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Abstract To address the problem of fault branch recognition in mine ventilation systems, a one-class classification algorithm is introduced to construct the MC-OCSVM ventilation system fault diagnosis model, which is integrated with multiple OCSVMs. This model adopts uniform hyperparameters and transforms the ventilation system fault diagnosis problem into a maximum decision distance problem, to realize the effective use of mine monitoring wind speed data. The experiments on public KEEL datasets verify that the one-class classification integration model can solve the multiclassification problem and that the MC-OCSVM model has better generalizability than other one-class classification integration models do. The experiment is carried out in the Buertai coal mine, and the results show that the proposed algorithm can identify fault branches quickly and accurately, with an accuracy of 93.2% and a single fault diagnosis time is 1.2 s, highlighting its strong robustness.

Abstract Background Medical education related to bone fracture must address numerous challenges including complex anatomical characteristics, diverse injury mechanisms, fracture typing, and treatment modalities. Our newly developed 3D printed model comprises components that may be combined or split to simulate various anatomical features, fracture types, and treatment modalities. This study aims to analyze the teaching utility of the new 3D-printed model compared with the traditional solid model. Methods This prospective study included 112 students randomly assigned to fracture-related education with a conventional model or the newly developed 3D-printed model. All students received 40 min of lecture, 20 min for femoral neck and 20 min for tibiofibular fractures, and a post-class quiz (10 min each) immediately followed. Scores on tests of fracture-related knowledge and user satisfaction were measured pre and post education for comparison. Results The 3D printing group had an advantage in retention of anatomic knowledge, fracture typing and choice of treatment for the femoral neck fracture (P

The western region is rich in coal seam resources, and the intensity of mining is high. Traditional mining methods can easily lead to the loss of water resources in aquifers, resulting in serious water shortage problems. Therefore, researching water conservation mining technology in shallow-buried strong water-rich areas is of great significance for ensuring water resource safety, maintaining ecological balance, and promoting economic development. By controlling the movement of rock strata to maintain the stability of aquifers, developing cost-effective and widely applicable water conservation mining technologies and materials, a green and efficient three-dimensional water conservation mining system for coal seams in shallow-buried strong water-rich areas can be formed, achieving dual goals of coal mining and water resource protection. This paper first analyzes the current situation and difficulties of water conservation mining, compares existing technologies from aspects of technological advancement and safety, and conducts in-depth research on materials, equipment, and processes, summarizing and analyzing the applicable conditions of different technologies. Then, taking the Jinjie coal mine as an example, based on the water conservation coal mining plan and the actual measured height of the water-conducting fracture zone, the mining field is divided into regions, proposing the principle of “regional classification management”. Innovatively, the paper proposes the technology of remaking the bottom water-blocking layer of the quaternary loose water-rich layer before mining, forming an effective isolation, achieving coordinated development of coal mining and water resource protection, and protecting natural topography and surface vegetation. At the same time, in response to the inefficiency of the current comprehensive mining frame back paste filling and the inability of the support to flexibly switch between filling and non-filling, a new type of filling and non-filling dual-use support is designed and proposed. It can be used as a filling support and can also be used for the disassembly of the rear support, installing the side protection plate of the protective beam, meeting the needs of ordinary support use, and improving the efficiency of equipment use. Finally, the paper summarizes the technology of grouting repair and transformation of the top of the water-conducting fracture zone after mining and the evaluation of grouting effects, and illustrates it with the application of the Jinjie coal mine. It has a wide guiding significance for similar conditions of coal seam mining in the Ordos Basin and provides important support for green mining in the coal industry.

Abstract Background To explore the associations of computed tomography (CT) image features with the serum cryptococcal antigen (CrAg) titers measured by the lateral flow assay (LFA) in localized pulmonary cryptococcosis patients. Methods A retrospective analysis of patients with pathologically confirmed pulmonary cryptococcosis admitted to the First Affiliated Hospital of Xiamen University from January 2016 to December 2022 was performed. Clinical data, CT results, serum CrAg-LFA test results, and follow-up data were collected and analyzed. Results A total of 107 patients with localized pulmonary cryptococcosis were included, of which 31 had a single lesion in chest CT and the other 76 had multiple lesions. The positivity rate was (94.74% vs 64.52%) and titers of serum CrAg-LFA (1.77 ± 0.87 vs 0.91 ± 0.98) in the multiple lesion group were higher than those in the single lesion group, respectively. Multivariate linear regression analysis showed that the serum CrAg titers were positively associated with the number of lesions (β, 0.08; 95% CI, 0.05 to 0.12) and the lesion size (β, 0.40; 95% CI, 0.31 to 0.50) after adjusting other covariates. The serum CrAg-LFA titers of 60 pulmonary cryptococcosis patients showed a decreasing trend with the reduction in pulmonary lesion size after effective therapy. Conclusion In pulmonary cryptococcosis patients, the number and size of lung lesions are positively correlated with the titers of the serum CrAg-LFA test. The CrAg-LFA test could be a useful tool for the diagnosis, severity assessment, and therapeutic monitoring of localized pulmonary cryptococcosis patients.

In Shendong mining area, there may be several abandoned roadways ahead of some mining faces due to the adjustment of the face layout. In order to avoid roof accidents when the mining face crossing abandoned roadways, the occurrence conditions of mining faces and abandoned roadways, mine pressure control methods and effects in Shendong mining area were summarized, and the mechanism of roof advance fracture when the working face crossing abandoned roadways was analyzed. With the consideration of the different supporting effects of abandoned roadways, pumping pillars, coal pillars and supports, numerical simulation was used to study the subsidence and bending tensile stress of the main roof under different coal pillar sizes, roof periodic fracture positions, widths of the abandoned roadways, and strength of the pumping pillars. Results show that with the inclined angle between the roadways and the working faces decreases from 90° vertical to 0° parallel, the advancing length of the working face affected by the abandoned roadways decreases, where the effect intensity increases. The mine pressure of working face when crossing the abandoned roadways is mainly control by the size of the coal pillar, the position of the previous roof periodic fracture before crossing the abandoned roadways, the width and the supporting strength of the abandoned roadways. Due to the inevitable failure of the coal pillars with the mining face approaches the abandoned roadways, and the width of the abandoned roadways is difficult to change, the strengthen supports of the abandoned roadways and waiting mine pressure before crossing the abandoned roadways are always adopted to prevent main roof from advance fracture in Shendong mining area. With the peak strength and elastic modulus of the pumping pillars increase, the roof of the abandoned roadways will be supported better, but the pumping pillars may failure under great load caused by the overlong roof hanging. If the adjacent twice roof periodic fracture occur before and after crossing the abandoned roadways, the main roof can bear most of the overlying load during crossing the abandoned roadways and the mine pressure can be controlled effectively. Otherwise, the advance fracture of the main roof will occur as well as the roof caving and supports crushing. Finally, the fully mechanized mining faces of Halagou coal mine in Shendong mining area are taking as examples, and the mine pressure control effects of pumping pillars and waiting mine pressure during the process of crossing the abandoned roadways were analyzed, which can provid reference for the mine pressure control when crossing the abandoned roadways in Shendong mining area and even other mines.

