≤2 mm and ＞2 mm(P＜0.05). CONCLUSIONS: Gingival biotype and keratinized mucosa width significantly influence peri-implant bone and soft tissue health as well as esthetic outcome of the papilla around single posterior maxillary implants, offering guidance for predicting the long-term success and esthetic outcomes of implants.

The long-term effects of perceived instructional leadership on teachers' psychological well-being during COVID-19.

The COVID-19 outbreak led to widespread school closures and the shift to remote teaching, potentially resulting in lasting negative impacts on teachers' psychological well-being due to increased workloads and a perceived lack of administrative support. Despite the significance of these challenges, few studies have delved into the long-term effects of perceived instructional leadership on teachers' psychological health. To bridge this research gap, we utilized longitudinal data from 927 primary and secondary school teachers surveyed in two phases: Time 1 in mid-November 2021 and Time 2 in early January 2022. Using hierarchical linear modeling (HLM), our findings revealed that perceptions of instructional leadership, especially the "perceived school neglect of teaching autonomy" at Time 1 were positively correlated with burnout levels at Time 2. Additionally, burnout at Time 2 was positively associated with psychological distress and acted as a mediator between the "perceived school neglect of teaching autonomy" and psychological distress. In light of these findings, we recommend that schools prioritize teachers' teaching autonomy and take proactive measures to mitigate burnout and psychological distress, aiming for the sustainable well-being of both teachers and students in the post-pandemic era.

Progress and Challenges of Topical Delivery Technologies Meditated Drug Therapy for Osteoarthritis.

Osteoarthritis (OA) is a degenerative disease commonly seen in middle-aged and elderly people. Multiple cytokines are involved in the local tissue damage in OA. Currently, non-pharmacologic and surgical interventions are the main conventional approaches for the treatment of OA. In terms of pharmaceutical drug therapy, NSAIDs and acetaminophen are mainly used to treat OA. However, it is prone to various adverse reactions such as digestive tract ulcer, thromboembolism, prosthesis loosening, nerve injury and so on. With the in-depth study of OA, more and more novel topical drug delivery strategies and vehicles have been developed, which can make up for the shortcomings of traditional dosage forms, improve the bioavailability of drugs, and significantly reduce drug side effects. This review summarizes the immunopathogenesis, treatment guidelines, and progress and challenges of topical delivery technologies of OA, with some perspectives on the future pharmacological treatment of OA proposed.

Key genes and regulatory networks for diabetic retinopathy based on hypoxia-related genes: a bioinformatics analysis.

AIM: To prevent neovascularization in diabetic retinopathy (DR) patients and partially control disease progression. METHODS: Hypoxia-related differentially expressed genes (DEGs) were identified from the GSE60436 and GSE102485 datasets, followed by gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Potential candidate drugs were screened using the CMap database. Subsequently, a protein-protein interaction (PPI) network was constructed to identify hypoxia-related hub genes. A nomogram was generated using the rms R package, and the correlation of hub genes was analyzed using the Hmisc R package. The clinical significance of hub genes was validated by comparing their expression levels between disease and normal groups and constructing receiver operating characteristic curve (ROC) curves. Finally, a hypoxia-related miRNA-transcription factor (TF)-Hub gene network was constructed using the NetworkAnalyst online tool. RESULTS: Totally 48 hypoxia-related DEGs and screened 10 potential candidate drugs with interaction relationships to upregulated hypoxia-related genes were identified, such as ruxolitinib, meprylcaine, and deferiprone. In addition, 8 hub genes were also identified: glycogen phosphorylase muscle associated (PYGM), glyceraldehyde-3-phosphate dehydrogenase spermatogenic (GAPDHS), enolase 3 (ENO3), aldolase fructose-bisphosphate C (ALDOC), phosphoglucomutase 2 (PGM2), enolase 2 (ENO2), phosphoglycerate mutase 2 (PGAM2), and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Based on hub gene predictions, the miRNA-TF-Hub gene network revealed complex interactions between 163 miRNAs, 77 TFs, and hub genes. The results of ROC showed that the except for GAPDHS, the area under curve (AUC) values of the other 7 hub genes were greater than 0.758, indicating their favorable diagnostic performance. CONCLUSION: PYGM, GAPDHS, ENO3, ALDOC, PGM2, ENO2, PGAM2, and PFKFB3 are hub genes in DR, and hypoxia-related hub genes exhibited favorable diagnostic performance.

