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Abstract Background Broilers stand out as one of the fastest-growing livestock globally, making a substantial contribution to animal meat production. However, the molecular and epigenetic mechanisms underlying the rapid growth and development of broiler chickens are still unclear. This study aims to explore muscle development patterns and regulatory networks during the postnatal rapid growth phase of fast-growing broilers. We measured the growth performance of Cornish (CC) and White Plymouth Rock (RR) over a 42-d period. Pectoral muscle samples from both CC and RR were randomly collected at day 21 after hatching (D21) and D42 for RNA-seq and ATAC-seq library construction. Results The consistent increase in body weight and pectoral muscle weight across both breeds was observed as they matured, with CC outpacing RR in terms of weight at each stage of development. Differential expression analysis identified 398 and 1,129 genes in the two dimensions of breeds and ages, respectively. A total of 75,149 ATAC-seq peaks were annotated in promoter, exon, intron and intergenic regions, with a higher number of peaks in the promoter and intronic regions. The age-biased genes and breed-biased genes of RNA-seq were combined with the ATAC-seq data for subsequent analysis. The results spotlighted the upregulation of ACTC1 and FDPS at D21, which were primarily associated with muscle structure development by gene cluster enrichment. Additionally, a noteworthy upregulation of MUSTN1, FOS and TGFB3 was spotted in broiler chickens at D42, which were involved in cell differentiation and muscle regeneration after injury, suggesting a regulatory role of muscle growth and repair. Conclusions This work provided a regulatory network of postnatal broiler chickens and revealed ACTC1 and MUSTN1 as the key responsible for muscle development and regeneration. Our findings highlight that rapid growth in broiler chickens triggers ongoing muscle damage and subsequent regeneration. These findings provide a foundation for future research to investigate the functional aspects of muscle development.

Abstract Objectives We hope to offer a comprehensive understanding of the advancements and patterns in research on PND. Methods: We performed a thorough search on the Web of Science Core Collection to locate relevant studies published from 1969 to 2022 and utilized four distinct tools, namely VOSviewer (J Data Inf Sci, 2017, 2, 1; J Am Soc Inf Sci, 1973, 24, 265; Amer Doc, 1963, 14, 10 and Scientometrics, 2010, 82, 581), CiteSpace (Scientometrics, 2010, 84, 523), Scimago Graphica, and R‐bibliometrix which allowed us to examine various aspects. Results: We included a total of 6787 articles and reviews for analysis which described PND research, the sources, and the subfields; highlighted the significant developments in this field; identified three main directions in PND.Conclusion: This study highlights the rapid growth of research on PND in recent years and provided an overview of previous studies in the field of PND, thereby establishing the overall landscape of PND research and identifying potential avenues for future investigations. Methods We performed a thorough search on the Web of Science Core Collection to locate relevant studies published from 1969 to 2022. To perform bibliometric analysis and network visualization, we utilized four distinct tools, namely VOSviewer (J Data Inf Sci, 2017, 2, 1; J Am Soc Inf Sci, 1973, 24, 265; Amer Doc, 1963, 14, 10 and Scientometrics, 2010, 82, 581), CiteSpace (Scientometrics, 2010, 84, 523), Scimago Graphica, and R‐bibliometrix. These tools allowed us to examine various aspects, including the yearly publication output, the contribution of different countries or regions, the involvement of active journals, co‐citation analysis, publication status, keywords, and terms, as well as scientific categories. We hope to offer a comprehensive understanding of the advancements and patterns in research on PND. The insights gained from this study can assist researchers and clinicians in enhancing the management and implementation of their work in this field. Results In this study, we included a total of 6787 articles and reviews for analysis. First, publication trends and contribution by country analysis described PND research. Second, a historical analysis described PND research, the sources, and the subfields. Third, an analysis of keywords highlighted the significant developments in this field. Fourth, an analysis of research themes identified three main directions in PND. Conclusion In summary, the research volume exhibits exponential growth over time. Furthermore, the majority of contributions originate from Western countries and China. The interdisciplinary nature of the field is evident, with its roots in biology and medicine and further branching into psychology and social sciences. POCD, delirium‐predominant associated clinical management were major research themes about PND.

Abstract Background Acute thrombotic events play a major role in various cardiovascular diseases. Therefore, direct thrombus imaging can be proved beneficial for early diagnosis and prompt therapy of thrombosis. Our study investigated targeted dual‐modality cyclic arginine‐glycine‐aspartic micro bubbles (cRGD‐MBs) for direct imaging of thrombi by fluorescence and ultrasound. Methods cRGD‐MBs were prepared by mechanical vibration and chemical chelation methods. Results Coulter counter analysis demonstrated that the cRGD‐MBs were well dispersed, with diameters ranging from 1 to 3 μm. They emitted bright red fluorescence under an excitation wavelength of 660 nm. In vivo fluorescence and ultrasound imaging revealed that cRGD‐MBs accumulated at the site of thrombus in the carotid artery with significant fluorescence and ultrasonic signal. Conclusions This study showed that novel microbubble cRGD‐MBs were successfully synthesized, and that these could potentially be used as contrast agents for immediate diagnosis of acute thrombus in vivo.

Abstract Background The breeding of layers emphasizes the continual selection of egg-related traits, such as egg production, egg quality and eggshell, which enhance their productivity and meet the demand of market. As the breeding process continued, the genomic homozygosity of layers gradually increased, resulting in the emergence of runs of homozygosity (ROH). Therefore, ROH analysis can be used in conjunction with other methods to detect selection signatures and identify candidate genes associated with various important traits in layer breeding. Results In this study, we generated whole-genome sequencing data from 686 hens in a Rhode Island Red population that had undergone fifteen consecutive generations of intensive artificial selection. We performed a genome-wide ROH analysis and utilized multiple methods to detect signatures of selection. A total of 141,720 ROH segments were discovered in whole population, and most of them (97.35%) were less than 3 Mb in length. Twenty-three ROH islands were identified, and they overlapped with some regions bearing selection signatures, which were detected by the De-correlated composite of multiple signals methods (DCMS). Sixty genes were discovered and functional annotation analysis revealed the possible roles of them in growth, development, immunity and signaling in layers. Additionally, two-tailed analyses including DCMS and ROH for 44 phenotypes of layers were conducted to find out the genomic differences between subgroups of top and bottom 10% phenotype of individuals. Combining the results of GWAS, we observed that regions significantly associated with traits also exhibited selection signatures between the high and low subgroups. We identified a region significantly associated with egg weight near the 25 Mb region of GGA 1, which exhibited selection signatures and has higher genomic homozygosity in the low egg weight subpopulation. This suggests that the region may be play a role in the decline in egg weight. Conclusions In summary, through the combined analysis of ROH, selection signatures, and GWAS, we identified several genomic regions that associated with the production traits of layers, providing reference for the study of layer genome.

Abstract Synthetic hexaploid wheats (SHWs) are effective genetic resources for transferring agronomically important genes from wild relatives to common wheat (Triticum aestivum L.). Dozens of reference-quality pseudomolecule assemblies of hexaploid wheat have been generated, but none is reported for SHW-derived cultivars. Here, we generated a chromosome-scale assembly for the SHW-derived cultivar ‘Chuanmai 104’ based on PacBio HiFi reads and chromosome conformation capture sequencing. The total assembly size was 14.81 Gb with a contig N50 length of 58.25 Mb. A BUSCO analysis yielded a completeness score of 99.30%. In total, repetitive elements comprised 81.36% of the genome and 122,554 high-confidence protein-coding gene models were predicted. In summary, the first chromosome-level assembly for a SHW-derived cultivar presents a promising outlook for the study and utilization of SHWs in wheat improvement, which is essential to meet the global food demand.