Abstract Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.

Abstract Chordoma is a rare bone cancer with variable clinical outcomes. Here, we recruited 184 sporadic chordoma patients from the US and Canada and collected their clinical and treatment data. The average age at diagnosis was 45.5 years (Range 5–78) and the chordoma site distribution was 49.2% clivus, 26.2% spinal, and 24.0% sacral. Most patients (97.5%) received surgery as the primary treatment, among whom 85.3% also received additional treatment. Except for the most prevalent cancers like prostate, lung, breast, and skin cancer, there was no discernible enrichment for any specific cancer type among patients or their family members. Among a subset of patients (N = 70) with tumor materials, we conducted omics analyses and obtained targeted panel sequencing and SNP array genotyping data for 51 and 49 patients, respectively. The most recurrent somatic driver mutations included PIK3CA (12%), followed by chromatin remodeling genes PBRM1 and SETD2. Amplification of the 6q27 region, containing the chordoma susceptibility gene TBXT, was detected in eight patients (16.3%). Clival patients appeared to be less likely to carry driver gene mutations, chromosome arm level deletion events (e.g., 5p, 5p, and 9p), or 6q27 amplification compared to sacral patients. After adjusting for age, sex, tumor site, and additional treatment, patients with somatic deletions of 14q (OR = 13.73, 95% CI 1.96–96.02, P = 0.008) and 18p (OR = 13.68, 95% CI 1.77–105.89, P = 0.012) were more likely to have persistent chordoma. The study highlights genomic heterogeneity in chordoma, potentially linked to location and clinical progression.

Abstract Background Macrophages play important roles in phagocytosing tumor cells. However, tumors escape macrophage phagocytosis in part through the expression of anti-phagocytic signals, most commonly CD47. In Ewing sarcoma (ES), we found that tumor cells utilize dual mechanisms to evade macrophage clearance by simultaneously over-expressing CD47 and down-regulating cell surface calreticulin (csCRT), the pro-phagocytic signal. Here, we investigate the combination of a CD47 blockade (magrolimab, MAG) to inhibit the anti-phagocytic signal and a chemotherapy regimen (doxorubicin, DOX) to enhance the pro-phagocytic signal to induce macrophage phagocytosis of ES cells in vitro and inhibit tumor growth and metastasis in vivo. Methods Macrophages were derived from human peripheral blood monocytes by granulocyte–macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). Flow cytometry- and microscopy-based in-vitro phagocytosis assays were performed to evaluate macrophage phagocytosis of ES cells. Annexin-V assay was performed to evaluate apoptosis. CD47 was knocked out by CRISPR/Cas9 approach. ES cell-based and patient-derived-xenograft (PDX)-based mouse models were utilized to assess the effects of MAG and/or DOX on ES tumor development and animal survival. RNA-Seq combined with CIBERSORTx analysis was utilized to identify changes in tumor cell transcriptome and tumor infiltrating immune cell profiling in MAG and/or DOX treated xenograft tumors. Results We found that MAG significantly increased macrophage phagocytosis of ES cells in vitro (p

ObjectivesWe aimed to quantitatively analyze wall shear stress (WSS) of the common carotid artery (CCA) and elucidate the relationship between WSS and cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) using ultrasound vector flow (V-Flow) imaging.MethodsA total of 109 T2DM patients were selected as the DM group, while 49 healthy volunteers served as the control group. V-Flow examination of the bilateral CCA was conducted. The maximum wall shear stress (WSSmax) and mean wall shear stress (WSSmean) at the bifurcation, proximal bifurcation and middle segment of the bilateral CCA were obtained.ResultsThe DM group showed decreased WSSmean in the middle region and proximal bifurcation of the CCA compared with the control group (p < 0.05). The WSSmean was further decreased in T2DM patients with CVD compared to those without CVD (middle region: 0.71 ± 0.17 Pa vs. 0.84 ± 0.24 Pa, p < 0.05; proximal bifurcation: 0.62 ± 0.22 Pa vs. 0.80 ± 0.21 Pa, p < 0.05). The receiver operating characteristic curve showed that a model combining with age, body mass index and WSSmean at the proximal carotid bifurcation had diagnostic value for detecting CVD in T2DM patients (area under the curve: 0.862, p < 0.05).ConclusionWSSmean has potential value for evaluation of atherosclerosis, as well as in detecting the occurrence of CVD in T2DM patients. Ultrasound V-Flow imaging may be an effective tool for non-invasive evaluation of WSS in the clinic.

BackgroundThe relationship between dietary antioxidants and fatty liver disease remains a topic of debate. This study aimed to examine the association between the Composite Dietary Antioxidant Index (CDAI) and nonalcoholic fatty liver disease (NAFLD)/metabolic-associated fatty liver disease (MAFLD).MethodsThe study analyzed data from the 2003–2018 cycles of the National Health and Nutrition Examination Survey. The study included 16,321 individuals aged 20–85 years. Food and nutrient intake data were based on the 24-h recall method. Multivariate logistic regression models were employed to examine the relationship between CDAI and NAFLD/MAFLD.ResultsIn the fully adjusted multivariate logistic regression model, CDAI demonstrated a significant negative correlation with NAFLD and MAFLD. Mediation analysis showed that inflammatory factors partially mediated the relationship between CDAI and NAFLD/MAFLD prevalence. The combination of high CDAI levels with effective physical activity was associated with a greater reduction in NAFLD/MAFLD prevalence than high CDAI levels alone.ConclusionOur study highlighted a negative association between CDAI and NAFLD/MAFLD, mediated by inflammatory factors. Additionally, participants with characteristics of active physical activity and high levels of CDAI were more strongly correlated with the reduced prevalence of NAFLD/MAFLD. Further research in clinical cohorts should be conducted to comprehensively investigate the impact of CDAI on NAFLD/MAFLD prevalence.

ABSTRACT: The Shitou goose, the largest meat-type goose breed, is an ideal model for offering insights into enhancing meat production efficiency through understanding its genetic regulation of muscle development. Here, through whole-transcriptomic analysis of embryonic leg muscles, we identified 847 differentially expressed genes (DEG), 244 differentially expressed lncRNAs (DEL), 37 differentially expressed circRNAs (DEC), and 84 differentially expressed miRNAs (DEM). Gene ontology (GO) analysis highlighted the significant enrichment of differentially expressed RNAs in muscle structure development, actin filament-based processes, and the actin cytoskeleton pathway. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified pathways associated with the FoxO signaling pathway, AMPK signaling pathway, Wnt signaling pathway and calcium signaling pathway. Furthermore, we utilized Miranda, TargetScan, and miRDB to identify regulatory networks that involve interactions between lncRNA-mRNA, circRNA-mRNA, miRNA-mRNA, lncRNA-miRNA-mRNA, and circRNA-miRNA-mRNA, which regulated the growth and development of skeletal muscle. Notably, differentially expressed genes within the ceRNA network were most significantly enriched in the regulation of actin cytoskeletal organization. Additionally, a lncRNA/circRNA-miRNA-mRNA ceRNA network related to muscle growth and development was constructed based on protein-protein interaction (PPI) analysis and hub genes selection using Cytoscape. This further elucidated the regulatory roles of noncoding RNAs (ncRNA) in the formation of muscle fibers in Shitou goose. In summary, this study provides a valuable transcriptional regulatory network for goose muscle development laying the groundwork for further exploration of the molecular regulatory mechanisms underlying the excellent meat production performance of Shitou goose.

