Novel evidence of CNV deletion in KCTD13 related to the severity of isolated hypospadias in Chinese population.

Background: CNV in KCTD13 has been identified to influence androgen receptor function via its changes in gene dosage, which might contribute to hypospadias. However, there is lack of population-level evidence to assess the contribution of KCTD13 CNV to hypospadias. Methods: 349 isolated hypospadias patients were recruited and their genotyping was performed using real-time qPCR. We use Database of Genomic Variants (DGV) and CNV calls from SNP-array intensity data in 1,008 Chinese healthy men as reference. Results: 11.17% of patients were identified to have KCTD13 CNV deletion, significantly higher than 0.05% in DGV (P < 0.001), but no cases found to have CNV duplication. Meanwhile, no CNV calls encompassing KCTD13 region were detected in Chinese healthy men. Incidence of KCTD13 CNV deletion was significantly increased with the severity of hypospadias, P _trend = 9.00 × 10-6. Compared to distal hypospadias, ORs for the proximal and midshaft were 10.07 (2.91-34.84) and 6.08 (1.69-21.84) respectively. In addition, the association between genital characteristics (stretched penile length and glans width) and KCTD13 CNV showed no significance in hypospadias children (P > 0.05). Conclusions: We demonstrate KCTD13 CNV deletion is strongly associated with hypospadias and its severity, but duplication is not, characterizing KCTD13 genetic variation in more detail than previously described.

Post-marketing drug safety surveillance of enfortumab vedotin: an observational pharmacovigilance study based on a real-world database.

Background: Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) that has been approved by the FDA for patients with locally advanced or metastatic urothelial carcinoma (UC). This study presents a comprehensive pharmacovigilance analysis of the post-marketing safety profile of EV in the real-world based on the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Adverse event (AE) reports regarding EV between January 2020 and December 2023 were obtained from the FAERS database. The standardized MedDRA query (SMQ) narrow search AEs on the preferred term (PT) level were used. Disproportionality analysis was performed to identify the AE signals for EV with the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN). Results: A total of 2,216 reports regarding EV were included in the present study. SMQ analysis results indicated that a stronger strength signal was found in severe cutaneous adverse reactions, retroperitoneal fibrosis, and peripheral neuropathy. A total of 116 significant disproportionality PTs referring to 14 system organ classes (SOCs) were retained by disproportionality analysis, with 49 PTs not listed on the EV drug label. Frequently reported EV-related AEs included rash, peripheral neuropathy, decreased appetite, alopecia, and pruritus. The time to onset of the majority of EV-related AEs was within 30 days (66.05%), with only 0.73% events occurring after 1 year. Conclusion: The disproportionality analysis highlights that dermatologic toxicity and peripheral neuropathy were the major AEs induced by EV. The potential AEs not listed on the drug label were mainly related to gastrointestinal, hepatic, and pulmonary events. Further research is needed to confirm and explore the EV-related AEs in clinical practice.

Superficial Vessel Density and Determinants of Macular Microvasculature in Healthy Chinese Subjects.

BACKGROUND: The purpose of this study was to investigate the vessel density (VD) of the macular superficial capillary plexus (SCP) and its associated factors in healthy subjects. METHODS: This prospective, cross-sectional study enrolled healthy Chinese volunteers. The optical coherence tomography angiography (OCTA) was used to measure the superficial VD in macula. A generalized estimation equation (GEE) model was used to analyze the ocular and systemic associated factors. RESULTS: A total of 516 eyes of 262 healthy subjects were included (mean age 38.59±21.03 years). The total VD of macular SCP was 16.85±2.28 mm- 1. The VD in the inner ring and outer ring were significantly higher than that in the central ring, with the density being highest in nasal quadrant and lowest in the superior quadrant. After adjusting the ocular and systemic factors, age (ß=-0.0085, P=0.0122) and SSI (ß=1.3261, P <0.001) were significantly associated with total VD of the macular SCP. CONCLUSIONS: Among the healthy Chinese subjects included in the study, the mean total VD of macular SCP was 16.85 ± 2.28mm-1. The macular superficial capillary density was positively associated with age and SSI. Further studies are still required to better understand the change of macular VD in aging and other pathological conditions.

