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AIM: To characterize the N6-methyladenosine (m6A) modification patterns in long non-coding RNAs (lncRNAs) in sporadic congenital cataract (CC) and age-related cataract (ARC). METHODS: Anterior capsule of the lens were collected from patients with CC and ARC. Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs. RESULTS: Large amount of m6A peaks within lncRNA were identified for both CC and ARC, while the level was much higher in ARC (49 870 peaks) than that in CC (18 688 peaks), yet those difference between ARC in younger age group (ARC-1) and ARC in elder age group (ARC-2) was quite slight. A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs, as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC. On the other hand, 5893 hypermethylated and 5213 hypomethylated lncRNAs, as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1. Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles, as well as nucleotide excision repair. CONCLUSION: Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC, providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

Although essential for cardiovascular therapy, the pleiotropic effects of statins on ischemic stroke lack clinical evidence. This study examined the effects of statins beyond low-density lipoprotein cholesterol (LDL-C) levels on mortality and stroke severity. A total of 825,874 patients with ischemic stroke were included in this study, of whom 125,650 statin users were 1:1 matched with non-users based on their LDL-C levels (±0.05 mmol/L), forming the LDL-C-matched cohort. Associations between preceding statin treatment, in-hospital mortality, and stroke severity (National Institutes of Health Stroke Scale score ≥16) were estimated by multivariate and conditional logistic regression models in overall cohort and LDL-C-matched cohort, respectively. The overall statin effects reduced in-hospital mortality (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.65–0.79, p

Abstract Background The sharp increase in fungal infections, insufficient diagnostic and treatment capabilities for fungal infections, poor prognosis of patients with fungal infections as well as the increasing drug resistance of fungi are serious clinical problems. It is necessary to explore the implementation and evaluation methods of antifungal stewardship (AFS) to promote the standardized use of antifungal drugs. Methods The AFS programme was implemented at a tertiary first-class hospital in China using a plan-do-check-act (PDCA) quality management tool. A baseline investigation was carried out to determine the utilization of antifungal drugs in pilot hospitals, analyse the existing problems and causes, and propose corresponding solutions. The AFS programme was proposed and implemented beginning in 2021, and included various aspects, such as team building, establishment of regulations, information construction, prescription review and professional training. The management effectiveness was recorded from multiple perspectives, such as the consumption of antifungal drugs, the microbial inspection rate of clinical specimens, and the proportion of rational prescriptions. The PDCA management concept was used for continuous improvement to achieve closed-loop management. Results In the first year after the implementation of the AFS programme, the consumption cost, use intensity and utilization rate of antifungal drugs decreased significantly (P

Abstract Objective This study aimed to evaluate the cost-utility of the addition of vericiguat for treating chronic heart failure (CHF) in China from the healthcare payer’s perspective. Methods A Markov model was built to estimate the cost and utility of treating CHF using vericiguat plus standard treatment (vericiguat group) vs. standard treatment alone (standard treatment group). The clinical parameters (mortality of cardiovascular and hospitalization rate of HF) were calculated according to the VICTORIA clinical trial. The HF cost and utility data were obtained from the literature published in China. One-way sensitivity analysis and probability sensitivity analysis were performed. Results According to the 13-year model, vericiguat was more expensive (155599.07 CNY vs. 259396.83 CNY) and more effective (4.41 QALYs vs. 4.54 QALYs). The incremental cost‐utility ratio (ICUR) was 802389.27 CNY per QALY. One-way sensitivity analysis revealed that cardiovascular mortality in the two groups was the parameter that had the greatest impact on the results. The GDP per capita in 2022 in China was 85,700 CNY. The probability sensitivity analysis (PSA) showed that the probability of vericiguat being cost-effective was only 41.7% at the willingness-to-pay (WTP) threshold of 3 times GDP per capita (257,100 CNY). Conclusions In China, the treatment of CHF with vericiguat is not cost-effective. The drug price could decrease to 145.8 CNY, which could be considered cost-effective.

AIM: To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress. METHODS: LECs were treated with hyperosmotic stress at the concentration of 270, 300, 400, 500, or 600 mOsm for 6, 12, 18, 24h in vitro. Polymerase chain reaction (PCR) was employed for the mRNA expression of autophagy-related genes, while Western blotting detected the targeted protein expression. The transfection of stub-RFP-sens-GFP-LC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux. Scanning electron microscopy was used to detect the existence of autolysosome. Short interfering RNA of autophagy-related gene (ATG) 7, transient receptor potential vanilloid (TRPV) 1 overexpression plasmid, related agonists and inhibitors were employed to their influence on autophagy related pathway. Flow cytometry was employed to test the apoptosis and intracellular Ca2+ level. Mitochondrial membrane potential was measured by JC-1 staining. The cell counting kit-8 assay was used to calculate the cellular viability. The wound healing assay was used to evaluate the wound closure rate. GraphPad 6.0 software was utilized to evaluate the data. RESULTS: The hyperosmotic stress activated autophagy in a pressure- and time-dependent manner in LECs. Beclin 1 protein expression and conversion of LC3B II to LC3B I increased, whereas sequestosome-1 (SQSTM1) protein expression decreased. Transient Ca2+ influx was stimulated caused by hyperosmotic stress, levels of mammalian target of rapamycin (mTOR) phosphorylation decreased, and the level of AMP-activated protein kinase (AMPK) phosphorylation increased in the early stage. Based on this evidence, autophagy activation through the Ca2+-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress. Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased. Inhibition of autophagy by ATG7 knockdown had similar results. TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress. CONCLUSION: A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

