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Abstract Background Puberty onset signifies the beginning of sexual maturation and reproductive phase in poultry indeed, and plays an essential role in genetics and breeding. Studying gonadal development is one of the important approaches to exploring the genetic mechanism of puberty onset. Result In our study, the phenotype data of the testes and ovaries of the 120-day-old Nonghua duck showed a large coefficient of variation, indicating that their gonads were in different developmental states. The CNV-based GWAS results for 358 Nonghua ducks showed two deleted-type CNVRs were associated with testicular weight (TW) and testicular percentage (TP), namely CNVR492 (Chr2: 59473501–59478500 bp) and CNVR494 (Chr2: 59514001–59517000 bp). Additionally, two both-type CNVRs were associated with ovarian weight (OW) and ovarian percentage (OP), namely CNVR557 (Chr2: 99951001–99956500 bp) and CNVR891 (Chr7: 39115001–39122500 bp). RNA-seq analysis showed 6228 and 1070 differentially expressed genes (DEGs) related to the TW and OW. These DEGs were mainly enriched in the MAPK signaling pathway, cytokine-cytokine receptor interaction, and focal adhesion, which were reported to affect gonadal development. Further, by joint analysis of CNV-based GWAS and RNA-seq data, 3 genes, including LOC106019197, CDH19 (LOC101793040), and TYW5 were identified as potential candidate genes for TW and OW. LOC106019197 and CDH19 were down-regulated in the heavier-testes group (> 5 g), while TYW5 was also down-regulated in the heavier-ovaries group (> 3 g). The qRT-PCR revealed that LOC106019197 and CDH19 exhibited higher expression levels in the wild/CN0 and CN0/CN0 genotypes compared to the wild/wild genotype. TYW5 showed the highest expression level in the wild/CN0 genotype and the lowest in the CN2/CN2 genotype. In addition, the expression levels of LOC106019197 and CDH19 were significantly higher at 0w than at 8w and 24w. Conclusion Our results revealed that LOC106019197 and CDH19 may act as inhibitors of duck testicular development. TYW5 may play a role in delaying ovarian development. These findings provide new insights into the mechanism of puberty onset in ducks.

As a widely spread Gram-negative bacteria, Klebsiella pneumoniae (KP) mainly causes acquired infections in hospitals, such as lung infections, urinary tract infections, and bloodstream infections. In recent years, the number of multidrug-resistant KP strains has increased dramatically, posing a great threat to human health. Carbapenem-resistant KP (CRKP) can be colonized in human body, especially in gastrointestinal tract, and some colonized patients can be infected during hospitalization, among which invasive operation, underlying disease, admission to intensive care unit, antibiotic use, severity of the primary disease, advanced age, operation, coma, and renal failure are common risk factors for secondary infection. Active screening and preventive measures can effectively prevent the occurrence of CRKP infection. Based on the epidemiological status, this study aims to discuss the correlation between colonization and secondary infection induced by CRKP and risk factors for their happening and provide some reference for nosocomial infection prevention and control.

Abstract Despite the well-established significance of transcription factors (TFs) in pathogenesis, their utilization as pharmacological targets has been limited by the inherent challenges in modulating their protein interactions. The lack of defined small-molecule binding pockets and the nuclear localization of TFs do not favor the use of traditional tools. Aptamers possess large molecular weights, expansive blocking surfaces and efficient cellular internalization, making them compelling tools for modulating TF interactions. Here, we report a structure-guided design strategy called Blocker-SELEX to develop inhibitory aptamers (iAptamers) that selectively block TF interactions. Our approach leads to the discovery of iAptamers that cooperatively disrupt SCAF4/SCAF8-RNAP2 interactions, dysregulating RNAP2-dependent gene expression, which impairs cell proliferation. This approach is further applied to develop iAptamers blocking WDR5-MYC interactions. Overall, our study highlights the potential of iAptamers in disrupting pathogenic TF interactions, implicating their potential utility in studying the biological functions of TF interactions and in nucleic acids drug discovery.

IntroductionExtensive trauma frequently disrupts endometrial regeneration by diminishing endometrial stem cells/progenitor cells, affecting female fertility. While bone marrow mesenchymal stem cell (BMSC) transplantation has been suggested as an approach to address endometrial injury, it comes with certain limitations. Recent advancements in endometrial epithelial organoids (EEOs) have displayed encouraging potential for endometrial regeneration. Therefore, this study aims to explore whether EEOs surpass BMSCs in their ability to repair injured endometrium and to examine whether the restoration process involves the integration of EEOs into the endometrial tissue of the recipient.MethodsWe developed rat EEOs (rEEOs) mimicking the features of the rat endometrium. Subsequently, we created a rat model of endometrial injury to compare the effects of rEEOs and rat BMSCs (rBMSCs) on endometrial regeneration and reproductive recovery. Bulk RNA-sequencing analysis was conducted to further investigate the capacity of rEEOs for endometrial regeneration and to identify discrepancies between rEEOs and rBMSCs. Additionally, to track the fate of the transplanted cells in vivo, we transplanted green fluorescent protein (GFP) -labelled rEEOs or red fluorescent protein (RFP) -labelled rBMSCs.ResultsIn a rat model of endometrial injury, we observed that fertility recovery in rats transplanted with rEEOs was more comparable to that of normal rats than in those treated with rBMSC. rEEOs possess a high concentration of endometrial epithelial stem/progenitor cells and secrete vascular endothelial growth factor (VEGF)-A to promote endometrial neovascularization. Significantly, we observed that cells from GFP-labelled rEEOs could integrate and differentiate into functional glands within the injured endometrium of recipient rats.DiscussionEEOs offer a transformative approach to address the challenges of endometrial trauma. Their remarkable regenerative potential holds promise for the restoration of damaged endometrium. As we venture into the future, the concept of utilizing patient-specific EEOs for transplantation emerges as a tantalizing prospect. However, the EEOs in our experiments were mainly cultured in Matrigel, which has barriers to clinical translation as a biomaterial, a new biomaterial to be explored. Secondly, our experiments have been successful only in rat models, and more efforts need to be made before clinical translation.

ABSTRACT The aim of this study was to explore the mechanisms and molecular epidemiology of carbapenem resistance in the carbapenem-resistant Enterobacter cloacae complex (CRECC) over a decade in a tertiary hospital in Zhejiang, China. From January 2011 to December 2021, we collected a total of 931 Enterobacter cloacae complex (ECC) isolates from a tertiary hospital in Zhejiang, China. Antimicrobial susceptibility tests were performed. Whole-genome sequencing was used to analyze the molecular characteristics of the CRECC isolates. For carbapenem-resistant strains, efflux inhibitor assay and quantitative real-time PCR (qRT-PCR) were performed to evaluate the function of efflux pumps. A total of 82 CRECC isolates were detected, and the rate of resistance for carbapenems was 8.8%, increasing from 5.5% in 2011 to 18.3% in 2019, with an overall increasing trend, with Enterobacter hormaechei subsp. hoffmannii being the predominant species. Among the CRECC, 24 (24/931) isolates were found to produce carbapenemases, including NDM-1, NDM-5, IMP-4, and KPC-2. Among all carbapenemases, NDM-1 was the most prevalent, accounting for 62.5% (15/24) of carbapenemases, followed by NDM-5 (5/24). Genes encoding extended-spectrum beta-lactamases (47/82) and AmpC (76/82) were also identified, with blaSHV-12 and blaACT being the predominant ones, respectively. Multilocus sequence typing revealed 28 different sequence types, among which ST78 was the predominant, followed by ST93 and ST177. IncFIB was the most common type of plasmid replicon. Efflux inhibitor assay and qRT-PCR indicated that the overexpression of efflux pumps was involved in carbapenem resistance mechanisms. Additionally, disrupted outer membrane proteins also contribute to carbapenem resistance. The detection rate of CRECC was rising in the tertiary hospital. BlaNDM-1 and blaNDM-5 were the main carbapenem resistance genes. Our study revealed the presence of carbapenem-resistant ECC strains, emphasizing the need for effective infection prevention approaches to reduce the prevalence of CRECC.IMPORTANCEThe emergence and spread of the carbapenem-resistant Enterobacter cloacae complex (CRECC) have become a significant public health problem. CRECC strains frequently harbor multiple drug resistance genes and can be epidemic within healthcare facilities. The study explored the characteristics and prevalence of CRECC strains in the same hospital over a decade, which provides a theoretical basis for epidemiologic surveillance and clinical treatment.