Abstract Drug screening based on in-vitro primary tumor cell culture has demonstrated potential in personalized cancer diagnosis. However, the limited number of tumor cells, especially from patients with early stage cancer, has hindered the widespread application of this technique. Hence, we developed a digital microfluidic system for drug screening using primary tumor cells and established a working protocol for precision medicine. Smart control logic was developed to increase the throughput of the system and decrease its footprint to parallelly screen three drugs on a 4 × 4 cm2 chip in a device measuring 23 × 16 × 3.5 cm3. We validated this method in an MDA-MB-231 breast cancer xenograft mouse model and liver cancer specimens from patients, demonstrating tumor suppression in mice/patients treated with drugs that were screened to be effective on individual primary tumor cells. Mice treated with drugs screened on-chip as ineffective exhibited similar results to those in the control groups. The effective drug identified through on-chip screening demonstrated consistency with the absence of mutations in their related genes determined via exome sequencing of individual tumors, further validating this protocol. Therefore, this technique and system may promote advances in precision medicine for cancer treatment and, eventually, for any disease.

The extraction and decolorization conditions for Spirulina platensis polysaccharides using hot alkali and hydrogen peroxide were investigated, and the process was optimized. Based on the results of a single-factor test, the yield and decolorization rate of polysaccharides were taken as indices to optimize the technological conditions for extracting polysaccharides from Spirulina platensis using the hot alkali method and decolorizing them with hydrogen peroxide using the response surface methodology. The optimal conditions for hot alkali extraction of polysaccharides from Spirulina platensis were determined as follows: NaOH concentration of 1.5%, extraction temperature of 90 ℃, extraction time of 4 hours, and material-to-liquid ratio of 1:20 g/mL. Under these conditions, the yield of polysaccharides from Spirulina platensis was 5.18%±0.23%. The optimal conditions for decolorization using hydrogen peroxide were found to be: 17% hydrogen peroxide solution, decolorization time of 55 minutes, and decolorization temperature of 50 ℃. Under these conditions, the actual decolorization rate was 82.54%±0.03%, and the retention rate of polysaccharides was 83.45%±0.13%. The findings of this study provide valuable insights for the development and utilization of Spirulina platensis polysaccharides.

Abstract Background Chronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era. Methods An ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits. Results A total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P

Abstract RNA-binding proteins (RBPs) contribute to the pathogenesis of proliferative diabetic retinopathy (PDR) by regulating gene expression through alternative splicing events (ASEs). However, the RBPs differentially expressed in PDR and the underlying mechanisms remain unclear. Thus, this study aimed to identify the differentially expressed genes in the neovascular membranes (NVM) and retinas of patients with PDR. The public transcriptome dataset GSE102485 was downloaded from the Gene Expression Omnibus database, and samples of PDR and normal retinas were analyzed. A mouse model of oxygen-induced retinopathy was used to confirm the results. The top 20 RBPs were screened for co-expression with alternative splicing genes (ASGs). A total of 403 RBPs were abnormally expressed in the NVM and retina samples. Functional analysis demonstrated that the ASGs were enriched in cell cycle pathways. Cell cycle-associated ASEs and an RBP–AS regulatory network, including 15 RBPs and their regulated ASGs, were extracted. Splicing factor proline/glutamine rich (SFPQ), microtubule-associated protein 1 B (MAP1B), heat-shock protein 90-alpha (HSP90AA1), microtubule-actin crosslinking factor 1 (MACF1), and CyclinH (CCNH) expression remarkably differed in the mouse model. This study provides novel insights into the RBP–AS interaction network in PDR and for developing screening and treatment options to prevent diabetic retinopathy-related blindness.

Abstract Background Centromeres are critical for maintaining genomic stability in eukaryotes, and their turnover shapes genome architectures and drives karyotype evolution. However, the co-evolution of centromeres from different species in allopolyploids over millions of years remains largely unknown. Results Here, we generate three near-complete genome assemblies, a tetraploid Brachypodium hybridum and its two diploid ancestors, Brachypodium distachyon and Brachypodium stacei. We detect high degrees of sequence, structural, and epigenetic variations of centromeres at base-pair resolution between closely related Brachypodium genomes, indicating the appearance and accumulation of species-specific centromere repeats from a common origin during evolution. We also find that centromere homogenization is accompanied by local satellite repeats bursting and retrotransposon purging, and the frequency of retrotransposon invasions drives the degree of interspecies centromere diversification. We further investigate the dynamics of centromeres during alloploidization process, and find that dramatic genetics and epigenetics architecture variations are associated with the turnover of centromeres between homologous chromosomal pairs from diploid to tetraploid. Additionally, our pangenomes analysis reveals the ongoing variations of satellite repeats and stable evolutionary homeostasis within centromeres among individuals of each Brachypodium genome with different polyploidy levels. Conclusions Our results provide unprecedented information on the genomic, epigenomic, and functional diversity of highly repetitive DNA between closely related species and their allopolyploid genomes at both coarse and fine scale.

Abstract Implantable medical devices have played an important role in human medicine in recent decades. However, traditional implanted devices require battery replacement and a second surgery for device removal, which can cause pain to the patient. This work presents a biodegradable triboelectric nanogenerator (BI-TENG) made from both natural and synthetic biodegradable materials that is utilized to collect mechanical energy in vivo and transduce it into electricity. Reed film and polylactic acid were chosen among different biodegradable materials as the triboelectric layers due to having the best generator output performance by providing voltages that reached 368 V. The biocompatibility of the friction layer and the device was verified via a blood test. After implantation in mice, the BI-TENG exhibited an open-circuit voltage of 0.176 V and a short-circuit current of 192 nA as generated from body movement. The BI-TENG was connected to an interdigital electrode to generate an electric field, which stimulated the accelerated release of doxorubicin (DOX) from red blood cells in targeted drug delivery systems. After stopping the electric field, the release of DOX normalized, facilitating the precise killing of cancer cells. Our work demonstrates the broad potential of BI-TENGs in the field of cancer treatment.

In this study, the freeze-dried powder of Lanmaoa asiatica enzymatic hydrolysates was used as the main material, and the optimal preparation process of Lanmaoa asiatica seasoning oil was obtained by optimizing the Maillard reaction conditions. The response values of the electronic nose sensor and the sensory evaluation scores were used as evaluation indicators. Single-factorial and orthogonal experiments were used to optimize the preparation process parameters of Lanmaoa asiatica seasoning oil. The results showed that the optimal preparation process was as follows: Mixing the freeze-dried powder of Lanmaoa asiatica enzymatic hydrolysates with corn oil in a ratio of 1:40 (w/w), adding 5% glucose and 3% L-glutamic acid, and conducting the Maillard reaction at 140 ℃ for 40 min. The seasoning oil prepared under these conditions had a rich and harmonious aroma with a unique flavor of Lanmaoa asiatica. Electronic nose analysis identified sulfur compounds, nitrogen oxides, aldehydes, and ketones as the main aroma components. Quality testing showed that the seasoning oil met national standards, containing 3693 kJ/100 g of energy and 99.8 g/100 g of fat.