Chronic prostatitis/chronic pelvic pain syndrome is a prevalent condition affecting the male urinary system. The urinary dysfunction resulting from this disorder has a direct or indirect impact on the patient’s quality of life. Recent studies have suggested that organ cross-sensitization between the prostate and bladder may elucidate this phenomenon; however, the specific molecular mechanisms remain unclear. In this study, we simulated the urinary symptoms of prostatitis patients using an animal model and examined the expression of relevant proteins within the prostate-bladder sensitized neural pathway. We found that transient receptor potential vanilloid 1 (TRPV1) protein is highly expressed in the dorsal root ganglia (DRG) that co-innervate both the prostate and bladder, potentially increasing the sensitivity of TRPV1 channels via the substance P-neurokinin 1 (SP-NK-1) pathway, which may exacerbate micturition symptoms. Furthermore, in the absence of bladder inflammation, elevated levels of neurogenic substances in bladder tissue were found to sensitize bladder sensory afferents. Collectively, these results underscore the significant role of TRPV1 in bladder sensitization associated with prostatitis, suggesting that the inhibition of TRPV1 along this sensitization pathway could be a promising approach to treating urinary dysfunction linked to prostatitis in the future.

ABSTRACT: This investigation sought to reveal the effects of heat stress on the meat quality of geese. Wuzong geese were subjected to heat stress at 35°C for 25 d or 4 h to examine different heat stress time on meat quality. Short-time heat stress reduced muscle drip loss and meat color L* value while increasing pH value and meat color a* and b* values. Long-time heat stress decreased body weight and increased leg muscle pH value and meat color b* value. Amino acid profile of geese breast muscle revealed that both LHS and SHS can induce L-Cystine but reduced L-Cystathionine, which were positive correlated with cooking loss and meat color lightness, respectively. Lipidome analysis indicated that heat stress would alter the synthesis of unsaturated fatty acids, and the difference between LHS and SHS on lipids mainly focused on Hex1Cer and TG. Non-target metabolome analysis indicated effects of heat stress on Glycerolipid metabolism, Arachidonic acid metabolism, and Pyrimidine metabolism. Proteome analysis showed that heat stress mainly affects cellular respiration metabolism and immune response. These findings highlight the diverse effects of heat stress on meat quality, amino acid composition, lipidome, metabolome, and proteome in geese.

The flavor profile of Linjiangsi broad bean paste (LBBP) is significantly influenced by fermentation environment and ripening time. This study aims to investigate the flavor of outdoor-treated (OT) and indoor-treated (IT) LBBP. Gas chromatography-mass spectrometry, electronic-nose, and electronic-tongue, combined with multivariate statistical analyses, were employed to identify the characteristic flavor profiles of OT and IT LBBP in ripening periods of one and three years. Overall, 95 volatile organic compounds (VOCs) were identified. Relative odor activity values and multivariate statistical analysis indicated that nine VOCs were responsible for the flavor differences. The most abundant VOCs in OT were aldehydes, providing caramel and nutty flavors, whereas the most abundant compounds in IT were esters, contributing fruity flavors to LBBP. Notably, three years of ripening significantly intensified the characteristic flavors of both OT and IT. These findings may elucidate the ripening time and fermentation environment effect on LBBP characteristic flavor profiles.

Chronic prostatitis is a prevalent male urinary system disorder characterized by pelvic discomfort or pain, bladder dysfunction, sexual dysfunction, and infertility. Pain and lower urinary tract symptoms (LUTS) are the most common symptoms, significantly impacting patients’ quality of life and driving them to seek medical attention. Transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective calcium ion-dependent cation channel in the TRPV channel family that is widely distributed in neural tissue and plays a role in signal transmission. In this review, we provide a comprehensive overview of the current understanding of the role of TRPV1 in chronic prostatitis. The discussion focuses on the connection between TRPV1 and prostatitis pain and LUTS, and highlights the potential for targeting this channel in the development of novel treatment strategies.

Background Pediatric patients with recurrent/metastatic Ewing sarcoma (ES) have a dismal 5-year survival. Novel therapeutic approaches are desperately needed. Natural killer (NK) cell number and function are low in ES patient tumors, in large part due to the immunosuppressive tumor microenvironment (TME). Melanoma cell adhesion molecule (MCAM) is highly expressed on ES and associated with ES metastasis. NKTR-255 is a polymer-conjugated recombinant human interleukin-15 (IL-15) agonist improving NK cell activity and persistence. Magrolimab (MAG) is a CD47 blockade that reactivates the phagocytic activity of macrophages.Methods Transcriptome profiling coupled with CIBERSORT analyses in both ES mouse xenografts and human patient tumors were performed to identify mechanisms of NK resistance in ES TME. A chimeric antigen receptor (CAR) NK cell targeting MCAM was engineered by CAR mRNA electroporation into ex vivo expanded NK cells. In vitro cytotoxicity assays were performed to investigate the efficacy of anti-MCAM-CAR-NK cell alone or combined with NKTR-255 against ES cells. Interferon-γ and perforin levels were measured by ELISA. The effect of MAG on macrophage phagocytosis of ES cells was evaluated by in vitro phagocytosis assays. Cell-based and patient-derived xenograft (PDX)-based xenograft mouse models of ES were used to investigate the antitumor efficacy of CAR-NK alone and combined with NKTR-255 and MAG in vivo.Results We found that NK cell infiltration and activity were negatively regulated by tumor-associated macrophages (TAM) in ES TME. Expression of anti-MCAM CAR significantly and specifically enhanced NK cytotoxic activity against MCAMhigh but not MCAM-knockout ES cells in vitro, and significantly reduced lung metastasis and extended animal survival in vivo. NKTR-255 and MAG significantly enhanced in vitro CAR-NK cytotoxicity and macrophage phagocytic activity against ES cells, respectively. By combining with NKTR-255 and MAG, the anti-MCAM-CAR-NK cell significantly decreased primary tumor growth and prolonged animal survival in both cell- and PDX-based ES xenograft mouse models.Conclusions Our preclinical studies demonstrate that immunotherapy via the innate immune system by combining tumor-targeting CAR-NK cells with an IL-15 agonist and a CD47 blockade is a promising novel therapeutic approach to targeting MCAMhigh malignant metastatic ES.

