Antimicrobial resistance and population genomics of emerging multidrug-resistant Salmonella 4,[5],12:i:- in Guangdong, China.

Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.

Pleomorphic rhabdomyosarcoma of the vagina: A case report.

BACKGROUND: Rhabdomyosarcoma (RMS) of the vagina in postmenopausal women is an extremely rare malignant tumor that was originally described as a unique group of soft tissue sarcomas originating from primitive mesenchymal cells. It was first reported in postmenopausal women in 1970, and fewer than 50 postmenopausal patients have been reported to date. CASE SUMMARY: A 68-year-old multiparous female was admitted to the hospital on October 11, 2023, with the chief complaint of a mass causing vaginal prolapse with incomplete urination that had persisted for 4 months. The vaginal mass was approximately the size of a pigeon egg; after lying down, the vaginal mass retracted. Complete resection was performed, and vaginal pleomorphic RMS was diagnosed based on pathology and immunohistochemical staining features. The patient is currently undergoing chemotherapy. The present study also reviewed the clinical, histological, and immunohistochemical features and latest treatment recommendations for vaginal RMS. Any abnormal vaginal mass should be promptly investigated through pelvic examination and appropriate imaging. The current initial treatment for vaginal RMS is biopsy and primary chemotherapy. CONCLUSION: When surgery is planned for vaginal RMS, an organ-preserving approach should be considered.

Associations between Physical Activity and the Incidence of Cerebrovascular Disease or All-Cause Mortality among 146,742 Older Adults: A 13-Year Prospective Cohort Study.

OBJECTIVES: Although studies have indicated that physical activity (PA) is related to cardiovascular disease, the specific association between PA and incident cerebrovascular disease (CBVD) remains uncertain. The current study aimed to investigate the associations between PA levels and the CBVD incidence or all-cause mortality. DESIGN: Prospective cohort study. SETTINGS AND PARTICIPANTS: Older participants (aged >60 years) from the UK Biobank. METHODS: The baseline PA was classified as total, light, moderate, and vigorous PA based on the metabolic equivalent-minutes per week (MET-min/wk) and considered as exposures, whereas CBVD incidence and all-cause mortality were considered as the outcomes. Cox proportional hazards were used to calculate the hazard ratios (HRs) and 95% CIs for the influence of the association between PA and CBVD incidence and all-cause mortality. RESULTS: A total of 146,742 participants aged 60 years and older were included. During a median follow-up period of 13.5 years (interquartile range of 12.8-14.2), 9338 older individuals developed CBVD and 3033 death were recorded (including 767 CBVD-related deaths). High volumes of PA were consistently associated with lower risks of CBVD and all-cause mortality. The lowest risk of CBVD incidence was observed at 2001-2500 MET-min/wk of total PA (HR 0.61, 95% CI 0.53-0.70), and the lowest risk of all-cause mortality was observed at 2501-5000 MET-min/wk (HR 0.52, 95% CI 0.43-0.63) in older adults. Total PA at 2001-2500 MET-min/wk significantly reduced the CBVD incidence in older women (HR 0.57, 95% CI 0.46-0.71), which was more pronounced than that in older men (HR for 2001-2500 MET-min/wk: 0.64, 95% CI 0.50-0.77). CONCLUSIONS AND IMPLICATIONS: Total PA at 2001-2500 MET-min/wk significantly reduced the risk of incident CBVD and all-cause mortality in adults aged >60 years, although the extents of risk reduction vary in men and women.

Deep Canonical Correlation Fusion Algorithm Based on Denoising Autoencoder for ASD Diagnosis and Pathogenic Brain Region Identification.