Methylparaben changes the community composition, structure, and assembly processes of free-living bacteria, phytoplankton, and zooplankton.

Parabens are common contaminants in river and lake environments. However, few studies have been conducted to determine the effects of parabens on bacteria, phytoplankton, and zooplankton communities in aquatic environments. In this study, the effect of methylparaben (MP) on the diversity and community structure of the aquatic plankton microbiome was investigated by incubating a microcosm with MP at 0.1, 1, 10, and 100 µg/L for 7 days. The results of the Simpson index showed that MP treatment altered the α-diversity of free-living bacteria (FL), phytoplankton, and zooplankton but had no significant effect on the α-diversity of particle-attached bacteria (PA). Further, the relative abundances of the sensitive bacteria Chitinophaga and Vibrionimonas declined after MP addition. Moreover, the relative abundances of Desmodesmus sp. HSJ717 and Scenedesmus armatus, of the phylum Chlorophyta, were significantly lower in the MP treatment group than in the control group. In addition, the relative abundance of Stoeckeria sp. SSMS0806, of the Dinophyta phylum, was higher than that in the control group. MP addition also increased the relative abundance of Arthropoda but decreased the relative abundance of Rotifera and Ciliophora. The ß-diversity analysis showed that FL and phytoplankton communities were clustered separately after treatment with different MP concentrations. MP addition changed community assembly mechanisms in the microcosm, including increasing the stochastic processes for FL and the deterministic processes for PA and phytoplankton. Structural equation modeling analysis showed a significant negative relationship between bacteria richness and phytoplankton richness, and a significant positive relationship between phytoplankton (richness and community composition) and zooplankton. Overall, this study emphasizes that MP, at environmental concentrations, can change the diversity and structure of plankton microbial communities, which might have a negative effect on ecological systems.

High-Capacity Zinc Anode Enabled by a Recyclable Biomass Bamboo Membrane Separator.

Aqueous zinc ion batteries have gained attention as viable energy storage systems, yet the occurrence of detrimental side reactions and Zn dendrite formation undermines the efficiency of Zn anodes. Controlling water activity have proven to be an effective strategy in mitigating these challenges. However, strategies such as electrolyte design and electrode protection layer show weakness to varying degrees. Here, a new oxygen-functionalized biomass bamboo membrane separator (denoted as BM) is proposed to restrain the activity of water molecules. This BM separator features a unique, multi-tiered 2D interlayer that facilitates rapid ion diffusion. Additionally, the oxygen functional groups of the BM separator can form hydrogen bonds with water molecules, effectively transforming water molecules from a free state to a bound state. Consequently, the Zn/Zn asymmetric coin cell using BM can work at the ultrahigh rate and capacity of 30 mA cm-2 and 30 mAh cm-2 for more than 80 h while its counterparts using glass fiber can barely work. Moreover, full cells using BM separator exhibited a capacity retention of 89.7% after 1000 cycles at 10 A g-1. This study reveals the important influence of water-limited activity on Zn anode protection and provides an avenue for the design of novel separator.

Soluble TGF-ß decoy receptor TGFBR3 exacerbates Alzheimer's disease pathology by modifying microglial function.

Alzheimer's disease (AD) is a major cause of progressive dementia characterized by memory loss and progressive neurocognitive dysfunction. However, the molecular mechanisms are not fully understood. To elucidate the molecular mechanism contributing to AD, an integrated analytical workflow was deployed to identify pivotal regulatory target within the RNA-sequencing (RNA-seq) data of the temporal cortex from AD patients. Soluble transforming growth factor beta receptor 3 (sTGFBR3) was identified as a critical target in AD, which was abnormally elevated in AD patients and AD mouse models. We then demonstrated that sTGFBR3 deficiency restored spatial learning and memory deficits in amyloid precursor protein (APP)/PS1 and streptozotocin (STZ)-induced neuronal impairment mice after its expression was disrupted by a lentiviral (LV) vector expressing shRNA. Mechanistically, sTGFBR3 deficiency augments TGF-ß signaling and suppressing the NF-κB pathway, thereby reduced the number of disease-associated microglia (DAMs), inhibited proinflammatory activity and increased the phagocytic activity of DAMs. Moreover, sTGFBR3 deficiency significantly mitigated acute neuroinflammation provoked by lipopolysaccharide (LPS) and alleviated neuronal dysfunction induced by STZ. Collectively, these results position sTGFBR3 as a promising candidate for therapeutic intervention in AD.