The degree of yellowness of the skin is an important factor affecting the market popularity and sales price of yellow-feathered broilers. Despite its commercial importance, the specific pigments and genetic mechanisms involved remain unclear. This study identified lutein as the primary carotenoid in the skin and established serum lutein concentration as a molecular marker for predicting skin yellowness in carcasses. Through RNA sequencing of broilers with varying yellowness, we identified key genes like CYP26A1, CYP1B1, CYP2C18, CYP2W1, HSD17B2, AOX1, KMO, PLIN1, and RET, which may regulate carotenoid absorption and deposition. Additionally, a single nucleotide polymorphism in the CYP1A1 gene was significantly associated with skin yellowness in Ma-Huang chickens. Overall, this study examined the primary pigment types that influence the skin yellowness of yellow-feathered broilers, emphasizing that lutein can serve as a molecular marker for skin yellowness and providing insights into the regulatory factors that regulate skin yellowness. These findings provide essential theoretical support for the breeding of skin color traits in yellow-feathered broilers.

ABSTRACT: Lutein is an antioxidant that can indicate the oxidative status of organisms through its coloration and may be involved in the development process of chicken skeletal muscle. In this study, after feeding Nanhai Yellow Chickens with lutein-containing feed for 21 d, the lutein group significantly increased the muscle fiber diameter and decreased the fiber density in the chicken's leg muscles compared to the control group. To elucidate the potential regulatory mechanisms by which lutein is involved in muscle development, RNA-seq was used to detect changes in gene expression in chicken leg muscle tissue. After data analysis, a total of 249 significantly differentially expressed genes (DEG) were identified, including TGF-β superfamily (MSTN and TGFB1) and nonreceptor tyrosine kinase c-Src (SRC). Results from GO and KEGG analysis showed that the DEGs were enriched in GO terms such as positive regulation of the ERK1/ERK2 cascade and negative regulation of myoblast differentiation, as well as signaling pathways including the Toll-like receptor signaling pathway and the MAPK signaling pathway. These significantly enriched GO terms and pathways are closely related to muscle development, suggesting that lutein may play an important role in the process of chicken muscle development. This study provides insights into the regulatory mechanisms of dietary lutein on chicken muscle development.

ABSTRACTBackground Tongue coating microbiota has aroused particular interest in profiling oral and digestive system cancers. However, little is known on the relationship between tongue coating microbiome and colorectal cancer (CRC).Methods Metagenomic shotgun sequencing was performed on tongue coating samples collected from 30 patients with CRC, 30 patients with colorectal polyps (CP), and 30 healthy controls (HC). We further validated the potential of the tongue coating microbiota to predict the CRC by a random forest model.Results We found a greater species diversity in CRC samples, and the nucleoside and nucleotide biosynthesis pathway was more apparent in the CRC group. Importantly, various species across participants jointly shaped three distinguishable fur types.The tongue coating microbiome profiling data gave an area under the receiver operating characteristic curve (AUC) of 0.915 in discriminating CRC patients from control participants; species such as Atopobium rimae, Streptococcus sanguinis, and Prevotella oris aided differentiation of CRC patients from healthy participants.Conclusion These results elucidate the use of tongue coating microbiome in CRC patients firstly, and the fur-types observed contribute to a better understanding of the microbial community in human. Furthermore, the tongue coating microbiota-based biomarkers provide a valuable reference for CRC prediction and diagnosis.

BackgroundMedulloblastoma is the most common malignant brain tumor in children. Most cases are sporadic, but well characterized germline alterations in APC, ELP1, GPR161, PTCH1, SUFU, and TP53 predispose to medulloblastoma. However, knowledge about pathogenic/likely pathogenic (P/LP) variants that predispose to medulloblastoma vary based on genes evaluated, patient demographics, and pathogenicity definitions.MethodsGermline exome sequencing was conducted on 160 childhood survivors of medulloblastoma. Analyses focused on rare variants in 239 known cancer susceptibility genes (CSGs). P/LP variants were identified using ClinVar and InterVar. Variants of unknown significance in known medulloblastoma predisposing genes (APC, ELP1, GPR161, PTCH1, SUFU, TP53) were further classified for loss of function variants. We compared the frequency of P/LP variants in cases to that in 1,259 cancer-free adult controls.ResultsTwenty cases (12.5%) had a P/LP variant in an autosomal dominant CSG versus 5% in controls (p=1.0 x10-3), and 10 (6.3%) of these were P/LP variants in a known medulloblastoma gene, significantly greater than 0.2% observed in controls (p=1.4x10-8). The CSGs with the most P/LP variants in cases, and significantly higher than controls, were ELP1 (p=3.0x10-4) and SUFU (p=1.4x10-3).ConclusionApproximately one in eight pediatric medulloblastoma survivors had an autosomal dominant P/LP CSG variant. We confirm several known associated genes and identify novel genes that may be important in medulloblastoma.

ABSTRACT: The introduction of exotic breeds and the cultivation of new lines by breeding companies have posed challenges to native chickens in South China, including loss of breed characteristics, decreased genetic diversity, and declining purity. Understanding the population genetic structure and genetic diversity of native chickens in South China is crucial for further advancements in breeding efforts. In this study, we analyzed the population genetic structure and genetic diversity of 321 individuals from 10 different breeds in South China. By comparing commercial chickens with native ones, we identified selection signatures occurring between local chickens and commercial breeds. The analysis of population genetic structure revealed that the native chicken populations in South China exhibited a considerable level of genetic diversity. Moreover, the commercial lines of Xiaobai chicken and Huangma chicken displayed even higher levels of genetic diversity, which distinguished them from other native varieties at the clustering level. However, certain individuals within these commercial varieties showed a discernible genetic relationship with the native populations. Notably, both commercial varieties also retained a significant degree of genetic similarity to their respective native counterparts. In order to investigate the genomic changes occurring during the commercialization of native chickens, we employed 4 methods (Fst, ROD, XPCLR, and XPEHH) to identify potential candidate regions displaying selective signatures in Southern Chinese native chicken population. A total of 168 (identified by Fst and ROD) and 86 (identified by XPCLR and XPEHH) overlapping genes were discovered. Functional annotation analysis revealed that these genes may be associated with reproduction and growth (SAMSN1, HYLS1, ROBO3, FGF14, PRSS23), musculoskeletal development (DNER, MYBPC1, DGKB, ORC1, KLF10), disease resistance and environmental adaptability (PUS3, CRB2, CALD1, USP15, SGCD, LTBP1), as well as egg production (ADGRB3, ACSF3). Overall, native chickens in South China harbor numerous selective sweep regions compared to commercial chickens, enriching valuable genomic resources for future genetic research and breeding conservation.

