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Abstract Understanding the genetic factors related to meat drip loss is of great importance for animal breeding and production. In this study, we employed a combination of genome‐wide association study (GWAS) mapping and RNA sequencing (RNA‐seq) data to effectively identify potentially functional single nucleotide polymorphisms (SNPs) as well as candidate genes associated with drip loss (DL) in Beijing Black pigs. Initially, we conducted a single‐ and multi‐trait GWAS on drip loss traits in 441 Beijing Black pigs at 24 (DL24) and 48 (DL48) hours postmortem using the Illumina pig 50K SNP chip. Five SNPs with annotations for four genes (FGGY, LHFPL6, OSBPL1A, and NMNAT3) were consistently identified in single or multiple trait GWAS results, indicating their potential pleiotropic effects on drip loss. Next, a comprehensive comparative transcriptomic analysis was performed on samples of Beijing Black pigs exhibiting extremely high and low drip loss, resulting in the identification of 21 differentially expressed genes (DGEs) as potential candidates. Additionally, protein–protein interaction (PPI) network analysis revealed reciprocal regulatory relationships between FOXO1, OSBPL1A, DOCK1 (identified from GWAS) and the candidate DGEs obtained from RNA‐seq data. Therefore, we propose that these genes may impact drip loss traits through gene interactions. In conclusion, our integrative analysis screened candidate genes that may affect the drip loss traits in Beijing Black pigs, which provides crucial insights into the molecular mechanisms of drip loss and serves as a theoretical reference for improving meat quality in Beijing Black pigs.

Abstract Trillions of microbes colonize the ungulate gastrointestinal tract, playing a pivotal role in enhancing host nutrient utilization by breaking down cellulose and hemicellulose present in plants. Here, through large-scale metagenomic assembly, we established a catalog of 131,416 metagenome-assembled genomes (MAGs) and 11,175 high-quality species-level genome bins (SGBs) from 17 species of ungulates in China. Our study revealed the convergent evolution of high relative abundances of carbohydrate-active enzymes (CAZymes) in the gut microbiomes of plateau-dwelling ungulates. Notably, two significant factors contribute to this phenotype: structural variations in their gut microbiome genomes, which contain more CAZymes, and the presence of novel gut microbiota species, particularly those in the genus Cryptobacteroides, which are undergoing independent rapid evolution and speciation and have higher gene densities of CAZymes. Furthermore, these enrichment CAZymes in the gut microbiomes are highly enrichment in known metabolic pathways for short-chain fatty acid (SCFA) production. Our findings not only provide a valuable genomic resource for understanding the gut microbiomes of ungulates but also offer fresh insights into the interaction between gut microbiomes and their hosts, as well as the co-adaptation of hosts and their gut microbiomes to their environments.

Abstract Introduction The role of complement system in late stage of IgA nephropathy (IgAN) remains unknown. We therefore investigated the effects of complement system on worsening kidney function in advanced (stage 4 CKD) IgAN. Methods Renal specimens of 69 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2021, were stained using immunofluorescence (IF) and immunohistochemistry (IHC) for glomerular complement components. The primary outcome was progression to end-stage renal disease (ESRD). Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses. Results During a median follow-up of 18.0 months, 26 (37.7%) patients progressed to ESRD and none died. C1q and C3 deposition were detected in 12 and 66 patients, respectively. Higher eGFR [hazards ratio (HR), 0.852, 95% confidence interval (CI), 0.756–0.959; P = 0.008], higher C3 intensity (HR, 2.955, 95%CI, 1.063–8.220; P = 0.038) and T1-2 score (HR, 2.576, 95%CI, 1.205–5.576, P = 0.015) were predictive of time to ESRD in CKD 4 stage IgAN. Significant expressions of C1q (P = 0.005), C4d (P

Abstract pH value is a crucial index used to evaluate pork quality due to its direct impact on specific meat characteristics. This study investigated the genetic mechanisms influencing pH values through measurements taken from the longissimus dorsi muscle of Beijing Black pigs at 2 h (pH2h) and 24 h (pH24h) postmortem. A total of 614 Beijing Black pigs were subsequently genotyped using the Illumina Porcine 50K SNP Chip. Heritability estimates for pH2h and pH24h were found to be 0.19 and 0.25, respectively, with a genetic correlation of 0.53. Furthermore, we conducted both a genome‐wide association study (GWAS) and an RNA sequencing (RNA‐seq) analysis, the latter of which identified differentially expressed genes (DEGs) between high and low pH groups. We identified 31, 6, and 32 single‐nucleotide polymorphisms in the pH2h, pH24h, and pH2–24h traits, respectively. The GWAS results revealed the presence of the SYT5 gene in both the pH2h and pH2–24h traits, while the SNX13 gene was simultaneously identified in the pH24h and pH2–24h traits. The RNA‐seq results also found SYT5 to be highly expressed, while SNX13 did not exhibit differential expression. Moreover, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses based on the DEGs revealed potential links between pH levels and the glycogen metabolic process as well as associations with the regulation of cell proliferation and calcium ion transmembrane transport. Ultimately, SYT5 and SNX13 emerged as key candidate genes affecting pH values at 2 and 24 h, respectively. These findings contribute to a better understanding of the genetic mechanisms affecting pork quality and safety and offer insights for enhancing meat quality through genetic improvement.

Abstract Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.

Abstract Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

Background This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy (MN).Methods First, we performed a systematic literature review of prevalence of malignancy in THSD7A-associated MN. Then, we conducted a retrospective analysis of 454 patients diagnosed with MN through renal biopsy at our hospital between January 2016 and December 2020. We assessed the presence of serum anti-THSD7A antibodies and performed immunohistochemical staining of renal tissue for THSD7A. Subsequently, we followed patients with THSD7A-associated MN for a minimum of 3–5 years, collecting their clinical, pathological characteristics, and prognosis. Additionally, we conducted a literature review on patients with THSD7A-associated MN in conjunction with malignancy.Results We identified a total of nine articles containing comprehensive data on THSD7A-associated MN and malignancy. Among 235 patients with THSD7A-positive MN, 36 individuals had concurrent malignancies, resulting in a malignancy prevalence of 13.3% (95% CI: 8.9–17.7%). In our center, we followed up with 15 patients diagnosed with THSD7A-associated MN and observed three cases of concomitant tumors: two cases of lung adenocarcinoma and one case of small cell lung cancer with multiple metastases. The prevalence of malignancy in our cohort was 20%. Notably, we detected positive THSD7A staining in both renal and lung cancer tissues in one patient with small cell lung cancer.Conclusions Patients with THSD7A-associated MN should undergo vigilant follow-up assessments, with a particular focus on actively seeking potential tumorigenic lesions to prevent misdiagnosis or oversight.