Autism Spectrum Disorder (ASD) is defined as a neurodevelopmental condition distinguished by unconventional neural activities. Early intervention is key to managing the progress of ASD, and current research primarily focuses on the use of structural magnetic resonance imaging (sMRI) or resting-state functional magnetic resonance imaging (rs-fMRI) for diagnosis. Moreover, the use of autoencoders for disease classification has not been sufficiently explored. In this study, we introduce a new framework based on autoencoder, the Deep Canonical Correlation Fusion algorithm based on Denoising Autoencoder (DCCF-DAE), which proves to be effective in handling high-dimensional data. This framework involves efficient feature extraction from different types of data with an advanced autoencoder, followed by the fusion of these features through the DCCF model. Then we utilize the fused features for disease classification. DCCF integrates functional and structural data to help accurately diagnose ASD and identify critical Regions of Interest (ROIs) in disease mechanisms. We compare the proposed framework with other methods by the Autism Brain Imaging Data Exchange (ABIDE) database and the results demonstrate its outstanding performance in ASD diagnosis. The superiority of DCCF-DAE highlights its potential as a crucial tool for early ASD diagnosis and monitoring.

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, China in 2019.

Objective: This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A (RVA) in the Pearl River Delta region of Guangdong Province, China. Methods: This study included individuals aged 28 days-85 years. A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens, including RVA, using a Gastrointestinal Pathogen Panel, followed by genotyping, virus isolation, and complete sequencing to assess the genetic diversity of RVA. Results: The overall RVA infection rate was 14.59% (103/706), with an irregular epidemiological pattern. The proportion of co-infection with RVA and other pathogens was 39.81% (41/103). Acute gastroenteritis is highly prevalent in young children aged 0-1 year, and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea. G9P[8] (58.25%, 60/103) was found to be the predominant genotype in the RVA strains, and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis. Recombination analysis showed that gene reassortment events, selection pressure, codon usage bias, gene polymorphism, and post-translational modifications (PTMs) occurred in the G9P[8] and G3P[8] strains. Conclusion: This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China, further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity. Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Multi-kernel Learning Fusion Algorithm Based on RNN and GRU for ASD Diagnosis and Pathogenic Brain Region Extraction.

Autism spectrum disorder (ASD) is a complex, severe disorder related to brain development. It impairs patient language communication and social behaviors. In recent years, ASD researches have focused on a single-modal neuroimaging data, neglecting the complementarity between multi-modal data. This omission may lead to poor classification. Therefore, it is important to study multi-modal data of ASD for revealing its pathogenesis. Furthermore, recurrent neural network (RNN) and gated recurrent unit (GRU) are effective for sequence data processing. In this paper, we introduce a novel framework for a Multi-Kernel Learning Fusion algorithm based on RNN and GRU (MKLF-RAG). The framework utilizes RNN and GRU to provide feature selection for data of different modalities. Then these features are fused by MKLF algorithm to detect the pathological mechanisms of ASD and extract the most relevant the Regions of Interest (ROIs) for the disease. The MKLF-RAG proposed in this paper has been tested in a variety of experiments with the Autism Brain Imaging Data Exchange (ABIDE) database. Experimental findings indicate that our framework notably enhances the classification accuracy for ASD. Compared with other methods, MKLF-RAG demonstrates superior efficacy across multiple evaluation metrics and could provide valuable insights into the early diagnosis of ASD.

Crosstalk between autophagy and ferroptosis mediate injury in ischemic stroke by generating reactive oxygen species.

Stroke represents a significant threat to global human health, characterized by high rates of morbidity, disability, and mortality. Predominantly, strokes are ischemic in nature. Ischemic stroke (IS) is influenced by various cell death pathways, notably autophagy and ferroptosis. Recent studies have increasingly highlighted the interplay between autophagy and ferroptosis, a process likely driven by the accumulation of reactive oxygen species (ROS). Post-IS, either the inhibition of autophagy or its excessive activation can escalate ROS levels. Concurrently, the interaction between ROS and lipids during ferroptosis further augments ROS accumulation. Elevated ROS levels can provoke endoplasmic reticulum stress-induced autophagy and, in conjunction with free iron (Fe2+), can trigger ferroptosis. Moreover, ROS contribute to protein and lipid oxidation, endothelial dysfunction, and an inflammatory response, all of which mediate secondary brain injury following IS. This review succinctly explores the mechanisms of ROS-mediated crosstalk between autophagy and ferroptosis and the detrimental impact of increased ROS on IS. It also offers novel perspectives for IS treatment strategies.