IntroductionEnterocytozoon bieneusi is one of the most important zoonotic pathogens, responsible for nearly 90% of human infections. Its host spectrum is broad in China, encompassing humans, non-human primates, domestic animals, wildlife, and wastewater. Wild rodents have the potential to act as carriers of E. bieneusi, facilitating the parasite’s transmission to humans and domestic animals.MethodsThe present study involved the collection of 344 wild rodents, representing nine species, from three provinces in China. The prevalence and genotypes of E. bieneusi were determined through amplification of the ITS gene. Evolutionary analysis was conducted using Mega 5.0 with the neighbor-joining method (Kimura 2-parameter model, 1,000 replicates).ResultsAmong the sampled wild rodents, 41 (11.92%) were tested positive for E. bieneusi. Rattus flavipectus exhibited the highest prevalence (11/39), while Bandicota indica and Rattus rattus sladeni showed no infections (0/39 and 0/5, respectively), highlighting significant differences. Environmental factors strongly influenced E. bieneusi infection; rodents residing in lake beaches (10.27%, 15/146) and fields (19.95%, 18/95) were more susceptible compared to those in mountainous areas (7.77%, 8/103). The study identified four known genotypes (D, Type IV, SDD5, PigEBITS7) and five novel genotypes (HNRV-1 to HNRV-3, GXRL-1, GXRL-2) in the investigated wild rodents, with Genotype D exhibiting the highest prevalence.DiscussionRemarkably, this study reports the presence of E. bieneusi, R. flavipectus, M. fortis, A. agrarius, R. losea, and N. lotipes for the first time. These findings underscore the common occurrence of E. bieneusi infection in wild rodents in China, highlighting its diverse nature and significant potential for zoonotic transmission. Hence, it is imperative to conduct a comprehensive epidemiological investigation of rodent infection with E. bieneusi, particularly focusing on wild rodents that are closely associated with humans. Additionally, developing appropriate measures and monitoring strategies to minimize the risk of infection is essential.

Abstract Background Lysine methyltransferase 2D (KMT2D) mediates mono‐methylation of histone H3 lysine 4 (H3K4me1) in mammals. H3K4me1 mark is involved in establishing an active chromatin structure to promote gene transcription. However, the precise molecular mechanism underlying the KMT2D‐mediated H3K4me1 mark modulates gene expression in triple‐negative breast cancer (TNBC) progression is unresolved. Methods and Results We recognized Y‐box‐binding protein 1 (YBX1) as a “reader” of the H3K4me1 mark, and a point mutation of YBX1 (E121A) disrupted this interaction. We found that KMT2D and YBX1 cooperatively promoted cell growth and metastasis of TNBC cells in vitro and in vivo. The expression levels of KMT2D and YBX1 were both upregulated in tumour tissues and correlated with poor prognosis for breast cancer patients. Combined analyses of ChIP‐seq and RNA‐seq data indicated that YBX1 was co‐localized with KMT2D‐mediated H3K4me1 in the promoter regions of c‐Myc and SENP1, thereby activating their expressions in TNBC cells. Moreover, we demonstrated that YBX1 activated the expressions of c‐Myc and SENP1 in a KMT2D‐dependent manner. Conclusion Our results suggest that KMT2D‐mediated H3K4me1 recruits YBX1 to facilitate TNBC progression through epigenetic activation of c‐Myc and SENP1. These results together unveil a crucial interplay between histone mark and gene regulation in TNBC progression, thus providing novel insights into targeting the KMT2D‐H3K4me1‐YBX1 axis for TNBC treatment. Highlights YBX1 is a KMT2D‐mediated H3K4me1‐binding effector protein and mutation of YBX1 (E121A) disrupts its binding to H3K4me1. KMT2D and YBX1 cooperatively promote TNBC proliferation and metastasis by activating c‐Myc and SENP1 expression in vitro and in vivo. YBX1 is colocalized with H3K4me1 in the c‐Myc and SENP1 promoter regions in TNBC cells and increased YBX1 expression predicts a poor prognosis in breast cancer patients.

IntroductionBlastocystis is one of the most critical intestinal protozoans in various hosts, including humans and mice. To determine the status of Blastocystis infection in wild rodents in China.MethodsA total of 344 faecal samples were collected from seven wild rodent species from three provinces, and the small subunit ribosomal RNA (SSU rRNA) genes of Blastocystis were amplified to determine their prevalence and subtypes.ResultsOf the 344 samples, 54 (15.70%) were detected as Blastocystis-positive. The prevalence of Blastocystis was 26.14% (40/153), 7.95% (7/88), and 6.80% (7/103) in wild rodents from Hunan Province, Yunnan Province, and Guangxi Province, respectively. The prevalence of Blastocystis in different wild rodent species varied from 0.00% (0/13) in Mus musculus to 40.00% (2/5) in Rattus rattus sladeni. The prevalence of Blastocystis in samples from the lake beach area (27.40%, 40/146) was significantly higher than in those from the mountain (6.80%, 7/103) and field regions (7.37%, 7/95). The prevalence in different seasons was 26.14% in summer (40/153), 7.95% in autumn (7/88), and 6.80% in winter (7/103). Moreover, a total of two Blastocystis subtypes were identified in the investigated wild rodents, including ST4 and ST5.DiscussionThe present study discovered the existence of Blastocystis infection in Rattus favipectus, Microtus fortis, Apodemus agrarius, Bandicota indica, Rattus rattus sladeni, and Rattus losea, expanding the host range of this parasite. The findings also demonstrate that wild rodents may be an important potential infection source for Blastocystis infection in humans and other animals.