Application of combined anesthesia with spontaneous breathing in the surgery of intertrochanteric fracture of femur in elderly patients.

OBJECTIVES: This study aims to investigate the feasibility and safety of combined anesthesia with spontaneous breathing in the operation of intertrochanteric fracture of femur in the elderly. PATIENTS AND METHODS: Between January 2020 and January 2023, a total of 141 elderly patients (45 males, 96 females; mean age: 72.5±6.8 years; range, 65 to 87 years) who underwent proximal femoral nail anti-rotation (PFNA) surgery for intertrochanteric fracture of femur were included in this single-blind, prospective, randomized-controlled study. The patients were randomly divided into three groups. Group A (experimental group) was a general anesthesia with laryngeal mask airway (LMA) group preserving spontaneous breathing, Group B (control group 1) was a general anesthesia with LMA group for mechanical ventilation, and Group C (control group 2) was a tracheal intubation anesthesia group for mechanical ventilation. The differences of related indexes among the three groups were compared. RESULTS: The mean onset time of anesthesia (6.23±1.45 vs. 12.78±2.78 vs. 13.73±2.43 min), postoperative recovery time of consciousness (8.13±0.83 vs. 11.34±0.89 vs. 12.45±0.86 min), and postoperative complete awakening time (10.45±2.34 vs. 18.87±2.56 vs. 19.62±2.93 min) were significantly shorter in Group A than in Groups B and C (p<0.05). The duration of analgesic effect was longer in Group A than in Groups B and C (p<0.05). After anesthesia, the Ramsay Sedation Scale and Visual Analog Scale (VAS) scores were significantly lower in Group A than the other groups (p<0.05). The mean Mini-Mental State Examination (MMS) scores were significantly higher in Group A than in Groups B and C (p<0.05). Hemodynamic parameters showed that blood pressure, heart rate, cardiac output, and cardiac index (CI) levels were significantly higher in Group A than the other groups (p<0.05). CONCLUSION: Our study results indicate that combined anesthesia preserving spontaneous breathing is safe and feasible in the operation of intertrochanteric fracture of femur in the elderly, with faster anesthesia recovery than the mechanical ventilation group.

Factors influencing innovation competence among children and adolescents in China - A multilevel, cross-cohort study.

Innovation competence is an essential core literacy skill for 21st century students. While some research exists on innovation competence in college students, there has been relatively little examination of the factors influencing this competence in children and adolescents aged 10 to 15. This study evaluated innovation competence among students from Suzhou, China, focusing on four key social and emotional skills: creativity, curiosity, cooperation, and responsibility. Data from the Organization for Economic Cooperation and Development were utilized for this analysis. Hierarchical linear modelling was applied to analyze potential factors at both individual and school levels influencing innovation competence across family and school environments. We calculated a t-test statistic to compare factors between the two cohorts. Factors significantly influencing children and adolescents' innovation competence included socio-economic status, time spent engaging in online gaming, time spent browsing the Internet for information, and the perceived cooperative climate atschool. Gender significantly influenced only adolescents' innovation competence, while teachers' disruptive behaviors had an impact solely on children's innovation competence. Apart from time spent engaging in online gaming and browsing the Internet for information, the effects of other variables showed significant differences between the groups. The findings highlight the need for targeted support from families, schools, and society to foster students' innovation competence.

Projection for dementia burden in China to 2050: a macro-simulation study by scenarios of dementia incidence trends.