Abstract Background Osteosarcoma (OS) is one of the most common aggressive bone malignancy tumors in adolescents. With the application of new chemotherapy regimens, finding new and effective anti-OS drugs to coordinate program implementation is urgent for the patients of OS. Oridonin had been proved to mediate anti-tumor effect on OS cells, but its mechanism has not been fully elucidated. Methods The effects of oridonin on the viability, clonal formation and migration of 143B and U2OS cells were detected by CCK-8, colony formation assays and wound-healing test. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore the mechanism of oridonin on OS. Western blot (WB), real-time quantitative PCR (qRT-PCR) were used to detect the expression levels of apoptosis and ferroptosis-relative proteins and genes. Annexin V-FITC apoptosis detection kit and flow cytometry examination were used to detect the level of apoptosis. Iron assay kit was used to evaluate the relative Fe2+ content. The levels of mitochondrial membrane potential and lipid peroxidation production was determined by mitochondrial membrane potential detection kit and ROS assay kit. Results Oridonin could effectively inhibit the survival, clonal formation and metastasis of OS cells. The KEGG results indicated that oridonin is associated with the malignant phenotypic signaling pathways of proliferation, migration, and drug resistance in OS. Oridonin was capable of inhibiting expressions of BAX, cl-caspase3, SLC7A11, GPX4 and FTH1 proteins and mRNA, while promoting the expressions of Bcl-2 and ACSL4 in 143B and U2OS cells. Additionally, we found that oridonin could promote the accumulation of reactive oxygen species (ROS) and Fe2+ in OS cells, as well as reduce mitochondrial membrane potential, and these effects could be significantly reversed by the ferroptosis inhibitor ferrostatin-1 (Fer-1). Conclusion Oridonin can trigger apoptosis and ferroptosis collaboratively in OS cells, making it a promising and effective agent for OS therapy.

Abstract The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression.

Abstract Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent’s concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin’s action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections. Graphical Abstract

Introduction: Cadonilimab (AK104) is an innovative human programmed cell death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody. Compared with the combination therapy of PD-1 and CTLA-4 blockers, less cellular toxicity of cadonilimab was significantly manifested. As one of the characteristic adverse effects of cadonilimab, infusion-related reactions (IRRs) represent fever, chills, rash, decreased blood pressure, and other symptoms. Case Presentation: Here, we documented seven cases of IRRs after the administration of cadonilimab. The symptoms of IRRs were relieved after the discontinuation of cadonilimab and the administration of diphenhydramine, dexamethasone, and cimetidine. Notably, 3 patients were able to tolerate the subsequent cadonilimab therapy under the pretreatment. Conclusion: In this study, we discovered that cadonilimab-related IRRs might be lessened or prevented by administering medication and the proper pretreatment and lowering the infusion rate.

Kidney transplantation is considered to be the best treatment for end-stage renal disease. To reduce the incidence of rejection and improve the survival of recipients and kidney grafts, kidney transplant recipients must take immunosuppressive agents, and some patients require them for the rest of their lifetime. These treatment regimens can result in susceptibility to opportunistic infections and disrupt the intestinal microbiota, thereby leading to diarrhea, which causes water and electrolyte metabolism disorder, nutrient malabsorption, and instability in the blood concentrations of the immunosuppressive agents. Fluctuating blood concentration levels of these agents necessitate frequent laboratory monitoring and dose adjustments to avoid poor adherence and increase the risk of graft rejection. Furthermore, severe diarrhea can cause kidney transplant failure or death. Clostridium difficile infection (CDI) is the leading cause of diarrhea after renal transplantation. Traditional antibiotics can kill C. difficile; however, spores can remain in the gut. Disruption of the intestinal flora caused by antibiotherapy increases the risk of developing recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) has been proven to be a safe and effective treatment for CDI and is recommended for rCDI owing to its convenient material acquisition method, high efficacy, and low incidence of adverse reactions. This review summarizes the recent progress in FMT for CDI-associated diarrhea after renal transplantation.

Extramammary Paget disease (EMPD) is a rare cutaneous intraepithelial adenocarcinoma, which is mostly distributed in areas with sweat gland cells and mainly occurs in the anogenital skin of women. The male genital tract involvement is extremely rare and often occurs with other malignant tumors. Paget’s disease in the scrotum with sweat gland carcinoma is even rarer. In the first report of scrotal endocrine sweat gland carcinoma associated with Paget disease by Saidi et al. in 1997, no more than 50 cases have been reported in the relevant research worldwide. Early EMPD combined with sweat gland carcinoma is mainly surgical treatment, and there is no standard treatment plan for advanced EMPD with sweat gland carcinoma. Previous article has reported that chemotherapy such as paclitaxel, fluorouracil, platinum, and vinblastine and molecular targeted therapy based on the genetic test results of patients have certain efficacy. Here, we report a 79-year-old male case diagnosed with human epidermal growth factor receptor 2 (HER-2) overexpression, which was effectively controlled by chemotherapy and anti–HER-2 treatment such as pyrotinib.

This study addresses the challenges of low detection precision and limited generalization across various ripeness levels and varieties for large non-green-ripe citrus fruits in complex scenarios. We present a high-precision and lightweight model, YOLOC-tiny, built upon YOLOv7, which utilizes EfficientNet-B0 as the feature extraction backbone network. To augment sensing capabilities and improve detection accuracy, we embed a spatial and channel composite attention mechanism, the convolutional block attention module (CBAM), into the head’s efficient aggregation network. Additionally, we introduce an adaptive and complete intersection over union regression loss function, designed by integrating the phenotypic features of large non-green-ripe citrus, to mitigate the impact of data noise and efficiently calculate detection loss. Finally, a layer-based adaptive magnitude pruning strategy is employed to further eliminate redundant connections and parameters in the model. Targeting three types of citrus widely planted in Sichuan Province—navel orange, Ehime Jelly orange, and Harumi tangerine—YOLOC-tiny achieves an impressive mean average precision (mAP) of 83.0%, surpassing most other state-of-the-art (SOTA) detectors in the same class. Compared with YOLOv7 and YOLOv8x, its mAP improved by 1.7% and 1.9%, respectively, with a parameter count of only 4.2M. In picking robot deployment applications, YOLOC-tiny attains an accuracy of 92.8% at a rate of 59 frames per second. This study provides a theoretical foundation and technical reference for upgrading and optimizing low-computing-power ground-based robots, such as those used for fruit picking and orchard inspection.

ABSTRACT: Sperm competition and cryptic female choice (CFC) are 2 significant mechanisms of postcopulatory sexual selection that greatly impact fertilization success in various species. Despite extensive research has conducted on sperm competition and the evolution of sperm traits in internal fertilization, our understanding of the female preferences in selecting sperm is still limited. Here, we aimed to investigate the characteristics of CFC in chickens by utilizing artificial insemination with mixed semen to control for variations in male fertilization success caused by female perception of male quality and mating order. Our results revealed that the offspring from multiple-mated females exhibited mixed paternity. Although the males had an equal number of viable sperm, 1 male consistently exhibited a 15% higher success rate on average, regardless of whether the insemination was performed with fresh or diluted semen. This result suggested that this male demonstrates superior performance in sperm competition, and exhibited a potential advantage in fertilization success. While the dominant male generally made a greater genetic contribution to most offspring, the degree of this advantage varied greatly, ranging from 11.11 to 75%. Furthermore, our study provided evidence of female preferences influenced the precedence of sperm from certain males over others. Interestingly, this bias is not consistently observed among all individuals, as offspring derived from some females were predominantly sired by an overall disadvantaged male while others were predominantly by a different disadvantaged male. Overall, these results underscored the complex processes involved in sperm selection and emphasized the importance of females in sexual selection theory.

