Fertilizer management for global ammonia emission reduction.

Crop production is a large source of atmospheric ammonia (NH3), which poses risks to air quality, human health and ecosystems1-5. However, estimating global NH3 emissions from croplands is subject to uncertainties because of data limitations, thereby limiting the accurate identification of mitigation options and efficacy4,5. Here we develop a machine learning model for generating crop-specific and spatially explicit NH3 emission factors globally (5-arcmin resolution) based on a compiled dataset of field observations. We show that global NH3 emissions from rice, wheat and maize fields in 2018 were 4.3 ± 1.0 Tg N yr-1, lower than previous estimates that did not fully consider fertilizer management practices6-9. Furthermore, spatially optimizing fertilizer management, as guided by the machine learning model, has the potential to reduce the NH3 emissions by about 38% (1.6 ± 0.4 Tg N yr-1) without altering total fertilizer nitrogen inputs. Specifically, we estimate potential NH3 emissions reductions of 47% (44-56%) for rice, 27% (24-28%) for maize and 26% (20-28%) for wheat cultivation, respectively. Under future climate change scenarios, we estimate that NH3 emissions could increase by 4.0 ± 2.7% under SSP1-2.6 and 5.5 ± 5.7% under SSP5-8.5 by 2030-2060. However, targeted fertilizer management has the potential to mitigate these increases.

Applications of protein ubiquitylation and deubiquitylation in drug discovery.

The ubiquitin (Ub)-proteasome system (UPS) is the major machinery mediating specific protein turnover in eukaryotic cells. By ubiquitylating unwanted, damaged, or harmful proteins and driving their degradation, UPS is involved in many important cellular processes. Several new UPS-based technologies, including molecular glue degraders and PROTACs (proteolysis-targeting chimeras) to promote protein degradation, and DUBTACs (deubiquitinase-targeting chimeras) to increase protein stability, have been developed. By specifically inducing the interactions between different Ub ligases and targeted proteins that are not otherwise related, molecular glue degraders and PROTACs degrade targeted proteins via the UPS; in contrast, by inducing the proximity of targeted proteins to deubiquitinases, DUBTACs are created to clear degradable poly-Ub chains to stabilize targeted proteins. In this review, we summarize the recent research progress in molecular glue degraders, PROTACs, and DUBTACs and their applications. We discuss immunomodulatory drugs, sulfonamides, cyclin-dependent kinase-targeting molecular glue degraders, and new development of PROTACs. We also introduce the principle of DUBTAC and its applications. Finally, we propose a few future directions of these three technologies related to targeted protein homeostasis.

Koumine inhibits RANKL-induced ubiquitination and NF-κB activation to prevent ovariectomy and aging-induced bone loss.

Osteoporosis (OP) is a bone remodeling disease characterized by an imbalance between bone resorption and formation. Osteoclasts are the primary therapeutic targets for treating bone destruction. Koumine (KM), the most bioactive component in Gelsemium alkaloids, exhibits antitumor, immunosuppressive, anti-inflammatory, and analgesic properties. However, the effects of bone loss have not been well studied. This study conducted in vitro and in vivo verification experiments on KM. The results showed that KM inhibited bone resorption and tartrate-resistant acid phosphatase positive (TRAP+) osteoclasts development by mature osteoclasts in a dose-dependent manner. Moreover, KM prevented OVX-induced OP in vivo and potentially inhibited ubiquitination, a process closely related to various biological activities, including protein interaction, transcription, and transmembrane signal transduction regulation, especially within the nuclear factor-κB (NF-κB) pathway. Previous studies have demonstrated that several proteins ubiquitination promotes osteoclastogenesis, our study indicated that KM inhibits early NF-κB activation and receptor activator of NF-κB ligand induced ubiquitination, a critical factor in osteoclast differentiation. In conclusion, our research suggests that KM holds potential as an effective therapeutic agent for OP.

Advances in mass spectrometry imaging for toxicological analysis and safety evaluation of pharmaceuticals.