Introduction: Vaccines remain the cornerstone for prevention of COVID-19. Particularly in rural areas, community pharmacists are among the most accessible healthcare professionals. Their advocacy for immunization can help overcome patients' vaccine hesitancy and close the disparity gap between rural and urban regions. This study explored factors influencing the willingness to recommend and administer COVID-19 vaccines among rural community pharmacists after the first U.S. vaccine rollout. Methods: A convenience sample of rural community pharmacists completed a selfadministered, validated paper/online survey (n = 86, 23.4% response rate). Measures included COVID-19 vaccination status, perceived benefits of offering COVID-19 immunization services at the pharmacy, and willingness to recommend and administer COVID-19 vaccines. Descriptive, bivariate, and multivariate statistics were used to analyze potential nonresponse bias, survey responses, and associations between variables as appropriate. Alpha was set at 0.05. Results: The proportion of pharmacists who were vaccinated against COVID-19 was 79.1%. Over 75% of participants were in favor of recommending COVID-19 immunizations to eligible family members and patients and almost 85% agreed that they would administer COVID-19 vaccines to their patients. Most pharmacists perceived COVID-19 immunization services to be beneficial, such as attracting more patients into the pharmacy (81.2%), increasing pharmacy revenue (75.3%), and enhancing relationships with local clinics/public health agencies (74.1%). COVID-19 vaccination status and the perceived benefit of offering immunization services at the pharmacy were significantly associated with pharmacists' willingness to recommend and administer COVID-19 vaccines. Conclusion: The relatively high rates of COVID-19 vaccination uptake and the strong willingness of rural community pharmacists to recommend and administer COVID-19 vaccines, after the first national vaccine rollout, were encouraging. The findings underscore the importance of engaging rural community pharmacists in efforts to prepare for and respond to future pandemics and public health crises.

ABSTRACT: Fluoride is one of the essential trace elements for body. However, excessive fluoride poses a major threat to human and animal health. Fluorosis may cause pathological damage of the duodenum, but the underlying mechanism needs to be further studied. This study was to investigate the effects of long-term exposure to sodium fluoride (0, 500, 1,000, 2,000 mg/kg) on the duodenum of chickens. The results showed that after NaF exposure, intestinal epithelial cells were disarranged, necrotic or even exfoliated, goblet cells and mucus secretion were increased, and inflammatory response was induced in duodenal tissue. Oxidative stress, endoplasmic reticulum stress (ERs), and heat shock proteins (HSPs) are an adaptive response, however long-term, excessive changes are detrimental. Fluorosis activates ERs through IRE1, PERK and ATF6 pathways, increases the expression of HSP60, HSP70 and HSP90, and causes apoptosis and oxidative damage in duodenal tissue. In addition, fluorosis can activate the MAPK signaling pathway. This article can provide a reference for exploring the potential duodenal toxicity of sodium fluoride.

The microbiota-associated factors that affect host susceptibility and adaptive immunity to influenza A virus (IAV) infection have not been fully elucidated. By comparing the microbiota composition between survivors and mice that succumbed to IAV strain PR8 infection, we identified that the commensal bacterium Blautia coccoides protects antibiotics (Abx)-treated or germ-free (GF) mice from PR8 infection by inducing functionally optimal virus-specific CD8+ T cell responses. Administration of exogenous acetate reproduced the protective effect of B. coccoides monocolonization in Abx and GF mice, enhancing oxidative phosphorylation and glycolysis as well as secretion of IFN-γ and granzyme B in virus-specific CD8+ T cells, dependent on GPR43 signaling and acetyl-CoA synthetase 2. Thus, we have demonstrated that microbiota-derived acetate possesses an antiviral effect that induces an optimal virus-specific CD8+ T cell response to IAV PR8 infection via GPR43-dependent metabolic reprogramming.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127−CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.

To investigate the epidemiology of ST20 carbapenem-resistant Klebsiella pneumoniae (CRKP) in China, and further explore the genomic characteristics of blaIMP-4 and blaNDM-1 coharboring isolates and plasmid contributions to resistance and fitness. Seven ST20 CRKP isolates were collected nationwide, and antimicrobial susceptibility testing was performed. Antimicrobial resistance genes, virulence genes, and plasmid replicons were identified via whole-genome sequencing, and clonality assessed via core-genome multilocus sequence typing. Furthermore, we found four dual-metallo-β-lactamases (MBL)-harbouring isolates, the gene location was detected by Southern blotting, and plasmid location analysis showed that blaIMP-4 was located on a separate plasmid, a self-conjugative fusion plasmid, or the bacterial chromosome. These isolates were subjected to long-read sequencing, the presence of blaIMP-4 in different locations was identified by genomic comparison, and transposon units were detected via inverse PCR. We subsequently found that blaIMP-4 on the fusion plasmid and bacterial chromosome was formed via intact plasmid recombination by the IS26 and ltrA, respectively, and the circular transposon unit was related to cointegration, however, blaIMP-4 in different locations did not affect the gene stability. The blaNDM-1-harbouring plasmid contributed to the increased resistance to β-lactams and shortened survival lag time which was revealed in plasmid cured isolates. In summary, the K. pneumoniae ST20 clone is a high-risk resistant clone. With the use of ceftazidime/avibactam, MBL-positive isolates, especially dual-MBL-harbouring isolates, should be given additional attention.

ObjectiveAcute kidney injury (AKI), a syndrome with high morbidity and mortality worldwide, frequently arises from renal ischemia-reperfusion (I/R) injury, particularly in surgical contexts. Despite extensive research, effective therapies for both AKI and its progression to renal interstitial fibrosis remain elusive. This study investigates the potential therapeutic efficacy of glucosamine (GS), an endogenous amino sugar, in alleviating I/R-induced AKI.MethodsA murine I/R injury model was utilized to evaluate the protective effects of GS. Mice were treated with GS prior to I/R injury, and renal tissues were harvested for biochemical, histological, and molecular analyses. Key markers of oxidative stress, mitochondrial integrity, and endoplasmic reticulum (ER) stress were measured. Additionally, inflammatory responses in proximal convoluted tubular epithelial cells exposed to TPHP, an environmental toxin, were assessed in vitro.ResultsGS administration markedly reduced oxidative stress levels, preserved mitochondrial structure, and mitigated ER stress in renal tissues following I/R injury. Moreover, GS significantly attenuated TPHP-induced inflammatory responses in proximal tubular epithelial cells, suggesting a targeted anti-inflammatory action.ConclusionThese findings highlight glucosamine’s potential as a therapeutic agent for AKI, offering protection through the modulation of oxidative, mitochondrial, and inflammatory pathways. This study provides foundational evidence for GS as a promising candidate for AKI intervention and opens avenues for further exploration of glucosamine in kidney disease therapeutics.