Serum brain-derived neurotrophic factor levels in type 2 diabetes mellitus patients and its association with cognitive impairment: A meta-analysis.

OBJECTIVE: To compare the serum levels of brain-derived neurotrophic factor (BDNF) in type 2 diabetes mellitus (T2DM) patients with healthy controls (HC) and evaluate the BDNF levels in T2DM patients with/without cognitive impairment. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for the published English literature on BDNF in T2DM patients from inception to December 2022. The BDNF data in the T2DM and HC groups were extracted, and the study quality was evaluated using the Agency for Healthcare Research and Quality. A meta-analysis of the pooled data was conducted using Review Manager 5.3 and Stata 12.0 software. RESULTS: A total of 18 English articles fulfilled with inclusion criteria. The standard mean difference of the serum BDNF level was significantly lower in T2DM than that in the HC group (SMD: -2.04, z = 11.19, P <0.001). Besides, T2DM cognitive impairment group had a slightly lower serum BDNF level compared to the non-cognitive impairment group (SMD: -2.59, z = 1.87, P = 0.06). CONCLUSION: BDNF might be involved in the neuropathophysiology of cerebral damage in T2DM, especially cognitive impairment in T2DM.

CE-GAN: Community Evolutionary Generative Adversarial Network for Alzheimer's Disease Risk Prediction.

In the studies of neurodegenerative diseases such as Alzheimer's Disease (AD), researchers often focus on the associations among multi-omics pathogeny based on imaging genetics data. However, current studies overlook the communities in brain networks, leading to inaccurate models of disease development. This paper explores the developmental patterns of AD from the perspective of community evolution. We first establish a mathematical model to describe functional degeneration in the brain as the community evolution driven by entropy information propagation. Next, we propose an interpretable Community Evolutionary Generative Adversarial Network (CE-GAN) to predict disease risk. In the generator of CE-GAN, community evolutionary convolutions are designed to capture the evolutionary patterns of AD. The experiments are conducted using functional magnetic resonance imaging (fMRI) data and single nucleotide polymorphism (SNP) data. CE-GAN achieves 91.67% accuracy and 91.83% area under curve (AUC) in AD risk prediction tasks, surpassing advanced methods on the same dataset. In addition, we validated the effectiveness of CE-GAN for pathogeny extraction. The source code of this work is available at https://github.com/fmri123456/CE-GAN.

SERPINB5 promotes colorectal cancer invasion and migration by promoting EMT and angiogenesis via the TNF-α/NF-κB pathway.

This study aimed to investigate the role of SERPINB5 in colorectal cancer (CRC). We established knockdown and overexpression models of SERPINB5 in CRC cells and conducted bioinformatics analysis to assess the clinicopathological significance of SERPINB5 expression in CRC patients. Human CRC cells were transfected with LV-SERPINB5 and sh-SERPINB5 lentivirus for subsequent functional and mechanistic studies. Results showed that high SERPINB5 expression correlated positively with CEA levels, N stage and lymphatic infiltration, while displaying a negative correlation with progression-free survival. Overexpression of SERPINB5 in CRC cells upregulated the expression of TNF-α, p-NF-κB/p65, N-cadherin, MMP2 and MMP9, accompanied by decreased E-cadherin expression. In addition, SERPINB5 overexpression enhanced the migration, invasion, and proliferation of CRC cells. Furthermore, overexpression of SERPINB5 in CRC cells increased VEGFA expression, and the conditioned medium from SERPINB5-overexpressing CRC cells promoted tube formation of HUVECs. Conversely, overexpression of SERPINB5 in HUVECs decreased VEGFA expression and inhibited tube formation. Notably, these changes in CRC cells were reversed by QNZ, a specific inhibitor of the TNF-α/NF-κB pathway. In summary, our findings revealed that high SERPINB5 expression correlated with poor progression-free survival in CRC patients. Moreover, SERPINB5 could induce EMT and angiogenesis by activating the TNF-α/NF-κB pathway, thereby promoting the invasion and migration of CRC cells.

An Energy-Efficient FD-fNIRS Readout Circuit Employing a Mixer-First Analog Frontend and a Σ-Δ Phase-to-Digital Converter.