Background This retrospective study aims to investigate the prevalence and immunopathologic characteristics of seropositive and seronegative hepatitis B virus-associated membranous nephropathy (HBV-MN).Methods Clinicopathologic and serologic records of 420 patients with histologically confirmed HBV-MN between January 2014 and July 2021 were examined to determine the prevalence of seropositive and seronegative HBV-MN. Serum anti-PLA2R antibody testing was conducted on 280 patients with HBV-associated membranous nephropathy (HBV-MN) from August 2018 to July 2021. Immunopathologic characteristics of HBV-MN patients and anti-PLA2R antibody positivity were analyzed.Results Among 420 pathologically confirmed HBV-MN patients, 230 (54.8%) were seropositive for HBV. The seropositive group exhibited higher blood creatinine values and incidence of liver function abnormalities than the seronegative group (p

Aim: The uplift of the Qinghai-Tibet Plateau provides an opportunity to understand the diversity patterns and their driving processes in high and low elevations regions of Qilian Mountains. However, the potential mechanisms leading to differences in multi-dimensional alpha diversity and beta diversity patterns between high and low elevation regions are unclear. Present study aims to investigate the response of bird communities respond to the overall elevation gradient and environmental factors drive different diversity patterns. Methods: The wild bird surveys were conducted during both the breeding and migration season in the north (NSQM) and south slopes (SSQM) of the Qilian Mountains from 2021 to 2022. Turnover and nestedness patterns within bird communities across elevational gradients were investigated in three dimensions (taxonomic, functional, and phylogenetic). Alpha diversity and beta diversity were compared between the two regions (NSQM and SSQM) in different dimensions. And it was assessed the potential non-linear relationships with environmental variables. Results: With the exception of nestedness, which predominates in bird functional beta diversity in the SSQM, turnover components dominated beta diversity in both the SSQM and NSQM. Bird diversities in three dimensions were significantly higher in the SSQM than in the NSQM, but has lower functional total beta diversity. Additionally, the predictive variables had different effects in the alpha and beta diversity of birds in different dimensions across different regions. Nighttime light and solar radiation were the most important factors in low elevation regions, while in high elevation region, slope and habitats are the most significant environmental variables. Conclusion: Our study emphasizes the potential role of environmental filtering and the importance of environmental variables in driving bird communities. While increasing elevation enhances diversity in different dimensions of bird communities, habitat fragmentation in high elevation regions reduces functional dissimilarity among communities.

The contamination of foodborne pathogenic bacteria poses great threats to human health. Conventional foodborne pathogen detection methods suffer from the shortcomings of time-consuming, cumbersome, and non-real time. Hence, it is of great significance to explore a sensitive, safe, simple and economical method for foodborne pathogen detection. Compared with the traditional methods, nano-biosensor-based detection assays possess merits such as exceptional sensitivity, high selectivity, real-time detection, low consumption and low limit of detection. In this article, these nano-biosensor-based methods are summarized, and the principles and advantages of single-, dual- and multi-mode detection are comprehensively discussed. Meanwhile, an outlook on the application of nano-biosensors for the detection of foodborne pathogens is given with the goal of providing a reference for the optimization of the existing detection methods for foodborne pathogenic bacteria.

Abstract The abuse of antibiotics urgently requires rapid identification of drug-resistant bacteria at the point of care (POC). Here we report a visual paper sensor that allows rapid (0.25-3 h) discrimination of the subtypes of β-lactamase (the major cause of bacterial resistance) for precision antibiotic therapy. The sensor exhibits high performance in identifying antibiotic-resistant bacteria with 100 real samples from patients with diverse bacterial infections, demonstrating 100% clinical sensitivity and specificity. Further, this sensor can enhance the accuracy of antibiotic use from 48% empirically to 83%, and further from 50.6% to 97.6% after eliminating fungal infection cases. Our work provides a POC testing platform for guiding effective management of bacterial infections in both hospital and community settings.

Abstract ChulaCov19 mRNA vaccine demonstrated promising phase 1 results. Healthy adults aged 18–59 years were double-blind randomised 4:1 to receive two intramuscular doses of ChulaCov19 50 µg or placebo. Primary endpoints were safety and microneutralization antibody against-wild-type (Micro-VNT50) at day 50. One hundred fifty adults with median (IQR) age 37 (30–46) years were randomised. ChulaCov19 was well tolerated, and most adverse events were mild to moderate and temporary. Geometric mean titres (GMT) of neutralizing titre against wild-type for ChulaCov19 on day 50 were 1367 IU/mL. T-cell IFN-γ-ELISpot showed the highest responses at one week (Day29) after dose 2 then gradually declined. ChulaCov19 50 µg is well tolerated and elicited high neutralizing antibodies and strong T-cell responses in healthy adults. Trial registration number: ClinicalTrials.gov Identifier NCT04566276, 28/09/2020.

Abstract Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen kinetics can change depending on the delivery method. To promote extended immunogen bioavailability and to present antigen in a multivalent form, native-HIV Env trimers are modified with short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide (pSer:alum). Here we explore the use of a combined adjuvant approach that incorporates pSer:alum-mediated antigen delivery with potent adjuvants (SMNP, 3M-052) in an extensive head-to-head comparison study with conventional alum to assess germinal center (GC) and humoral immune responses. Priming with pSer:alum plus SMNP induces additive effects that enhance the magnitude and persistence of GCs, which correlate with better GC-TFH cell help. Autologous HIV-neutralizing antibody titers are improved in SMNP-immunized animals after two immunizations. Over 9 months after priming immunization of pSer:alum with either SMNP or 3M-052, robust Env-specific bone marrow plasma cells (BM BPC) are observed. Furthermore, pSer-modification of Env trimer reduce targeting towards immunodominant non-neutralizing epitopes. The study shows that a combined adjuvant approach can augment humoral immunity by modulating immunodominance and shows promise for clinical translation.

Abstract This study was conducted to investigate the relationship between atrial fibrillation and the clinical prognosis of patients with sepsis in intensive care unit. A total of 21,538 sepsis patients were enrolled in the study based on the Medical Information Mart for Intensive Care IV database, of whom 6,759 had AF. Propensity score matching was used to compare the clinical characteristics and outcomes of patients with and without AF. Besides, the inverse probability of treatment weighting, univariate and multivariate Cox regression analyzes were performed. Of the 21,538 patients, 31.4% had AF. The prevalence of AF increased in a step-by-step manner with growing age. Patients with AF were older than those without AF. After PSM, 11,180 patients remained, comprising 5,790 matched pairs in both groups. In IPTW, AF was not associated with 28-day mortality [hazard ratio (HR), 1.07; 95% confidence interval (CI), 0.99–1.15]. In Kaplan-Meier analysis, it was not observed difference of 28-day mortality between patients with and without AF. AF could be associated with increased ICU LOS, hospital LOS and need for mechanical ventilation; however, it does not remain an independent short-term predictor of 28-day mortality among patients with sepsis after PSM with IPTW and multivariate analysis.

As wildlife protection continue to strengthen, research on the gut microbiota of wildlife is increasing. Carrying out conservation and research on endangered species in the Qinghai Tibet Plateau plays an important role in global biodiversity conservation. This study utilized 16S rRNA sequencing of fecal samples to investigate the composition, function, and changes of the gut microbiota of bharal in different environments, seasons, and genders. The results showed that Firmicutes and Bacteroidota were the dominant phyla and UCG-005, Bacteroides, UCG-010 were the dominant genera of bharal. In the wild, the abundance of Firmicutes increased which was conducive to the decomposition and utilization of cellulose, hemicellulose, and carbohydrate. Due to the variety of food types and nutrition in different seasons, the composition and function of gut microbiota were obviously different between genders. Compared with zoo, higher alpha diversity, a more complex gut microbiota network structure, and stronger metabolic function were conducive bharal to adapting to the wild environment. In the zoo, captive bharals were fed foods rich in high fat and protein, which increased the abundance of Bacteroidota and reduced the alpha diversity of gut microbiota. A fixed diet unified the gut microbiota between genders of bharal. It is very important to pay attention to the impact of captive environments and maintain the native gut microbiota of wildlife.