ABSTRACT Background The incidence of small cell lung cancer (SCLC) among Asian patients is on the rise. Nevertheless, there remains a deficiency in precise prognostic models tailored to the specific needs of this patient population. It is imperative to develop a novel nomogram aimed at forecasting the prognosis of Asian SCLC patients. Methods The SEER database supplied data on 661 Asian SCLC patients, who were then divided into training and internal validation sets through a random selection process. In addition, we identified 212 patients from a Chinese medical institution for the purpose of creating an external validation cohort. To forecast survival, we employed both univariate and multivariate analyses. The performance of our nomogram was assessed through calibration plots, the concordance index (C‐index), and decision curve analysis (DCA). Results Five independent prognostic factors were determined and integrated into the nomogram. C‐index values for the training and internal validation cohorts were 0.774 (95% confidence interval [CI] = 0.751–0.797) and 0.731 (95%CI = 0.690–0.772), respectively. In the external validation cohort, the C‐index is 0.712 (95% CI = 0.655–0.7692). Calibration curves demonstrated highly accurate predictions. When compared to the AJCC staging system, our model exhibited improved net benefits in DCA. Furthermore, the risk stratification system effectively differentiated patients with varying survival risks. Conclusion We have created a novel nomogram for predicting the survival of Asian patients with SCLC. This nomogram has been subjected to external validation and has shown its superiority over the conventional TNM staging system. It offers a more precise and reliable means of forecasting the prognosis of Asian SCLC patients.

As a high-intensity, high-standard institutional mechanism in land supervision and management, the State Land Supervision System (SLSS) plays a crucial role in deterring land-related violations, enforcing farmland protection, ensuring national food security, and facilitating sustainable agricultural development. However, previous research has seldom examined how the SLSS contributes to the low-carbon transformation of agriculture (LCTA). This study treats China’s routine land inspections as a quasi-natural experiment, utilizing panel data from 283 prefecture-level and higher cities from 2005 to 2016 to empirically analyze whether and how the SLSS supports LCTA. The findings reveal that the SLSS significantly advances LCTA, with the low-carbon agricultural development level in inspected cities increasing by approximately 2.17%. The SLSS promotes LCTA primarily through enhancing agricultural technological progress and encouraging agricultural scale operations. Compared to major grain-producing regions, high-poverty areas, and regions under significant fiscal pressure, the SLSS more effectively fosters LCTA in non-grain-producing areas, regions with lower poverty rates, and areas facing less fiscal strain. Furthermore, the SLSS has a more pronounced effect on advancing low-carbon agricultural development in cities that already demonstrate higher levels of low-carbon progress. This study provides novel empirical evidence regarding the environmental impacts of SLSS in the agricultural sector, offering insights relevant to the pursuit of agricultural modernization.

ABSTRACT: China has abundant local duck resource populations, and evaluating the characteristics of these breeds will help improve development and utilization. In this study, we conducted the first investigations of growth and slaughter performance on Sichuan Shelduck (n = 240), an endangered duck local breed. The average body weight is 1497.91 g at 90 d of age. According to the growth curve through data recorded every 2 wk, we observed a low relative growth rate (RGR) for the early growth stage. The RGR shows a decreasing trend with age increasing in the stage from 0 to 56 d of age. The SNP-based heritability estimation showed the growth rate has a relatively high heritability, indicating high genetic stability for this trait. In the correlation analysis, the percentage of leg muscle is positively correlated with the absolute growth rate (AGR) at 28 to 42 d of age, whereas it is negatively correlated with the earlier stages, exhibiting a time-specific correlation result. Additionally, genome-wide association studies (GWAS) identified PCSK6, TOX2, and TOMM7 as potential candidate genes influencing AGR (42–56) and AGR (56–90), while the candidate genes of slaughter traits were PTP4A2, FAM110B, TOX, UBXN2B, and FCHSD2. These results provide an important reference for further understanding the genetic basis of growth and meat production performance of Sichuan Shelduck.

Abstract Background Amino acids are the basic components of protein and an important index to evaluate meat quality. With the rapid development of genomics, candidate regions and genes affecting amino acid content in livestock and poultry have been gradually revealed. Hence, genome-wide association study (GWAS) can be used to screen candidate loci associated with amino acid content in duck meat. Result In the current study, the content of 16 amino acids was detected in 358 duck breast muscles. The proportion of Glu to the total amino acid content was relatively high, and the proportion was 0.14. However, the proportion of Met content was relatively low, at just 0.03. By comparative analysis, significant differences were found between males and females in 3 amino acids, including Ser, Met, and Phe. In addition, 12 SNPs were significantly correlated with Pro content by GWAS analysis, and these SNPs were annotated by 7 protein-coding genes; 8 significant SNPs were associated with Tyr content, and these SNPs were annotated by 6 protein-coding genes. At the same time, linkage disequilibrium (LD) analysis was performed on these regions with significant signals. The results showed that three SNPs in the 55–56 Mbp region of chromosome 3 were highly correlated with the leader SNP (chr3:55526954) that affected Pro content (r 2 > 0.6). Similarly, LD analysis showed that there were three SNPs in the 21.2–21.6 Mbp region of chromosome 13, which were highly correlated with leader SNP (chr13:21421661) (r 2 > 0.6). Moreover, Through functional enrichment analysis of all candidate genes. The results of GO enrichment analysis showed that several significant GO items were associated with amino acid transport function, including amino acid transmembrane transport and glutamine transport. The results further indicate that these candidate genes are closely associated with amino acid transport. Among them, key candidate genes include SLC38A1. For KEGG enrichment analysis, CACNA2D3 and CACNA1D genes were covered by significant pathways. Conclusion In this study, GWAS analysis found a total of 28 significant SNPs affecting amino acid content. Through gene annotation, a total of 20 candidate genes were screened. In addition, Through LD analysis and enrichment analysis, we considered that SERAC1, CACNA2D3 and SLC38A1 genes are important candidate genes affecting amino acid content in duck breast muscle.

Abstract Background Mucosal-associated invariant T (MAIT) cells have been reported to regulate tumor immunity. However, the immune characteristics of MAIT cells in non-small cell lung cancer (NSCLC) and their correlation with the treatment efficacy of immune checkpoint inhibitors (ICIs) remain unclear. Patients and methods In this study, we performed single-cell RNA sequencing (scRNA-seq), flow cytometry, and multiplex immunofluorescence assays to determine the proportion and characteristics of CD8+MAIT cells in patients with metastatic NSCLC who did and did not respond to anti-PD-1 therapy. Survival analyses were employed to determine the effects of MAIT proportion and C-X-C chemokine receptor 6 (CXCR6) expression on the prognosis of patients with advanced NSCLC. Results The proportion of activated and proliferating CD8+MAIT cells were significantly higher in responders-derived peripheral blood mononuclear cells (PBMCs) and lung tissues before anti-PD-1 therapy, with enhanced expression of cytotoxicity-related genes including CCL4, KLRG1, PRF1, NCR3, NKG7, GZMB, and KLRK1. The responders’ peripheral and tumor-infiltrating CD8+MAIT cells showed an upregulated CXCR6 expression. Similarly, CXCR6+CD8+MAIT cells from responders showed higher expression of cytotoxicity-related genes, such as CST7, GNLY, KLRG1, NKG7, and PRF1. Patients with ≥15.1% CD8+MAIT cells to CD8+T cells ratio and ≥35.9% CXCR6+CD8+MAIT cells to CD8+MAIT cells ratio in peripheral blood showed better progression-free survival (PFS) after immunotherapy. The role of CD8+MAIT cells in lung cancer immunotherapy was potentially mediated by classical/non-classical monocytes through the CXCL16-CXCR6 axis. Conclusion CD8+MAIT cells are a potential predictive biomarker for patients with NSCLC responding to anti-PD-1 therapy. The correlation between CD8+MAIT cells and immunotherapy sensitivity may be ascribed to high CXCR6 expression.