IntroductionThe prognosis for glioma is generally poor, and the 5-year survival rate for patients with this disease has not shown significant improvement over the past few decades. Parkinson’s disease (PD) is a prevalent movement disorder, ranking as the second most common neurodegenerative disease after Alzheimer’s disease. Although Parkinson’s disease and glioma are distinct diseases, they may share certain underlying biological pathways that contribute to their development.ObjectiveThis study aims to investigate the involvement of genes associated with Parkinson’s disease in the development and prognosis of glioma.MethodsWe obtained datasets from the TCGA, CGGA, and GEO databases, which included RNA sequencing data and clinical information of glioma and Parkinson’s patients. Eight machine learning algorithms were used to identify Parkinson-Glioma feature genes (PGFGs). PGFGs associated with glioma prognosis were identified through univariate Cox analysis. A risk signature was constructed based on PGFGs using Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) method. We subsequently validated its predictive ability using various methods, including ROC curves, calibration curves, KM survival analysis, C-index, DCA, independent prognostic analysis, and stratified analysis. To validate the reproducibility of the results, similar work was performed on three external test datasets. Additionally, a meta-analysis was employed to observe the heterogeneity and consistency of the signature across different datasets. We also compared the differences in genomic variations, functional enrichment, immune infiltration, and drug sensitivity analysis based on risk scores. This exploration aimed to uncover potential mechanisms of glioma occurrence and prognosis.ResultsWe identified 30 PGFGs, of which 25 were found to be significantly associated with glioma survival. The prognostic signature, consisting of 19 genes, demonstrated excellent predictive performance for 1-, 2-, and 3-year overall survival (OS) of glioma. The signature emerged as an independent prognostic factor for glioma overall survival (OS), surpassing the predictive performance of traditional clinical variables. Notably, we observed differences in the tumor microenvironment (TME), levels of immune cell infiltration, immune gene expression, and drug resistance analysis among distinct risk groups. These findings may have significant implications for the clinical treatment of glioma patients.ConclusionThe expression of genes related to Parkinson’s disease is closely associated with the immune status and prognosis of glioma patients, potentially regulating glioma pathogenesis through multiple mechanisms. The interaction between genes associated with Parkinson’s disease and the immune system during glioma development provides novel insights into the molecular mechanisms and targeted therapies for glioma.

Abstract Objective This study aims to report a severe phenotype of Arboleda‐Tham syndrome in a 20‐month‐old girl, characterized by global developmental delay, distinct facial features, intellectual disability. Arboleda‐Tham syndrome is known for its wide phenotypic spectrum and is associated with truncating variants in the KAT6A gene. Methods To diagnose this case, a combination of clinical phenotype assessment and whole‐exome sequencing technology was employed. The genetic analysis involved whole‐exome sequencing, followed by confirmation of the identified variant through Sanger sequencing. Results The whole‐exome sequencing revealed a novel de novo frameshift mutation c.3048del (p.Leu1017Serfs*17) in the KAT6A gene, which is classified as likely pathogenic. This mutation was not found in the ClinVar and HGMD databases and was not present in her parents. The mutation leads to protein truncation or activation of nonsense‐mediated mRNA degradation. The mutation is located within exon 16, potentially leading to protein truncation or activation of nonsense‐mediated mRNA degradation. Protein modeling suggested that the de novo KAT6A mutation might alter hydrogen bonding and reduce protein stability, potentially damaging the protein structure and function. Conclusion This study expands the understanding of the genetic basis of Arboleda‐Tham syndrome, highlighting the importance of whole‐exome sequencing in diagnosing cases with varied clinical presentations. The discovery of the novel KAT6A mutation adds to the spectrum of known pathogenic variants and underscores the significance of this gene in the syndrome's pathology.

Abstract Porous Ionic Liquids (PILs) have gained attention but facing challenges in catalysis, especially in liquid‐liquid two‐phase reactions due to limited catalytic sites and hydrophilicity control. This work engineered a Type III PILs (PILS‐M) using zeolitic imidazolate framework‐8 (ZIF‐8) confined phosphomolybdic acid (HPMo) as the microporous framework and N‐butyl pyridine bis(trifluoromethane sulfonyl) imide ionic liquid ([Bpy][NTf2]) as the solvent. The PILS‐M not only combines the advantages of traditional ionic liquids and microporous frameworks, including excellent extraction, high dispersion of catalytically active species, remarkable stability, etc., but also can make the inner surface of ZIF‐8 turned to be hydrophilic that favors the contact between aqueous hydrogen peroxide oxidant and catalytically active sites for the promotion of catalytic performance in reactive extractive desulfurization (REDS) processes of fuel oils. This study demonstrates Type III PILs' potential as catalysts for sustainable chemical processes, offering insights into versatile PILs applications in diverse fields.

Abstract Background Malnutrition is a common geriatric syndrome and can be targeted preoperatively to decrease the risk of postoperative delirium (POD) in older adult patients. To analyze the value of the prognostic nutritional index (PNI) to predict the incidence of POD in older adult patients with hip fractures. Methods This was a prospective, observational, cohort study of older adult patients with hip fractures. Preoperative PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/μL) using preoperative laboratory results. Patients were divided into POD and non-POD groups using the Confusion Assessment Method (CAM). The risk factors associated with POD as well as the relationship between PNI values and the incidence of POD were analyzed using univariate and multivariate logistic regression analyses. The predictive value of PNI for POD was assessed using receiver operating characteristic curve analysis. Results In this cohort of 369 patients who underwent hip fracture surgery, 67 patients (18.2%) were diagnosed with POD by the CAM results. Low PNI increased the risk of POD (odds ratio (OR) = 0.928, 95% confidence interval (CI): 0.864–0.997). General anesthesia (OR = 2.307, 95% CI: 1.279–4.162) and Mini-Mental State Examination (MMSE) score (OR = 0.956, 95% CI: 0.920–0.994) were also identified as risk factors for POD. Receiver operating characteristic curve analysis suggested that PNI combined with the anesthetic method and MMSE score may be used as a potential predictive indicator of POD after hip fracture surgery. Conclusion Preoperative PNI value is related to POD in older adult patients with hip fractures. Trial registration This secondary analysis study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (approval No. M2022578) and registered in the Chinese Clinical Trial Registry (ChiCTR2300070569).

Abstract Background Extensive local invasion of glioblastoma (GBM) cells within the central nervous system (CNS) is one factor that severely limits current treatments. The aim of this study was to uncover genes involved in the invasion process, which could also serve as therapeutic targets. For the isolation of invasive GBM cells from non-invasive cells, we used a three-dimensional organotypic co-culture system where glioma stem cell (GSC) spheres were confronted with brain organoids (BOs). Using ultra-low input RNA sequencing (ui-RNA Seq), an invasive gene signature was obtained that was exploited in a therapeutic context. Methods GFP-labeled tumor cells were sorted from invasive and non-invasive regions within co-cultures. Ui-RNA sequencing analysis was performed to find a gene cluster up-regulated in the invasive compartment. This gene cluster was further analyzed using the Connectivity MAP (CMap) database. This led to the identification of SKF83566, an antagonist of the D1 dopamine receptor (DRD1), as a candidate therapeutic molecule. Knockdown and overexpression experiments were performed to find molecular pathways responsible for the therapeutic effects of SKF83566. Finally, the effects of SKF83566 were validated in orthotopic xenograft models in vivo. Results Ui-RNA seq analysis of three GSC cell models (P3, BG5 and BG7) yielded a set of 27 differentially expressed genes between invasive and non-invasive cells. Using CMap analysis, SKF83566 was identified as a selective inhibitor targeting both DRD1 and DRD5. In vitro studies demonstrated that SKF83566 inhibited tumor cell proliferation, GSC sphere formation, and invasion. RNA sequencing analysis of SKF83566-treated P3, BG5, BG7, and control cell populations yielded a total of 32 differentially expressed genes, that were predicted to be regulated by c-Myc. Of these, the UHRF1 gene emerged as the most downregulated gene following treatment, and ChIP experiments revealed that c-Myc binds to its promoter region. Finally, SKF83566, or stable DRD1 knockdown, inhibited the growth of orthotopic GSC (BG5) derived xenografts in nude mice. Conclusions DRD1 contributes to GBM invasion and progression by regulating c-Myc entry into the nucleus that affects the transcription of the UHRF1 gene. SKF83566 inhibits the transmembrane protein DRD1, and as such represents a candidate small therapeutic molecule for GBMs.