Summary: Unraveling the connection between gut microbiota and adaptability in wild species in natural habitats is imperative yet challenging. We studied the gut microbiota of sympatric and allopatric populations of two closely related species, the Procapra picticaudata and P. przewalskii, with the latter showing lower adaptability and adaptive potential than the former. Despite shared habitat, sympatric populations showed no convergence in gut microbiota, revealing distinct microbiota-environment relationships between the two gazelle species. Furthermore, the gut microbiota assembly process of the P. przewalskii was shifted toward homogeneous selection processes relative to that of the P. picticaudata. Those taxa which contributed to the shift were mainly from the phyla Firmicutes and Verrucomicrobiota, with functions highly related to micronutrient and macronutrient metabolism. Our study provides new insights into the complex dynamics between gut microbiota, host adaptability, and environment in wildlife adaptation and highlights the need to consider host adaptability when examining wildlife host-microbiome interplay.

National parks in China play a vital role in preserving biodiversity, protecting endangered species, maintaining ecological balance, and promoting sustainable development amid global biodiversity decline. Boundary delimitation and functional zoning within these parks are crucial for preserving ecosystem integrity and species diversity. In the case study of Kunlun Mountains National Park (KMNP, Qinghai section), an extensive wildlife background survey yielded 4,523 occurrence records (3,921 after optimization) for 16 nationally protected wildlife species. Using the ecological niche model, this study aimed to explore the boundary range, functional zoning, and protection gap areas within KMNP by simulating the suitable spatial distribution of wildlife species, taking into account their protection and endangered statuses. The findings indicated that the primary habitat for key protected species in KMNP mainly occupied meadow and steppe in terms of vegetation types, along with grassland and unused land in terms of land use types, with average annual precipitation from 200 mm to 400 mm, elevations ranging from 4,100 m to 4,700 m, and average annual temperatures from −4.5℃ to −2℃. The suitable distribution of different wildlife species in the Kunlun Mountains area showed variations, mainly concentrated in the southwestern, central, and southeastern regions. The optimized KMNP covered around 49,800 km2, a 16.3 % reduction from the selected area, with the core protection zone at 16,300 km2 and the general control zone at 33,200 km2. The suitability of 93.75 % (15/16) species within the core protection area of KMNP was higher comparing to the optimized area, selected area, and Mangya-Golmud-Dulan area, indicating that the boundary delimitation and functional zoning of KMNP were highly rational. The boundary range and functional zoning method developed in this study provide a crucial scientific foundation for KMNP's conservation and management, and valuable guidance for national park construction, ecosystem preservation, biodiversity conservation, and the promotion of key species' reproduction and survival on the Qinghai-Tibet Plateau, with promising future applications.

Volatile organic compounds (VOCs) are a class of hazardous gases that are widely present in the atmosphere and cause great harm to human health. In this paper, a ratiometric fluorescent probe (Dye@Eu-MOFs) based on a dye-functionalized metal–organic framework was designed to detect VOCs, which showed high sensitivity and specificity for acetaldehyde solution and vapor. A linear correlation between the integrated fluorescence intensity (I510/I616) and the concentration of acetaldehyde was investigated, enabling a quantitative analysis of acetaldehyde in the ranges of 1 × 10−4~10−5 μL/mL, with a low detection limit of 8.12 × 10−4 mg/L. The selective recognition of acetaldehyde could be clearly distinguished by the naked eye under the excitation of UV light. The potential sensing mechanism was also discussed. Significantly, a molecular logic gate was constructed based on the whole system, and finally, a molecular logic network system for acetaldehyde detection connecting basic and integrated logic operations was realized. This strategy provided an effective guiding method for constructing a molecular-level logic gate for acetaldehyde detection on a simple platform.

ABSTRACTThe adaptive immunity against SARS-CoV-2 prototype strain and Omicron sublineages induced by BA.1 breakthrough infection in vaccinees of inactivated COVID-19 vaccines have not been well characterized. Here, we report that BA.1 breakthrough infection induced mucosal sIgA and resulted in higher IgG titers against prototype strain and Omicron sublineages in vaccinees than in vaccine naïve-infected individuals. BA.1 breakthrough infection boosted antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis to prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.2.75 but not BA.4/5 and induced neutralization against prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5 but not BF.7, BQ.1, and XBB. In total, BA.1 breakthrough infection individuals produced less extensive sIgA, plasma IgG and NAb responses against Omicron sublineages compared with those against prototype strain. Further, BA.1 breakthrough infection induced recall B cell response to prototype strain and Omicron variant, primarily targeting memory B cells producing conserved epitopes. Memory T cell responses against Omicron is largely preserved. Individuals with vaccine booster did not induce more beneficial immune responses to Omicron sublineages upon BA.1 breakthrough infection than those with primary vaccine dose only. The breakthrough infection individuals produced stronger adaptive immunity than those of inactivated vaccine-healthy individuals. These data have important implications for understanding the vaccine effectiveness and adaptive immunity to breakthrough infection in individuals fully immunized with inactivated vaccines. Omicron sublineages, especially for those emerged after BA.4/5 strain, evade NAb responses induced by BA.1 breakthrough infection. It is urgent to optimize the vaccine immunogen design and formulations to SARS-CoV-2 variants.