Laparoscopic surgery is extensively applied in the treatment of hepatobiliary diseases. Hepatic artery pseudoaneurysm (HAP) is a rare complication following hepatic biliary surgery through laparoscopy. The clinical manifestations of HAP are diverse and can be fatal. Given its severity, rapid assessment and management are crucial to ensuring a good prognosis. Here, we report three cases of HAP; two underwent laparoscopic surgery due to cholelithiasis, and another caused by trauma. The first case exhibited a pseudoaneurysm involving the distal portion of the right hepatic artery main trunk. The second patient had a pseudoaneurysm at the bifurcation of the left and right hepatic arteries. The third case involved a patient with a pseudoaneurysm involving a branch of the right hepatic artery. The main clinical manifestations of all three cases were bleeding from the biliary tract (the first two cases showed postoperative bleeding in the T-tube, while the third case exhibited gastrointestinal bleeding). The final diagnosis was obtained through digital subtraction angiography. The three patients underwent successful transcatheter arterial embolization operation and a follow-up revealed they were disease-free and alive. This article aims to highlight a rare complication of laparoscopic hepatobiliary surgery and share our experience in early diagnosis and treatment of HAP.

In the evolving realm of ergonomics, there is a growing demand for enhanced comfortability, visibility, and accessibility in the operation of engineering machinery. This study introduces an innovative approach to assess the ergonomics of a driller’s cabin by utilizing a digital human. Through the utilization of inertial motion capture sensors, the method enables the operation of a virtual driller animated by real human movements, thereby producing more precise and realistic human–machine interaction data. Additionally, this study develops a simplified model for the human upper limbs, facilitating the calculation of joint forces and torques. An ergonomic analysis platform, encompassing a virtual driller’s cabin and a digital human model, is constructed using Unity 3D. This platform enables the quantitative evaluation of comfortability, visibility, and accessibility. Its versatility extends beyond the current scope, offering substantial support for product development and enhancement.

Background: Resistance to oxaliplatin (L-OHP) is a major barrier in the treatment of colorectal cancer (CRC). Autophagy is the main cause of L-OHP tolerance in CRC cells. Method: The human colon cancer cell lines HCT116 and SW480 were treated with L-OHP to obtain the drug-resistant cell lines HCT116/L-OHP and SW480/L-OHP, respectively. To probe the relationship between autophagy and L-OHP tolerance of growth factor independent 1 (Gfi-1) and high-mobility group protein 1 (HMGB1) in CRC cells, gene knockout or overexpression was performed, and Western blotting was used to determine the levels of drug tolerance interrelated proteins. Transwell and CCK-8 assays were employed to analyze the proliferation of cancer cells. Immunofluorescence detection of LC3 reflected autophagy levels. Finally, the relationship between Gfi-1 and HMGB1 was detected by chromatin immunoprecipitation (ChIP). Result: Compared to normal CRC cells, L-OHP-tolerant CRC cells exhibited greater autophagy (8.2 times greater in HCT116/L-OHP cells and 7.4 times greater in SW480/L-OHP cells). In addition, we detected low levels of Gfi-1 (0.6-fold for HCT116/L-OHP cells and 0.4-fold for SW480/L-OHP cells), and OE-Gfi-1 decreased HMGB1 levels (0.6-fold for HCT116/L-OHP + OE-Gfi-1 cells and 0.5-fold for SW480/L-OHP + OE-Gfi-1 cells). The inhibition of Gfi-1 further enhanced cell viability (1.7 times in HCT116+sh-Gfi-1 cells and 1.2 times in SW480+sh-Gfi-1 cells) and invasion (1.8 times in HCT116+sh-Gfi-1 cells and 2.1 times in SW480+sh-Gfi-1 cells) in CRC cells, thus promoting oxaliplatin resistance in these cells. The autophagy inhibitor 3-MA reversed the above effects. Furthermore, we noted that Gfi-1 can restrain HMGB1 expression by binding to its promoter (0.5 times in HCT116+OE-Gfi-1 cells and 0.5 times in SW480+OE-Gfi-1 cells). The inhibitory influence of 3-MA on HMGB1 reversed the influence of Gfi-1 on autophagy and malignant progression in CRC cells. Conclusion: Our study suggested that Gfi-1 inhibited HMGB1 to reduce CRC autophagy levels, increasing CRC sensitivity to L-OHP.