Safety issues caused by pharmaceuticals have frequently occurred worldwide, posing a tremendous threat to human health. As an essential part of drug development, the toxicological analysis and safety evaluation is of great significance. In addition, the risk of pharmaceuticals accumulation in the environment and the monitoring of the toxicity from natural medicines have also received ongoing concerns. Due to a lack of spatial distribution information provided by common analytical methods, analyses that provide spatial dimensions could serve as complementary safety evaluation methods for better prediction and evaluation of drug toxicity. With advances in technical solutions and software algorithms, mass spectrometry imaging (MSI) has received increasing attention as a popular analytical tool that enables the simultaneous implementation of qualitative, quantitative, and localization without complex sample pretreatment and labeling steps. In recent years, MSI has become more attractive, powerful, and sensitive and has been applied in several scientific fields that can meet the safety assessment requirements. This review aims to cover a detailed summary of the various MSI technologies utilized in the biomedical and pharmaceutical area, including technical principles, advantages, current status, and future trends. Representative applications and developments in the safety-related issues of different pharmaceuticals and natural medicines are also described to provide a reference for pharmaceutical research, improve rational clinical medicine use, and ensure public safety.

Characterizing the antigenic evolution of pandemic influenza A (H1N1) pdm09 from 2009 to 2023.

The H1N1pdm09 virus has been a persistent threat to public health since the 2009 pandemic. Particularly, since the relaxation of COVID-19 pandemic mitigation measures, the influenza virus and SARS-CoV-2 have been concurrently prevalent worldwide. To determine the antigenic evolution pattern of H1N1pdm09 and develop preventive countermeasures, we collected influenza sequence data and immunological data to establish a new antigenic evolution analysis framework. A machine learning model (XGBoost, accuracy = 0.86, area under the receiver operating characteristic curve = 0.89) was constructed using epitopes, physicochemical properties, receptor binding sites, and glycosylation sites as features to predict the antigenic similarity relationships between influenza strains. An antigenic correlation network was constructed, and the Markov clustering algorithm was used to identify antigenic clusters. Subsequently, the antigenic evolution pattern of H1N1pdm09 was analyzed at the global and regional scales across three continents. We found that H1N1pdm09 evolved into around five antigenic clusters between 2009 and 2023 and that their antigenic evolution trajectories were characterized by cocirculation of multiple clusters, low-level persistence of former dominant clusters, and local heterogeneity of cluster circulations. Furthermore, compared with the seasonal H1N1 virus, the potential cluster-transition determining sites of H1N1pdm09 were restricted to epitopes Sa and Sb. This study demonstrated the effectiveness of machine learning methods for characterizing antigenic evolution of viruses, developed a specific model to rapidly identify H1N1pdm09 antigenic variants, and elucidated their evolutionary patterns. Our findings may provide valuable support for the implementation of effective surveillance strategies and targeted prevention efforts to mitigate the impact of H1N1pdm09.

Salmonella spvC gene suppresses macrophage/neutrophil antibacterial defense mediated by gasdermin D.

OBJECTIVE: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a representative model organism for investigating host-pathogen interactions. It was reported that S. Typhimurium spvC gene alleviated intestinal inflammation to aggravate systemic infection, while the precise mechanisms remain unclear. In this study, the influence of spvC on the antibacterial defense of macrophage/neutrophil mediated by gasdermin D (GSDMD) was investigated. METHODS: Mouse macrophage-like cell lines J774A.1 and RAW264.7, neutrophil-like cells derived from HL-60 cells (human promyletic leukemia cell lines) were infected with S. Typhimurium wild type, spvC deletion and complemented strains. Cell death was evaluated by LDH release and Annexin V-FITC/PI staining. Macrophage pyroptosis and neutrophil NETosis were detected by western blotting, live cell imaging and ELISA. Flow cytometry was used to assess the impact of spvC on macrophage-neutrophil cooperation in macrophage (dTHP-1)-neutrophil (dHL-60) co-culture model pretreated with GSDMD inhibitor disulfiram. Wild-type and Gsdmd-/- C57BL/6J mice were utilized for in vivo assay. The degree of phagocytes infiltration and inflammation were analyzed by immunofluorescence and transmission electron microscopy. RESULTS: Here we find that spvC inhibits pyroptosis in macrophages via Caspase-1/Caspase-11 dependent canonical and non-canonical pathways, and restrains neutrophil extracellular traps extrusion in GSDMD-dependent manner. Moreover, spvC could ameliorate macrophages/neutrophils infiltration and cooperation in the inflammatory response mediated by GSDMD to combat Salmonella infection. CONCLUSIONS: Our findings highlight the antibacterial activity of GSDMD in phagocytes and reveal a novel pathogenic mechanism employed by spvC to counteract this host defense, which may shed new light on designing effective therapeutics to control S. Typhimurium infection.