Abstract Purpose To assess the efficacy of neoadjuvant endocrine therapy in female HR‐positive/HER2‐negative breast cancer patients. Data and Methods We identified female patients aged ≥18 years with cT1‐4N0‐XM0, HR(+), and HER2(−) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as “surgery‐first,” while those who received NET before surgery were classified as “NET.” Propensity score‐matching, Cox proportional‐hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes. Results Among 432,387 cases, 2914 NET patients and 2914 surgery‐first patients were matched. Compared with the surgery‐first group, the NET group received less adjuvant chemotherapy (p

ABSTRACT: Meat quality traits are essential for producing high-quality broilers, but the genetic improvement has been limited by the complexity of measurement methods and the numerous traits involved. To systematically understand the meat quality characteristics of different broiler breeds, this study collected data on slaughter performance, skin color, fat deposition, and meat quality traits of 434 broilers from 12 different breeds in South China. The results showed that there was no significant difference in the live weight and slaughter weight of various broiler breeds at their respective market ages. Commercial broiler breeds such as Xiaobai and Huangma chickens had higher breast muscle and leg muscle rates. The skin and abdominal fat of Huangma chickens cultivated in the consumer market in South China exhibited significantly higher levels of yellowness compared to other varieties. Concerning fat traits, we observed that Wenchang chickens exhibited a strong ability to fat deposition, while the younger breeds showed lower fat deposition. Additionally, there were significant positive correlations found among different traits, including traits related to weight, traits related to fat, and skin color of different parts. Hierarchical clustering analysis revealed that fast-growing and large broiler Xiaobai chickens formed a distinct cluster based on carcass characteristics, skin color, and meat quality traits. Principal component analysis (PCA) was used to extract multiple principal components as substitutes for complex meat quality indicators, establishing a chicken meat quality evaluation model to differentiate between different breeds of chickens. At the same time, we identified 46, 22, and 20 SNP loci and their adjacent genes that were significantly associated with muscle mass traits, fat deposition, and skin color through genome-wide association studies (GWAS). The above results are helpful for systematically understanding the differences and characteristics of meat quality traits among different breeds.

Current literature suggests that one of the impressive benefits of digital game-based language learning is its potential to create engaging vocabulary learning experiences. However, this literature is dominated by game-play approaches, rather than game-making approaches. Drawing upon constructivist, motivation, dual-coding, and constructionist theories, this study examined elementary English language learners’ vocabulary learning experiences in a game-based learning context and investigated their experience as they built their own games based on their understanding of different non-fiction texts. This mixed-methods case study involved novel use of network analysis to examine student learning, investigate the relationships between various aspects of learner experiences, and evaluate the strengths and weaknesses of the program. Findings indicated that a complex set of interdependencies between enactments of theoretical principles including generativity, agency, tinkering, intrinsic motivation, and contextualized learning lead to enjoyment and powerful language learning experiences. Design principles for future digital game-based language learning include optimizing visual aspects, spending more time on technical skill development, increasing learner agency, and focusing more on generative and joyful learning experiences.

【Objective】Excessive deposition of abdominal fat reduces disease resistance and slaughter rate of broilers. RNA alternative splicing is an important regulatory modality that affects gene function. Systematic analysis of RNA alternative splicing events during broiler abdominal fat deposition contributes to further understanding of the molecular regulation mechanism of broiler abdominal fat deposition.【Method】The transcriptome sequencing results of liver and abdominal fat tissues in high-fat-fed and normal-fed broilers were used to identify the differentially expressed and alternative spliced genes in abdominal fat and liver tissues during high-fat feeding. Significantly differentially spliced genes were analyzed by GO functional annotation, KEGG pathway enrichment analysis and Metascape enrichment analysis, and visualization processing was conducted for the significantly differential alternative splicing events, then splicing factors regulating these differential splicing events were analyzed.【Result】Transcriptome sequencing was performed on the abdominal fat and liver tissues of high-fat-fed broilers and normal-fed broilers. 233 significantly differentially expressed genes and 349 significantly differentially alternative spliced genes were found in the abdominal fat tissues. It was found that the significantly differential spliced genes were mainly enriched in cell proliferation, such as cell division and cell growth, as well as in pathways related to adipogenesis, such as glycerophospholipid metabolism and insulin signaling pathway. In liver tissues, 276 significantly differentially expressed genes and 224 significantly differential spliced genes were found, and the enrichment analysis of the significantly differential spliced genes revealed that these genes were mainly enriched in biological processes related to cellular metabolism such as protein acetylation, intra-protein amino acid acetylation and mRNA processing and also enriched in adipogenesis-related pathways such as insulin signaling pathway, glucagon signaling pathway and AMPK signaling pathway. Among the significantly differential spliced genes in abdominal fat and liver, a total of four candidate genes related to influencing abdominal fat deposition traits in broiler were screened, including GPAT4, RELCH, CYP39A1, and PPARA.【Conclusion】The results preliminarily revealed the patterns of RNA alternative splicing regulation in abdominal fat and liver tissues of broilers under high-fat feeding. It was inferred that high-fat feeding may lead to abdominal fat deposition in broilers by affecting the alternative splicing process of genes, which may activate the proliferation of preadipocytes and the metabolism of adipogenesis-related cells. Regulation of target genes by splicing factors was significantly involved in influencing the process of abdominal fat deposition in broilers.

Abstract Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10−6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10−8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10−6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.

Abstract The relationship between serum uric acid and lung function has been controversial. This study aims to determine whether there is an independent relationship between serum uric acid and lung function in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Serum uric acid was considered the exposure variable, and lung function (FEV1 and FVC) was the outcome variable. Multivariable linear regression was conducted with adjustments for potential confounders. The total number of participants from NHANES (2007–2012) was 30,442, of which 7514 were included in our analysis after applying exclusion criteria. We observed that serum uric acid was negatively associated with FEV1 and FVC after adjusting for confounders (β for FEV1 [− 24.77 (− 36.11, − 13.43)] and FVC [− 32.93 (− 47.42, − 18.45)]). Similarly, serum uric acid showed a negative correlation with FEV1 and FVC after adjusting for confounding variables both in male and female populations. The relationship between serum uric acid and FEV1 and FVC remained consistent and robust in various subgroups within both male and female populations, including age, race, BMI, alcohol consumption, smoking status, and income-poverty ratio. Serum uric acid is negatively associated with FEV1 and FVC in the US general healthy population. This negative relationship is significant in both the male and female populations.

Using Monte Carlo simulations, this study compared the performance of various approaches to the specification of random effects structures in linear mixed effects models (LMMs), including the minimal approach, the maximal approach, the forward search, the backward search, and the all-possible structures approach. The results showed that if the predictor of interest is at the within-cluster level or involves a cross-level interaction, the maximal approach, the best-path forward search, and the best-path backward search are all desirable methods. If the predictor of interest is at the cluster level, it is not essential to specify random slopes of Level-1 predictors. In addition, it is important to specify random slopes of within-cluster control variables, as they can increase the statistical power for testing the main within-cluster variables, especially when the sample size is small and the variance of the random slope of the control variable is large.

Abstract In high-income countries, mosaic chromosomal alterations in peripheral blood leukocytes are associated with an elevated risk of adverse health outcomes, including hematologic malignancies. We investigate mosaic chromosomal alterations in sub-Saharan Africa among 931 children with Burkitt lymphoma, an aggressive lymphoma commonly characterized by immunoglobulin-MYC chromosomal rearrangements, 3822 Burkitt lymphoma-free children, and 674 cancer-free men from Ghana. We find autosomal and X chromosome mosaic chromosomal alterations in 3.4% and 1.7% of Burkitt lymphoma-free children, and 8.4% and 3.7% of children with Burkitt lymphoma (P-values = 5.7×10−11 and 3.74×10−2, respectively). Autosomal mosaic chromosomal alterations are detected in 14.0% of Ghanaian men and increase with age. Mosaic chromosomal alterations in Burkitt lymphoma cases include gains on chromosomes 1q and 8, the latter spanning MYC, while mosaic chromosomal alterations in Burkitt lymphoma-free children include copy-neutral loss of heterozygosity on chromosomes 10, 14, and 16. Our results highlight mosaic chromosomal alterations in sub-Saharan African populations as a promising area of research.