Abstract Background and purpose Nonvalvular atrial fibrillation (NVAF) is a risk factor for stroke. This study was undertaken to determine the influence of NVAF on the mortality and recurrent stroke after a minor stroke event. Methods Data were derived from the Third China National Stroke Registry (CNSR-III) which enrolled 15,166 subjects during August 2015 through March 2018 in China. Patients with minor stroke (NIHSS ≤ 5) within 24 h after onset were included. Clinical outcomes including all-cause mortality, cardiovascular death, recurrent ischemic stroke, and recurrent hemorrhagic stroke were collected. The Cox proportional hazards models were used to determine the association between NVAF and clinical outcomes. Results A total of 4,753 patients were included in our study. Of them, 222 patients had NVAF (4.7%) (mean age, 71.1 years) and 4,531 patients were without AF (95.3%) (mean age, 61.4 years). NVAF was associated with 12-month cardiovascular mortality in both univariate (hazards ratio [HR], 4.13; 95% confidence interval [CI], 1.84 to 9.31; P

Objective With the development of drilling technology for deep strata, the study of the dynamic characteristics and parametric response law of drill bits and deep complex strata during drilling has become a key and difficult point in research. Methods In this paper, a combination of numerical simulation and response surface analysis was used to study the dynamic characteristics of PDC bits and typical complex strata in the drilling process, and parametric analysis was carried out. In this paper, soft-hard-staggered strata with dip angles as a typical complex formation were studied, the dynamic damage finite element simulation model between the PDC drill bit and the soft-hard-staggered strata with the full real size was established based on Abaqus, and the dynamic characteristics of the drill bit subjected to the reaction force of the strata during drilling were derived. Numerical simulation experiments were also conducted by orthogonal tests to investigate the dynamic characteristics of the PDC bit under different formation parameters and drilling parameters. Results The single factor analysis and response surface analysis were used to model and identify the relationship between drilling parameters and stratigraphic parameters and the reaction force on the drill bit by the stratum and to obtain the changing trend and regression model of the reaction force on the drill bit by the stratum under multiple parameters. The results showed that the higher the inclination angle of soft-hard-staggered strata, the higher the average value and peak impact value of the bit subjected to the stratigraphic reaction force. The larger the ratio of softness to the hardness of the strata is, the larger the average and peak reaction forces on the drill bit. Within a certain range, increasing the rotational speed will reduce the impact of the reaction force on the drill bit. Conclusion The research results provide a basis for predicting the bit reaction force during drilling in deep and complex formations and guide the control of the drilling trajectory in deep and complex formations, which is of great significance for deep geological drilling.

Acute transient or permanent retinal arterial ischemia is ocular and systemic emergency requiring immediate diagnosis and treatment. Transient monocular vision loss is transient retinal arterial ischemia which leaves no permanent deficits. Central retinal arterial occlusion and branch retinal arterial occlusion lead to permanent visual function deficits in the majority of patients. Current treatment include lowering intraocular pressure, dilating blood vessels, hyperbaric oxygen therapy, intravenous or intra-arterial thrombolysis and so on, but there is still no standard treatment procedure. High risk groups should receive primary prevention measures in order to reduce the incidence of the disease. Patients with acute retinal arterial ischemia are at high risk of subsequent stroke and adverse cardiovascular events. Relevant risk factors should be identified in time, the primary disease should be treated actively, and appropriate secondary prevention measures should be taken to improve the prognosis. This review summarizes the recent treatment and prevention procedures of acute retinal arterial ischemia, to provide references for the management of these diseases.

Aviation-integrated communication equipment is integral to modern aircraft to ensure its performance and safety. The heat dissipation problems of equipment have become increasingly prominent for the high electronic integration and system power consumption. To solve the above problem, the heat dissipation performance of aviation-integrated communication equipment based on graphene films is deeply studied. This paper establishes a three-dimensional model of aviation-integrated communication equipment to simulate the distribution of temperature fields. The influence between aluminum alloy and graphene films on the surface of magnesium alloy on the heat dissipation performance of aviation-integrated communication equipment is studied. The simulation results show that the heat balance time of the equipment using graphene films on the surface of magnesium alloy is reduced from 3600 s to 800 s, representing an approximately 77.78% improvement; the measured equipment exhibited a reduction in its overall thermal equilibrium temperature, decreasing from 68.1 °C to 66.3 °C, representing an improvement of approximately 2.64%.

Abstract Background Rehabilitation improves functional recovery in subarachnoid hemorrhage (SAH) patients, and assessing patients for rehabilitation is the first step in this process. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation for patients with SAH. Methods To identify patients hospitalized with SAH and to analyze rehabilitation assessment rates, we used data for 11,234 SAH patients admitted to 861 hospitals from the China Stroke Center Alliance from August 2015 to July 2019. We examined factors for rehabilitation assessment and analyzed the relationship between rehabilitation assessment and outcomes in these patients. Results Among 11,234 patients with SAH, 6,513 (58.0%) were assessed for rehabilitation. Assessed patients had an increased length of stay (mean ± SD days: 17.3 ± 12.5 versus 11.6 ± 10.5, P = 49.4), a higher Glasgow Coma Scale (GCS) score on admission (mean ± SD GCS score: 12.3 ± 3.8 versus 11.8 ± 4.4, P = 12.2), and were more likely to be admitted to the stroke unit (19.6% versus 13.8%, P = 15.6). In multivariable analysis, factors associated with an increased likelihood of a rehabilitation assessment (p

Summary: N-α-acetyltransferase D (NatD) mediates N-α-terminal acetylation of histone H4 (Nt-Ac-H4), but its role in breast cancer metastasis remains unknown. Here, we show that depletion of NatD directly represses the expression of FOXA2, and is accompanied by a significant reduction in Nt-Ac-H4 enrichment at the FOXA2 promoter. We show that NatD is commonly upregulated in primary breast cancer tissues, where its expression level correlates with FOXA2 expression, enhanced invasiveness, and poor clinical outcomes. Furthermore, we show that FOXA2 promotes the migration and invasion of breast cancer cells by activating MMP14 expression. MMP14 is also upregulated in breast cancer tissues, where its expression level correlates with FOXA2 expression and poor clinical prognosis. Our study shows that the NatD-FOXA2-MMP14 axis functions as a key signaling pathway to promote the migratory and invasive capabilities of breast cancer cells, suggesting that NatD is a critical epigenetic modulator of cell invasion during breast cancer progression.