Introduction: Primary pleural epithelial angiosarcoma (EAS) is an extremely rare tumor with no specific clinical symptoms. Clinical data on primary pleural EAS are limited, and misdiagnosis often occurs. Case Presentation: The present study reports the case of a 31-year-old patient diagnosed with primary pleural EAS with lung and bone metastases. The patient presented with persistent right chest pain for 5 months and dyspnea for 2 months. Chest computed tomography (CT) scan revealed right hydropneumothorax, diffuse thickening of the right pleura, passive atelectasis, and scattered nodules in the left lung. A medical thoracoscopic pleural biopsy revealed a vasogenic tumor. To further confirm the diagnosis, positron emission tomography/CT (PET/CT) examination was recommended to determine the biopsy site after multidisciplinary discussion. Increased 18F-FDG uptake in the right pleura and hypermetabolic nodules in the right chest wall, first lumbar vertebrae, second sacral vertebrae, and bilateral iliac crest was detected via PET/CT. CT-guided chest wall and lung biopsies were performed. Immunohistochemistry of specific markers was performed according to remote consultation with a pathologist, and tumor cells with strong positive expression of CD31, CD34, and ETS-related genes led to the final diagnosis of primary pleural EAS. Conclusion: Primary pleural EAS should be considered for hydropneumothorax of an unknown cause. PET/CT can accurately locate the lesion. The pathological examination is the basis for primary pleural EAS diagnosis. Moreover, multidisciplinary discussion and remote expert consultation can improve the diagnosis rate of primary pleural EAS.

Abstract Background Hybridization is a useful strategy to produce offspring with more desirable phenotypic characteristics than those of parents. The hybrid grouper derived from the cross of Cromileptes altivelis (♀, 2n = 48) with Epinephelus lanceolatus (♂, 2n = 48) exhibits improved growth compared with its female parent, which makes it valuable to aquaculture. However, the genetic traits of the hybrid grouper are poorly understood. Results The observations showed that the hybrid grouper was diploid (2n = 48) and displayed intermediate morphology with the parent's measurable characteristics. The ribosomal DNA (rDNA) and mitochondria DNA (mtDNA) were characterized at molecular and phylogenetic level. High similarity and low genetic distance of 5S rDNA and mtDNA sequences between the hybrid grouper and C. altivelis showed that the hybrid grouper had a closer genetic relationship with female parents. The reconstructed phylogenetic tree based on COI gene and D-loop region of mtDNA recovered that mtDNA was maternally inherited in the hybrid grouper. Additionally, the DNA methylation level of 5S rDNA intergenic spacers (IGS) sequence was tested in here. The results showed that the DNA methylation status of the hybrid grouper was significantly lower than that of C. altivelis. Conclusion Results of this study provide important data on the genetic characteristics of the hybrid derived from the cross of C. altivelis and E. lanceolatus, and contribute the knowledge of both evolution and marine fish breeding.

Abstract Purpose Patellofemoral arthroplasty (PFA) was shown to be a potentially effective surgical technique for isolated patellofemoral osteoarthritis but varying reports on PFA-related implant failure and complications have rendered the procedure controversial. This study aimed to identify impactful publications, research interests/efforts, and collaborative networks in the field of PFA research. Methods The study used the Web of Science Core Collection (WOSCC) database, Medline, Springer, BIOSIS Citation Index, and PubMed to retrieve relevant publications on PFA research published between 1950–2022. Statistical tests in R software were used for analysis while VOSviewer, Bibliometrix, and CiteSpace were employed for data visualization. Results Two hundred forty-one articles were analyzed with the number of published papers increasing over time. Knee was the most frequent journal and Clinical Orthopaedics and Related Research was the most cited journal. Clinical outcomes, such as prosthesis survival, revision, and complications, were researched most frequently as demonstrated by keyword analysis. The United States was the top contributor to cooperative networks, followed by the United Kingdom while Technical University Munich formed close ties among authors. Conclusion Publications on PFA research have witnessed a notable surge. They primarily came from a limited number of centers and were characterized by low-level evidence. The majority of studies primarily focused on the clinical outcomes of PFA, while revision of PFA and patient satisfaction have emerged as new research areas.

Abstract Background Identifying the key factors that underlie complex traits during domestication is a great challenge for evolutionary and biological studies. In addition to the protein-coding region differences caused by variants, a large number of variants are located in the noncoding regions containing multiple types of regulatory elements. However, the roles of accumulated variants in gene regulatory elements during duck domestication and economic trait improvement are poorly understood. Results We constructed a genomics, transcriptomics, and epigenomics map of the duck genome and assessed the evolutionary forces that have been in play across the whole genome during domestication. In total, 304 (42.94%) gene promoters have been specifically selected in Pekin duck among all selected genes. Joint multi-omics analysis reveals that 218 genes (72.01%) with selected promoters are located in open and active chromatin, and 267 genes (87.83%) with selected promoters were highly and differentially expressed in domestic trait-related tissues. One important candidate gene ELOVL3, with a strong signature of differentiation on the core promoter region, is known to regulate fatty acid elongation. Functional experiments showed that the nearly fixed variants in the top selected ELOVL3 promoter in Pekin duck decreased binding ability with HLF and increased gene expression, with the overexpression of ELOVL3 able to increase lipid deposition and unsaturated fatty acid enrichment. Conclusions This study presents genome resequencing, RNA-Seq, Hi-C, and ATAC-Seq data of mallard and Pekin duck, showing that selection of the gene promoter region plays an important role in gene expression and phenotypic changes during domestication and highlights that the variants of the ELOVL3 promoter may have multiple effects on fat and long-chain fatty acid content in ducks.

Abstract A set of high-quality pan-genomes would help identify important genes that are still hidden/incomplete in bird reference genomes. In an attempt to address these issues, we have assembled a de novo chromosome-level reference genome of the Silkie (Gallus gallus domesticus), which is an important avian model for unique traits, like fibromelanosis, with unclear genetic foundation. This Silkie genome includes the complete genomic sequences of well-known, but unresolved, evolutionarily, endocrinologically, and immunologically important genes, including leptin, ovocleidin-17, and tumor-necrosis factor-α. The gap-less and manually annotated MHC (major histocompatibility complex) region possesses 38 recently identified genes, with differentially regulated genes recovered in response to pathogen challenges. We also provide whole-genome methylation and genetic variation maps, and resolve a complex genetic region that may contribute to fibromelanosis in these animals. Finally, we experimentally show leptin binding to the identified leptin receptor in chicken, confirming an active leptin ligand-receptor system. The Silkie genome assembly not only provides a rich data resource for avian genome studies, but also lays a foundation for further functional validation of resolved genes.