Tackling Challenges in Assessing the Economic Value of Tumor-Agnostic Therapies: A Cost-Effectiveness Analysis of Pembrolizumab as a Case Study.

OBJECTIVES: Assessing the value of tumor-agnostic drugs (TAD) is challenging given the potential variability in treatment effects, trials with small sample sizes, different standards of care (SoC), and lack of comparative data from single-arm basket trials. Our study developed and applied novel methods to assess the value of pembrolizumab compared with SoC to inform coverage decisions. METHODS: We developed a partitioned survival model to evaluate the cost-utility of pembrolizumab for previously treated patients with 8 advanced or metastatic microsatellite instability-high or mismatch repair-deficient cancers from a US commercial payer perspective. Efficacy of pembrolizumab was based on data from trials directly or with adjustment using Bayesian hierarchical models. Eight chemotherapy-based external control arms were constructed from the TriNetX electronic health record databases. Tumor-specific health-state utility values were applied. All costs were adjusted to 2022 US dollars. RESULTS: At a lifetime horizon, pembrolizumab was associated with increased effectiveness compared with chemotherapies in colorectal (quality-adjusted life years [QALYs]: +0.64, life years [LYs]: +0.64), endometrial (QALYs: +3.79, LYs: +5.47), and small intestine cancers (QALYs: +1.73, LYs: +2.48), but not for patients with metastatic gastric, cholangiocarcinoma, pancreatic, ovarian, and brain cancers. Incremental cost-effectiveness ratios varied substantially across tumor types. Pembrolizumab was found to be cost-effective in treating colorectal and endometrial cancers (incremental cost-effectiveness ratios: $121 967 and $139 257, respectively), and not cost-effective for other assessed cancers at a $150 000 willingness-to-pay/QALY threshold, compared with SoC chemotherapies. CONCLUSIONS: The cost-effectiveness of TADs can vary by cancers. Using analytic tools such as external controls and Bayesian hierarchical models can tackle several challenges in assessing the value of TADs and uncertainties from basket trials.

Rapid analysis of bioactive compounds from citrus samples by direct analysis in real-time mass spectrometry combined with chemometrics.

Renowned for their nutritional benefits, citrus fruits are harvested at various stages in China for functional food production. This study introduces an innovative analytical method, DART-MS, enabling direct qualitative analysis of citrus samples without the need for preprocessing. Simultaneously, the combination of chemometrics can be applied to distinguish between three different citrus samples: Citri Reticulatae Pericarpium, Citri Reticulatae Pericarpium Viride, and Citri Reticulatae "Chachi". Notably, given the international regulatory concerns surrounding synephrine, a precise quantitative analysis method for synephrine was developed. The limit of detection (LOD) and the limit of quantification (LOQ) were 39 ng mL-1 and 156 ng mL-1, respectively. The recovery rates obtained varied from 98.46% to 100.71%. Furthermore, the intra-day and inter-day precision demonstrated robust consistency, with values spanning 5.0-6.1% and 5.03-6.08%, respectively, offering quicker results compared to those from HPLC-MS, promising a safer assessment of herbal and food products.

Genome-wide identification of XTH gene family in Musa acuminata and response analyses of MaXTHs and xyloglucan to low temperature.

Banana (Musa spp.) production is seriously threatened by low temperature (LT) in tropical and subtropical regions. Xyloglucan endotransglycosylase/hydrolases (XTHs) are considered chief enzymes in cell wall remodelling and play a central role in stress responses. However, whether MaXTHs are involved in the low temperature stress tolerance in banana is not clear. Here, the identification and characterization of MaXTHs were carried out, followed by prediction of their cis-acting elements and protein-protein interactions. In addition, candidate MaXTHs involved in banana tolerance to LT were screened through a comparison of their responses to LT between tolerant and sensitive cultivars using RNA-Seq analysis. Moreover, immunofluorescence (IF) labelling was employed to compare changes in the temporal and spatial distribution of different types of xyloglucan components between these two cultivars upon stress. In total, 53 MaXTHs have been identified, and all were predicted to be located in the cell wall, 14 of them also in the cytoplasm. Only 11 MaXTHs have been found to interact with other proteins. Among 16 MaXTHs with LT responsiveness elements, MaXTH26/29/32/35/50 (Group I/II members) and MaXTH7/8 (Group IIIB members) might be involved in banana tolerance to LT stress. IF results suggested that the content of xyloglucan components recognized by CCRC-M87/103/104/106 antibodies might be negatively related to banana chilling tolerance. In conclusion, we have identified the MaXTH gene family and assessed cell wall re-modelling under LT stress. These results will be beneficial for banana breeding against stresses and enrich the cell wall-mediated resistance mechanism in plants to stresses.