Objectives This study aimed to investigate factors associated with undergoing dysphagia screening (DS) and developing pneumonia, as well as the relationship between DS and pneumonia in patients with intracerebral haemorrhage (ICH).Design Our study was a cross-sectional hospital-based retrospective study.Study design and settings We derived data from the China Stroke Centre Alliance, a nationwide clinical registry of ICH from 1476 participating hospitals in mainland China. To identify predictors for pneumonia, multivariable logistic regression models were used to identify patient characteristics that were independently associated with DS and pneumonia.Participants We included 31 546 patients in this study with patient characteristics, admission location, medical history, hospital characteristics and hospital grade from August 2015 to July 2019.Primary and secondary outcome measures The primary outcomes were DS and pneumonia during acute hospitalisation.Results In total, 25 749 (81.6%) and 7257 (23.0%) patients with ICH underwent DS and developed pneumonia. Compared with patients without pneumonia, those who developed pneumonia were older and had severe strokes (Glasgow Coma Scale 9–13: 52.7% vs 26.9%). Multivariable analyses revealed that a higher pneumonia risk was associated with dysphagia (OR, 4.34; 95% CI, 4.02 to 4.68), heart failure (OR, 1.85; 95% CI, 1.24 to 2.77) and smoking (OR, 1.12; 95% CI, 1.12 to 0.20). DS was associated with lower odds of pneumonia (OR, 0.65; 95% CI, 0.44 to 0.95).Conclusion Our findings further confirm that dysphagia is an independent risk factor for pneumonia; one-fifth of patients with ICH did not undergo DS. However, comprehensive dysphagia evaluation and effective management are crucial. Nursing processes ensure the collection of complete and accurate information during evaluation of patients. There is a need to increase the rate of DS in patients with ICH, especially those with severe stroke or older. Further, randomised controlled trials are warranted to determine the effectiveness of DS on clinical outcomes.

Abstract Background The gut microbiota plays an essential role in maintaining gut homeostasis and improving performance, with the composition of microbial communities visibly differing across different laying stages in hens and significantly correlating with egg production. To gain further insights into the association between microbial community characteristics and laying periods in Hy-Line variety brown and Isa brown laying hens, we conducted a 16S rRNA amplicon sequencing survey. Results Our result revealed the diversity of bacteria in the early laying period was commonly higher than peak, and in Hy-Line variety brown laying hens were generally higher than Isa brown. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) revealed that the structure and composition of the gut microbiota of laying hens exhibited significant differences among different groups. Phylum Firmicutes, Bacteroidota, Proteobacteria, and Fusobacteriota were found that dominant in the host’s feces. Therein, the abundance of Fusobacteriota was higher in the peak period than in the early period, while the abundance of Cyanobacteria in the early period was higher in two breeds of hens. Furthermore, random forest based on machine learning showed that there were several distinctly abundant genera, which can be used as potential biomarkers to differentiate the different groups of laying periods and breeds. In addition, the prediction of biological function indicated the existing discrepancy in microbial function among the microbiota of four groups. Conclusions Our findings offer new insights into the bacterial diversity and intestinal flora composition of different strains of laying hens during various laying periods, contributing significantly to the improvement of production performance and the prevention of chicken diseases.

Abstract Genomic studies have demonstrated a high frequency of genetic alterations in components of the SWI/SNF complex including the core subunit SMARCA4. However, the mechanisms of tumorigenesis driven by SMARCA4 mutations, particularly in colorectal cancer (CRC), remain largely unknown. In this study, we identified a specific, hotspot mutation in SMARCA4 (c. 3721C>T) which results in a conversion from arginine to tryptophan at residue 1157 (R1157W) in human CRC tissues associated with higher-grade tumors and controls CRC progression. Mechanistically, we found that the SMARCA4R1157W mutation facilitated its recruitment to PRMT1-mediated H4R3me2a (asymmetric dimethylation of Arg 3 in histone H4) and enhanced the ATPase activity of SWI/SNF complex to remodel chromatin in CRC cells. We further showed that the SMARCA4R1157W mutant reinforced the transcriptional expression of EGFR and TNS4 to promote the proliferation of CRC cells and patient-derived tumor organoids. Importantly, we demonstrated that SMARCA4R1157W CRC cells and mutant cell-derived xenografts were more sensitive to the combined inhibition of PRMT1 and SMARCA4 which act synergistically to suppress cell proliferation. Together, our findings show that SMARCA4-R1157W is a critical activating mutation, which accelerates CRC progression through facilitating chromatin recruitment and remodeling. Our results suggest a potential precision therapeutic strategy for the treatment of CRC patients carrying the SMARCA4R1157W mutation.