Abstract Background Astragalus grows mainly in drought areas. Cycloastragenol (CAG) is a tetracyclic triterpenoid allelochemical extracted from traditional Chinese medicine Astragalus root. Phospholipase C (PLC) and Gα-submit of the heterotrimeric G-protein (GPA1) are involved in many biotic or abiotic stresses. Nitric oxide (NO) is a crucial gas signal molecule in plants. Results In this study, using the seedlings of Arabidopsis thaliana (A. thaliana), the results showed that low concentrations of CAG induced stomatal closure, and high concentrations inhibited stomatal closure. 30 µmol·L−1 CAG significantly increased the relative expression levels of PLC1 and GPA1 and the activities of PLC and GTP hydrolysis. The stomatal aperture of plc1, gpa1, and plc1/gpa1 was higher than that of WT under CAG treatment. CAG increased the fluorescence intensity of NO in guard cells. Exogenous application of c-PTIO to WT significantly induced stomatal aperture under CAG treatment. CAG significantly increased the relative expression levels of NIA1 and NOA1. Mutants of noa1, nia1, and nia2 showed that NO production was mainly from NOA1 and NIA1 by CAG treatment. The fluorescence intensity of NO in guard cells of plc1, gpa1, and plc1/gpa1 was lower than WT, indicating that PLC1 and GPA1 were involved in the NO production in guard cells. There was no significant difference in the gene expression of PLC1 in WT, nia1, and noa1 under CAG treatment. The gene expression levels of NIA1 and NOA1 in plc1, gpa1, and plc1/gpa1 were significantly lower than WT, indicating that PLC1 and GPA1 were positively regulating NO production by regulating the expression of NIA1 and NOA1 under CAG treatment. Conclusions These results suggested that the NO accumulation was essential to induce stomatal closure under CAG treatment, and GPA1 and PLC1 acted upstream of NO.

ABSTRACT: Improving feed utilization is a vital strategy to meet the growing global demand for meat and promote sustainable food production. Over the past few decades, significant improvements in the feed intake (FI) and feed utilization efficiency of broilers have been achieved through advanced breeding procedures, although dynamic changes in FI and their effects on the feed conversion ratio (FCR) have remained unclear. In this study, we measured individual weekly FI and body weight of 274 male broilers to characterize the dynamic FI patterns and investigate their relationship with growth performance. The broilers were from 2 purebred lines and their crossbreed and measurements were collected from 4 to 6 wk of age. Overall, a continuous increase in the weekly FI occurred from 4 to 6 wk of age, whereas the body weight gain (BWG) reached an inflection point in wk 5. The dynamic change in weekly FI was observed to follow 3 distinct FI patterns: pattern 1, a continuous weekly increase in FI; pattern 2, an increase followed by a plateau; pattern 3, an increase followed by a decrease. The prevalence of these patterns was similar in the purebred and crossbred populations: pattern 2 was most frequent, followed by a moderate proportion of pattern 1, and the lowest proportion of pattern 3. Broilers following pattern 1 displayed significantly better growth performance and feed utilization efficiency than those following pattern 3, emphasizing the importance of maintaining good appetite in the last stage of broiler production. In summary, this study has characterized the dynamic patterns of FI and their association with growth performance. Our results offer a new foundation for improving feed utilization efficiency and investigating feeding regulation in broilers.

ABSTRACT: Seminal fluid, once believed to be sterile, is now recognized as constituting a complex and dynamic environment inhabited by a diverse community of micro-organisms. However, research on the seminal microbiota in chickens is limited, and microbiota variations among different chicken breeds remain largely unexplored. In this study, we collected semen samples from Beijing You Chicken (BYC) and Tibetan Chicken (TC) and explored the characteristics of the microbiota using 16S rRNA gene sequencing. Additionally, we collected cloacal samples from the TC to control for environmental contamination. The results revealed that the microbial communities in the semen were significantly different from those in the cloaca. Firmicutes and Actinobacteriota were the predominant phyla in BYC and TC semen, respectively, with Lactobacillus and Phyllobacterium being the dominant genera in each group. Additionally, the seminal microbiota of BYC exhibited greater richness and evenness than that of TC. Principal coordinate analysis (PCoA) indicated significant intergroup differences between the seminal microbiotas of BYC and TC. Subsequently, by combining linear discriminant analysis effect size and random forest analyses, we identified Lactobacillus as the predominant microorganism in BYC semen, whereas Phyllobacterium dominated in TC semen. Furthermore, co-occurrence network analysis revealed a more intricate network in the BYC group than in the TC group. Additionally, unique microbial functional characteristics were observed in each breed, with TC exhibiting metabolic features potentially associated with their ability to adapt to high-altitude environments. The results of this study emphasized the unique microbiota present in chicken semen, which may be influenced by genetics and evolutionary history. Significant variations were observed between low-altitude and high-altitude breeds, highlighting the breed-specific implications of the seminal microbiota for reproduction and high-altitude adaptation.

ABSTRACT: Long-term intensive genetic selection has led to significant differences between broiler and layer chickens, which are evident during the embryonic period. Despite this, there is a paucity of research on the genetic regulation of the initial formation of muscle fiber morphology in chick embryos. Embryonic d 17 (E17) is the key time point for myoblast fusion completion and muscle fiber morphology formation in chickens. This study aimed to explore the genetic regulatory mechanisms underlying the early muscle fiber morphology establishment in broiler chickens of Cornish (CC) and White Plymouth Rock (RR) and layer chickens of White Leghorn (WW) at E17 using the transcriptomic and chromatin accessibility sequencing of pectoral major muscles. The results showed that broiler chickens exhibited significant higher embryo weight and pectoral major muscle weight at E17 compared to layer chickens (P = 0.000). A total of 1,278, 1,248, and 892 differentially expressed genes (DEGs) of RNA-seq data were identified between CC vs. WW, RR vs. WW, and CC vs. RR, separately. All DEGs were combined for cluster analysis and they were divided into 6 clusters, including cluster 1 with higher expression in broilers and cluster 6 with higher expression in layers. DEGs in cluster 1 were enriched in terms related to macrophage activation (P = 0.002) and defense response to bacteria (P = 0.002), while DEGs in cluster 6 showed enrichment in protein-DNA complex (P = 0.003) and monooxygenase activity (P = 0.000). ATAC-seq data analysis identified a total of 38,603 peaks, with 13,051 peaks for CC, 18,780 peaks for RR, and 6,772 peaks for WW. Integrative analysis of transcriptomic and chromatin accessibility data revealed GOLM1, ISLR2, and TOPAZ1 were commonly upregulated genes in CC and RR. Furthermore, screening of all upregulated DEGs in cluster 1 from CC and RR identified GOLM1, ISLR2, and HNMT genes associated with neuroimmune functions and MYOM3 linked to muscle morphology development, showing significantly elevated expression in broiler chickens compared to layer chickens. These findings suggest active neural system connectivity during the initial formation of muscle fiber morphology in embryonic period, highlighting the early interaction between muscle fiber formation morphology and the nervous system. This study provides novel insights into late chick embryo development and lays a deeper foundation for further research.

Children diagnosed with Autism Spectrum Disorder (ASD) often struggle to grasp social conventions and promptly recognize others' emotions. Recent advancements in the application of deep learning (DL) to emotion recognition are solidifying the role of AI-powered assistive technology in supporting autistic children. However, the cost of collecting and annotating large-scale high-quality human emotion data and the phenomenon of unbalanced performance on different modalities of data challenge DL-based emotion recognition. In response to these challenges, this paper explores transfer learning, wherein large pre-trained models like Contrastive Language-Image Pre-training (CLIP) and wav2vec 2.0 are fine-tuned to improve audio- and video-based emotion recognition with text- based guidance. In this work, we propose the EmoAsst framework, which includes a visual fusion module and emotion prompt fine-tuning for CLIP, in addition to leveraging CLIP's text encoder and supervised contrastive learning for audio-based emotion recognition on the wav2vec 2.0 model. In addition, a joint few-shot emotion classifier enhances the accuracy and offers great adaptability for real-world applications. The evaluation results on the MELD dataset highlight the outstanding performance of our methods, surpassing the majority of existing video and audio-based approaches. Notably, our research demonstrates the promising potential of the proposed text-based guidance techniques for improving video and audio-based Emotion Recognition and Classification (ERC).