Convolutional Neural Networks Facilitate Process Understanding of Megacity Ozone Temporal Variability.

Ozone pollution is profoundly modulated by meteorological features such as temperature, air pressure, wind, and humidity. While many studies have developed empirical models to elucidate the effects of meteorology on ozone variability, they predominantly focus on local weather conditions, overlooking the influences from high-altitude and broader regional meteorological patterns. Here, we employ convolutional neural networks (CNNs), a technique typically applied to image recognition, to investigate the influence of three-dimensional spatial variations in meteorological fields on the daily, seasonal, and interannual dynamics of ozone in Shenzhen, a major coastal urban center in China. Our optimized CNNs model, covering a 13° × 13° spatial domain, effectively explains over 70% of daily ozone variability, outperforming alternative empirical approaches by 7 to 62%. Model interpretations reveal the crucial roles of 2-m temperature and humidity as primary drivers, contributing 16% and 15% to daily ozone fluctuations, respectively. Regional wind fields account for up to 40% of ozone changes during the episodes. CNNs successfully replicate observed ozone temporal patterns, attributing -5-6 µg·m-3 of interannual ozone variability to weather anomalies. Our interpretable CNNs framework enables quantitative attribution of historical ozone fluctuations to nonlinear meteorological effects across spatiotemporal scales, offering vital process-based insights for managing megacity air quality amidst changing climate regimes.

IRF1 suppresses colon cancer proliferation by reducing SPI1-mediated transcriptional activation of GPX4 and promoting ferroptosis.

IRF1 is a tumor suppressor gene in colon cancer. This study aimed to explore the potential regulation of IRF1 on the ferroptosis of colon cancer and the mechanisms underlying its regulation of GPX4 transcription. IRF1 interacting transcription factors regulating GPX4 transcription were predicted and validated. The role of the IRF1/SPI1-GPX4 axis on the ferroptosis of colon cancer cells was explored. Results showed that IRF1 overexpression reduced GPX4 transcription, increased reactive oxygen species (ROS) and lipid ROS accumulation, and enhanced erastin-induced colon cancer cell growth in vitro and in vivo. SPI1 could directly bind to the GPX4 promoter (-414 to -409) and activate its transcription. IRF1 could bind to SPI1 and suppress its transcriptional activating effects on GPX4 expression. SPI1 overexpression reduced ROS and lipid ROS accumulation and increased colon cancer cell viability and colony formation upon erastin induction. These trends were reversed by IRF1 overexpression. In conclusion, this study revealed a novel oncogenic mechanism of SPI1 by reducing erastin-induced ferroptosis in colon cancer. IRF1 interacts with SPI1 and suppresses its transcriptional activating effect on GPX4 expression. Through this mechanism, IRF1 can enhance erastin-induced ferroptosis of colon cancer. The IRF1/SPI1-GPX4 axis might play a crucial role in modulating ferroptosis in colon cancer and might serve as a potential therapeutic target in the future.

Synthesis of X@DRHC (X=Co, Ni, Mn) catalyst from comprehensive utilization of waste rice husk and spent lithium-ion batteries for efficient peroxymonosulfate (PMS) activation.