Background: Atrial fibrillation is the most common tachyarrhythmia, while catheter ablation is an effective therapy for atrial fibrillation. However, pain and nervousness may occur during the procedure. Moreover, a consensus has still not been reached on which is the best kind of analgesic and sedative to use in these procedures. Therefore, we conducted a network meta-analysis to evaluate the efficacy and safety of analgesics and sedatives used in catheter ablation for atrial fibrillation. Methods: We searched PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, and Baidu Wenku document download website for randomized controlled trials from their inception to February 26, 2023. Only studies that made comparisons among analgesics or sedatives and involved patients with atrial fibrillation undergoing radiofrequency catheter ablation were included. The efficacy endpoints were Ramsay sedation scores and visual analog scale scores during the radiofrequency catheter ablation for atrial fibrillation. The safety endpoints were the incidence of respiratory depression, hypotension, nausea, and vomiting. Pairwise comparisons and frequency method analyses were conducted. Results were reported as odds ratio (OR), mean difference (MD), and corresponding 95% confidence intervals (CIs). We assessed the risk bias of the studies in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Results: Out of the 709 articles initially retrieved, 14 studies, with a total of 1156 participants, were included. In terms of efficacy, patients receiving dexmedetomidine during radiofrequency ablation for atrial fibrillation had higher Ramsay sedation scores than those receiving midazolam plus fentanyl, or its derivatives (MD –0.88, 95% CI [–0.04 to –0.72]). Compared with morphine, dezocine (MD 1.88, 95% CI [1.16 to 2.60]), hydromorphone (MD 4.07, 95% CI [3.56 to 4.58]), butorphanol (MD 3.18, 95% CI [2.38 to 3.96]), and fentanyl or its derivatives (MD 1.57, 95% CI [1.25 to 1.89]) had a better analgesic effect. In terms of safety, propofol (OR 16.46; 95% CI [1.54 to 175.95]) and midazolam plus fentanyl or its derivatives (OR 7.02; 95% CI [1.33 to 36.99]) significantly increased the incidence of respiratory depression compared with dexmedetomidine plus fentanyl or its derivatives. Dexmedetomidine plus fentanyl or its derivatives reduced the incidence of nausea and vomiting compared with fentanyl alone (OR 4.74; 95% CI [1.01 to 22.22]). Propofol was associated with a lower incidence of nausea and vomiting than hydromorphone (OR 0.01; 95% CI [0.00 to 0.59]) and fentanyl or its derivatives (OR 0.01; 95% CI [0.00 to 0.51]). There was no statistically significant difference in the incidence of hypotension between any two strategies. Conclusions: Hydromorphone and butorphanol had better analgesic effects than fentanyl or its derivates. Dexmedetomidine had better sedative effects. In terms of safety, dexmedetomidine, oxymorphone, and butorphanol were superior. It is necessary to explore the regimen that can consider both the effectiveness and safety during radiofrequency catheter ablation for atrial fibrillation (AF). The PROSPERO Registration: This study was registered with PROSPERO, number: CRD42023403661.

HIV-1 vaccine design aims to induce broadly neutralizing antibodies such as IOMA, the only described antibody in its class. Here, the authors present the isolation, characterisation and structure of three additional antibodies within the IOMA class

The Qinghai-Tibet Plateau (QTP) contains a significant amount of biodiversity which provides a wide range of habitats for a great quantity of wildlife, especially various birds, on account of the unique climatic conditions and geography. However, the QTP has shown more sensitivity and vulnerability to global climate change than other regions, and the change pose a threat to the birds. Here, we used the MaxEnt and the barycenter shift analysis for analyzing the effects of global warming on the potential future habitat of the threatened birds on the QTP by using the ACCESS-ESM1-5 global climate model of the Coupled Model Intercomparison Projects Phase 6 (cmip6) climate pattern with three Shared Socioeconomic Pathway (SSP). The results demonstrated that the climatically suitable habitats for the threatened birds are mainly distributed in the eastern and central regions of the QTP. Moreover, over 81% of the threatened birds would experience a reduction in suitable habitat area within the next 30–50 years in the different future global warming scenario. Satyr tragopan (Tragopan satyra) would lose the most habitat (57.15%), while the Tibetan babax (Pterorhinus koslowi) would lose the least (0.35%) in comparing to these birds. Nonetheless, some threatened birds showed an increase in their future habitat area because of their physiological characteristics which are more adaptable to a wide range of climate. The climatic suitable habitat for all the threatened birds, except for the Tibetan eared pheasant (Crossoptilon harmani), would move to higher altitudes or higher latitudes regions. Simultaneously, the threatened birds in the order of Galliformes had a higher risk of extinction due to their weak flight and extended migratory distances on the QTP in the future. Our study provides provide a data foundation for the conservation of biodiversity and wild birds on the QTP.

Objective This study was conducted to identify the functional long non-coding RNAs (lncRNAs) for swine lactation by RNA-seq data of mammary gland. Methods According to the RNA-seq data of swine mammary gland, we screened lncRNAs, performed differential expression analysis, and confirmed the functional lncRNAs for swine lactation by validation of genome wide association study (GWAS) signals, functional annotation and weighted gene co-expression network analysis (WGCNA). Results We totally identified 286 differentially expressed (DE) lncRNAs in mammary gland at different stages from 14 days prior to (-) parturition to day 1 after (+) parturition, and the expressions of most of lncRNAs were strongly changed from day −2 to day +1. Further, the GWAS signals of sow milk ability trait were significantly enriched in DE lncRNAs. Functional annotation revealed that these DE lncRNAs were mainly involved in mammary gland and lactation developing, milk composition metabolism and colostrum function. By performing weighted WGCNA, we identified 7 out of 12 lncRNA-mRNA modules that were highly associated with the mammary gland at day −14, day −2, and day +1, in which, 35 lncRNAs and 319 mRNAs were involved. Conclusion This study suggested that 18 lncRNAs and their 20 target genes were promising candidates for swine parturition and colostrum occurrence processes. Our research provided new insights into lncRNA profiles and their regulating mechanisms from colostrogenesis to lactogenesis in swine.

Background: This paper aimed to appraise the diagnostic precision of assorted methodologies to identify left atrial/left atrial appendage (LA/LAA) thrombus through a network meta-assessment. Methods: Methodologically, we conducted a comprehensive literature search across multiple databases. Utilizing the risk of bias tool from the Cochrane Collaboration, methodological quality of included studies was critically assessed and potential publication bias was examined via funnel plots. The subsequent data analysis was executed using Stata software, with the most efficacious diagnostic modalities being determined based on cumulative ranking curve (SUCRA) values. Results: We scrutinized a sum of 18 papers, comprising 4102 subjects and utilizing 10 different diagnostic techniques. The hierarchical results derived from the network meta-analysis indicated that in regards to sensitivity, the dual-source cardiac computed tomography (DSCT) was superior (with a SUCRA value of 71.7%), it was succeeded by 3-minute delayed cardiac computed tomography (CCT) (scoring 66.8%), which surpassed the transesophageal echocardiography (TEE) (holding a SUCRA value of 57.5%). In terms of specificity, DSCT was the best (SUCRA value of 84.3%), followed by three dimensional (3D) cardiac magnetic resonance imaging (3D-CMRI) (SUCRA value of 78.0%), which was better than TEE (SUCRA value of 66.6%). In terms of positive likelihood ratio (PLR), 6-minute delayed CCT (SUCRA value of 85.6%) was superior to 3-minute delayed CCT (SUCRA value of 80.1%), both of which were superior to TEE (SUCRA value of 69.1%). DSCT (SUCRA value of 89.3%) had the best negative likelihood ratio (NLR), while DSCT (SUCRA value of 79.9%) had the highest accuracy. Conclusions: This study demonstrated that DSCT outperformed TEE in sensitivity, specificity, NLR, and accuracy in identifying thrombus of LA/LAA among patients suffering from atrial fibrillation. Our conclusion is that DSCT is the best in diagnosing LA/LAA. In addition, 3D-CMRI and 3-minute delayed CCT are expected to replace TEE.