Background: It is unclear how temporal trends in dementia incidence, alongside fast-changing demography, will influence China's future dementia burden. We developed a Markov model that combines population trends in dementia, mortality, and dementia-related comorbidities, to forecast and decompose the burden of dementia in China to 2050. Methods: Population-based Chinese ageing cohorts provided input data for a 10-health-state Markov macrosimulation model, IMPACT-China Ageing Model (CAM), to predict sex- and age-specific dementia prevalence among people aged 50+ by year to 2050. We assumed three potential future scenarios representing the range of likely dementia incidence trends: upward (+2.9%), flat (0%) or downward (-1.0%). Sensitivity analyses were conducted to examine uncertainty associated with trends in mortality rates and CVD incidence. The projected dementia burden was decomposed into population growth, population ageing, and changing dementia prevalence corresponding to the three incidence trend scenarios. Findings: Under the upward trend scenario, the estimated number of people living with dementia is projected to rise to 66.3 million (95% uncertainty interval (UI) 64.7-68.0 million), accounting for 10.4% of the Chinese population aged 50+ by 2050. This large burden will be lower, 43.9 (95% UI 42.9-45.0) million and 37.5 (95% UI 36.5-38.4) million, if dementia incidence remains constant or decreases. Robustness of the projection is confirmed by sensitivity analyses. Decomposition of the change in projected dementia cases indicates dominate effects of increasing dementia prevalence and population ageing, and a relatively minor contribution from negative population growth. Interpretation: Our findings highlight an impending surge in dementia cases in China in the forthcoming decades if the upward trend in dementia incidence continues. Public health interventions geared towards dementia prevention could play a pivotal role in alleviating this burgeoning disease issue. Funding: National Science Foundation of China/UK Economic and Social Research Council.

[Study on related influencing factors on the occurrence of redundant sign in the cauda equina in lumbar spinal stenosis].

OBJECTIVE: To analyze the relational factors influencing the formation of cauda equina redundant nerve roots (RNRs) of the lumbar spinal stenosis. METHODS: Clinical data of 116 patients with lumbar spinal stenosis treated from January 2016 to June 2019 were retrospectively analyzed. The patients were divided into redundant nerve roots(RNRs) group and non-RNRs group based on the presence or absence of RNRs on sagittal T2-weighted MRI. In the non-RNRs group, there were 74 patients, including 38 males and 36 females with an average age of (62.00±10.41) years old, the body mass index (BMI) was (23.09±2.22) kg·m-2;the maximum stenosis segment was L2-L3 in 12 cases, L3-L4 in 38, L4-L5 in 20, and L5S1 in 4, respectively. In the RNRs group, there were 42 patients, including 18 males and 24 females with an average age of (63.36±8.73) years old, the BMI was (22.63±2.60) kg·m-2;the maximum stenosis segment was L2-L3 in 3 cases, L3-L4 in 9, L4-L5 in 27 and L5S1 in 3, respectively. MRI was performed in the supine position to observe the conshape and morphology of the redundant nerve in the sagittal position. The preoperative low back and leg pain visual analogue scale(VAS), and preoperative Oswestry disability index(ODI) were analyzed, and the rate of spondylolisthesis and ligamentum flavum hypertrophy were compared. Simultaneously, the inter-vertebral height, intervertebral foramen height, inter-vertebral height+vertebral height, median sagittal diameter at the inter-vertebral space level(DIW-MSD), median sagittal diameter at the pedicel level(DV-MSD), range of motion(ROM) of the stenotic segment were measured and analyzed. RESULTS: Among the 116 patients with lumbar spinal stenosis, 42 patients developed RNRs, with an incidence of 36.2%. There were no significant differences in gender, age, BMI, preoperative VAS for lumbar and leg pain and ODI between two groups(P>0.05). There were statistically significant differences regard to the duration of symptoms and the rate of spondylolisthesis and ligamentum flavum hypertrophy (P<0.05);the inter-vertebral height, intervertebral foramen height, inter-vertebral height+vertebral height, DIW-MSD, ROM of the stenotic segment were also significantly different between two groups(P<0.05). However, there was no significant difference in DV-MSD between two groups(P>0.05). CONCLUSION: The inter-vertebral height, inter-vertebral foramen height, inter-vertebral height+vertebral height, DIW-MSD and ROM of the stenotic segment were the crucial factors related to RNRs in lumbar spinal stenosis.