Highly efficient resource recycling and comprehensive utilization play a crucial role in achieving the goal of reducing resource wasting, environmental protection, and achieving goal of sustainable development. In this work, the two kinds waste resources of agricultural rice husk and metal ions (Co, Ni, and Mn) from spent lithium-ion batteries have been skillfully utilized to synthesize novel Fenton-like catalysts. Desiliconized rice husk carbon (DRHC) with rich pore structure and large specific surface area from rice husk has been prepared and used as scalable carrier, and dandelion-like nanoparticles cluster could be grown in situ on the surface of the carrier by using metal ions contained waste water. The designed catalysts (X@DRHC) as well as their preparation process were characterized in detail by SEM, TEM, BET, XRD and XPS, respectively. Meanwhile, their catalytic abilities were also studied by activating potassium peroxomonosulfate (PMS) to remove methylene blue (MB). The results indicate X@DRHC displays excellent degradation efficiency on MB with wide pH range and stable reusability, which is suitable for the degradation of various dyes. This work has realized the recycling and high-value utilization of waste resources from biomass and spent lithium-ion batteries, which not only creates an efficient way to dispose waste resources, but also shows high economic benefits in large-scale water treatment.

Loss of fragile WWOX gene leads to senescence escape and genome instability.

Induction of DNA damage response (DDR) to ensure accurate duplication of genetic information is crucial for maintaining genome integrity during DNA replication. Cellular senescence is a DDR mechanism that prevents the proliferation of cells with damaged DNA to avoid mitotic anomalies and inheritance of the damage over cell generations. Human WWOX gene resides within a common fragile site FRA16D that is preferentially prone to form breaks on metaphase chromosome upon replication stress. We report here that primary Wwox knockout (Wwox-/-) mouse embryonic fibroblasts (MEFs) and WWOX-knockdown human dermal fibroblasts failed to undergo replication-induced cellular senescence after multiple passages in vitro. Strikingly, by greater than 20 passages, accelerated cell cycle progression and increased apoptosis occurred in these late-passage Wwox-/- MEFs. These cells exhibited γH2AX upregulation and microsatellite instability, indicating massive accumulation of nuclear DNA lesions. Ultraviolet radiation-induced premature senescence was also blocked by WWOX knockdown in human HEK293T cells. Mechanistically, overproduction of cytosolic reactive oxygen species caused p16Ink4a promoter hypermethylation, aberrant p53/p21Cip1/Waf1 signaling axis and accelerated p27Kip1 protein degradation, thereby leading to the failure of senescence induction in Wwox-deficient cells after serial passage in culture. We determined that significantly reduced protein stability or loss-of-function A135P/V213G mutations in the DNA-binding domain of p53 caused defective induction of p21Cip1/Waf1 in late-passage Wwox-/- MEFs. Treatment of N-acetyl-L-cysteine prevented downregulation of cyclin-dependent kinase inhibitors and induced senescence in Wwox-/- MEFs. Our findings support an important role for fragile WWOX gene in inducing cellular senescence for maintaining genome integrity during DDR through alleviating oxidative stress.

Compliance analysis of oral nutritional supplements in hospitalized postsurgical patients with colorectal cancer: A prospective study.

PURPOSE: There are few reports on compliance with oral nutritional supplements (ONS) after surgery in hospitalized patients. This study aimed to investigate the compliance with ONS and its influencing factors after surgery in colorectal cancer patients. METHODS: STROBE checklist was used during the preparation of this paper. A total of 103 postoperative colorectal cancer patients were selected from November 2020 to April 2021 from the Department of Anorectal Surgery in our institution, which is a tertiary hospital in Hangzhou, China. The compliance with ONS was recorded by a self-record sheet, and sociodemographic and disease-related information of these patients was gathered through a self-designed questionnaire. RESULTS: The overall ONS compliance rate of patients with colorectal cancer was 57.6%. Results of univariate analysis revealed that ONS compliance rate was related to sex, admission body mass index, abdominal distension, attitude towards ONS, and satisfaction with ONS. Multi-factor analysis showed that age, sex, and perceived benefits of nutrition therapy independently influenced the ONS compliance rate. CONCLUSIONS: The postoperative ONS compliance rate of colorectal cancer patients needs to be further improved. Healthcare professionals should pay more attention to the postoperative ONS compliance and acknowledging the influence of age, gender, and attitudes towards ONS on ONS compliance. Notably, patients' perspectives towards ONS play a crucial and modifiable role in determining ONS compliance. Nurses ought to assist patients in cultivating a positive attitude towards ONS. RELEVANCE TO CLINICAL PRACTICE: Dosage form and delivery method are also influence factors that deserves further exploration in the future. Future research endeavours should endeavour to craft tailored, meticulous nutritional intervention strategies tailored to the diverse factors that influence ONS compliance, ultimately leading to enhanced ONS adherence. Our findings could serve as valuable evidence for the development of strategies aimed at enhancing ONS usage practices.