The Tibetan antelope is an endangered species suffering from poaching and habitat fragmentation. The intestinal flora and metabolites play a crucial role in the physiological homeostasis of hosts, which are influenced by various environmental factors like seasonal variation. In this particular research, our main goal was to explore the alterations in the metabolism and gut microbiota of Tibetan antelopes between the cold season (XB) and warm season (DA), using untargeted metabolomics and 16S rRNA gene-sequencing analyses. The findings indicated that Tibetan antelopes had a higher alpha-diversity of intestinal microbes during the cold season than during the warm season. Principal co-ordinate analysis revealed notable seasonal discrepancies in the function and structure of intestinal microbes in Tibetan antelopes. The relative abundance of Firmicutes was significantly increased during the cold season compared to during the warm season. Furthermore, the Tibetan antelope’s primary metabolic functions of the intestinal micro-organisms were significantly higher during the cold season. The untargeted metabolomics analysis results showed a total of 532 metabolites that were significantly different between the cold season and warm season groups. These metabolites were found to be enriched in a total of 62 metabolic pathways. Among the most significant pathways of enrichment were the purine metabolism and pyrimidine metabolism. The levels of related metabolites in those pathways were remarkably higher in the warm season compared to the cold season. The comprehensive analysis of 16S rRNA and the metabolome reveals there is a significant correlation between differential microbiota and differential metabolites. Therefore, the gut microbiota changes caused by seasonal changes influenced the metabolites as well. This research reveals the function of seasonal changes in the intestinal flora and metabolites in the adaptation of Tibetan antelopes to environmental fluctuations and supplies a theoretical basis for instructing the protection management of Tibetan antelopes.

IntroductionSARS-CoV-2 is a respiratory pathogen currently causing a worldwide pandemic, with resulting pathology of differing severity in humans, from mild illness to severe disease and death. The rhesus macaque model of COVID-19 was utilized to evaluate the added benefit of prophylactic administration of human post-SARS-CoV-2 infection convalescent plasma (CP) on disease progression and severity.MethodsA pharmacokinetic (PK) study using CP in rhesus monkeys preceded the challenge study and revealed the optimal time of tissue distribution for maximal effect. Thereafter, CP was administered prophylactically three days prior to mucosal SARS-CoV-2 viral challenge.ResultsResults show similar viral kinetics in mucosal sites over the course of infection independent of administration of CP or normal plasma, or historic controls with no plasma. No changes were noted upon necropsy via histopathology, although there were differences in levels of vRNA in tissues, with both normal and CP seemingly blunting viral loads.DiscussionResults indicate that prophylactic administration with mid-titer CP is not effective in reducing disease severity of SARS-CoV-2 infection in the rhesus COVID-19 disease model.

Abstract Background High-Frequency Irreversible Electroporation (H-FIRE) is a novel technology for non-thermal ablation. Different from Irreversible electroporation (IRE), H-FIRE delivers bipolar electrical pulses without muscle contraction and does not cause electrolysis. Currently, little is known regarding the cardiac safety during the administration of H-FIRE on liver. The aim of this study was to evaluate the changes of electrocardiogram (ECG) and biomarkers of cardiac damage during asymmetrical waveform of H-FIRE therapy in vivo. Methods The swines (n = 7) in IRE group, which used 100 pulses (2200 V, 100–100 μs configuration), were administrated with muscle relaxant under anesthesia. In the absence of muscle relaxant, 7 swines in H-FIRE group were performed with 2400 pulses (3000 V, 5–3–3–5 μs configuration). Midazolam (0.5 mg/kg) and xylazine hydrochloride (20 mg/kg) were given to induce sedation, followed by Isoflurane (2.5%, 100% oxygen, 3 L/min) to maintain sedation in all the swines. Limb lead ECG recordings were analyzed by two electrophysiologists to judge the arrhythmia. Cardiac and liver tissue was examined by pathology technique. Results The ablation zones were larger in H-FIRE than IRE. Both IRE and H-FIRE did not affect the autonomous cardiac rhythm. Even when the electrical signal of IRE and H-FIRE fell on ventricular vulnerable period. Moreover, cTnI in IRE group showed an increase in 4 h after ablation, and decreased to baseline 72 h after ablation. However, cTnI showed no significant change during the administration of H-FIRE. Conclusions The study suggests an asymmetrical waveform for H-FIRE is a promising measure for liver ablation. The results were based on normal liver and the swines without potential cardiac diseases. With the limitations of these facts, asymmetrical waveform for H-FIRE of liver tissue seems relatively safe without major cardiac complications. The safety of asymmetrical waveform for H-FIRE needs to evaluate in future.

Abstract Background The critical role of antibody Fc-mediated effector functions in immune defense has been widely reported in various viral infections. These effector functions confer cellular responses through engagement with innate immune cells. The precise mechanism(s) by which immunoglobulin G (IgG) Fc domain and cognate receptors may afford protection are poorly understood, however, in the context of HIV/SHIV infections. Many different in vitro assays have been developed and utilized to measure effector functions, but the extent to which these assays capture distinct antibody activities has not been fully elucidated. Results In this study, six Fc-mediated effector function assays and two biophysical antibody profiling assays were performed on a common set of samples from HIV-1 infected and vaccinated subjects. Biophysical antibody profiles supported robust prediction of diverse IgG effector functions across distinct Fc-mediated effector function assays. While a number of assays showed correlated activities, supervised machine learning models indicated unique antibody features as primary contributing factors to the associated effector functions. Additional experiments established the mechanistic relevance of relationships discovered using this unbiased approach. Conclusions In sum, this study provides better resolution on the diversity and complexity of effector function assays, offering a clearer perspective into this family of antibody mechanisms of action to inform future HIV-1 treatment and vaccination strategies.

Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. However, bNAbs are extremely difficult to induce by vaccination. Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses.

Abstract Sanjiangyuan National Park (SNP), the first national park in China, is one of the most important biodiversity conservation areas in the Sanjiangyuan National Nature Reserve (SNNR) and even the world. The threatened ungulates play an irreplaceable role in maintaining the ecosystem diversity and stability in SNNR. Here, based on 1434 occurrence records of six ungulates, the maximum entropy model, with two different strategies, was utilized to determine the priority reserves. The results indicated that the priority reserves in SNNR was mainly located in and around SNP, which were mainly distributed in the middle east, middle west, and southwest of SNNR. Six ungulates shared preference for altitude ranging 4000–5000 m, the average annual temperature below −3.0°C, and average annual precipitation ranging 200–400 mm on meadow, steppe, and unused land. The proportion of high and medium suitable areas for ungulates in SNP was higher than that in SNNR. As the SNP is not contiguously spaced in space, and some core wildlife habitats are not included, it is suggested to optimize the functional areas and adjust the boundary range on the basis of the pilot scope of SNP, so as to enhance the integrity and connectivity of each functional area.