Correlation of bone age development with overweight and obesity in 23,305 children from Beijing.

PURPOSE: The aim of this study was to observe the influence of differential nutritional status on bone age (BA) change according to body mass index (BMI) and analyze the risk of advanced bone age in children with overweight and obesity. METHODS: In total 23,305 children from Beijing were included in this cross-sectional study. Childhood overweight and obesity were defined according to the China and World Health Organization growth criteria. The data were analyzed by the R coding platform version 4.3.0. RESULTS: Under the Chinese criteria, 29%, 15%, and 4% of boys with overweight; 33%, 33%, and 3% of boys with obesity; 39%, 25%, and 2% of girls with overweight; and 37%, 42% and 1% of girls with obesity had advanced, significantly advanced and delayed BA, respectively. After adjustment, overweight (odds ratio, 95% confidence interval, P under the Chinese criteria: 2.52, 2.30-2.75, <0.001 and 4.54, 4.06-5.09, <0.001) and obesity (4.31, 3.85-4.82, <0.001 and 14.01, 12.39-15.85, <0.001) were risk factors for both advanced BA and significantly advanced BA. CONCLUSIONS: Different nutritional statuses lead to differences in children's BA development. Children with overweight and obesity have higher rates of advanced BA under two growth criteria, and girls have more advances in BA than boys do. Overweight and obesity are risk factors for advanced BA.

Discovery of a novel Xanthone derivative P24 for anti-AD via targeting sTGFBR3.

Soluble transforming growth factor beta receptor 3 (sTGFBR3) antagonist is a new focus in the research and development of Alzheimer's disease (AD) drugs. Our previous studies have identified sTGFBR3 as a promising new target for AD, with few targeted antagonists identified. In this study, we performed structural modeling of sTGFBR3 using AlphaFold2, followed by high-throughput virtual screening and surface plasmon resonance assays. which collectively identified Xanthone as potential compounds for targeting sTGFBR3. After optimizing the sTGFBR3-Xanthone complex using molecular dynamics (MD) simulations, we prepared a series of novel Xanthone derivatives and evaluated their anti-inflammatory activity, toxicity, and structure-activity relationship in BV2 cell model induced by lipopolysaccharides (LPS) or APP/PS1/tau mouse brain extract (BE). Several derivatives with the most potent anti-inflammatory activity were tested for blood-brain barrier permeability and sTGFBR3 affinity. Derivative P24, selected for its superior properties, was further evaluated in vitro. The results indicated that P24 increased the activation of TGF-ß signaling and decreased the activation of IκBα/NF-κB signaling by targeting sTGFBR3, thereby regulating the inflammation-phagocytosis balance in microglia. Moreover, the low acute toxicity, long half-life, and low plasma clearance of P24 suggest that it can be sustained in vivo. This property may render P24 a more effective treatment modality for chronic diseases, particularly AD. The study demonstrates P24 serve as potential novel candidates for the treatment of AD via antagonizing sTGFBR3.

Wearable Smart Silicone Belt for Human Motion Monitoring and Power Generation.

Human physical activity monitoring plays a crucial role in promoting personalized health management. In this work, inspired by an ancient Chinese belt, a belt-type wearable sensor (BWS) based on a triboelectric nanogenerator (TENG) is presented to monitor daily movements and collect the body motion mechanical energy. The developed BWS consists of a soft silicone sheet and systematically connected sensing units made from triboelectric polymer materials including polytetrafluoroethylene (PTFE) and polyamide (PA). A parameter study of the sensing units is firstly conducted to optimize the structure of BWS. The experimental studies indicate that the parameter-optimized BWS unit achieves a maximum output voltage of 47 V and a maximum current of 0.17 µA. A BWS with five sensing units is manufactured to record body movements, and it is able to distinguish different physical activities including stillness, walking, running, jumping, normal breathing, cessation of breathing, and deep breathing. In addition, the developed BWS successfully powers electronic devices including a smartphone, digital watch, and LED lights. We hope this work provides a new strategy for the development of wearable self-powered intelligent devices.