Multimorbidity measures associated with cognitive function among community-dwelling older Chinese adults.

INTRODUCTION: Older adults with multimorbidity are at high risk of cognitive impairment development. There is a lack of research on the associations between different multimorbidity measures and cognitive function among older Chinese adults living in the community. METHODS: We used the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 and included data on dementia-free participants aged ≥65 years. Multimorbidity measures included condition counts, multimorbidity patterns, and trajectories. The association of multimorbidity measures with cognitive function was examined by generalized estimating equation and linear and logistic regression models. RESULTS: Among 14,093 participants at baseline, 43.2% had multimorbidity. Multimorbidity patterns were grouped into cancer-inflammatory, cardiometabolic, and sensory patterns. Multimorbidity trajectories were classified as "onset-condition," "newly developing," and "severe condition." The Mini-Mental State Examination scores were significantly lower for participants with more chronic conditions, with cancer-inflammatory/cardiometabolic/sensory patterns, and with developing multimorbidity trajectories. DISCUSSION: Condition counts, sensory pattern, cardiometabolic pattern, cancer-inflammatory pattern, and multimorbidity developmental trajectories were prospectively associated with cognitive function. HIGHLIGHTS: Elderly individuals with a higher number of chronic conditions were associated with lower MMSE scores in the Chinese Longitudinal Healthy Longevity Survey data. MMSE scores were significantly lower for participants with specific multimorbidity patterns. Individuals with developing trajectories of multimorbidity were associated with lower MMSE scores and a higher risk of mild cognitive impairment.

Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

Examining the knowledge level of nurses regarding aseptic non touch technique in nurses: a cross-sectional study.

BACKGROUND: Healthcare-associated infections (HAIs) are important indicators of healthcare quality. The aseptic non touch technique (ANTT), a standardised aseptic technique, is a crucial preventative measure against HAIs. However, there is insufficient evidence currently available regarding ANTT awareness and proficiency among nurses. This study aimed to investigate the status of ANTT proficiency in a cohort of nurses and analyse the associated risk factors, with the ultimate goal of providing a reference for promoting the application of ANTT in clinical practice. METHODS: The study population was sampled from nurses working in a tertiary hospital in Zhejiang Province, China, in January 2024. A cross-sectional survey was conducted using a self-designed questionnaire to assess ANTT knowledge. Multivariate linear regression analysis was used to analyse the risk factors influencing ANTT knowledge in nurses. RESULTS: A total of 458 nurses were included in this study. The cohort had an overall score of 49.7% correct responses on the ANTT knowledge questionnaire, with a mean score of 12.4 ± 2.4 out of 25, and 30.1% of the nurses felt that they did not need training related to ANTT. Multivariate linear regression analysis indicated that professional title, educational level, and the need for ANTT training were independently associated with ANTT knowledge in nurses. Nurses with Master's degrees and associated chief nurses were observed to have higher levels of ANTT knowledge compared to the rest. CONCLUSIONS: ANTT knowledge is insufficient among nurses in China, and its importance is not widely recognised. Continuous efforts are required to strengthen this knowledge. Constructing sustained, multiform, and stratified training programmes may represent an effective method to strengthen ANTT knowledge among nurses and promote its clinical use.

Ocular characteristics and outcomes of phacoemulsification in patients with cataract after renal transplantation.

PURPOSE: To explore ocular characteristics of patients with cataracts after renal transplantation and analyze the results of phacoemulsification combined with intraocular lens (IOL) implantation. METHODS: Patients with cataracts after renal transplantation and control patients who underwent phacoemulsification combined with IOL implantation were enrolled. All patients underwent phacoemulsification combined with IOL implantation. Visual acuity, intraocular pressure, type of lens opacity, corneal endothelial cell density, and ocular biological parameters were evaluated before surgery. Visual prognosis, dry eye, and postoperative complications were monitored for 6 months after phacoemulsification. RESULTS: We analyzed 25 eyes of 16 patients after renal transplantation and 30 eyes of 21 control patients. The most common type of cataract of renal transplantation group was posterior subcapsular, while the most common type of cataract of control group was cortical. Significant differences in corneal astigmatism, white-to-white ratio, and keratometry values were observed between the groups. The postoperative visual acuity of both groups significantly improved following surgery. Postoperative complications, such as the degree of anterior and posterior capsule opacification and the incidence of a requirement of neodymium-doped yttrium aluminum garnet laser capsulotomy, were significantly lower in the renal transplantation group. Moreover, secondary glaucoma occurred in two eyes in the renal transplantation group. CONCLUSION: This study showed that cataracts after renal transplantation were mostly posterior subcapsular. Postoperative visual acuity recovered well in most patients, with reduced incidence of postoperative complications. This study suggested that phacoemulsification combined with IOL implantation was safe and effective, providing a reference for multi-focal IOL implantation in kidney transplant recipients.