ObjectiveThe safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain uncertain. This study aims to comprehensively estimate and rank the relative safety outcomes with different doses of SGLT-2i for T2DM.MethodsPubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to 31 May 2023. We included double-blind randomized controlled trials (RCTs) comparing SGLT-2i with placebo or another antihyperglycemic as oral monotherapy in the adults with a diagnosis of T2DM.ResultsTwenty-five RCTs with 12,990 patients randomly assigned to 10 pharmacological interventions and placebo were included. Regarding genital infections (GI), all SGLT-2i, except for ertugliflozin and ipragliflozin, were associated with a higher risk of GI compared to placebo. Empagliflozin 10mg/d (88.2%, odds ratio [OR] 7.90, 95% credible interval [CrI] 3.39 to 22.08) may be the riskiest, followed by empagliflozin 25mg/d (83.4%, OR 7.22, 95%CrI 3.11 to 20.04)) and canagliflozin 300mg/d (70.8%, OR 5.33, 95%CrI 2.25 to 13.83) based on probability rankings. Additionally, dapagliflozin 10mg/d ranked highest for urinary tract infections (UTI, OR 2.11, 95%CrI 1.20 to 3.79, 87.2%), renal impairment (80.7%), and nasopharyngitis (81.6%) when compared to placebo and other treatments. No increased risk of harm was observed with different doses of SGLT-2i regarding hypoglycemia, acute kidney injury, diabetic ketoacidosis, or fracture. Further subgroup analysis by gender revealed no significantly increased risk of UTI. Dapagliflozin 10mg/d (91.9%) and canagliflozin 300mg/d (88.8%) ranked first in the female and male subgroups, respectively, according to the probability rankings for GI.ConclusionCurrent evidence indicated that SGLT-2i did not significantly increase the risk of harm when comparing different doses, except for dapagliflozin 10mg/d, which showed an increased risk of UTI and may be associated with a higher risk of renal impairment and nasopharyngitis. Additionally, compared with placebo and metformin, the risk of GI was notably elevated for empagliflozin 10mg/d, canagliflozin 300mg/d, and dapagliflozin 10mg/d. However, it is important to note that further well-designed RCTs with larger sample sizes are necessary to verify and optimize the current body of evidence.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023396023.

BackgroundSince abnormal aerobic glycolysis was first identified in cancer cells, many studies have focused on its mechanisms. The purpose of this study was to analyze the global research status of the Warburg effect in cancer using bibliometrics.MethodsArticles published from 01 January 2013 to 31 December 2022 (n=2,067) were retrieved from the Web of Science core collection database and analyzed using VOSviewer and CiteSpace software.ResultsOver the past decade, there was an overall increase in the number of annual publications. China was the most productive country with 790 articles, while the United States received the most citations, with 25,657 citations in total. Oncotarget was the most productive and most cited journal, with 99 articles and 4,191 citations, respectively. International cooperation was common, with the USA cooperating most with other countries. Lactate metabolism, citrate production, and non-coding RNAs related to the Warburg effect have received increasing attention in cancer research. These areas may become future research trends.ConclusionThe study findings help summarize the research status and hotspots of the Warburg effect cancer, and will inform subsequent research.

Familial exudative vitreoretinopathy(FEVR)is a hereditary disorder of retinal angiogenesis, of which the most typical clinical feature is the peripheral avascular area. The progression of the disease can lead to retinal detachment(RD), followed by secondary complications such as cataracts, glaucoma, corneal opacification, and even bulbi phthisis. As one of the main reasons for the RD in Asian children and juvenile, FEVR-associated retinal detachment(FEVR-RD)is mainly treated by surgery, including pars plana vitrectomy, scleral bucking, and combined with retinal photocoagulation or anti-vascular endothelial grouth factor(VEGF)sometimes. The surgery of FEVR-RD requires careful pre/intra-operative evaluation to determine the best surgical procedure and its outcome, including the nature of the affected eye, the stage, the fibrosis of fiber proliferation and the anterior complications, and the anatomy and prognosis of eyes in different stages vary greatly. Adult patients with rhegmatogenous RD have a higher rate of post-operative retina reattachment compared to young patients with tractional RD. In young or advanced patients, surgery is difficult and the prognosis is less optimistic, thus the surgery strategy is controversial. This article reviews the surgical outcomes and progress of FEVR-associated RD.

AIM: To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5C retinopathy of prematurity (ROP) with corneal opacification. METHODS: This was a retrospective, interventional, consecutive case series. Twenty-two eyes of 18 stage 5C ROP patients with corneal opacification were included. Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus. Staged lensectomy and posterior vitrectomy were performed. The anatomical and visual outcomes were reviewed at the final follow-up visit. RESULTS: The mean gestational age of ROP patients was 29.3±1.6wk (range: 27-32wk), comprising 8 males and 10 females. The average birth weight was 1363.0±300.0 g. All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively. Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia. Six eyes had posterior pupillary synechiae or membranes. Seven (31.8%) eyes had vascularly active retinas. The average interval between two procedures was 6.8±4.6mo (2.5-18.5mo). After surgeries, all the patients had normal anterior chambers. Fourteen eyes had clear corneas. The intraocular pressure of 3 eyes with glaucoma was controlled by medication. Two eyes had ocular phthisis. The retina was reattached in 3 eyes and partially attached in 11 eyes. Visual acuity ranged from no light perception to hand motion. CONCLUSION: Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage 5C ROP patients with corneal opacification. The earlier the lensectomy is performed, the better the prognosis is.

The genetic bases of yak adaptations to extreme conditions remains elusive. This study compares yak and cattle at a genomic and transcriptomic level, revealing a new type of endothelial cell and candidate genes related with elastic fiber formation in yak lungs that might contribute to high altitude adaptation.