Diagnosis of disorders of consciousness (DOC) remains a formidable challenge. Deep learning methods have been widely applied in general neurological and psychiatry disorders, while limited in DOC domain. Considering the successful use of resting-state functional MRI (rs-fMRI) for evaluating patients with DOC, this study seeks to explore the conjunction of deep learning techniques and rs-fMRI in precisely detecting awareness in DOC. We initiated our research with a benchmark dataset comprising 140 participants, including 76 unresponsive wakefulness syndrome (UWS), 25 minimally conscious state (MCS), and 39 Controls, from three independent sites. We developed a cascade 3D EfficientNet-B3-based deep learning framework tailored for discriminating MCS from UWS patients, referred to as “DeepDOC”, and compared its performance against five state-of-the-art machine learning models. We also included an independent dataset consists of 11 DOC patients to test whether our model could identify patients with cognitive motor dissociation (CMD), in which DOC patients were behaviorally diagnosed unconscious but could be detected conscious by brain computer interface (BCI) method. Our results demonstrate that DeepDOC outperforms the five machine learning models, achieving an area under curve (AUC) value of 0.927 and accuracy of 0.861 for distinguishing MCS from UWS patients. More importantly, DeepDOC excels in CMD identification, achieving an AUC of 1 and accuracy of 0.909. Using gradient-weighted class activation mapping algorithm, we found that the posterior cortex, encompassing the visual cortex, posterior middle temporal gyrus, posterior cingulate cortex, precuneus, and cerebellum, as making a more substantial contribution to classification compared to other brain regions. This research offers a convenient and accurate method for detecting covert awareness in patients with MCS and CMD using rs-fMRI data.

A novel nanocomposite hydrogel with photothermal therapeutic properties, which could enhance the healing of surgical wounds, was developed. The composite comprises functionalized silica nanoparticles (FSNs) loaded with desferoxamine (DFO) as the core and a dexamethasone (Dex) filled hyaluronic acid–chitosan hydrogel (HA-CS) as the shell. Dex can effectively control inflammation at the wound site, and DFO is beneficial in proliferating the skin cells. The two drugs effectively promote wound healing at the surgical site. The aim of this approach is to demonstrate the hierarchical and continuous release of Dex and DFO from the FSNs@DFO-H@Dex system to reduce wound inflammation and promote healing. Furthermore, the controlled release of DFO can be achieved by controlling the near-infrared illumination. The composite nano hydrogel has a photothermal response, which accelerates wound healing by effectively reducing inflammation through the controlled release of drugs and regulating the immunological response of damaged skin tissue.

Abstract The USP19 deubiquitinase is found in a locus associated with Parkinson’s Disease (PD), interacts with chaperonins, and promotes secretion of α-synuclein (α-syn) through the misfolding-associated protein secretion (MAPS) pathway. Since these processes might modulate the processing of α-syn aggregates in PD, we inactivated USP19 (KO) in mice expressing the A53T mutation of α-syn and in whom α-syn preformed fibrils (PFF) had been injected in the striatum. Compared to WT, KO brains showed decreased accumulation of phospho-synuclein (pSyn) positive aggregates. This improvement was associated with less activation of microglia and improved performance in a tail-suspension test. Exposure of primary neurons from WT and KO mice to PFF in vitro also led to decreased accumulation of pSyn aggregates. KO did not affect uptake of PFF nor propagation of aggregates in the cultured neurons. We conclude that USP19 instead modulates intracellular dynamics of aggregates. At an early time following PFF injection when the number of pSyn-positive neurons were similar in WT and KO brains, the KO neurons contained less aggregates. KO brain aggregates stained more intensely with anti-ubiquitin antibodies. Immunoprecipitation of soluble proteins from WT and KO brains with antibodies to pSyn showed higher levels of ubiquitinated oligomeric species in the KO samples. We propose that the improved pathology in USP19 KO brains may arise from decreased formation or enhanced clearance of the more ubiquitinated aggregates and/or enhanced disassembly towards more soluble oligomeric species. USP19 inhibition may represent a novel therapeutic approach that targets the intracellular dynamics of α-syn complexes.

Objective To summarize and analyze the dermoscopic features of scabies. Methods Dermoscopic images of 101 patients with scabies were collected from the dermatology clinic from January 2022 to April 2023, and the microscopic features were analyzed. Results The burrows were visible in all cases (100%). Triangular structure in coffee color and brown dotted structure were observed in 97 cases (96.04%) and 10 cases (9.90%), respectively. Eight patients (7.92%) had "gray-edged line" sign and 2 cases (1.98%) showed a gray-white structure in the middle of burrow. Light-brown and dark-red transparent mites were found in 4 cases (3.96%) and 1 case (0.99%), respectively. Conclusions The characteristics of scabies under a dermoscope include burrows and coffee-colored triangular structure. Other non-specific structures, such as brown dots, "gray-edged line" sign and gray-white structure in the center of burrows, are also helpful for the dermoscopic diagnosis of scabies.

Cold stress causes considerable damage to tender tea seedlings. Previous studies have explored changes in the physiological and biochemical factors of tea in response to cold stress; however, the mechanisms of cold resistance in ancient tea tree plants are unclear. The aim of this study was to analyze the effects of 0 °C cold stress for 15 days and 24 °C ambient temperature recovery for 5 days on the physiological and biochemical characteristics of two representative old tea varieties: Dali tea and Siqiu tea. The results revealed significant changes in antioxidant, photosynthetic efficiency, and physiological and biochemical indicators in response to cold stress, with the two species exhibiting different patterns. Cold stress decreased chlorophyll and carotene content, Fv/Fm, Y(II), non-photochemical quenching coefficient, photochemical quenching, and superoxide dismutase (SOD) activity, and increased intercellular CO2 concentration and ascorbate peroxidase activity. Siqiu tea showed a higher increase in soluble sugar content and antioxidant enzyme activity and a lower accumulation of malondialdehyde and minimal fluorescence (F0) than Dali, indicating a greater tolerance to cold stress. Based on partial least-squares discriminant analysis, six key differential physiological indicators of cold resistance—water-soluble sugar, F0, peroxidase, catalase, SOD, and gas conductance—were identified. Our findings provide technical support for identifying ways to protect ancient tea trees from extreme weather conditions.