Different effects of air pollutant concentrations on influenza A and B in Sichuan, China.

BACKGROUND: The detrimental effects of air pollution on the respiratory system are well documented. Previous research has established a correlation between air pollutant concentration and the frequency of outpatient visits for influenza-like illness. However, studies investigating the variations in infection among different influenza subtypes remain sparse. We aimed to determine the correlation between air pollutant levels and different influenza subtypes in Sichuan Province, China. METHODS: A generalized additive model and distributed lag nonlinear model were employed to assess the association between air pollutants and influenza subtypes, utilizing daily influenza data obtained from 30 hospitals across 21 cities in Sichuan Province. The analysis considered the temporal effects and meteorological factors. The study spanned from January 1, 2017, to December 31, 2019. To provide a more precise evaluation of the actual impact of air pollution on different subtypes of influenza, we also performed subgroup analyses based on factors such as gender, age, and geography within the population. RESULTS: During the investigation, 17,462 specimens from Sichuan Province tested positive for influenza. Among these, 12,607 and 4855 were diagnosed with Flu A and B, respectively. The related risk of influenza A infection significantly increased following exposure to PM2.5 on Lag2 days (RR=1.008, 95 % confidence interval [CI]: 1.000-1.016), SO2 and CO on Lag1 days (RR=1.121, 95 % CI: 1.032-1.219; RR=1.151, 95 % CI: 1.030-1.289), and NO2 on Lag0 day (RR=1.089, 95 % CI: 1.035-1.145). PM10 and SO2 levels on Lag0 day, PM2.5 levels on Lag1 day, and CO levels on Lag6 day, with a reduced risk of influenza B (RR=0.987, 95 % CI: 0.976-0.997; RR=0.817, 95 % CI: 0.676-0.987; RR=0.979, 95 % CI: 0.970-0.989; RR=0.814, 95 % CI: 0.561-0.921). CONCLUSION: The findings from the overall population and subgroup analyses indicated that the impact of air pollutant concentrations on influenza A and B is inconsistent, with influenza A demonstrating greater susceptibility to these pollutants. Minimizing the levels of SO2, CO, NO2, and PM2.5 can significantly decrease the likelihood of contracting influenza A. Analyzing the influence of environmental contaminants on different influenza subtypes can provide insights into seasonal influenza trends and guide the development of preventive and control strategies.

Solvent Effects on the Phenolic Compounds and Antioxidant Activity Associated with Camellia polyodonta Flower Extracts.

Camellia polyodonta flowers contain limited information available regarding the composition of their bioactive compounds and activity. The objective of this study was to identify phenolic compounds and investigate the effect of different solvents (ethanol and methanol) on the phenolic content and antioxidant activity in C. polyodonta flowers. The analysis using UPLC-Q-TOF-MS/MS revealed the presence of 105 phytochemicals and the most common compounds were flavonols, procyanidins, and ellagitannins. Interestingly, flavonol triglycosides were identified for the first time in these flowers. The study demonstrated that the concentration of the solvent had a significant impact on the total phenolic compound (TPC), total flavonoid compound (TFC), and total proanthocyanidin content (TPAC). The TPC, TFC, and TPAC showed a remarkable increase with the increasing concentration of the solvent, reaching their maximum levels (138.23 mg GAE/g DW, 421.62 mg RE/g DW, 60.77 mg PB2E/g DW) at 70% ethanol. However, the total anthocyanin content reached its maximum at low concentrations (0.49 mg CGE/g DW). Similar trends were observed in the antioxidant activity, as measured by the DPPH· assay (DPPH radical scavenging activity), ABTS·+ assay (ABTS radical cation scavenging activity), and FRAP assay (Ferric reducing antioxidant power). The maximum antioxidant activity was observed at 100% solvents and 70% methanol. Among the 14 individual phenolic compounds, 70% methanol yielded the highest content for 8 (cyanidin-3-O-glucoside, procyanidin B2, procyanidin B4, epicatechin, rutin, kaempferol-3-O-rutinoside, astragaline and quercitrin) out of the 14 compounds. Additionally, it was found that epicatechin was the most abundant phenolic compound, accounting for approximately 20339.37 µg/g DW. Based on these findings, it can be concluded that 70% methanol is the most effective solvent for extracting polyphenols from C. polyodonta flowers. These results provided chemical information and potential antioxidant value for further research in C. polyodonta flowers.