ObjectivesIgA nephropathy (IgAN) is the most common primary glomerular disease, and is the leading cause of chronic renal failure. Because mesangial lesions are the main pathological changes seen in IgAN, we investigated factors associated with the progression of mesangial lesions in IgAN.MethodsWe enrolled participants with IgAN who underwent repeat renal biopsies. Based on the progression of mesangial proliferative lesions, the participants were divided into progressive and stable groups. The progression group included participants with a ratio of mesangial cell proliferation score ≥ 1.1 (i.e., proliferation of > 10%) in the second biopsy specimen compared to the first biopsy specimen. The stable group included participants who did not fulfill the aforementioned criteria. We recorded the laboratory parameters, expression of renin-angiotensin system (RAS) receptors (angiotensin II type 1 receptor [AT1R], angiotensin II type 2 receptor [AT2R], Mas receptor [MasR], and the Mas-related G protein-coupled receptor, member D [MrgD]) and mesangial matrix proteins (collagen [Col] IV, fibronectin [FN] and laminin) at the first and second renal biopsies, and the use of immunosuppressive therapy and/or RAS blockers after the first biopsy.ResultsWe enrolled 24 patients with IgAN who underwent repeat renal biopsies. Half of patients showed progression of mesangial lesions on repeat renal biopsy after a median of 4.3 (1–6) years. The progression group had significantly higher expression levels of AT1R and mesangial matrix proteins (Col IV and FN), and significantly lower expression of AT2R and MasR, compared to the stable group. Multivariate analysis showed that the use of RAS blockers (hazard ratio [HR], 0.27; 95% CI, 0.08–0.97; p < 0.05) and the level of proteinuria (HR, 1.8; 95% CI, 1.04–3.12; p < 0.05) were associated with progression of mesangial lesions. Additionally, the progression group exhibited a more rapid decline of renal function compared to the stable group (0.38 and 0.012 ml/min/1.73 m2/month, respectively; p = 0.004).ConclusionsContinuous activation of the intrarenal RAS and massive proteinuria correlate with histological progression of mesangial lesions in IgAN patients, which may further accelerate the deterioration of renal function.

Grassland is not only the natural habitats for the survival of wild animals, but also the material guarantees for livestock husbandry. However, the previous studies on grassland carrying capacity are mostly only considering livestock but wild herbivores were ignored. In this study, the population of large wild herbivores, Tibetan wild ass, Tibetan gazelle and Tibetan antelope, and livestock were surveyed, and the grassland forage yield was estimated by a remote sensing-process coupled model in Qumahe Township in Three-River Headwaters, Qinghai-Tibetan in 2020. The actual carrying capacity (AC) was calculated from the both wildlife and livestock and the theoretical carrying capacity (TC) in the term on edible herbage and crude protein was estimated. Grazing pressure index was measured by the ratio of AC to TC in this region. The results showed the AC was contributed by about 20,700 standard sheep units (SHU) from wild large herbivores, and 256,500 SHU from the livestock. The theoretical carrying capacity of edible herbage, which is 274,800 SHU, was lower than the theoretical carrying capacity of crude protein in the region. If only considering livestock, the grazing capacity pressure index is 0.93, but the index will be 1.01 if the both wildlife and livestock were considered, and wildlife contributes 7.5% to the grazing pressure. This study suggested the wildlife population should be calculated in grassland ecological carrying capacity estimation though domestic livestock contributed much more to grazing pressure than wild herbivores. The new indicator would be useful in grassland management to maintain ecosystem and biodiversity balance, and society-economy sustainability.

BackgroundTo investigate the relationship between membranous nephropathy (MN) and lung cancer.MethodsTo report patients with lung cancer detected by follow-up after the diagnosis of MN by renal biopsy in China-Japan Friendship Hospital from January 2010 to December 2019, and to study the prognosis of lung cancer-associated MN and have a review of the literature.ResultsLung cancer was detected in six patients followed for 1–27 months (median 8 months) after the diagnosis of MN: including four cases of lung adenocarcinoma, one case of carcinoma in situ, and one case of small cell lung cancer with multiple metastases. Five cases were in remission after surgical resection, and one case was remitted after chemotherapy. Six patients were negative for serum anti-PLA2R antibodies, and glomerular IgG subclass deposition detected by immunofluorescence was positive for IgG1 and IgG2. Glomerular PLA2R, THSD7A, and NELL-1 stainings were assessed in all six patients; one patient was positive for glomerular PLA2R staining, two patients were positive for glomerular THSD7A staining, and all patients were negative for NELL-1 staining. A literature review of the relationship between MN and lung cancer was performed: seven articles about cancer-associated MN were searched, reporting 32 cases of MN associated with lung cancer, among which 14 cases had nephropathy as the first manifestation and only five patients had remission of MN after treatment of lung cancer.ConclusionsA few lung cancer patients have nephropathy as the first clinical manifestation, and MN can also be remitted after treatment of lung cancer.

The novel coronavirus SARS-CoV-2 emerged in late 2019, rapidly reached pandemic status, and has maintained global ubiquity through the emergence of variants of concern. Efforts to develop animal models have mostly fallen short of recapitulating severe disease, diminishing their utility for research focusing on severe disease pathogenesis and life-saving medical countermeasures. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species of nonhuman primates (Macaca mulatta; rhesus macaques; RM, Chlorocebus atheiops; African green monkeys; AGM). Species-specific cohorts were experimentally infected with SARS-CoV-2 by either direct mucosal (intratracheal + intranasal) instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated analogous viral loads in all compartments by either exposure route although the magnitude and duration of viral loading was marginally greater in AGMs than RMs. Clinical onset was nearly immediate (+1dpi) in the mucosal exposure cohort whereas clinical signs and cytokine responses in aerosol exposure animals began +7dpi. Pathologies conserved in both species and both exposure modalities include pulmonary myeloid cell influx, development of pleuritis, and extended lack of regenerative capacity in the pulmonary compartment. Demonstration of conserved pulmonary pathology regardless of species and exposure route expands our understanding of how SARS-CoV-2 infection may lead to ARDS and/or functional lung damage and demonstrates the near clinical response of the nonhuman primate model for anti-fibrotic therapeutic evaluation studies.

Abstract Background The development of skeletal muscle in pigs during the embryonic stage is precisely regulated by transcriptional mechanisms, which depend on chromatin accessibility. However, how chromatin accessibility plays a regulatory role during embryonic skeletal muscle development in pigs has not been reported. To gain insight into the landscape of chromatin accessibility and the associated genome-wide transcriptome during embryonic muscle development, we performed ATAC-seq and RNA-seq analyses of skeletal muscle from pig embryos at 45, 70 and 100 days post coitus (dpc). Results In total, 21,638, 35,447 and 60,181 unique regions (or peaks) were found across the embryos at 45 dpc (LW45), 70 dpc (LW70) and 100 dpc (LW100), respectively. More than 91% of the peaks were annotated within − 1 kb to 100 bp of transcription start sites (TSSs). First, widespread increases in specific accessible chromatin regions (ACRs) from embryos at 45 to 100 dpc suggested that the regulatory mechanisms became increasingly complicated during embryonic development. Second, the findings from integrated ATAC-seq and RNA-seq analyses showed that not only the numbers but also the intensities of ACRs could control the expression of associated genes. Moreover, the motif screening of stage-specific ACRs revealed some transcription factors that regulate muscle development-related genes, such as MyoG, Mef2c, and Mef2d. Several potential transcriptional repressors, including E2F6, OTX2 and CTCF, were identified among the genes that exhibited different regulation trends between the ATAC-seq and RNA-seq data. Conclusions This work indicates that chromatin accessibility plays an important regulatory role in the embryonic muscle development of pigs and regulates the temporal and spatial expression patterns of key genes in muscle development by influencing the binding of transcription factors. Our results contribute to a better understanding of the regulatory dynamics of genes involved in pig embryonic skeletal muscle development.