This paper presents a low-power frequency-domain functional near-infrared spectroscopy (FD-fNIRS) readout circuit for the absolute value measurement of tissue optical characteristics. The paper proposes a mixer-first analog front-end (AFE) structure and a 1-bit Σ-Δ phase-to-digital converter (PDC) to reduce the required circuit bandwidth and the laser modulation frequency, thereby saving power while maintaining high resolution. The proposed chip achieves sub-0.01° phase resolution and consumes 6.8 mW of power. Nine optical solid phantoms are produced to evaluate the chip. Compared to a self-built high-precision measurement platform that combines a network analyzer with an avalanche photodiode (APD) module, the maximum measuring errors of the absorption coefficient and reduced scattering coefficient are 10.6% and 12.3%, respectively.

Gene-gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy.

Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING_TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders.

Mechanisms of intermittent theta-burst stimulation attenuating nerve injury after ischemic reperfusion in rats through endoplasmic reticulum stress and ferroptosis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) exerts neuroprotective effects early in cerebral ischemia/reperfusion (I/R) injury. Intermittent theta-brust stimulation (iTBS), a more time-efficient modality of rTMS, improves the efficiency without at least decreasing the efficacy of the therapy. iTBS elevates cortical excitability, and in recent years it has become increasingly common to apply iTBS to patients in the early post-IS period. However, little is known about the neuroprotective mechanisms of iTBS. Endoplasmic reticulum stress (ERS), and ferroptosis have been shown to be involved in the development of I/R injury. We aimed to investigate the potential regulatory mechanisms by which iTBS attenuates neurological injury after I/R in rats. METHODS: Rats were randomly divided into three groups: sham-operated group, MCAO/R group, and MCAO/R + iTBS group, and were stimulated with iTBS 36 h after undergoing middle cerebral artery occlusion (MCAO) or sham-operated. The expression of ERS, ferroptosis, and apoptosis-related markers was subsequently detected by western blot assays. We also investigated the mechanism by which iTBS attenuates nerve injury after ischemic reperfusion in rats by using the modified Neurological Severity Score (mNSS) and the balance beam test to measure nerve function. RESULTS: iTBS performed early in I/R injury attenuated the levels of ERS, ferroptosis, and apoptosis, and improved neurological function, including mNSS and balance beam experiments. It is suggested that this mode of stimulation reduces the cost per treatment by several times without compromising the efficacy of the treatment and could be a practical and less costly intervention.

Preconditioning exercise reduces brain damage of ischemic stroke in rats via PI3K-AKT pathway by bioinformatic analysis.

Ischemic stroke is one of the most vital causes of high neurological morbidity and mortality in the world. Preconditioning exercise is considered as the primary prevention of stroke to resistance to subsequent injury. We tried to research the underlying biological mechanisms of this exercise. Forty-two SD rats were randomly divided into three groups: middle cerebral artery occlusion (MCAO) group, exercise group with MCAO (EX + MCAO) group, and sham group, with 14 rats in each group. The EX + MCAO group underwent exercise preconditioning for 3 weeks before occlusion, and the other two groups were fed and exercised normally. After 3 weeks, MCAO model was made by thread plug method in the EX + MCAO group and MCAO group. After successful modeling, the Longa scale was used to evaluate the neurological impairment of rats at day 0, day 1, and day 2. The rats in each group were killed on the third day after modeling. TTC staining measured the infarct volume of each group. The morphology and apoptosis of cortical cells were observed by HE and Tunel staining. Three rats in each group underwent high-throughput sequencing. Bioinformatic analysis was used to find the deferentially expressed genes (DEGs) and predict the transcription factor binding sites (TFBS) of the next-generation sequencing results. Gene enrichment (GSEA) was used to analyze potential functional genes and their corresponding signaling pathways. The Longa scale showed EX + MCAO group had the neurological function better than the modeling group (P < 0.001). TTC staining showed that the infarct size of EX + MCAO group was less than MCAO group (P < 0.05). HE and Tunel staining showed that the cells in the EX + MCAO group and the sham group had normal morphology and fewer apoptotic cells than MCAO group. A new gene named 7994 was discovered and TFBS of this gene was predicted, which could interact with key genes such as Foxd3, Foxa2, NR4A2, SP1, CEBPA, and SOX10. GSEA showed that EX + MCAO group could promote and regulate angiogenesis and apoptosis through PI3K-AKT pathway. Preconditioning exercise could improve nerve function and reduce infarct size in rats. The underlying mechanism is to regulate the PI3K-AKT pathway through several key genes, promote cerebral angiogenesis, and reduce apoptosis.