Abstract The “shuttle effect” issue severely hinders the practical application of lithium–sulfur (Li–S) batteries, which is primarily caused by the significant accumulation of lithium polysulfides in the electrolyte. Designing effective catalysts is highly desired for enhancing polysulfide conversion to address the above issue. Here, the one‐step flash‐Joule‐heating route is employed to synthesize a W‐W2C heterostructure on the graphene substrate (W‐W2C/G) as a catalytic interlayer for this purpose. Theoretical calculations reveal that the work function difference between W (5.08 eV) and W2C (6.31 eV) induces an internal electric field at the heterostructure interface, accelerating the movement of electrons and ions, thus promoting the sulfur reduction reaction (SRR) process. The high catalytic activity is also confirmed by the reduced activation energy and suppressed polysulfide shuttling by in situ Raman analyses. With the W‐W2C/G interlayer, the Li–S batteries exhibit an outstanding rate performance (665 mAh g−1 at 5.0 C) and cycle steadily with a low decay rate of 0.06% over 1000 cycles at a high rate of 3.0 C. Moreover, a high areal capacity of 10.9 mAh cm−2 (1381.4 mAh g−1) is obtained with a high area sulfur loading of 7.9 mg cm−2 but a low electrolyte/sulfur ratio of 9.0 µL mg−1.

As exemplified by the COVID-19 pandemic, the design and implementation of data-driven health surveillance, like digital contact tracing (DCT) apps, carry significant implications for society. However, its rushed development calls for careful consideration from all involved stakeholders to achieve a shared understanding and engage in joint-sensemaking in order to implement DCT collaboratively and effectively utilize it in the fight against the pandemic. Yet, the empirical ground truth and theoretical mechanism of joint-sensemaking are both unclear. Drawing on this gap, this article applies a multistep approach, including sentiment analysis, topic analysis coupled with regression and unique network analysis, to thoroughly explore, examine, and explain the dynamic process of joint-sensemaking in the context of a public crisis. Based on evidence from 113,264 Weibo posts, we illustrate two joint-sensemaking pathways and three key interventions using the case of China's Health Code in the context of the DCT. We reveal that the effectiveness of different interventions and contributions made by stakeholders vary significantly between different joint-sensemaking pathways. Specifically, we find that official media and opinion leaders act as crucial mediators in bridging intervention conductors and the public. However, their influence presents heterogeneity toward different network modularity, thus leading to distinct patterns. Additionally, inconsistent with previous literature, we find that within the context of the China Health Code, official media has a greater impact on opinion leaders in engaging the public.

ABSTRACT: The primary feathers of ducks have important economic value in the poultry industry. This study quantified the primary feather phenotype of Nonghua ducks, including the primary feathers' length, area, distribution of black spots, and feather symmetry. And genome-wide association analysis was used to screen candidate genes that affect the primary feather traits. The genome-wide association study (GWAS) results identified the genetic region related to feather length (FL) on chromosome 2. Through Linkage disequilibrium (LD) analysis, candidate regions (chr2: 115,246,393–116,501,448 bp) were identified and were further annotated to 5 genes: MRS2, GPLD1, ALDH5A1, KIAA0319, and ATP9B. Secondly, candidate regions related to feather black spots were identified on chromosome 21. Through LD analysis, the candidate regions (chr21: 163,552–2,183,853 bp) were screened and further annotated to 47 genes. Among them, STK4, CCN5, and YWHAB genes were related to melanin-related pathways or pigment deposition, which may be key genes affecting the distribution of black spots on feathers. In addition, we also screened 125 genes on multiple chromosomes that may be related to feather symmetry. Among them, significant SNPs on chromosome 1 were further identified as candidate regions (chr1: 142,118,209–142,223,605 bp) through LD analysis and annotated into 2 genes, TGFBRAP1 and LOC113839965. These results reported the genetic basis of the primary feather from multiple phenotypes, and offered valuable insights into the genetic basis for the growth and development of duck feathers and feather color pattern.

Objective: This study aims to diagnose Rotator Cuff Tears (RCT) and classify the severity of RCT in patients with Osteoporosis (OP) through the analysis of shoulder joint anteroposterior (AP) X-ray-based localized proximal humeral bone mineral density (BMD) measurements and clinical information based on machine learning (ML) models. Methods: A retrospective cohort of 89 patients was analyzed, including 63 with both OP and RCT (OPRCT) and 26 with OP only. The study analyzed a series of shoulder radiographs from April 2021 to April 2023. Grayscale values were measured after plotting ROIs based on AP X-rays of shoulder joint. Five kinds of ML models were developed and compared based on their performance in predicting the occurrence and severity of RCT from ROIs' greyscale values and clinical information (age, gender, advantage side, lumbar BMD, and acromion morphology (AM)). Further analysis using SHAP values illustrated the significant impact of selected features on model predictions. Results: R1-6 had a positive correlation with BMD respectively. The nine variables, including greyscale R1-6, age, BMD, and AM, were used in the prediction models. The RF model was determined to be superior in effectively diagnosing RCT in OP patients, with high AUC scores of 0.998, 0.889, and 0.95 in the training, validation, and testing sets, respectively. SHAP values revealed that the most influential factors on the diagnostic outcomes were the grayscale values of all cancellous bones in ROIs. A column-line graph prediction model based on nine variables was constructed, and DCA curves indicated that RCT prediction in OP patients was favored based on this model. Furthermore, the RF model was also the most superior in predicting the types of RCT within the OPRCT group, with an accuracy of 86.364% and 73.684% in the training and test sets, respectively. SHAP values indicated that the most significant factor affecting the predictive outcomes was the AM, followed by the grayscale values of the greater tubercle, among others. Conclusions: ML models, particularly the RF algorithm, show significant promise in diagnosing RCT occurrence and severity in OP patients using conventional shoulder X-rays based on the nine variables. This method presents a cost-effective, accessible, and non-invasive diagnostic strategy that has the potential to substantially enhance the early detection and management of RCT in OP patient population.

There are no standard third-line or beyond treatments for patients with driver mutation-positive advanced lung adenocarcinoma (LUAD). Anlotinib was approved as a third-line multitarget drug in China in 2018. Limited data are available regarding the efficacy and safety of anlotinib compared with chemotherapy. To investigate the efficacy and safety of anlotinib compared with traditional chemotherapy in patients with epidermal growth factor receptor (EGFR)-positive advanced LUAD. We conducted a retrospective study of 83 EGFR mutation-positive patients with advanced LUAD between 2011 and 2022. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, whereas the objective response rate (ORR) and disease control rate (DCR) were the secondary endpoints. Anlotinib-related adverse events (AEs) were recorded to evaluate the safety of anlotinib. 39 patients with LUAD received anlotinib and 44 patients with LUAD received chemotherapy were enrolled in the study. Patients treated with anlotinib exhibited longer PFS (11.2 vs 4.5 months, P

The Late Quaternary activity characteristics of secondary faults located between the main active faults at the boundaries of large basins are of great significance to the overall understanding of regional seismic hazards. The Wulashan Northern Fault (WNF) is located on the northern side of the Ordos Block, within the Northern Margin Fault Basin in North China, between the Sertengshan Piedmont Fault and Daqingshan Piedmont Fault. Current research on the geometry and kinematics of the WNF needs to be improved. In this study, we aimed to determine the shallow structural characteristics and Late Quaternary activity of the WNF using shallow seismic exploration and composite drilling geological cross-sectional analysis. The results indicate that the WNF is not a single surface fault but multiple branches with a northward-dipping stepped surface distribution. The latest activity of the F1 branch with a maximum coseismic vertical dislocation of 0.9 m occurred before 47.08 ± 3.7 ka B.P. The latest and older activities of the branch of F2 with a maximum coseismic vertical dislocation of 0.96 m and 1.15 m occurred before 73.8 ± 2.8 ka B.P. and 91.2 ± 4.4 ka B.P., respectively. According to a series of empirical relationships between length of surface rupture and magnitude, the maximum potential magnitude of the earthquake was determined to be M = 6.5–7.0. We argue that even though the Late Quaternary activity of the WNF was weaker than that of the other boundary faults of the Hetao Basin, the local urban and rural planning and land and resources construction in the Hetao Basin region should pay attention to the seismic risk of the WNF as an independent section in the future for the effect of secular tectonic loading.