Tibetan medicinal materials play a significant role in Tibetan culture. However, some types of Tibetan medicinal materials share similar shapes and colors, but possess different medicinal properties and functions. The incorrect use of such medicinal materials may lead to poisoning, delayed treatment, and potentially severe consequences for patients. Historically, the identification of ellipsoid-like herbaceous Tibetan medicinal materials has relied on manual identification methods, including observation, touching, tasting, and nasal smell, which heavily rely on the technicians’ accumulated experience and are prone to errors. In this paper, we propose an image-recognition method for ellipsoid-like herbaceous Tibetan medicinal materials that combines texture feature extraction and a deep-learning network. We created an image dataset consisting of 3200 images of 18 types of ellipsoid-like Tibetan medicinal materials. Due to the complex background and high similarity in the shape and color of the ellipsoid-like herbaceous Tibetan medicinal materials in the images, we conducted a multi-feature fusion experiment on the shape, color, and texture features of these materials. To leverage the importance of texture features, we utilized an improved LBP (local binary pattern) algorithm to encode the texture features extracted by the Gabor algorithm. We inputted the final features into the DenseNet network to recognize the images of the ellipsoid-like herbaceous Tibetan medicinal materials. Our approach focuses on extracting important texture information while ignoring irrelevant information such as background clutter to eliminate interference and improve recognition performance. The experimental results show that our proposed method achieved a recognition accuracy of 93.67% on the original dataset and 95.11% on the augmented dataset. In conclusion, our proposed method could aid in the identification and authentication of ellipsoid-like herbaceous Tibetan medicinal materials, reducing errors and ensuring the safe use of Tibetan medicinal materials in healthcare.

Gut microbiota of mammals participates in host nutrient metabolism and plays an important role in host adaptation to the environment. Herein, to understand the relationship between environment differences and the composition and abundance of the gut microbiota of Przewalski’s gazelle (Procapra przewalskii) in almost all its habitats, high throughput sequencing of the 16S rRNA gene was used to compared the characteristics of the gut microbiota based on total 120 fecal samples. The results showed that Przewalski’s gazelle exhibited different characteristics of microbiota diversity in different habitats. The Jiangxigou Rescue Station (JX), Nongchang (NC), and Ganzihe and Haergai townships (GH) groups had a relatively high microbiota diversity, while the Niaodao scenic area (ND) group had the lowest diversity. This finding seemed to follow a similar pattern of change in the population of Przewalski’s gazelle. Bacteroidetes and Actinobacteria were the phyla with significant differences, especially between the Wayu township (WY) and the other groups. The difference in the microbiota mainly included the Ruminococcaceae UCG-005, Christensenellaceae R-7 group, and Bacteroidaceae and was enriched in the ND, WY, and other regions. We speculated that the difference in the gut microbiota was due to a difference in environmental characteristics, particularly the food resources that the host can obtain. We speculated that a similar microbiome has important functions for species survival and represents the evolutionary commonality of Przewalski’s gazelle, while a different microbiome plays an important role in the adaptation of Przewalski’s gazelle to a different environment. The results of this study illustrate how the same species adapts to different environments from the perspective of gut microbiota plasticity and therefore are of great significance for the protection and restoration of the population of this species.

ObjectivesConverging evidence points towards a role of the complement system in the pathogenesis of diabetic nephropathy (DN). The classification system of diabetic kidney lesions devised by the Renal Pathology Society (RPS) in 2010 are based on the pathogenic process of DN. Therefore, we investigated the correlation between glomerular C3 deposits and RPS DN classification and the combined deleterious effects thereof on kidney function.MethodsThe study analyzed data from 217 diabetic patients who underwent renal biopsy between 2010 and 2021 and were found to have DN as the only glomerular disease. C3 deposition was considered positive if the glomerular C3 immunofluorescence intensity was at the trace or ≥1+ level. We divided DN into five glomerular lesion classes and separately evaluated the degree of interstitial and vascular involvement. The primary outcome was the composite of a ≥50% decline from the initial estimated glomerular filtration rate, end-stage renal disease, and death.ResultsNone of the patients were classified into class I, and few were classified into classes IIa (7.8%) and IV (9.2%). Most patients were classified as IIb (30.9%) and III (52.1%). C3 deposition was detected in 53.9% of patients. Multivariate logistic regression analysis showed that DN class was significantly correlated with C3 deposits [odds ratio, 1.59; 95% confidence interval (CI), 1.08–2.36; p = 0.02). During a median follow-up of 22 months, 123 (56.7%) patients reached the composite outcome. The endpoints occurred more frequently in patients with C3 deposition (69.2 vs. 42%) compared with those without C3 deposition. Patients with C3 deposition in either class IIb [hazards ratio (HR), 3.9 (95% CI, 1.14–13.17) vs. 2.46 (95% CI, 0.68–8.89)] or III [HR, 4.98 (95% CI, 1.53–16.23) vs. 2.63 (95% CI, 0.77–9.0)] had a higher risk of adverse kidney outcomes than those without C3 deposition. The prognostic accuracy of the combination of DN class and C3 deposits at 1 and 3 years was higher than that for DN class only.ConclusionsComplement deposition together with DN class predicts more rapid deterioration of kidney function in DN, which underlines the clinical significance of the DN phenotype according to the RPS classification.

IntroductionKey genes involved in tubulointerstitial injury may influence the development and progression of diabetic nephropathy (DN). We investigated whether complement-related genes are linked to the mechanism underlying tubulointerstitial injury in DN.MethodsWe analyzed the microarray data of 17 tubulointerstitial tissue samples from DN patients and 21 normal controls from the Gene Expression Omnibus. A gene co-expression network was constructed, and genes were divided into modules by weighted gene co-expression network analysis (WGCNA). We also investigated the association of C3 and C1q deposits in kidney tissues with a composite outcome of end-stage renal disease or a 50% reduction in the estimated glomerular filtration rate (eGFR) in DN patients. Finally, we performed immunohistochemical analyses of C3, C1q, C5b-9, mannose-binding lectin (MBL), and factor B in kidney tissues.ResultsNine co-expression modules were constructed using 12,075 genes from the 38 human tubulointerstitial tissue samples. Black module with more genes was positively correlated with tubulointerstitial injury in DN. C3, one of the top 10 genes in tubulointerstitial injury, was verified in an independent dataset; C3 was significantly overexpressed in tubulointerstitial tissue from patients with DN compared to the normal controls. The mRNA level of C3 in renal tubulointerstitium was negatively correlated with eGFR in DN patients (r = −0.75; p = 0.001). Analysis of the follow-up data of 54 DN patients demonstrated that codeposits of C3 and C1q in kidney tissues were independently associated with the renal outcome in DN (hazard ratio, 2.3, 95% confidence interval, 1.01–5.2, p < 0.05). Immunohistochemical analysis showed that patients with higher C1q, C3, C5b-9, MBL, or factor B expression in renal tubulointerstitium were more likely to progress to kidney failure.ConclusionLocal complement activation of the classical, lectin and alternative pathways appears linked to tubulointerstitial injury and disease progression in DN.