Ecological intensification of agriculture is crucial for sustainable food production, yet the complex soil-microbial interactions in integrated farming systems remain poorly understood. This five-year study compared a Rice-Loach-Shrimp (RLS) integrated system with conventional Rice Monoculture (RM) using advanced multivariate techniques, including correlation analysis, Principal Component Analysis, Random Forest modeling, and Structural Equation Modeling. The RLS system exhibited higher values for key soil health indicators compared to RM, although the overall correlation patterns were similar. Stronger correlations among soil organic matter, enzyme activities, and microbial populations were observed in RLS, suggesting a more tightly coupled soil ecosystem. Available phosphorus and soil organic matter were identified as primary drivers of microbial community structure. The RLS system showed a slightly higher mean pH and weaker correlations between pH and other indicators compared to RM, indicating potential altered biogeochemical processes. Complex cascading effects among soil properties, enzyme activities, and microbial populations were revealed in RLS. These soil health benefits persisted throughout the study period, demonstrating the potential of RLS as an effective ecological intensification strategy for sustainable rice production.

Molecular breeding accelerates animal breeding and improves efficiency by utilizing genetic mutations. Structural variations (SVs), a significant source of genetic mutations, have a greater impact on phenotypic variation than SNPs. Understanding SV functional mechanisms and obtaining precise information are crucial for molecular breeding. In this study, association analysis revealed significant correlations between 198-bp SVs in the GSTA2 promoter region and abdominal fat weight, intramuscular fat content, and subcutaneous fat thickness in chickens. High expression of GSTA2 in adipose tissue was positively correlated with the abdominal fat percentage, and different genotypes of GSTA2 exhibited varied expression patterns in the liver. The 198-bp SVs regulate GSTA2 expression by binding to different transcription factors. Overexpression of GSTA2 promoted preadipocyte proliferation and differentiation, while interference had the opposite effect. Mechanistically, the 198-bp fragment contains binding sites for transcription factors such as C/EBPα that regulate GSTA2 expression and fat synthesis. These SVs are significantly associated with chicken fat traits, positively influencing preadipocyte development by regulating cell proliferation and differentiation. Our work provides compelling evidence for the use of 198-bp SVs in the GSTA2 promoter region as molecular markers for poultry breeding and offers new insights into the pivotal role of the GSTA2 gene in fat generation.

Abstract The neutron capture cross section of $$ ^{181} $$ 181 Ta is relevant to s-process of nuclear astrophysics, extraterrestrial samples analysis in planetary geology and new generation nuclear energy system design. The $$^{181}$$ 181 Ta( $$n,\gamma $$ n , γ ) cross section had been measured between 1 eV and 800 keV at the back-streaming white neutron facility (Back-n) of China spallation neutron source(CSNS) using the time-of-flight (TOF) technique and $$\hbox {C}_{6}\,\hbox {D}_{6}$$ C 6 D 6 liquid scintillator detectors. The experimental results are compared with the data of several evaluated libraries and previous experiments in the resolved and unresolved resonance region. Resonance parameters are extracted using the R-Matrix code SAMMY in the 1–700 eV region. The astrophysical Maxwell average cross section(MACS) from kT = 5 to 100 keV is calculated over a sufficiently wide range of neutron energies. For the characteristic thermal energy of an astrophysical site, at kT = 30keV the MACS value of $$^{181}$$ 181 Ta is 834 ± 75 mb, which shows an obvious discrepancy with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNiS) recommended value 766 ± 15 mb. The new measurements strongly constrain the MACS of $$^{181}$$ 181 Ta( $$n,\gamma $$ n , γ ) reaction in the stellar s-process temperatures.

Abstract Background Periodontitis is a common and chronic inflammatory disease characterized by irreversible destruction of the tooth surrounding tissues, especially intrabony defects, which eventually lead to tooth loss. In recent years, stem cell-based therapy for periodontitis has been gradually applied to the clinic, but whether stem cell-based therapy plays a positive role in periodontal regeneration is unclear at present. Methods The clinical studies related to the evaluation of mesenchymal stem cells for periodontal regeneration in PubMed, Cochrane Central Register of Controlled trials (CENTRAL), Web of Science (WOS), Embase, Scopus, Wanfang and China national knowledge infrastructure (CNKI) databases were searched in June 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell free therapy for the treatment periodontitis, and to have a follow-up for at least six months. Two evaluators searched, screened, and assessed the quality and the risk of bias in the included studies independently. Review Manager 5.4 software was used to perform the meta-analysis, and GRADEpro GDT was used to evaluate the level of the evidence. Results Five randomized controlled trials (RCTs) including 118 patients were analyzed. The results of this meta-analysis demonstrated that stem cell-based therapy showed better therapeutic effects on clinical attachment level (CAL) (MD = − 1.18, 95% CI = − 1.55, − 0.80, P < 0.00001), pocket probing depth (PPD) (MD = − 0.75, 95% CI = − 1.35, − 0.14, P = 0.020), and linear distance from bone crest to bottom of defect (BC-BD)( MD = − 0.95, 95% CI = − 1.67, − 0.23, P = 0.010) compared with cell-free group. However, stem cell-based therapy presented insignificant effects on gingival recession (P = 0.14), linear distance from cementoenamel junction to bottom of defect (P = 0.05). Conclusion The results demonstrate that stem cell-based therapy may be beneficial for CAL, PPD and BC-BD. Due to the limited number of studies included, the strength of the results in this analysis was affected to a certain extent. The high‐quality RCTs with large sample size, multi-blind, multi-centric are still required, and the methodological and normative clinical study protocol should be established and executed in the future.

Abstract Background Myoblast differentiation requires metabolic reprogramming driven by increased mitochondrial biogenesis and oxidative phosphorylation. The canonical GH-GHR-IGFs axis in liver exhibits a great complexity in response to somatic growth. However, the underlying mechanism of whether local GHR acts as a control valve to regulate mitochondrial function through mitochondrial biogenesis during myoblast differentiation remains unknown. Methods We manipulated the GHR expression in chicken primary myoblast to investigate its roles in mitochondrial biogenesis and function during myoblast differentiation. Results We reported that GHR is induced during myoblast differentiation. Local GHR promoted mitochondrial biogenesis during myoblast differentiation, as determined by the fluorescence intensity of Mito-Tracker Green staining and MitoTimer reporter system, the expression of mitochondrial biogenesis markers (PGC1α, NRF1, TFAM) and mtDNA encoded gene (ND1, CYTB, COX1, ATP6), as well as mtDNA content. Consistently, local GHR enhanced mitochondrial function during myoblast differentiation, as determined by the oxygen consumption rate, mitochondrial membrane potential, ATP level and ROS production. We next revealed that the regulation of mitochondrial biogenesis and function by GHR depends on IGF1. In terms of the underlying mechanism, we demonstrated that IGF1 regulates mitochondrial biogenesis via PI3K/AKT/CREB pathway. Additionally, GHR knockdown repressed myoblast differentiation. Conclusions In conclusion, our data corroborate that local GHR acts as a control valve to enhance mitochondrial function by promoting mitochondrial biogenesis via IGF1-PI3K/AKT/CREB pathway during myoblast differentiation. Video Abstract

Abstract Purpose We aimed to study the association between adjusted mtDNA levels in human trophectoderm biopsy samples and the developmental potential of euploid and mosaic blastocysts. Methods We analyzed relative mtDNA levels in 2,814 blastocysts obtained from 576 couples undergoing preimplantation genetic testing for aneuploidy from June 2018 to June 2021. All patients underwent in vitro fertilization in a single clinic; the study was blinded—mtDNA content was unknown at the time of single embryo transfer. The fate of the euploid or mosaic embryos transferred was compared with mtDNA levels. Results Euploid embryos had lower mtDNA than aneuploid and mosaic embryos. Embryos biopsied on Day 5 had higher mtDNA than those biopsied on Day 6. No difference was detected in mtDNA scores between embryos derived from oocytes of different maternal ages. Linear mixed model suggested that blastulation rate was associated with mtDNA score. Moreover, the specific next-generation sequencing platform used have a significant effect on the observed mtDNA content. Euploid embryos with higher mtDNA content presented significantly higher miscarriage rates and lower live birth rates, while no significant difference was observed in the mosaic cohort. Conclusion Our results will aid in improving methods for analyzing the association between mtDNA level and blastocyst viability.