Heterosis formation mechanism, prediction methods, and their application and prospect in pig production.

Heterosis is the phenomenon that the hybrid offspring outperform two-parent population. Hybridisation has been widely used in plant and animal production as it effectively improves the growth and developmental performance, reproductive performance and disease resistance of the offspring. Hybridization can effectively improve the growth and development performance, reproductive performance and disease resistance of offspring, so it is widely used in animal and plant production. Researchers have used cross-breeding techniques to cultivate excellent new agricultural and animal husbandry strains and supporting lines such as super-excellent Chaoyou 1000 hybrid rice, Xiaoyan No.6 hybrid wheat, Dumeng sheep, and Shanxia black pigs. However, there are still some urgent problems in the current hybrid dominance research: the existing hybrid dominance theory can only partially explain the phenomenon of plant and animal hybrid dominance, and the theory of animal hybrid dominance is less researched, and the accuracy of the existing hybrid dominance prediction methods is limited. China is the world's largest pork production and consumption country. Heterosis can effectively improve the production performance of pigs, and its application in the pig industry has important economic and research value. However, the existing research on pig hybrid production is in its infancy and needs to be further studied. In this review, we summarize the existing heterosis theory, heterosis prediction methods, and their application in pig production, to provide a reference for the application of heterosis in pig breeding.

Anopheles gambiae lacking AgTRIO probe inefficiently on a mammalian host.

Malaria is initiated as Plasmodium sporozoites are injected into the dermis when an infected mosquito probes on a vertebrate host for a blood meal. Factors in the mosquito saliva, such as AgTRIO, can alter the ability of Anopheles gambiae to transmit Plasmodium. We therefore used CRISPR-Cas9-mediated genome editing to generate AgTRIO knockout (KO) A. gambiae and examined the ability of these mosquitoes to probe on a vertebrate host. AgTRIO KO mosquitoes showed a diminished host probing capacity and required repetitive probing to locate a blood resource to complete a blood meal. This increased probing resulted in enhanced Plasmodium transmission to the vertebrate host. Our data demonstrate the importance of the A. gambiae saliva protein AgTRIO in probing and its influence on the ability of mosquitoes to transmit malaria.

CentIER: accurate centromere identification for plant genome.

This paper introduces CentIER, the first bioinformatic tool designed to detect complete centromeric regions without additional wet experiments. The accuracy of CentIER was validated on diverse plant genomes such as Arabidopsis, rice, maize and mulberry, and the results show that CentIER can perform significantly more complete and accurate detection than the existing tool.

Contactin -Associated protein1 Regulates Autophagy by Modulating the PI3K/AKT/mTOR Signaling Pathway and ATG4B Levels in Vitro and in Vivo.

Contactin-associated protein1 (Caspr1) plays an important role in the formation and stability of myelinated axons. In Caspr1 mutant mice, autophagy-related structures accumulate in neurons, causing axonal degeneration; however, the mechanism by which Caspr1 regulates autophagy remains unknown. To illustrate the mechanism of Caspr1 in autophagy process, we demonstrated that Caspr1 knockout in primary neurons from mice along with human cell lines, HEK-293 and HeLa, induced autophagy by downregulating the PI3K/AKT/mTOR signaling pathway to promote the conversion of microtubule-associated protein light chain 3 I (LC3-I) to LC3-II. In contrast, Caspr1 overexpression in cells contributed to the upregulation of this signaling pathway. We also demonstrated that Caspr1 knockout led to increased LC3-I protein expression in mice. In addition, Caspr1 could inhibit the expression of autophagy-related 4B cysteine peptidase (ATG4B) protein by directly binding to ATG4B in overexpressed Caspr1 cells. Intriguingly, we found an accumulation of ATG4B in the Golgi apparatuses of cells overexpressing Caspr1; therefore, we speculate that Caspr1 may restrict ATG4 secretion from the Golgi apparatus to the cytoplasm. Collectively, our results indicate that Caspr1 may regulate autophagy by modulating the PI3K/AKT/mTOR signaling pathway and the levels of ATG4 protein, both in vitro and in vivo. Thus, Caspr1 can be a potential therapeutic target in axonal damage and demyelinating diseases.