Abstract Background Intrauterine growth restriction (IUGR) remains a major problem associated with swine production. Thus, understanding the physiological changes of postnatal IUGR piglets would aid in improving growth performance. Moreover, liver metabolism plays an important role in the growth and survival of neonatal piglets. Results By profiling the transcriptome of liver samples on postnatal Days 1, 7, and 28, our study focused on characterizing the growth, function, and metabolism in the liver of IUGR neonatal piglets. Our study demonstrates that the livers of IUGR piglets were associated with a series of complications, including inflammatory stress and immune dysregulation; cytoskeleton and membrane structure disorganization; dysregulated transcription events; and abnormal glucocorticoid metabolism. In addition, the abnormal liver function index in the serum [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total protein (TP)], coupled with hepatic pathological and ultrastructural morphological changes are indicative of liver damage and dysfunction in IUGR piglets. Moreover, these results reveal the sex-biased developmental dynamics between male and female IUGR piglets, and that male IUGR piglets may be more sensitive to disrupted metabolic homeostasis. Conclusions These observations provide a detailed reference for understanding the mechanisms and characterizations of IUGR liver functions, and suggest that the potential strategies for improving the survival and growth performance of IUGR offspring should consider the balance between postnatal catch-up growth and adverse metabolic consequences. In particular, sex-specific intervention strategies should be considered for both female and male IUGR piglets.

Abstract Interactions between gut microbiota not only regulate physical health, but also form a vital bridge between the environment and the host, thus helping the host to better adapt to the environment. The improvement of modern molecular sequencing techniques enables in‐depth investigations of the gut microbiota of vertebrate herbivores without harming them. By sequencing the 16S rRNA V4‐V5 region of the gut microbiota of both the captive and wild kiang in winter and summer, the diversity and function of the microbiota could be compared. The reasons for observed differences were discussed. The results showed that the dominant phyla of the kiang were Bacteroidetes and Firmicutes, and the structure and abundance of the gut microbiota differed significantly between seasons and environments. However, the relatively stable function of the gut microbiota supplies the host with increased adaptability to the environment. The diversity of the intestinal flora of the kiang is relatively low in captivity, which increases their risk to catch diseases to some extent. Therefore, importance should be attached to the impact of captivity on wildlife.

Abstract Background Runs of homozygosity (ROHs) are homozygous segments of the genome where the two haplotypes inherited from the parents are identical. The current availability of genotypes for a very large number of single nucleotide polymorphisms (SNPs) is leading to more accurate characterization of ROHs in the whole genome. Here, we investigated the occurrence and distribution of ROHs in 3,692 Large White pigs and compared estimates of inbreeding coefficients calculated based on ROHs (F ROH), homozygosity (F HOM), genomic relationship matrix (F GRM) and pedigree (F PED). Furthermore, we identified genomic regions with high ROH frequencies and annotated their candidate genes. Results In total, 176,182 ROHs were identified from 3,569 animals, and all individuals displayed at least one ROH longer than 1 Mb. The ROHs identified were unevenly distributed on the autosomes. The highest and lowest coverages of Sus scrofa chromosomes (SSC) by ROH were on SSC14 and SSC13, respectively. The highest pairwise correlation among the different inbreeding coefficient estimates was 0.95 between F ROH_total and F HOM, while the lowest was − 0.083 between F GRM and F PED. The correlations between F PED and F ROH using four classes of ROH lengths ranged from 0.18 to 0.37 and increased with increasing ROH length, except for ROH > 10 Mb. Twelve ROH islands were located on four chromosomes (SSC1, 4, 6 and 14). These ROH islands harboured genes associated with reproduction, muscular development, fat deposition and adaptation, such as SIRT1, MYPN, SETDB1 and PSMD4. Conclusion F ROH can be used to accurately assess individual inbreeding levels compared to other inbreeding coefficient estimators. In the absence of pedigree records, F ROH can provide an alternative to inbreeding estimates. Our findings can be used not only to effectively increase the response to selection by appropriately managing the rate of inbreeding and minimizing the negative effects of inbreeding depression but also to help detect genomic regions with an effect on traits under selection.

Objective To investigate the clinical features, pathological renal findings, and outcomes in young adults with anti-neutrophil cytoplasmic antibody (ANCA) seropositivity. Methods Adults aged ≤35 years, with ANCA seropositivity, who underwent renal biopsy and received treatment comprising a combination of corticosteroids and cyclophosphamide between January 2004 and May 2018, were retrospectively enrolled. Results Thirteen patients with ANCA seropositivity were included, all of whom presented with kidney disease at diagnosis: 10 (76.9%) with ANCA-associated pauci-immune glomerulonephritis, one with ANCA-associated crescentic glomerulonephritis with immune complex deposition, one with immunoglobulin A nephropathy, and one with membranous nephropathy. The median serum creatinine level was 183.2 μmol/l (range, 55.0–1024.0 μmol/l). Respiratory symptoms (9/13 [69.2%]) and nonspecific gastrointestinal symptoms (5/13 [38.5%]) were the most common extrarenal manifestations. Remission was achieved in 10 (91%) of 11 ANCA-associated nephritis cases, and median interval from diagnosis to relapse was 30 months (range, 9–63 months). Cumulative relapse-free survival rates at 1 and 5 years were 100% and 88.9%, respectively. Overall, 1-year and 5-year renal survival rates were 80.8% and 58.9%, respectively. Conclusion Renal histopathology varied in young adults with ANCA seropositivity. Although relapse rates in this young adult population were generally low, long-term renal survival rates remain unsatisfactory.

The lateral pressure generated by liquefied soil on pile is a critical parameter in the analysis of soil-pile interaction in liquefaction-susceptible sites. Previous studies have shown that liquefied sand behaves like a non-Newton fluid, and its effect on piles has rate-dependent properties. In this study, a simplified pseudo-static method for liquefiable soil-pile interaction analysis is proposed by treating the liquefied soil as a thixotropic fluid, which considers the rate-dependent behavior. The viscous shear force generated by the relative movement between the viscous fluid (whose viscosity coefficient varies with excess pore pressure and shear strain rate) and the pile was assumed to be the lateral load on the pile. The results from the simplified analysis show that the distribution of bending moment is in good agreement with experiments data. Besides, the effects of various parameters, including relative density, thickness ratio of nonliquefiable layer to liquefiable layer, and frequency of input ground motion, on the pile-soil rate-dependent interaction were discussed in detail.

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.

SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral administration of two high-affinity anti-SARS-CoV-2 monoclonal antibodies (mAbs; C144-LS and C135-LS) expressly developed to neutralize the virus and modified to extend their pharmacokinetics. After completion of kinetics study of mAbs in the primate, combination treatment was administered prophylactically to mucosal viral challenge. Results showed near complete virus neutralization evidenced by no measurable titer in mucosal tissue swabs, muting of cytokine/chemokine response, and lack of any discernable pathologic sequalae. Blocking infection was a dose-related effect, cohorts receiving lower doses (6, 2 mg/kg) resulted in low grade viral infection in various mucosal sites compared to that of a fully protective dose (20 mg/kg). A subset of animals within this cohort whose infectious challenge was delayed 75 days later after mAb administration were still protected from disease. Results indicate this combination mAb effectively blocks development of COVID-19 in the rhesus disease model and accelerates the prospect of clinical studies with this effective antibody combination.