Abstract Liver fibrosis can cause hepatitis B virus (HBV)‐associated hepatocellular carcinoma. Menstrual blood‐derived mesenchymal stem cells (MenSCs) can ameliorate liver fibrosis through paracrine. Single‐cell RNA sequencing (scRNA‐seq) may be used to explore the roadmap of activated hepatic stellate cell (aHSC) inactivation to target liver fibrosis. This study established HBV transgenic (HBV‐Tg) mouse model of carbon tetrachloride (CCl4)‐induced liver fibrosis and demonstrated that MenSCs migrated to the injured liver to improve serological indices and reduce fibrotic accumulation. RNA‐bulk analysis revealed that MenSCs mediated extracellular matrix accumulation and cell adhesion. Liver parenchymal cells and nonparenchymal cells were identified by scRNA‐seq in the control, CCl4, and MenSC groups, revealing the heterogeneity of fibroblasts/HSCs. A CellChat analysis revealed that diminished intercellular adhesion molecule (ICAM) signaling is vital for MenSC therapy. Specifically, Icam1 in aHSCs acted on Itgal/Itgb2 and Itgam/Itgb2 in neutrophils, causing decreased adhesion. The expression of Itgal, Itgam, and Itgb2 was higher in CCl4 group than in the control group and decreased after MenSC therapy in neutrophil clusters. The Lcn2, Pglyrp1, Wfdc21, and Mmp8 had high expression and may be potential targets in neutrophils. This study highlights interacting cells, corresponding molecules, and underlying targets for MenSCs in treating HBV‐associated liver fibrosis.

We proposed an original type of multipass cell named symmetric optical multipass matrix system (SMMS), in which the same matrix patterns of various sizes can be formed on both sides. According to its special symmetric configurations, the SMMS design problem is modeled as a variant of the classical traveling salesman problem, which can be rapidly solved by evolutionary optimization algorithms. Two sets of 3-mirror SMMSs are designed, analyzed and built, which show superior characteristics of high stability, desirable beam quality and adjustable optical path lengths. Additionally, they can support simultaneous detection of multiple species with multi-laser channels. The proposed method is further extended to design a 4-mirror SMMS, which verifies the universality and robustness of the design methodology. The experimental observations are in consistent with the theoretical calculations. The newly proposed SMMSs have a broad application prospect in trace gas measurement.

Edible fungus polysaccharides have garnered significant attention from scholars due to their safety and potential anti-inflammatory activity. However, comprehensive summaries of their anti-inflammatory properties are still rare. This paper provides a detailed overview of the anti-inflammatory effects and mechanisms of these polysaccharides, as well as their impact on inflammation-related diseases. Additionally, the relationship between their structure and anti-inflammatory activity is discussed. It is believed that this review will greatly enhance the understanding of the application of edible fungus polysaccharides in anti-inflammatory treatments, thereby significantly promoting the development and utilization of edible fungi.

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T–B‐cell interactions may contribute to its pathogenesis. This study aimed to investigate the characteristics and roles of CD4+ programmed death 1 (PD‐1)+Foxp3− T cells in relation to the B‐cell response in patients with RA. Methods This study included 155 patients with RA and 36 age‐ and sex‐matched healthy controls (HCs) from the Second Hospital of Dalian Medical University in China. Flow cytometry was used to assess the proportion and properties of peripheral CD4+PD‐1+Foxp3+ T cells, including their proliferation, activation, cytokine production, and capacity to induce B‐cell differentiation. Results The proportion of CD4+PD‐1+Foxp3− T cells was increased in patients with RA compared with HCs ([10.78 ± 0.60]% vs. [5.67 ± 0.40]%, p

Abstract Commensal bacteria generate immensely diverse active metabolites to maintain gut homeostasis, however their fundamental role in establishing an immunotolerogenic microenvironment in the intestinal tract remains obscure. Here, we demonstrate that an understudied murine commensal bacterium, Dubosiella newyorkensis, and its human homologue Clostridium innocuum, have a probiotic immunomodulatory effect on dextran sulfate sodium-induced colitis using conventional, antibiotic-treated and germ-free mouse models. We identify an important role for the D. newyorkensis in rebalancing Treg/Th17 responses and ameliorating mucosal barrier injury by producing short-chain fatty acids, especially propionate and L-Lysine (Lys). We further show that Lys induces the immune tolerance ability of dendritic cells (DCs) by enhancing Trp catabolism towards the kynurenine (Kyn) pathway through activation of the metabolic enzyme indoleamine-2,3-dioxygenase 1 (IDO1) in an aryl hydrocarbon receptor (AhR)-dependent manner. This study identifies a previously unrecognized metabolic communication by which Lys-producing commensal bacteria exert their immunoregulatory capacity to establish a Treg-mediated immunosuppressive microenvironment by activating AhR-IDO1-Kyn metabolic circuitry in DCs. This metabolic circuit represents a potential therapeutic target for the treatment of inflammatory bowel diseases.

Abstract Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.

Abstract Immune checkpoint inhibitors have transformed the treatment landscape of non-small cell lung cancer (NSCLC). However, accurately identifying patients who will benefit from immunotherapy remains a challenge. This study aimed to discover potential biomarkers for predicting immunotherapy response in NSCLC patients. Single-cell mass cytometry (CyTOF) was utilized to analyze immune cell subsets in peripheral blood mononuclear cells (PBMCs) obtained from NSCLC patients before and 12 weeks after single-agent immunotherapy. The CyTOF findings were subsequently validated using flow cytometry and multiplex immunohistochemistry/immunofluorescence in PBMCs and tumor tissues, respectively. RNA sequencing (RNA-seq) was performed to elucidate the underlying mechanisms. In the CyTOF cohort (n = 20), a high frequency of CD57+CD8+ T cells in PBMCs was associated with durable clinical benefit from immunotherapy in NSCLC patients (p = 0.034). This association was further confirmed in an independent cohort using flow cytometry (n = 27; p

Aiming to solve the problems that a wind turbine foundation with a foundation pipe may suffer from grouting, where the concrete around the interface collapses and the interface disintegrates under a long-term wind load, a kind of wind turbine foundation with a constrained structural shear connector is proposed. In this article, the scaling model tests and a finite element simulation of a traditional stud foundation pipe, perforated steel shear connector foundation pipe, and three groups of constrained structural shear connector foundation pipes with different anchored depths are presented. The force transmission mechanism and damage mechanism of constrained structural shear connector wind turbine foundations are revealed, and the shear resistance of a constrained structural shear connector is analyzed. The influences of buried depth and other parameters on the mechanical properties of the shear connector are also investigated. The results show that the constrained structural shear connector has the advantages of stronger interfacial stiffness and significant force transfer and diffusion, and can more effectively connect the foundation pipe and concrete foundation to work together. It can give full play to the material advantages of concrete and reinforcements, and effectively improve the embedded stiffness and durability of concrete foundations. It can solve the problem of cracks in concrete caused by local pressure. At the same time, it is suggested that the diameter of the surrounding concrete should be in the range of 3 to 4 D, and the embedment depth of the stud should not be less than 0.4 D to give full play to the performance of the constrained structural shear connector.