Porous Photocrosslinkable Hydrogel Functionalized with USC Derived Small Extracellular Vesicles for Corpus Spongiosum Repair.

Reconstruction of a full-thickness spongy urethra is difficult because a corpus spongiosum (CS) defect cannot be repaired using self-healing or substitution urethroplasty. Small extracellular vesicles (sEVs) secreted by urine-derived stem cells (USC-sEVs) strongly promote vascular regeneration. In this study, it is aimed to explore whether USC-sEVs promote the repair of CS defects. To prolong the in vivo effects of USC-sEVs, a void-forming photoinduced imine crosslinking hydrogel (vHG) is prepared and mixed with the USC-sEV suspension. vHG encapsulated with USC-sEVs (vHG-sEVs) is used to repair a CS defect with length of 1.5 cm and width of 0.8 cm. The results show that vHG-sEVs promote the regeneration and repair of CS defects. Histological analysis reveals abundant sinusoid-like vascular structures in the vHG-sEV group. Photoacoustic microscopy indicates that blood flow and microvascular structure of the defect area in the vHG-sEV group are similar to those in the normal CS group. This study confirms that the in situ-formed vHG-sEV patch appears to be a valid and promising strategy for repairing CS defects.

METTL1/FOXM1 promotes lung adenocarcinoma progression and gefitinib resistance by inhibiting PTPN13 expression.

INTRODUCTION: Lung adenocarcinoma (LUAD) is the most common malignant tumor in respiratory system. Methyltransferase-like 1 (METTL1) is a driver of m7G modification in mRNA. This study aimed to demonstrate the role of METTL1 in the proliferation, invasion and Gefitinib-resistance of LUAD. METHODS: Public datasets were downloaded from the Gene Expression Profiling Interactive Analysis (GEPIA) and GSE31210 datasets. Malignant tumor phenotypes were tested in vitro and in vivo through biological function assays and nude mouse with xenograft tumors. RNA immunoprecipitation assays were conducted to determine the interaction between METTL1 protein and FOXM1 mRNA. Public transcriptional database, Chromatin immunoprecipitation and luciferase report assays were conducted to detect the downstream target of a transcriptional factor FOXM1. Half maximal inhibitory concentration (IC50) was calculated to evaluate the sensitivity to Gefitinib in LUAD cells. RESULTS: The results showed that METTL1 was upregulated in LUAD, and the high expression of METTL1 was associated with unfavorable prognosis. Through the m7G-dependent manner, METTL1 improved the RNA stability of FOXM1, leading to the up-regulation of FOXM1. FOXM1 transcriptionally suppressed PTPN13 expression. The METTL1/FOXM1/PTPN13 axis reduced the sensitivity of LUAD cells to Gefitinib. Taken together, our data suggested that METTL1 plays oncogenic role in LUAD through inducing the m7G modification of FOXM1, therefore METTL1 probably is a new potential therapeutic target to counteract Gefitinib resistance in LUAD.

Ferroptosis-related lncRNAs: Distinguishing heterogeneity of the tumour microenvironment and predicting immunotherapy response in bladder cancer.