Phage-induced "one-to-many" FRET sensor for highly sensitive detection of Escherichia coli O157:H7.

As a foodborne pathogen capable of causing severe illnesses, early detection of Escherichia coli O157:H7 (E. coli O157:H7) is crucial for ensuring food safety. While Förster resonance energy transfer (FRET) is an efficient and precise detection technique, there remains a need for amplification strategies to detect low concentrations of E. coli O157:H7. In this study, we presented a phage (M13)-induced "one to many" FRET platform for sensitively detecting E. coli O157:H7. The aptamers, which specifically recognize E. coli O157:H7 were attached to magnetic beads as capture probes for separating E. coli O157:H7 from food samples. The peptide O157S, which specifically targets E. coli O157:H7, and streptavidin binding peptide (SBP), which binds to streptavidin (SA), were displayed on the P3 and P8 proteins of M13, respectively, to construct the O157S-M13K07-SBP phage as a detection probe for signal output. Due to the precise distance (≈3.2 nm) between two neighboring N-terminus of P8 protein, the SA-labeled FRET donor and acceptor can be fixed at the Förster distance on the surface of O157S-M13K07-SBP via the binding of SA and SBP, inducing FRET. Moreover, the P8 protein, with ≈2700 copies, enabled multiple FRET (≈605) occurrences, amplifying FRET in each E. coli O157:H7 recognition event. The O157S-M13K07-SBP-based FRET sensor can detect E. coli O157:H7 at concentration as low as 6 CFU/mL and demonstrates excellent performance in terms of selectivity, detection time (≈3 h), accuracy, precision, practical application, and storage stability. In summary, we have developed a powerful tool for detecting various targets in food safety, environmental monitoring, and medical diagnosis.

Sirt1 m6A modification-evoked Leydig cell senescence promotes Cd-induced testosterone decline.

Diminished testosterone levels have been documented as a key factor in numerous male health disorders. Both human and animal studies have consistently demonstrated that cadmium (Cd), a pervasive environmental heavy metal, results in decreased testosterone levels. However, the exact mechanism through which Cd interferes with testosterone synthesis remains incompletely elucidated. This research sought to examine the impact of cellular senescence on Cd-suppressed testosterone synthesis. We also investigated the related m6A modification mechanism. The results demonstrated that Cd (100 mg/L) led to a decrease in testosterone levels, along with downregulated expression of testosterone synthase in C57BL/6 N male mice. Furthermore, Cd significantly increased ß-galactosidase staining intensity, senescence-related proteins, and senescence-related secretory phenotypes in mouse testicular Leydig cells. Subsequent investigations revealed that Cd decreased the mRNA and protein levels of NAD-dependent deacetylase Sirtuin-1 (SIRT1) in Leydig cells. Mechanistically, mice treated with resveratrol (50 mg/kg), a specific SIRT1 activator, mitigated Leydig cell senescence and reversed Cd-reduced testosterone levels in mouse testes. These effects were also restored by SIRT1 overexpression in Leydig cells. Additionally, we found that Cd increased the level of methyltransferase enzyme METTL3 and Sirt1 m6A modification in Leydig cells. Mettl3 siRNA effectively restored Cd-enhanced Sirt1 m6A level and reversed Cd-downregulated Sirt1 mRNA expression in Leydig cells. Overall, our findings suggest that Cd exposure inhibits testosterone synthesis via Sirt1 m6A modification-mediated senescence in mouse testes. These results offer an experimental basis for investigating the causes and potential treatments of hypotestosteronemia induced by environmental factors.