Summary: Many Gram-negative bacteria use type Ⅲ secretion system (T3SS) to inject effector proteins and subvert host signaling pathways, facilitating the growth, survival, and virulence. Notably, some bacteria harbor multiple distinct T3SSs with different functions. An extraordinary T3SS, the Escherichia coli Type III Secretion System 2 (ETT2), is widespread among Escherichia coli (E. coli) strains. Since many ETT2 carry genetic mutations or deletions, it is thought to be nonfunctional. However, increasing studies highlight ETT2 contributes to E. coli pathogenesis. Here, we present a comprehensive overview of genetic distribution and characterization of ETT2. Subsequently, we outline its functional potential, contending that an intact ETT2 may retain the capacity to translocate effector proteins and manipulate the host’s innate immune response. Given the potential zoonotic implications associated with ETT2-carrying bacteria, further investigations into the structure, function and regulation of ETT2 are imperative for comprehensive understanding of E. coli pathogenicity and the development of effective control strategies.

ABSTRACT: Endogenous retroviruses (ERV) are viral genomes integrated into the host genome and can be stably inherited. Although ERV sequences have been reported in some avian species’ genome, the duck endogenous retroviruses (DERV) genome has yet to be quantified. This study aimed to identify ERV sequences and characterize genes near ERVs in the duck genome by utilizing LTRhavest and LTRdigest tools to forecast the duck genome and analyze the distribution of ERV copies. The results revealed 1,607, 2,031, and 1,908 full-length ERV copies in the Pekin duck (ZJU1.0), Mallard (CAU_wild_1.0), and Shaoxing duck (CAU_laying_1.0) genomes, respectively, with average lengths of 7,046, 7,027, and 6,945 bp. ERVs are mainly distributed on the 1, 2, and sex chromosomes. Phylogenetic analysis demonstrated the presence of Betaretrovirus in 3 duck genomes, whereas Alpharetrovirus was exclusively identified in the Shaoxing duck genome. Through screening, 596, 315, and 343 genes adjacent to ERV were identified in 3 duck genomes, respectively, and their functions of ERV neighboring genes were predicted. Functional enrichment analysis of ERV-adjacent genes revealed enrichment for Focal adhesion, Calcium signaling pathway, and Adherens junction in 3 duck genomes. The overlapped genes were highly expressed in 8 tissues (brain, fat, heart, kidney, liver, lung, skin, and spleen) of 8-wk-old Mallard, revealing their important expression in different tissues. Our study provides a new perspective for understanding the quantity and function of DERVs, and may also provide important clues for regulating nearby genes and affecting the traits of organisms.

ABSTRACT: The cage-rearing model of the modern poultry industry makes the bones of birds, especially egg-laying birds, more vulnerable to fracture, which poses serious damage to the health of birds. Research confirms that genetic material plays an important role in regulating bone growth, development, and remodeling. However, the genetic architecture underlying bone traits is not well understood. The objectives of this study are to identify valuable genes and genetic markers through a genome-wide association study (GWAS) for breeding to improve the duck bone quality. First, we quantified the tibia and femur quality traits of 260 laying ducks. Based on GWAS, a total of 75 SNP loci significantly associated with bone quality traits were identified, and 67 potential candidate genes were annotated. According to gene function analysis, genes P4HA2, WNT3A, and BST1 et al may influence bone quality by regulating bone cell activity, calcium and phosphate metabolism, or bone collagen maturation and cross-linking. Meanwhile, combined with the transcriptome results, we found that HOXB cluster genes are also important in bone growth and development. Therefore, our findings were helpful in further understanding the genetic architecture of the duck bone quality and provided a worthy theoretical basis and technological support to improve duck bone quality by breeding.

Abstract Methyltransferase-like 3 (METTL3) is the key subunit of methyltransferase complex responsible for catalyzing N6-methyladenosine (m6A) modification on mRNA, which is the most prevalent post-transcriptional modification in eukaryotes. In this study, we utilized online databases to analyze the association between METTL3 expression and various aspects of tumorigenesis, including gene methylation, immunity, and prognosis. Our investigation revealed that METTL3 serves as a prognostic marker and therapeutic target for liver hepatocellular carcinoma (LIHC). Through experimental studies, we observed frequent upregulation of METTL3 in LIHC tumor tissue and cells. Subsequent inhibition of METTL3 using a novel small molecule inhibitor, STM2457, significantly impeded tumor growth in LIHC cell lines, spheroids, and xenograft tumor model. Further, transcriptome and m6A sequencing of xenograft bodies unveiled that inhibition of METTL3-m6A altered genes enriched in SMAD and MAPK signaling pathways that are critical for tumorigenesis. These findings suggest that targeting METTL3 represents a promising therapeutic strategy for LIHC.

Abstract Background Omalizumab is a valuable alternative treatment for allergic bronchopulmonary aspergillosis (ABPA). The effectiveness and safety of this medication have not been confirmed. The main purpose of this study was to evaluate the effectiveness and safety of omalizumab for ABPA. Methods This study involved a retrospective chart review. The main indicators used were asthma control test (ACT) scores, lung function parameters, doses of corticosteroids, acute exacerbation, hospitalization rates, total serum immunoglobulin E (IgE) levels, and blood eosinophil counts. Related adverse events were also reviewed to evaluate the safety of omalizumab. Results Fourteen patients with ABPA were included, of whom 10 (71%) concurrently had allergic rhinitis (AR). There were improvements in the mean percentages of the forced vital capacity, percentages of the forced expiratory volume in 1 s, and ACT score after omalizumab administration (p

ZnIn2S4 nanosheets are a promising photoanode for driving photoelectrochemical (PEC) hydrogen fuel production; nevertheless, poor charge separation and sluggish surface reaction kinetics hinder its PEC performance to an extreme degree. Herein, a facile element doping strategy (i.e., P element) was developed to obtain the desired photoanode. As a result, the ZnIn2S4-P (ZIS-P5) photoanode exhibits a remarkable photocurrent density of 1.66 mA cm−2 at 1.23 V versus a reversible hydrogen electrode (VRHE) and a much lower onset potential of 0.12 V vs. RHE for water oxidation. Careful electrochemical analysis confirms that the P doping and sulfur vacancies (Sv) not only facilitate the hole transfer, but also boost surface reaction kinetics. Finally, the “killing two birds with one stone” goal can be achieved. Moreover, the optimized photoanode also presents high PEC performance for urea oxidation, obtaining a photocurrent density of 4.13 mA cm−2 at 1.23 V vs. RHE. This work provides an eco-friendly, simple and effective method to realize highly efficient solar-to-hydrogen conversion.

Proteins serve as the building blocks of life and play essential roles in almost every cellular process [...]

Brucellosis is a global problem, with the causative agent being the genus Brucella. B. canis can cause undulant fever in dogs, which is a zoonotic disease that can spread not only among dogs but also to humans. This poses a public health threat to society. In this study, a rapid and straightforward immune colloidal gold test strip was developed for the diagnosis of canine brucellosis through the detection of anti-LPS antibodies in serum samples. Rabbit anti-canine IgG conjugated with colloidal gold was employed as the colloidal gold-labeled antibody. The extracted high-purity R-LPS was employed as the capture antigen in the test line (T-line), while goat anti-rabbit IgG was utilized as the capture antibody in the control line (C-line). The colloidal gold strip exhibited high specificity in the detection of brucellosis, with no cross-reaction observed with the common clinical canine diseases caused by Canine coronavirus (CCV), Canine distemper virus (CDV), and Canine parvovirus (CPV). In comparison to the commercial iELISA kit, the sensitivity and specificity of the colloidal gold test strip were found to be 95.23% and 98.76%, respectively. The diagnostic coincidence rate was 98.47%. The findings of this study indicate that colloidal gold test strips may be employed as a straightforward, expeditious, sensitive, and specific diagnostic instrument for the identification of canine brucellosis, particularly in resource-limited regions.