Ferroptosis, a cell death pathway dependent on iron, has been shown in research to play a role in the development, advancement, and outlook of tumours through ferroptosis-related lncRNAs (FRLRs). However, the value of the FRLRs in bladder cancer (BLCA) has not been thoroughly investigated. This research project involved developing a predictive model using ten specific FRLRs (AC099850.4, AL731567.1, AL133415.1, AC021321.1, SPAG5-AS1, HMGA2-AS1, RBMS3-AS3, AC006160.1, AL583785.1, and AL662844.4) through univariate COX and LASSO regression techniques. The validation of this signature as a standalone predictor was confirmed in a group of 65 patients from the urology bladder tumour database at the First Affiliated Hospital of Wenzhou Medical University in Wenzhou, China. Patients were categorized based on their median risk score into either a low-risk group or a high-risk group. Enrichment analysis identified possible molecular mechanisms that could explain the variations in clinical outcomes observed in high-risk and low-risk groups. Moreover, we explored the correlation between FLPS and immunotherapy-related indicators. The ability of FLPS to forecast the effectiveness of immunotherapy was validated by the elevated levels of immune checkpoint genes (PD-L1, CTLA4, and PD-1) in the group at high risk. We also screened the crucial FRLR (HMGA2-AS1) through congruent expression and prognostic conditions and established a ceRNA network, indicating that HMGA2-AS1 may affect epithelial-mesenchymal transition by modulating the Wnt signalling pathway through the ceRNA mechanism. We identified the top five mRNAs (NFIB, NEGR1, JAZF1, JCAD, and ESM1) based on random forest algorithm and analysed the relationship between HMGA2-AS1, the top five mRNAs, and immunotherapy, and their interactions with drug sensitivities. Our results suggest that patients with BLCA have a greater sensitivity to four drugs (dasatinib, pazopanib, erismodegib and olaparib). Our study provides new insights into the TME, key signalling pathways, genome, and potential therapeutic targets of BLCA, with future guidance for immunotherapy and targeted precision drugs.

The association between telomere length and blood lipids: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa. Methods: We obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis. Results: In the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (ß=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (ß=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (ß=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (ß=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10-5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%). Conclusions: Our study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.

Purification of Phenolic Compounds from Camellia polyodonta Flower: Composition Analysis, Antioxidant Property, and Hypolipidemic Activity In Vitro and In Vivo.

Camellia polyodonta flowers are rich sources of phenolics and less attention has been paid to their potential biological activity. This study aims to explore the crude extracts and resulting purified fractions (CPFP-I, II, III, and IV) through compositional analysis and antioxidant and hypolipidemic activities in vitro and in vivo. Among four fractions, CPFP-II contained the highest total phenolic content and flavonoid content, while CPFP-III exhibited the greatest total proanthocyanidin content. Among the 14 phenolic compounds, CPFP-II displayed the highest content of procyanidin B2, B4, and C1, whereas CPFP-III contained the highest amount of 1,2,3,6-tetragalloylglucose. The DPPH, ABTS, and FRAP assessments demonstrated a consistent trend: CPFP-II > CPFP-III > CPFP-I > CPFP-IV. In vivo experiments showed that that all four fractions significantly reduced lipid levels in hyperlipidemic C. elegans (p < 0.05), with CPFP-II exhibiting the most potent effect. Furthermore, CPFP-II effectively bound to bile acids and inhibited the enzymatic activity of pancreatic lipase in vitro. Consequently, CPFP-II should be prioritized as a promising fraction for further exploration and should provide substantial support for the feasibility of the C. polyodonta flower as a natural alternative.

Modeling multi-source plastic pollution yield and transport driven by catchment hydrometeorological processes.

Plastic pollution has emerged as a global environmental concern, impacting both terrestrial and marine ecosystems. However, understanding of plastic sources and transport mechanism at the catchment scale remains limited. This study introduces a multi-source plastic yield and transport model, which integrates catchment economic activities, climate data, and hydrological processes. Model parameters were calibrated using a combination of field observations, existing literature, and statistical random sampling techniques. The model demonstrated robust performance in simulating both plastic yield and transport from 2010 to 2020 in the upper and middle Mulan River Catchment, located in southeast China. The annual average yield coefficients were found to closely align with existing estimations, and the riverine outflow exhibited a high correlation coefficient of 0.97, with biases ranging from -63.0 % to -21.4 % across all monitoring stations. The analysis reveals that, on average, 12.5 ± 2.5 % of the total plastic yield is transported to rivers annually, with solid waste identified as the primary source, accounting for 37.8 ± 20.7 % of the total load to rivers, followed by agricultural film (26.4 ± 9.8 %), impermeable surfaces (21.5 ± 10.3 %), urban and rural sewage (10.4 ± 5.0 % and 3.0 ± 1.5 %, respectively), and industrial wastewater (0.9 ± 0.7 %). The annual average outflow was estimated to between 9.3 and 43.0 ton/year (median: 23.1) at a 95 % confidence level. This study not only provides insights into the primary sources and transport pathways of plastic pollution at the catchment scale, but also offers a valuable tool for informing effective plastic pollution mitigation strategies.