Multiple Stimuli-Responsive Color-Changing Polymer Materials for Reversible Writing and Anti-Counterfeiting.

Polymer materials with multiple stimuli-responsive properties have demonstrated many potential and practical applications. By covalently introducing spiropyran (SP1) and spirothiopyran (STP) into the polyurethane backbone, photochromic, mechanochromic, and thermally discolored polymer materials have been prepared. In this work, we report for the first time that white light (violet, blue, and green light) above a certain intensity can activate STP to green color. Based on the above discovery, the polyurethane with SP1 and STP can exhibit reversible three-color changes (brown, green, and purple) in response to four stimuli: ultraviolet irradiation, white light irradiation, mechanical stress, and heat. The color-changing polymer materials have high color contrast and excellent reversibility, and can be used for reversible writing, anticounterfeiting and information encryption, etc.

Risk factors for pathological upgrading and noncurative resection in patients with gastric mucosal lesions after endoscopic submucosal dissection.

BACKGROUND: The pathological results obtained from endoscopic forceps biopsy (EFB) do not always align with the findings of postoperative endoscopic submucosal dissection (ESD). Furthermore, as ESD becomes more widespread, the number of noncurative endoscopic cases increases; thus, an accurate preoperative diagnosis and an appropriate treatment method are crucial. The purpose of this study was to explore the risk factors for postoperative pathological upgrading and noncurative resection and to gather experience in clinical and pathological diagnosis. METHODS: From March 2016 to November 2023, 292 ESD specimens were collected from 262 patients with gastric mucosal lesions. Clinicopathological information, the coincidence rate of pathological diagnosis between EFB and ESD specimens, and risk factors related to noncurative resection were analyzed retrospectively. RESULTS: The overall upgraded pathological diagnosis rate between EFB and ESD was 26.4%. The independent predictors for the upgraded group included proximal stomach lesions, lesion size > 2 cm, surface ulceration, and surface nodules. Twenty of the 235 early gastric cancer (EGC) patients underwent noncurative ESD resection. Multivariate analysis showed that undifferentiated carcinoma and tumor infiltration into the submucosa were significantly associated with noncurative resection. CONCLUSION: Biopsy cannot fully represent the lesions of gastric intraepithelial neoplasia (GIN). When a suspected epithelial dysplasia is suspected, a careful endoscopic examination should be conducted to evaluate the lesion site, size, and surface characteristics to ensure an accurate diagnosis. Noncurative endoscopic resection is associated with undifferentiated carcinoma and submucosal infiltration. Clinicians must be familiar with these predictive factors for noncurative resection and select the appropriate treatment for their patients.

Biomedical potentials of alginate via physical, chemical, and biological modifications.

Alginate is a linear polysaccharide with a modifiable structure and abundant functional groups, offers immense potential for tailoring diverse alginate-based materials to meet the demands of biomedical applications. Given the advancements in modification techniques, it is significant to analyze and summarize the modification of alginate by physical, chemical and biological methods. These approaches provide plentiful information on the preparation, characterization and application of alginate-based materials. Physical modification generally involves blending and physical crosslinking, while chemical modification relies on chemical reactions, mainly including acylation, sulfation, phosphorylation, carbodiimide coupling, nucleophilic substitution, graft copolymerization, terminal modification, and degradation. Chemical modified alginate contains chemically crosslinked alginate, grafted alginate and oligo-alginate. Biological modification associated with various enzymes to realize the hydrolysis or grafting. These diverse modifications hold great promise in fully harnessing the potential of alginate for its burgeoning biomedical applications in the future. In summary, this review provides a comprehensive discussion and summary of different modification methods applied to improve the properties of alginate while expanding its biomedical potentials.