Modelling of aggressive lymphomas, such as double hit lymphoma, has been challenging. Here the authors engineer a CRISPR activation mouse to enable the generation of these aggressive lymphomas and identify the pro-survival BCL-2 protein A1 as a venetoclax resistance factor.

AIM: To investigate the role of procollagen C-proteinase enhancer 1 (PCPE1) in retinal angiogenesis and relevant mechanisms. METHODS: The Pcolce1-knockout (KO) mice were used to explore the effect of PCPE1 on retinal angiogenesis in vivo. Pcolce1 siRNA were designed, cell count kit 8 (CCK8) assays and tube formation assays were performed to investigate the cell proliferation and tube formation abilities of retinal microvascular endothelial cells (hRMECs) in vitro. Mouse embryo fibroblasts (MEF) cells were isolated and cultured to analyze the effect of PCPE1 on enhancing procollagen cleavage. RESULTS: In vivo studies showed that the retinal vascular density of Pcolce1-/- mice was significantly lower than that of the control group. Furthermore, silencing of Pcolce1 inhibited cell proliferation and tube formation abilities of hRMECs in vitro. Additionally, much more pro-collagen was found in Pcolce1-/- MEF cells, compared to wild type MEF cells. CONCLUSION: PCPE1 may promote physiological retinal angiogenesis by regulating the processing of collagen, which may provide a potential therapeutic target of retinal vascular disease.

Abstract Introduction A high residual risk of subsequent stroke suggested that the predictive ability of Stroke Prognosis Instrument‐II (SPI‐II) and Essen Stroke Risk Score (ESRS) may have changed over the years. Aim To explore the predictive values of the SPI‐II and ESRS for 1‐year subsequent stroke risk in a pooled analysis of three consecutive national cohorts in China over 13 years. Results In the China National Stroke Registries (CNSRs), 10.7% (5297/50,374) of the patients had a subsequent stroke within 1 year; area under the curve (AUC) of SPI‐II and ESRS was .60 (95% confidence interval [CI]: .59–.61) and .58 (95% CI: .57–.59), respectively. For SPI‐II, the AUC was .60 (95% CI: .59–.62) in CNSR‐I, .60 (95% CI: .59–.62) in CNSR‐II, and .58 (95% CI: .56–.59) in CNSR‐III over the past 13 years. The declining trend was also found in ESRS scale (CNSR‐I: .60 [95% CI: .59–.61]; CNSR‐II: .60 [95% CI: .59–.62]; and CNSR‐III: .56 [95% CI: .55–.58]). Conclusions The predictive power of the traditional risk scores SPI‐II and ESRS was limited and gradually decreased over the past 13 years, thus the scales may not be useful for current clinical practice. Further derivation of risk scales with additional imaging features and biomarkers may be warranted.

Chronic liver disease or repeated damage to hepatocytes can give rise to hepatic fibrosis. Hepatic fibrosis (HF) is a pathological process of excessive sedimentation of extracellular matrix (ECM) proteins such as collagens, glycoproteins, and proteoglycans (PGs) in the hepatic parenchyma. Changes in the composition of the ECM lead to the stiffness of the matrix that destroys its inherent mechanical homeostasis, and a mechanical homeostasis imbalance activates hepatic stellate cells (HSCs) into myofibroblasts, which can overproliferate and secrete large amounts of ECM proteins. Excessive ECM proteins are gradually deposited in the Disse gap, and matrix regeneration fails, which further leads to changes in ECM components and an increase in stiffness, forming a vicious cycle. These processes promote the occurrence and development of hepatic fibrosis. In this review, the dynamic process of ECM remodeling of HF and the activation of HSCs into mechanotransduction signaling pathways for myofibroblasts to participate in HF are discussed. These mechanotransduction signaling pathways may have potential therapeutic targets for repairing or reversing fibrosis.

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

AIM: To determine the anatomic and visual outcomes of prophylactic juxtapapillary laser photocoagulation treatment alone in the prevention of retinal detachment (RD) in a cohort of pediatric patients diagnosed with morning glory syndrome (MGS). METHODS: A total of 24 eyes of 22 consecutive patients aged 0-15y diagnosed with MGS treated with prophylactic juxtapapillary laser photocoagulation alone were reviewed. Data including demographics, ocular examination, anatomic and visual outcomes, following treatment and complications were collected. RESULTS: Two patients had bilateral laser treatment and 20 had monocular laser treatment. The age at treatment of 13 (59.1%) patients was less than 12mo. The presenting symptoms included strabismus (6/22, 27.3%), decreased vision (2/22, 9.1%), and routine fundus screening (14/22, 63.6%). Fifteen (68.2%) patients underwent cranial magnetic resonance imaging (MRI) examinations, and 3 of those 15 (20.0%) had abnormal findings in the nervous system. Based on preoperative wide-field fundus photography and B-scan echography, all (100.0%) eyes had no obvious RD. On postoperative 1mo and 6mo and the following follow-ups, the anatomic outcomes of all eyes remained stable. The mean follow-up duration was 27.7±17.5mo. No severe complications were found. Preoperative visual acuity acquired from 2 (9.1%) patients ranged from light perception to 20/200. Postoperative acuity acquired from 11 (50.0%) patients ranged from light perception to 20/125. CONCLUSION: The preliminary anatomic and visual outcomes of prophylactic juxtapapillary laser treatment alone in pediatric MGS patients are relatively stable in a short-term follow-up. Further long-term clinical observation will be needed to confirm its efficacy and safety.