Highly Reversible Tin Film Anode Guided via Interfacial Coordination Effect for High Energy Aqueous Acidic Batteries.

Sn metal is a preferable choice as anode material for aqueous acidic batteries due to its acid-tolerance, non-toxicity, and ease of recycling. However, the large size and irregular deposition morphology of polyhedral Sn particles are bad for constructing stable and high-capacity Sn metal anode because of severe hydrogen evolution and metal shedding. To tackle this critical issue, 4-tert-octylphenol pentaethoxylate (POPE) is used as an electrolyte additive to generate a thin-film Sn anode with reversible stripping/plating behavior. POPE can not only induce homogeneous surface chemistry by adsorbing on the Sn surface via coordination bonds but also inhibit hydrogen evolution by modulating the solvation shell of Sn2+. The Sn film anode delivers improved electrochemical stability over 480 h with satisfactory rate performance and low polarization. Moreover, the as-assembled PbO2//Sn battery can also provide outstanding durability at 10 mAh cm-2. This work offers new inspiration for developing a reversible Sn metal film anode.

A novel NTRK1 splice site variant causing congenital insensitivity to pain with anhidrosis in a Chinese family.

Background: Congenital insensitivity to pain with anhidrosis (CIPA, OMIM #256800), also known as hereditary sensory and autonomic neuropathy type Ⅳ (HSAN-IV), is a rare autosomal recessive disorder characterized by recurrent episodic fevers, anhidrosis, insensitivity to noxious stimuli, self-mutilating behavior and intellectual disability. CIPA can be caused by the variants in NTRK1 gene, which encodes a high-affinity tyrosine kinase receptor for nerve growth factor. To ascertain the hereditary cause of a patient with CIPA accompanied by the additional symptoms of mild growth retardation, prone to fracture, underdeveloped nails of fingers and toes, irregular tooth alignment, enamel hypoplasia, postoperative wound healing difficulty, hand and limb deformity, and dislocation of hip joint, whole exome sequencing was used and revealed a compound heterozygous variant in NTRK1. Methods: DNA was extracted from peripheral blood samples of pediatric patients and their parents, and subjected to comprehensive analysis using whole-exome sequencing (WES), followed by verification of variant sites in the NTRK1 gene through Sanger sequencing. To elucidate the functional impact of the newly discovered variants, an in vitro experimental system was established. Splicing analysis was conducted using PCR and Sanger sequencing, while expression levels were assessed through qPCR and Western blot techniques. Results: One hotspot variant c.851-33T>A(ClinVar ID: 21308) and a novel variant c.850 + 5G>A(ClinVar ID:3069176) was inherited from her father and mother, respectively, identified in the affected individuals. The c.850 + 5G>A variant in NTRK1 resulted in two forms of aberrant mRNA splicing: 13bp deletion (c.838_850del13, p. Val280Ser fs180) and 25bp deletion (826_850del25, p. Val276Ser fs180) in exon 7, both leading to a translational termination at a premature stop codon and forming a C-terminal truncated protein. The expression of two abnormal splicing isoforms was decreased both in the level of mRNA and protein. Conclusion: In conclusion, this study elucidated the genetic cause of a patient with CIPA and identified a novel variant c.850 + 5G>A in NTRK1, which broadened the and enriched the NTRK1 mutation spectrum.

Four-Leaf Clover Shape Agglomerate Keratoacanthomas: A Case Report.

Keratoacanthoma (KA) is a papule, plaque, or nodule in an exposed area, with a crater-like horn plug in the center. Multiple KAs are rare disorders, especially when the lesions are agglomerated together. Herein, we report a case of 65-year-old man who presented with four red nodules of different sizes on the right side of the chest. The lesions were clustered, with central keratotic cores, similar in appearance to a four-leaf clover. The nodules were completely removed by excisional surgery and the diagnosis of Agglomerate KAs was made based on clinical and pathological results. A 6-year follow-up found no recurrence.