ABSTRACT: The industry of egg-type chicken has shown a trend of extending the rearing period, with the goal of breeding chicken breeds capable of producing 500 qualified eggs by 700 d of age. However, the rapid decline in eggshell quality during the late laying period is one of the major challenges. In this study, a total of 3,261 Rhode Island Red chickens were used to measure eggshell quality traits including eggshell strength (ESS), eggshell thickness (EST), eggshell color (ESC) and eggshell gloss (ESG) at seven age points ranging from 36 to 90 wk of age. Phenotypic variations increased with the aging process, especially during the late laying period (> 55 wk), and the heritability during this period decreased by 22.7 to 81.4% compared to the initial and peak laying periods. Then we performed genome-wide association study (GWAS) to identify the genomic variants that associated with eggshell quality, with a custom Illumina 50K BeadChip, named PhenoixChip-I. The results indicated that 2 genomic regions on GGA1(23.24-25.15Mb; 175.95-176.05 Mb) were significantly (P < 4.48E-06) or suggestively (P < 8.97E-05) associated with ESS, which can explain 9.59% and 0.48% of the phenotypic variations of ESS46 and ESS36, respectively. Three genes, FRY, PCNX2, and ENSGALG00000052468, were considered to be the candidate genes for ESS. For other traits, the genome-wide suggestive SNPs were identified at each age point, exhibiting a certain trend with aging process. Additionally, SNP enrichment analysis and functional annotation of cross-tissue regulatory elements to ESS36 revealed a high concentration of enhancer elements specific to shell gland and kidney tissues. This study, deepened our knowledge of eggshells and laying a valued scientific foundation for chicken molecular breeding.

ABSTRACT: The growth rate of chickens has made remarkable progress in recent decades through continuous breeding efforts. However, this advancement has also led to a decline in fertility among commercially bred chickens. Therefore, it is crucial to understand and improve factors that influence fertility to ensure the continued success of the industry. Here, we conduct a 3-generation selection experiment within 2 purebred female lines, with the aim of increasing the duration of fertility (DF). Duration of fertility refers to the length of time hens remain capable of producing fertilized eggs and is a crucial factor that directly impacts chick output. The results showed that significant genetic progress was achieved in embryo survival rates and the fertility duration day during both the peak and late laying periods. Moreover, after 3 generations of selective breeding, the disparities in embryo survival and chick health rates from setting eggs between 8-d and 5-d insemination intervals in the grandparent stock were significantly reduced. The rates decreased from 1.83% and 2.39 to 0.72% and 0.33%, respectively. Surprisingly, the hatching performances of hens with an 8-d interval were comparable to those hens that had not undergone genetic selection for DF and had a 5-d interval. We further discussed the possibility of extending the insemination interval to 8 d in parent stock for commercial practices. The parental populations exhibited remarkable performance in terms of percentages of embryo survival and healthy chicks from the setting eggs, with rates exceeding 94 and 90%, respectively. Thus, it can be inferred that an extended insemination interval is feasible by genetic selection for DF. These findings will provide valuable insights into the efficacy of genetic selection in enhancing DF and its practical application in commercial breeding programs.

Background Resilience is vital for improving mental health and well-being during adolescence, which is an important yet vulnerable period. Previous research has indicated that physical activity enhances individual resilience. However, limited studies have examined underlying psychological mechanisms between them. The current study aimed to investigate the effect of physical activity on adolescent resilience via self-efficacy and basic psychological needs. Methods A cross-sectional survey was conducted with 1,732 high school students aged 16 to 20 years old (mean age: 16.51 ± 0.77 years), with nearly equal number of boys (47.63%) and girls (52.37%). They each completed the Physical Exercise Questionnaire, Basic Psychological Needs in Exercise Scale, General Self-Efficacy Scale, and Resilience Scale, respectively. A serial indirect model was constructed to examine how physical activity influences resilience. Results Structural equation model analysis revealed that physical activity significantly and directly predicted resilience. When self-efficacy and basic psychological needs were included in the model, both direct and indirect effects were observed. Specifically, the positive relationship between physical activity and resilience was partially mediated by self-efficacy and basic psychological needs. In addition, basic psychological needs and self-efficacy were found to serially mediate the direct relathonship between physical activity and resilience. Conclusions The present study provides novel theoretical insights into sports psychology by establishing a link between basic psychological needs and self-efficacy. The findings have implications for school administrators and physical education instructors in designing targeted interventions to promote adolescent resilience. These interventions may involve creating supportive environment conductive to fulfilling students’ basic psychological needs, implementing strategies to enhance self-efficacy beliefs, and providing opportunities for skill development and mastery experiences in sports and physical activities.

Diabetic retinopathy (DR) is a highly tissue-specific neurovascular complication of type 1 and type 2 diabetes mellitus and is among the leading causes of blindness worldwide. Pathophysiological changes in DR encompass neurodegeneration, inflammation, and oxidative stress. Current treatments for DR, including anti-vascular endothelial growth factor, steroids, laser photocoagulation, and vitrectomy have limitations and adverse reactions, necessitating the exploration of novel treatment strategies. This review aims to summarize the current pathophysiology, therapeutic approaches, and available drug-delivery methods for treating DR, and discuss their respective development potentials. Recent research indicates the efficacy of novel receptor inhibitors and agonists, such as aldose reductase inhibitors, angiotensin-converting enzyme inhibitors, peroxisome proliferator-activated receptor alpha agonists, and novel drugs in delaying DR. Furthermore, with continuous advancements in nanotechnology, a new form of drug delivery has been developed that can address certain limitations of clinical drug therapy, such as low solubility and poor penetration. This review serves as a theoretical foundation for future research on DR treatment. While highlighting promising therapeutic targets, it underscores the need for continuous exploration to enhance our understanding of DR pathogenesis. The limitations of current treatments and the potential for future advancements emphasize the importance of ongoing research in this field.

Summary: The molecular mechanism of ibrutinib-induced atrial fibrillation (AF) remains unclear. We here demonstrate that treating rats with ibrutinib for 4 weeks resulted in the development of inducible AF, left atrial enlargement, atrial fibrosis, and downregulation of connexin expression, which were associated with C-terminal Src kinase (CSK) inhibition and Src activation. Ibrutinib upregulated angiotensin-converting enzyme (ACE) protein expression in human pulmonary microvascular endothelial cells (HPMECs) by inhibiting the PI3K-AKT pathway, subsequently increasing circulating angiotensin II (Ang II) levels. However, the expression of ACE and Ang II in the left atria was not affected. Importantly, we observed that perindopril significantly mitigated ibrutinib-induced left atrial remodeling and AF promotion by inhibiting the activation of the ACE and its downstream CSK-Src signaling pathway. These findings indicate that the Ibrutinib-induced activation of the ACE contributes to AF development and could serve as a novel target for potential prevention strategies.