The influence of a company is not only related to its industry competitiveness, but also affects its public reputation and future development.However, there has been no unified standard for evaluating the influence of a company.GitHub is a representative open-source platform for software development code repositories.Existing research typically used the total number of stars a company receives for projects posted on GitHub to measure its influence, but this approach is difficult to measure the potential of small, micro, and nascent companies.The paper predicted the future influence level of a company by introducing the scientist's influence measure h-index, using GitHub as the information source, and modeling the company network.Features was extracted features based on this network to build the classifier, which predicted the future influence level of the company.The SHAP model explanation technique was further applied on this basis to identify the important features that determined the influence of a company.The experimental results showed that the XGBoost model achieved an accuracy of 0.92 and an average AUC of 0.93 on the real-world GitHub dataset.In summary, the proposed method could accurately and reliably predict the influence of companies.

BackgroundTo date, the clinical modulation for bone metabolism based on the neuro-bone mass regulation theory is still not popular. The stimulation of nerve systems to explore novel treatments for Postmenopausal osteoporosis (PMOP) is urgent and significant. Preliminary research results suggested that changes brain function and structure may play a crucial role in bone metabolism with PMOP. Thus, we set up a clinical trial to investigate the effect of the combination of repetitive transcranial magnetic stimulation (rTMS) and catgut embedding in acupoints (CEA) for PMOP and to elucidate the central mechanism of this neural stimulation in regulating bone metabolism.MethodThis trial is a prospective and randomized controlled trial. 96 PMOP participants will be randomized in a 1:1:1 ratio into a CEA group, an rTMS group, or a combined one. Participants will receive CEA, rTMS, or combined therapy for 3 months with 8 weeks of follow-up. The primary outcomes will be the changes in Bone Mineral Density scores, total efficiency of Chinese Medicine Symptoms before and after treatment. Secondary outcomes include the McGill Pain Questionnaire Short-Form, Osteoporosis Symptom Score, Mini-Mental State Examination, and Beck Depression Inventory-II. The leptin, leptin receptor, and norepinephrine levels of peripheral blood must be measured before and after treatment. Adverse events that occur during the trial will be recorded.DiscussionCEA achieves brain-bone mass regulation through the bottom-up way of peripheral-central while rTMS achieves it through the top-down stimulation of central-peripheral. CEA combined with rTMS can stimulate the peripheral-central at the same time and promote peripheral bone mass formation. The combination of CEA and rTMS may play a coordinating, synergistic, and side-effect-reducing role, which is of great clinical significance in exploring better treatment options for PMOP.Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300073863.

The 3D culture of intestinal organoids entails embedding isolated intestinal crypts and bone marrow mesenchymal stem cells within a growth factor-enriched matrix gel. This process leads to the formation of hollow microspheres with structures resembling intestinal epithelial cells, which are referred to as intestinal organoids. These structures encompass various functional epithelial cell types found in the small intestine and closely mimic the organizational patterns of the small intestine, earning them the name “mini-intestines”. Intestinal tumors are prevalent within the digestive system and represent a significant menace to human health. Through the application of 3D culture technology, miniature colorectal organs can be cultivated to retain the genetic characteristics of the primary tumor. This innovation offers novel prospects for individualized treatments among patients with intestinal tumors. Presently established libraries of patient-derived organoids serve as potent tools for conducting comprehensive investigations into tissue functionality, developmental processes, tumorigenesis, and the pathobiology of cancer. This review explores the origins of intestinal organoids, their culturing environments, and their advancements in the realm of precision medicine. It also addresses the current challenges and outlines future prospects for development.

Sensorineural hearing loss (SNHL) is a category of hearing loss that often leads to difficulty in understanding speech and other sounds. Auditory system dysfunction, including deafness and auditory trauma, results in cognitive deficits via neuroplasticity. Cognitive impairment (CI) refers to an abnormality in the brain’s higher intellectual processes related to learning, memory, thinking and judgment that can lead to severe learning and memory deficits. Studies have established a strong correlation between SNHL and CI, but it remains unclear how SNHL contributes to CI. The purpose of this article is to describe three hypotheses regarding this relationship, the mainstream cognitive load hypothesis, the co-morbidity hypothesis, and the sensory deprivation hypothesis, as well as the latest research progress related to each hypothesis.

ABSTRACT: Allometric growth of the forelimb and hindlimb is a widespread phenomenon observed in vertebrates. As a typical precocial bird, ducks exhibit more advanced development of their hindlimbs compared to their forelimbs, enabling them to walk shortly after hatching. This phenomenon is closely associated with the development of long bones in the embryonic stage. However, the molecular mechanism governing the allometric growth of duck forelimb and hindlimb bones is remains elusive.In this study, we employed phenotypic, histological, and gene expression analyses to investigate developmental differences between the humerus (forelimb bone) and tibia/femur (hindlimb bones) in duck embryos. Our results revealed a gradual increase in weight and length disparity between the tibia and humerus from E12 to E28 (embryo age). At E12, endochondral ossification was observed solely in the tibia but not in the humerus. The number of differentially expressed genes (DEGs) gradually increased at H12 vs. T12, H20 vs. T20, and H28 vs. T28 stages consistent with phenotypic variations. A total of 38 DEGs were found across all 3 stages. Protein-protein interaction network analysis demonstrated strong interactions among members of HOXD gene family (HOXD3/8/9/10/11/12), HOXB gene family (HOXB8/9), TBX gene family (TBX4/5/20), HOXA11, SHOX2, and MEIS2. Gene expression profiling indicated higher expression levels for all HOXD genes in the humerus compared to tibia while opposite trends were observed for HOXA/HOXB genes with low or no expression detected in the humerus. These findings suggest distinct roles played by different clusters within HOX gene family during skeletal development regulation of duck embryo's forelimbs versus hind limbs. Notably, TBX4 exhibited high expression levels specifically in tibia whereas TBX5 showed similar patterns exclusively within humerus as seen previously across other species’ studies. In summary, this study identified key regulatory genes involved in allometric growth of duck forelimb and hindlimb bones during embryonic development. Skeletal development is a complex physiological process, and further research is needed to elucidate the regulatory role of candidate genes in endochondral ossification.

Abstract Background The genetic locus responsible for duck body size has been fully explained before, but the growth trait-related genetic basis is still waiting to be explored. For example, the genetic site related to growth rate, an important economic trait affecting marketing weight and feeding cost, is still unclear. Here, we performed genome wide association study (GWAS) to identify growth rate-associated genes and mutations. Result In the current study, the body weight data of 358 ducks were recorded every 10 days from hatching to 120 days of age. According to the growth curve, we evaluated the relative and absolute growth rates (RGR and AGR) of 5 stages during the early rapid growth period. GWAS results for RGRs identified 31 significant SNPs on autosomes, and these SNPs were annotated by 24 protein-coding genes. Fourteen autosomal SNPs were significantly associated with AGRs. In addition, 4 shared significant SNPs were identified as having an association with both AGR and RGR, which were Chr2: 11483045 C>T, Chr2: 13750217 G>A, Chr2: 42508231 G>A and Chr2: 43644612 C>T. Among them, Chr2: 11483045 C>T, Chr2: 42508231 G>A, and Chr2: 43644612 C>T were annotated by ASAP1, LYN and CABYR, respectively. ASAP1 and LYN have already been proven to play roles in the growth and development of other species. In addition, we genotyped every duck using the most significant SNP (Chr2: 42508231 G>A) and compared the growth rate difference among each genotype population. The results showed that the growth rates of individuals carrying the Chr2: 42508231 A allele were significantly lower than those without this allele. Moreover, the results of the Mendelian randomization (MR) analysis supported the idea that the growth rate and birth weight had a causal effect on the adult body weight, with the growth rate having a greater effect size. Conclusion In this study, 41 SNPs significantly related to growth rate were identified. In addition, we considered that the ASAP1 and LYN genes are essential candidate genes affecting the duck growth rate. The growth rate also showed the potential to be used as a reliable predictor of adult weight, providing a theoretical reference for preselection.