Enriched environment treatment promotes neural functional recovery together with microglia polarization and remyelination after cerebral ischemia in rats.

BACKGROUND: Microglia activation and oligodendrocyte maturation are critical for remyelination after cerebral ischemia. Studies have shown that enriched environment (EE) can effectively alleviate stroke-induced neurological deficits. However, little is known about the mechanism associated with glial cells underlying the neuroprotection of EE. Therefore, this study focuses on investigating the effect of EE on activated microglia polarization as well as oligodendrogenesis in the progress of remyelination following cerebral ischemia. METHODS: The ischemia/reperfusion (I/R) injury model was established by middle cerebral artery occlusion (MCAO) in rats. Animals executed 4 weeks of environmental intervention after performing MCAO or sham surgery and were divided into sham, MCAO, and MCAO+EE groups. Cognitive function, myelin damage, microglia activation and polarization, inflammation, oligodendrogenesis, remyelination, and protein expression of the PI3K/AKT/GSK3ß signaling pathway were determined. RESULTS: The staining of NeuN indicated that the infarct size of MCAO rats was decreased under EE. EE intervention improved animal performance in the Morris water maze test and novel object recognition test, promoting the recovery of cognitive function after I/R injury. EE treatment alleviated myelin damage in MCAO rats, as evidenced by the lower fluorescence intensity ratio of SMI-32/MBP in MCAO+EE group. EE increased the fluorescence intensity ratio of NG2+/Ki67+/Olig2+, MBP, and MOG, enhancing the proliferation and differentiation of OPCs and oligodendrogenesis after MCAO. In terms of remyelination, more myelinated axons and lower G/ratio were detected in MCAO+EE rats compared with MCAO group. Moreover, EE treatment decreased the number of Iba1+/CD86+ M1 microglia, increased the number of Iba1+/CD206+ M2 microglia, and suppressed the inflammation response after I/R injury, which could be attributed to the augmented expression of PI3K/AKT/GSK3ß axis. CONCLUSION: EE improved long­term recovery of cognitive function after cerebral I/R injury, at least in part by promoting M2 microglia transformation through activation of the PI3K/AKT/GSK3ß signaling pathway, inhibiting inflammation to provide a favorable microenvironment for oligodendrocyte maturation and remyelination. The effect of the EE on myelin and inflammation could account for the neuroprotection provided by EE.

Global and Regional Burden and Trend of Neoplasms Attributable to Alcohol Consumption in the Past 3 Decades.

OBJECTIVES: To provide valuable insights for targeted cancer screening among high-risk patients, we analyzed the global and regional burden of neoplasms resulting from alcohol consumption between 1990 and 2019. METHODS: The information used in this study was collected from the Global Burden of Disease 2019 dataset. Initially, the database was used to extract details of mortality rates, disability-adjusted life years (DALYs), and the number of individuals affected by alcohol-related neoplasms (ARNs). Subsequently, the data were compared by cancer type, sex, age, region, and sociodemographic index. Furthermore, the study involved the calculation and comparison of estimated annual percentage changes in age-standardized DALYs rates (ASDRs) and mortality rates. RESULTS: The impact of alcohol on the burden of cancer varied by type of cancer, sex, age, and geographical location. Notably, males exhibited significantly higher ASDRs compared with females. Specifically, in 2019, alcohol emerged as the primary contributor to the number of DALYs associated with esophageal cancer, followed by liver cancer and colorectal cancer in men. Patients aged 50+ years exhibited a heightened rate of DALYs associated with ARNs. From 1990 to 2019, ASDRs among individuals with ARNs did not exhibit a decline in low-middle and low sociodemographic index regions. CONCLUSIONS: Alcohol consumption represents a significant risk factor for the burden of cancer, particularly within the realm of digestive system malignancies. Consequently, targeted cancer screening efforts should be directed toward the population that engages in alcohol drinking, with a particular focus on men aged 50 years and older, residing in economically disadvantaged areas.

Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 µg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1ß, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1ß. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

Structure Mapping Generative Adversarial Network for Multi-View Information Mapping Pattern Mining.

Multi-view learning is dedicated to integrating information from different views and improving the generalization performance of models. However, in most current works, learning under different views has significant independency, overlooking common information mapping patterns that exist between these views. This paper proposes a Structure Mapping Generative adversarial network (SM-GAN) framework, which utilizes the consistency and complementarity of multi-view data from the innovative perspective of information mapping. Specifically, based on network-structured multi-view data, a structural information mapping model is proposed to capture hierarchical interaction patterns among views. Subsequently, three different types of graph convolutional operations are designed in SM-GAN based on the model. Compared with regular GAN, we add a structural information mapping module between the encoder and decoder wthin the generator, completing the structural information mapping from the micro-view to the macro-view. This paper conducted sufficient validation experiments using public imaging genetics data in Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. It is shown that SM-GAN outperforms baseline and advanced methods in multi-label classification and evolution prediction tasks.

Enriched environment enhanced the astrocyte-derived BDNF and VEGF expression and alleviate white matter injuries of rats with ischemic stroke.

OBJECTIVES: Numerous studies have shown that an enriched environment can promote ischemic stroke and improve cognitive function. In addition, white matter is closely related to cognitive function. The effects and mechanisms of the enriched environment on white matter recovery after stroke have not been elucidated. This study will analyse the effects of the enriched environment on white matter and cognitive function in the post-stroke brain from the perspective of astrocytes and their secretions. METHODS: Stroke models were used for middle cerebral artery occlusion model. post-operative rats were divided into sham-operated, standard and enriched environment groups. The degree of cerebral infarction was assessed by TTC staining and the degree of white matter damage was assessed by Luxol-Fast Blue staining. The prognosis after stroke was assessed using the longa score and Morris water maze test. Western Blot and immunofluorescence were used to quantify and localize astrocytes and their associated secretory factors and myelin protein markers. RESULTS: We found that ischemic stroke can cause severe demyelination. After EE treatment, there was a significant increase in cerebral remyelination and a significant improvement in neurological and cognitive functions. Astrocyte, BDNF, and VEGF expression were significantly higher than in rats in the standard circumstances of stroke model. CONCLUSION: These data suggest that the enriched environment contributes to brain white matter recovery and improvement of cognitive function after stroke. The mechanism is related to astrocytes and their secretions. EE can activate astrocytes to secrete BDNF and VEGF, which may be crucial to promote white matter recovery.

X-ray-induced piezoresponse during X-ray photon correlation spectroscopy of PbMg1/3Nb2/3O3.

X-ray photon correlation spectroscopy (XPCS) holds strong promise for observing atomic-scale dynamics in materials, both at equilibrium and during non-equilibrium transitions. Here an in situ XPCS study of the relaxor ferroelectric PbMg1/3Nb2/3O3 (PMN) is reported. A weak applied AC electric field generates strong response in the speckle of the diffuse scattering from the polar nanodomains, which is captured using the two-time correlation function. Correlated motions of the Bragg peak are also observed, which indicate dynamic tilting of the illuminated volume. This tilting quantitatively accounts for the observed two-time speckle correlations. The magnitude of the tilting would not be expected solely from the modest applied field, since PMN is an electrostrictive material with no linear strain response to the field. A model is developed based on non-uniform static charging of the illuminated surface spot by the incident micrometre-scale X-ray beam and the electrostrictive material response to the combination of static and dynamic fields. The model qualitatively explains the direction and magnitude of the observed tilting, and predicts that X-ray-induced piezoresponse could be an important factor in correctly interpreting results from XPCS and nanodiffraction studies of other insulating materials under applied AC field or varying X-ray illumination.