Background: Cancer immunotherapies aimed at activating immune system, especially by blocking immune checkpoints, have become a successful modality for treating patients with advanced cancers. However, its clinical practice is frequently conceded by high outcomes, low initial response rates and severe side effects. New strategies are necessary to complement and advance this biological therapy. Erzhi Pills (EZP) have diverse pharmaceutical effects including immune regulation, anti-tumor and anti-senescence. We hypothesized that EZP could exert its antitumor effect through immunomodulation. Purpose: The aim of this study was to investigate the effects of EZP on anti-tumor activities, and define its molecular mechanisms. Methods: By applying melanoma model with high immune infiltrates, we determined the anti-melanoma effect of EZP. To identify whether this effect was mediated by direct targeting tumor cells, cell viability and apoptosis were examined in vitro. Network pharmacology analysis was used to predict the potential mechanisms of EZP for melanoma via immune response. Flow cytometry, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA) and crystal violet (CV) experiments were performed to detect T cell infiltrations and functions mediated by EZP. The mechanism of EZP was further investigated by western blotting both in vivo and in vitro. Results: The administration of EZP significantly inhibited tumor weight and volume. EZP extract could only slightly reduce cell viability and induce melanoma apoptosis. Network pharmacology analysis predicted that JAK-STAT signaling pathway and T cell receptor signaling pathway might be involved during EZP treatment. Flow cytometry and IHC analyses showed that EZP increased the number of CD4+ T cells and enhanced the function of CD8+ T cells. In co-culture experiments, EZP elevated killing ability of T cells. Western blotting showed that EZP treatment reduced PD-L1 signaling pathway. Conclusion: These findings indicated that EZP exerted anti-melanoma effects by inducing apoptosis and blocking PD-L1 to activate T cells. EZP might represent a promising candidate drug for cancer immunotherapies.

Abstract Objective To study the development of microalbuminuria (MAU) in essential hypertension (EHT), we investigated the association of MAU with central blood pressure (CBP), direct renin concentration (DRC), plasma aldosterone (PA), and uric acid (UA). Method We determined 24 h-urinary albumin excretion (24 h-UAE) in patients with EHT who were hospitalized at TEDA International Cardiovascular Hospital from June 2020 to May 2022. We defined MAU as 24 h-UAE in the range of 30 mg/24 h to 300 mg/24 h. Univariate and multivariate analyses were conducted to determine the associations of MAU with CBP, DRC, PA, and UA in EHT, considering demographic and clinical information. We also plotted receiver operating characteristic curves (ROCs) for predicting MAU using these results. Results More than a quarter of patients (26.5%, 107/404, 95% CI: 22.2–31.1%) were diagnosed with MAU in EHT. A higher body mass index (BMI), longer duration of hypertension, and higher severity were associated with MAU. Also, nearly 10% more creatinine levels were recorded in the MAU group than in the control group (69.5 ± 18.7 µmol/L vs. 64.8 ± 12.5 µmol/L, P = 0.004). The increase was also observed for PA (15.5, 9.7–20.6 ng/dL vs. 12.3, 9.0–17.3 ng/dL, P = 0.024) and UA (419.8 ± 105.6 µmol/L vs. 375.1 ± 89.5 µmol/L, P

Abstract Sound vibration is one of natural stimuli trigging physiological changes in plants. Recent studies showed that sound waves stimulated production of a variety of plant secondary metabolites, including flavonoids, in order to enhance seed germination, flowering, growth or defense. In this review, we examine the potential role of sound stimulation on the biosynthesis of secondary metabolites and the followed cascade of physiological changes in plants, from the perspective of transcriptional regulation and epigenetic regulation for the first time. A systematic summary showed that a wide range of factors may regulate the production of secondary metabolites, including plant species, growth stage, sound types, sound frequency, sound intensity level and exposure time, etc. Biochemical and physiological changes due to sound stimulation were thoroughly summarized as well, for secondary metabolites can also act as a free radical scavenger, or a hormone signaling molecule. We also discussed the limits of previous studies, and the future application of sound waves in biosynthesis of plant secondary metabolites.

Abstract Background Patient safety is a global challenge influenced by perceived patient safety culture. However, limited knowledge exists regarding the patient safety culture perceived by hospital clinical managers and its associated factors. This study aims to investigate the perceptions of patient safety culture and associated factors among clinical managers of tertiary hospitals in China. Methods A cross-sectional survey was conducted from June 19 to July 16, 2021, involving 539 clinical managers from four tertiary hospitals in Changsha City of Hunan Province. The Hospital Survey on Patient Safety Culture (HSOPSC) was utilized to assess perceived patient safety culture. Bivariate, multivariable linear regression, and logistic regression analyses were performed. Results The mean score for the total HSOPSC was 72.5 ± 7.6, with dimensional scores ranging from 62.1 (14.9) to 86.6 (11.7). Three dimensions exhibited positive response rates (PRRs)

Abstract Coagulation system activation is commonly observed in tumor patients, including prostate cancer (PCa), with coagulation markers proposed as potential prognostic indicators for cancer severity. However, the correlation between these markers and clinicopathological features in PCa remains unclear. Thus, this study investigates the association between comprehensive coagulation markers and clinicopathological characteristics in PCa patients. A retrospective evaluation of 162 PCa patients diagnosed and categorized into low-intermediate-risk or high-risk groups based on clinical and pathological features was conducted. Coagulation markers, including fibrinogen (FIB), d-dimer (DD), activated partial thromboplastin time (APTT), prothrombin time (PT), prothrombin activity (PTA), thrombin time (TT), platelet count (PLT), and international normalized ratio (INR), were assessed. Univariate and multivariate logistic regression analyses were performed to determine associations with clinicopathological features. FIB and DD were confirmed as independent factors associated with high-risk PCa. Furthermore, FIB and DD levels showed significant positive correlations with clinical parameters, including PSA levels, ISUP grade, T stage, N stage, and M stage. Our findings suggest that FIB and DD hold promise as independent prognostic biomarkers for risk stratification in PCa. These coagulation markers may aid in assessing PCa severity and guiding personalized treatment strategies.

Abstract Background Methane (CH4) is a major greenhouse gas, and ruminants are one of the sources of CH4 which is produced by the rumen microbiota. Modification of the rumen microbiota compositions will impact the CH4 production. In this study, the effects of melatonin on methane production in cows were investigated both in the in vitro and in vivo studies. Results Melatonin treatment significantly reduced methane production in both studies. The cows treated with melatonin reduced methane emission from their respiration by approximately 50%. The potential mechanisms are multiple. First, melatonin lowers the volatile fatty acids (VFAs) production in rumen and reduces the raw material for CH4 synthesis. Second, melatonin not only reduces the abundance of Methanobacterium which are responsible for generating methane but also inhibits the populations of protozoa to break the symbiotic relationship between Methanobacterium and protozoa in rumen to further lowers the CH4 production. The reduced VFA production is not associated with food intake, and it seems also not to jeopardize the nutritional status of the cows. This was reflected by the increased milk lipid and protein contents in melatonin treated compared to the control cows. It is likely that the energy used to synthesize methane is saved to compensate the reduced VFA production. Conclusion This study enlightens the potential mechanisms by which melatonin reduces rumen methane production in dairy cows. Considering the greenhouse effects of methane on global warming, these findings provide valuable information using different approaches to achieve low carbon dairy farming to reduce the methane emission. Video Abstract

Abstract During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013–2022), the first ten-year stage of the lifespan CCNP (2013–2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0–17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the “Chinese Data-sharing Warehouse for In-vivo Imaging Brain” in the Chinese Color Nest Project (CCNP) – Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

Abstract Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens. Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis. Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins (DEPs) interacted with differentially acetylated proteins (DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group (P

Deep generative models are becoming a tool of choice for exploring the molecular space. One important application area of deep generative models is the reverse design of drug compounds for given attributes (solubility, ease of synthesis, etc.). Although there are many generative models, these models cannot generate specific intervals of attributes. This paper proposes a AC-ModNet model that effectively combines VAE with AC-GAN to generate molecular structures in specific attribute intervals. The AC-ModNet is trained and evaluated using the open 250K ZINC dataset. In comparison with related models, our method performs best in the FCD and Frag model evaluation indicators. Moreover, we prove the AC-ModNet created molecules have potential application value in drug design by comparing and analyzing them with medical records in the PubChem database. The results of this paper will provide a new method for machine learning drug reverse design.