Survival After Sentinel Lymph Node Biopsy Compared with Axillary Lymph Node Dissection for Female Patients with T3-4c Breast Cancer.

BACKGROUND: For patients with cN0 and T1-2 breast cancer, sentinel lymph node biopsy (SLNB) can provide survival results equivalent to axillary lymph node dissection (ALND). However, whether it can be performed on T3-4c patients is still controversial. MATERIALS AND METHODS: Female patients diagnosed with cN0, T3-4c, and M0 breast cancer from 2004 to 2019 were identified using the surveillance, epidemiology and end results (SEER) database and divided into 2 groups, the SLNB group (1-5 regional lymph nodes examined) and the ALND group (≥10 regional lymph nodes examined). Finally, only those with pN0 disease were included in the SLNB group. The baseline differences in clinicopathological characteristics between groups were eliminated by propensity score matching (PSM). We also conducted subgroup analyses according to age, overall TNM stage, breast cancer subtypes, surgical approaches, radiation therapy, and chemotherapy. The primary endpoint was survival. RESULTS: With a mean follow-up of 75 months, a total of 186 deaths were reported among 864 patients. The overall survival (OS) and breast cancer-specific survival (BCSS) in the SLNB group were 78.2% and 87.5%, respectively, and that in the ALND group were 78.7% and 87.3%, respectively. The unadjusted hazard ratio (HR) for OS and BCSS in the SLNB group (vs. the ALND group) was 0.922 (95% CI, 0.691-1.230, P = .580) and 0.874 (95% CI, 0.600-1.273, P = .481), respectively. Besides, the OS and BCSS between the 2 groups were also similar in all subgroup analyses. CONCLUSIONS: SLNB may be performed on female patients with cN0, T3-4c, and M0 breast cancer.

Aerobic exercises regulate the epididymal anion homeostasis of high-fat diet-induced obese rats through TRPA1-mediated Cl- and HCO3- secretion†.

Aerobic exercises could improve the sperm motility of obese individuals. However, the underlying mechanism has not been fully elucidated, especially the possible involvement of the epididymis in which sperm acquire their fertilizing capacity. This study aims to investigate the benefit effect of aerobic exercises on the epididymal luminal milieu of obese rats. Sprague-Dawley male rats were fed on a normal or high-fat diet (HFD) for 10 weeks and then subjected to aerobic exercises for 12 weeks. We verified that TRPA1 was located in the epididymal epithelium. Notably, aerobic exercises reversed the downregulated TRPA1 in the epididymis of HFD-induced obese rats, thus improving sperm fertilizing capacity and Cl- concentration in epididymal milieu. Ussing chamber experiments showed that cinnamaldehyd (CIN), agonist of TRPA1, stimulated an increase of the short-circuit current (ISC) in rat cauda epididymal epithelium, which was subsequently abolished by removing the ambient Cl- and HCO3-. In vivo data revealed that aerobic exercises increased the CIN-stimulated Cl- secretion rate of epididymal epithelium in obese rats. Pharmacological experiments revealed that blocking cystic fibrosis transmembrane regulator (CFTR) and Ca2+-activated Cl- channel (CaCC) suppressed the CIN-stimulated anion secretion. Moreover, CIN application in rat cauda epididymal epithelial cells elevated intracellular Ca2+ level, and thus activate CACC. Interfering with the PGHS2-PGE2-EP2/EP4-cAMP pathway suppressed CFTR-mediated anion secretion. This study demonstrates that TRPA1 activation can stimulate anion secretion via CFTR and CaCC, which potentially forming an appropriate microenvironment essential for sperm maturation, and aerobic exercises can reverse the downregulation of TRPA1 in the epididymal epithelium of obese rats.