With the application of artificial intelligence in modern industry, the demand for intelligent fault diagnosis systems is increasing, which has attracted much attention of researchers. There is a popular methodology to use the knowledge or rules defined by experts for fault diagnosis. However, the expert defined information that needs to be manually annotated for faults by human with expertise knowledge costs too expensive in real industrial scenarios and is not always practicable to unknown fault category. In order to realize the zero-shot intelligent fault diagnosis and extend to a more general case, we propose an intelligent fault diagnosis system in this paper, using the statistical attributes automatically extracted from the vibration signal-self. To obtain the statistical attributes, the signals are decomposed by Ensemble Empirical Mode Decomposition (EEMD) to get their detailed time and frequency characteristics. And the statistical description of the time and frequency domains is taken as the attributes to relate the unseen categories with the seen ones. With the attributes, Gaussian models of the seen categories are established. And those of the unseen category are estimated by the attribute strength relation between the seen and unseen categories. The unseen category is finally predicted by Maximum A Posterior probability (MAP). The experiments on fault dataset show that the proposed system can obtain well recognition performance compared with the classic methods. Among them, the accuracy of zero-shot fault diagnosis can approach to 86%. And the performance can be further improved through attribute selection.

Long-short pile composite foundation (PC-LSPCF) composed of part-screw pile and cement-soil compaction pile is a new railway foundation treatment method, which has been widely used in high-speed railway construction projects in China. To explore the dynamic characteristics and deformation characteristics of railway PC-LSPCF under long-term train loads, the dynamic characteristics of long piles, short piles, and soil between piles under long-term train loads are tested by an indoor dynamic model test. The dynamic amplification of pile and soil under dynamic load and the temporal and spatial distribution of peak response are analyzed, and the stress and deformation development mechanism of PC-LSPCF under cyclic loading of large-cycle trains is revealed. The results show that the neutral point of the long pile is at 1/2 of the pile length and that of the short pile is at 3/8 of the pile length. The part-screw pile has a certain absorption effect on vibration energy. The deformation of a long-short pile composite foundation under long-term train loads can be divided into three stages: extreme growth, transition, and stability. The train speed is negatively correlated with the cumulative settlement of the long-short pile composite foundation. The higher the train speed, the smaller the cumulative settlement, and the smaller the number of cycles of the N-S curve entering the gentle period. As the number of train cyclic loads increases, the load-sharing relationship of the long pile-short pile-soil system will be redistributed. The research results have important reference significance for the optimization design of high-speed railway foundation treatment.

Cancer cachexia is a multifactorial syndrome defined by progressive loss of body weight with specific depletion of skeletal muscle and adipose tissue. Since there are no FDA-approved drugs that are available, nutritional intervention is recommended as a supporting therapy. Creatine supplementation has an ergogenic effect in various types of sports training, but the regulatory effects of creatine supplementation in cancer cachexia remain unknown. In this study, we investigated the impact of creatine supplementation on cachectic weight loss and muscle loss protection in a tumor-bearing cachectic mouse model, and the underlying molecular mechanism of body weight protection was further assessed. We observed decreased serum creatine levels in patients with cancer cachexia, and the creatine content in skeletal muscle was also significantly decreased in cachectic skeletal muscle in the C26 tumor-bearing mouse model. Creatine supplementation protected against cancer cachexia-associated body weight loss and muscle wasting and induced greater improvements in grip strength. Mechanistically, creatine treatment altered the dysfunction and morphological abnormalities of mitochondria, thus protecting against cachectic muscle wasting by inhibiting the abnormal overactivation of the ubiquitin proteasome system (UPS) and autophagic lysosomal system (ALS). In addition, electron microscopy revealed that creatine supplementation alleviated the observed increase in the percentage of damaged mitochondria in C26 mice, indicating that nutritional intervention with creatine supplementation effectively counteracts mitochondrial dysfunction to mitigate muscle loss in cancer cachexia. These results uncover a previously uncharacterized role for creatine in cachectic muscle wasting by modulating cellular energy metabolism to reduce the level of muscle cell atrophy.

Based on the analysis of earthquakes with M≥5 in Huayingshan fault zone and the present moderate and small seismicity, the background and regional seismicity characteristics in this area are discussed. It is considered that the southern section of the fault zone is the main seismicity area, especially in Yibin, followed by the middle and northern sections. The distribution characteristics of “quiet-active” period of earthquakes with M≥5, the law of “weak activity-enhancement” of earthquakes with M≥3, and the acceleration of strain energy release rate after Changning MS6.0 earthquake in 2019 provide references for the prediction of earthquakes with M≥5 in this area.

The preparation of nanocages with unprecedented architectures may lead to new functions. Here the authors report the self-assembly of organic cages featuring twin cavities; the geometry and pocket size determine the molecular packing and the proton conductivity performance.

Convergence of ICDT is one of the important technical trends in the evolution of wireless mobile communication.How to realize the convergence of wireless network and AI technology is an important topic in the evolution of wireless network.Based on the concept of native AI, AI was applied for wireless resources optimization.6G context-aware wireless network architecture was proposed and AI was introduced into RRM to form an intelligent controller (AI-driven RRM), which completed the intelligent wireless resource management.Driven by big data and artificial intelligence, intelligent management of wireless resources was realized.In the deployment, the intelligent controller is deployed according to its functions and supports dynamic function scaling, so that it can be deployed independently of base station to minimize the cost of hardware.