Abstract Despite the advent of precision medicine and immunotherapy, mortality due to lung cancer remains high. The sonic hedgehog (SHH) cascade and its key terminal factor, glioma-associated oncogene homolog 1 (GLI1), play a pivotal role in the stemness and drug resistance of lung cancer. Here, we investigated the molecular mechanism of non-canonical aberrant GLI1 upregulation. The SHH cascade was upregulated in stem spheres and chemo-resistant lung cancer cells and was accountable for drug resistance against multiple chemotherapy regimens. GLI1 and the long non-coding RNA SOX2OT were positively regulated, and the GLI1-SOX2OT loop mediated the proliferation of parental and stem-like lung cancer cells. Further mechanistic investigation revealed that SOX2OT facilitated METTL3/14/IGF2BP2-mediated m6A modification and stabilization of the GLI1 mRNA. Additionally, SOX2OT upregulated METTL3/14/IGF2BP2 by sponging miR-186-5p. Functional analysis corroborated that GLI1 acted as a downstream target of METTL3/14/IGF2BP2, and GLI1 silencing could block the oncogenicity of lung cancer stem-like cells. Pharmacological inhibition of the loop remarkably inhibited the oncogenesis of lung cancer cells in vivo. Compared with paired adjacent normal tissues, lung cancer specimens exhibited consistently upregulated GLI1/SOX2OT/METTL3/14/IGF2BP2. The m6A-modified GLI1-SOX2OT loop may serve as a potential therapeutic target and prognostic predictor for lung cancer therapy and diagnosis in the clinic.

Abstract Background BI-RADS 4 breast lesions are suspicious for malignancy with a range from 2 to 95%, indicating that numerous benign lesions are unnecessarily biopsied. Thus, we aimed to investigate whether high-temporal-resolution dynamic contrast-enhanced MRI (H_DCE-MRI) would be superior to conventional low-temporal-resolution DCE-MRI (L_DCE-MRI) in the diagnosis of BI-RADS 4 breast lesions. Methods This single-center study was approved by the IRB. From April 2015 to June 2017, patients with breast lesions were prospectively included and randomly assigned to undergo either H_DCE-MRI, including 27 phases, or L_DCE-MRI, including 7 phases. Patients with BI-RADS 4 lesions were diagnosed by the senior radiologist in this study. Using a two-compartment extended Tofts model and a three-dimensional volume of interest, several pharmacokinetic parameters reflecting hemodynamics, including Ktrans, Kep, Ve, and Vp, were obtained from the intralesional, perilesional and background parenchymal enhancement areas, which were labeled the Lesion, Peri and BPE areas, respectively. Models were developed based on hemodynamic parameters, and the performance of these models in discriminating between benign and malignant lesions was evaluated by receiver operating characteristic (ROC) curve analysis. Results A total of 140 patients were included in the study and underwent H_DCE-MRI (n = 62) or L_DCE-MRI (n = 78) scans; 56 of these 140 patients had BI-RADS 4 lesions. Some pharmacokinetic parameters from H_DCE-MRI (Lesion_Ktrans, Kep, and Vp; Peri_Ktrans, Kep, and Vp) and from L_DCE-MRI (Lesion_Kep, Peri_Vp, BPE_Ktrans and BPE_Vp) were significantly different between benign and malignant breast lesions (P

The global demand for protein is on an upward trajectory, and peanut protein powder has emerged as a significant player, owing to its affordability and high quality, with great future market potential. However, the industry currently lacks efficient methods for rapid quality testing. This research paper addressed this gap by introducing a portable device with employed near-infrared spectroscopy (NIR) to quickly assess the quality of peanut protein powder. The principal component analysis (PCA), partial least squares (PLS), and generalized regression neural network (GRNN) methods were used to construct the model to further enhance the accuracy and efficiency of the device. The results demonstrated that the newly established NIR method with PLS and GRNN analysis simultaneously predicted the fat, protein, and moisture of peanut protein powder. The GRNN model showed better predictive performance than the PLS model, the correlation coefficient in calibration (Rcal) of the fat, the protein, and the moisture of peanut protein powder were 0.995, 0.990, and 0.990, respectively, and the residual prediction deviation (RPD) were 10.82, 10.03, and 8.41, respectively. The findings unveiled that the portable NIR spectroscopic equipment combined with the GRNN method achieved rapid quantitative analysis of peanut protein powder. This advancement holds a significant application of this device for the industry, potentially revolutionizing quality testing procedures and ensuring the consistent delivery of high-quality products to fulfil consumer desires.

Surface-coupled transition metal oxyhydroxide (TMOOH) on semiconductor (SC)-based photoanodes are effective strategies for improving photoelectrochemical (PEC) performance. However, there is a substantial difference between the current density and theoretical value due to the inevitable interfacial charge recombination of SC/TMOOH. Here, we employ BiVO4/FeNiOOH as a model, constructing the BiVO4/MnOx/CoOx/FeNiOOH integrated system by introducing a novel hetero-interface regulation unit, i.e., MnOx/CoOx. As expected, the optimized integrated system demonstrates a photocurrent density as high as 5.0 mA/cm2 at 1.23 V versus the reversible hydrogen electrode (RHE) under 1 sun AM 1.5G illumination, accompanied by 12-h stability. The detailed electrochemical analysis and intensity modulated photocurrent spectroscopy (IMPS) have confirmed that the high PEC performance mainly originates from the hetero-interface structure, which not only suppresses the interfacial charge recombination by accelerating the photogenerated hole transfer kinetics from BiVO4 to FeNiOOH but promotes the kinetics of surface oxygen evolution reaction (OER). Notably, these findings can also be extended to other structures (CeOx/CoOx), reflecting its universality. This finding has provided a new insight into the highly efficient solar energy conversion in the SC/TMOOH system.

AbstractBackground In order to better understand the interplay between ferroptosis and autophagy, enhance the interpretation of the crosstalk between these two forms of regulated cell death, develop the effective pharmacological mechanisms for cancer treatment, discover novel biomarkers for better diagnostic, and envisage the future hotspots of the research on ferroptosis and autophagy, we harnessed bibliometric tools to study the articles published from 2012 to 2022 on the relationship between ferroptosis and autophagy.Methods Web of Science Core Collection (WOSCC) database was used to conduct a comprehensive search and analysis of articles in this field from January 1, 2012, to September 1, 2022. The Citespace 6.1.R2 software and VOS viewer 6.1.8 software were utilized to analyze the overall structure of the network, network clusters, links between clusters, key nodes or pivot points, and pathways.Results A total of 756 articles associated with the crosstalk between ferroptosis and autophagy were published in 512 journals by 4183 authors in 980 organizations from 55 countries or regions. The distribution of countries and organizations was demonstrated using CiteSpace and VOS viewer. The top three countries with the most articles were China (n = 511), United States (n = 166), and Germany (n = 37). The most productive institutions were Guangzhou Medical University and Central South University (n = 42), but their centralities were relatively low, which values were respective 0.04 and 0.03. Kang and Tang published the most articles related to ferroptosis and autophagy (n = 49), followed by Jiao Liu (n = 22), Guido Kroemer (n = 20), and Daniel Klionsky (n = 12). Published studies on ferroptosis and asthma have the most cited counts. The top three keywords with the highest frequencies were autophagy (n = 283), cell death (n = 243), and oxidative stress (n = 165).Conclusion Our results provide insights into the development of recognition related to the crosstalk between ferroptosis and autophagy, and the current molecular crosslinked mechanisms in the context of common signal transduction pathways or affecting cellular environment to induce the adaptive stress response and to activate the particular form of regulated cell death (RCD), and the development of cancer treatment based on novel targets and signaling regulatory networks provided by ferroptosis and autophagy.