ObjectiveThere is currently no non-invasive examination that can fully determine the diagnosis of osteomyelitis. SPECT/CT tomographic fusion imaging can provide both local metabolic activity and anatomical information to determine the condition and location. This study evaluates the diagnostic efficacy of 99mTc-MDP SPECT/CT in bone infections, compared to MRI.MethodsIn this multicenter retrospective study, 363 patients with suspected bone and joint infections or osteomyelitis were included. Participants underwent 99mTc-MDP SPECT/CT and/or MRI examinations, supplemented by pathogenic bacterial cultures and histopathological analysis.ResultsOnly SPECT/CT was tested in 169 patients, and only MRI was used in 116. 78 people have implemented both inspections and have detailed information. The diagnostic sensitivity and specificity of SPECT/CT for infection were 96% and 92% respectively, with an accuracy of 96%. For MRI, these figures were 88%, 84%, and 87% respectively.ConclusionThis represents the largest global study to date evaluating osteomyelitis and bone infection diagnosis using 99mTc-MDP SPECT/CT tomographic fusion imaging. The findings indicate that 99mTc-MDP SPECT/CT fusion imaging offers superior diagnostic accuracy compared to MRI. This is particularly evident in cases involving metallic implants and chronic infections. 99mTc-MDP SPECT/CT fusion imaging emerges as a highly suitable non-invasive diagnostic modality, facilitating enhanced clinical follow-up and treatment.

BackgroundThe molecular mechanisms of hepatic fibrosis (HF), closely related to autophagy, remain unclear. This study aimed to investigate autophagy characteristics in HF.MethodsGene expression profiles (GSE6764, GSE49541 and GSE84044) were downloaded, normalized, and merged. Autophagy-related differentially expressed genes (ARDEGs) were determined using the limma R package and the Wilcoxon rank sum test and then analyzed by GO, KEGG, GSEA and GSVA. The infiltration of immune cells, molecular subtypes and immune types of healthy control (HC) and HF were analyzed. Machine learning was carried out with two methods, by which, core genes were obtained. Models of liver fibrosis in vivo and in vitro were constructed to verify the expression of core genes and corresponding immune cells.ResultsA total of 69 ARDEGs were identified. Series functional cluster analysis showed that ARDEGs were significantly enriched in autophagy and immunity. Activated CD4 T cells, CD56bright natural killer cells, CD56dim natural killer cells, eosinophils, macrophages, mast cells, neutrophils, and type 17 T helper (Th17) cells showed significant differences in infiltration between HC and HF groups. Among ARDEGs, three core genes were identified, that were ATG5, RB1CC1, and PARK2. Considerable changes in the infiltration of immune cells were observed at different expression levels of the three core genes, among which the expression of RB1CC1 was significantly associated with the infiltration of macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell. In the mouse liver fibrosis experiment, ATG5, RB1CC1, and PARK2 were at higher levels in HF group than those in HC group. Compared with HC group, HF group showed low positive area in F4/80, IL-17 and CD56, indicating decreased expression of macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell. Meanwhile, knocking down RB1CC1 was found to inhibit the activation of hepatic stellate cells and alleviate liver fibrosis.ConclusionATG5, RB1CC1, and PARK2 are promising autophagy-related therapeutic biomarkers for HF. This is the first study to identify RB1CC1 in HF, which may promote the progression of liver fibrosis by regulating macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell.

Immunoregulation is one of the important factors in wound healing. Currently, wound dressings with immunoregulation is necessary to overcome the complicated interventions, high-cost treatments and uncontrolled release behaviors. In this study, a novel Cu and Zn loaded nanofiber dressing (FM-Cu-Zn) with immunoregulation and controllable release without external intervention was prepared by electrospinning. The dressing is composed of ZnCl2, CuS nano particles, poly-3-hydroxybutyrate-co-4-hydroxybutyrate (P34HB). Where Zn2+ is the “promoter” of immunotherapeutic activity by reducing the environmental pH to trigger H2S and Cu2+ releasing from CuS. Then, H2S and Cu2+ can regulate the inflammatory response and accelerate wound healing. The results in vivo indicated the FM-Cu-Zn nanofiber dressing showed better anti-inflammatory and wound healing ability, the wound healing rate was upto 95 % after 11 days treatment by the obtianed dressing, which was much higher compared to control groups. Notably, the dressing can promote macrophage polarization toward a pro-regenerative M2 phenotype without any external intervention. Therefore, the FM-Cu-Zn nanofiber with the immunomodulatory property can serve as a promising dressing in wound healing field.

Thyroid carcinoma (THCA) is a tumor commonly occurring in the endocrine system, and its incidence rate is increasing yearly. Anoikis is a type of cell death involved in the carcinogenesis process. This study aimed to investigate the prognosis and immune correlations of anoikis in THCA. Our study used several bioinformatics algorithms (co-expression analysis, univariate and multivariate Cox analysis) to screen anoikis-related genes (ARGs) to construct risk models. Through receiver operating characteristic (ROC) curve, nomogram, and independent prognostic analysis found that the constructed model had ideal predictive value for THCA. The consensus clustering method was used to divide ARG patterns into three subgroups, and there were significant differences in survival among the three subgroups. The CIBERSORT algorithm demonstrated strong correlations among immune infiltrating cells, prognostic genes, and risk scores. Univariate and multivariate Cox analysis showed that CDKN2A is an independent prognostic gene. Basic experiments (immunohistochemistry, qRT-PCR, etc.) showed that the expression levels of CDKN2A mRNA and protein were highly expressed in THCA, which was consistent with the results of bioinformatics analysis. In vitro, the knockdown of CDKN2A significantly inhibited the proliferation and migration of THCA cells. In summary, our study utilized eight ARGs to construct an accurate risk model. ARGs, especially CDKN2A, play a crucial role in the occurrence and development of THCA and can become potential targets for treating THCA patients.

ABSTRACT: Carcass traits in broiler chickens are complex traits that are influenced by multiple genes. To gain deeper insights into the genetic mechanisms underlying carcass traits, here we conducted a weighted single-step genome-wide association study (wssGWAS) in a population of Chinese yellow-feathered chicken. The objective was to identify genomic regions and candidate genes associated with carcass weight (CW), eviscerated weight with giblets (EWG), eviscerated weight (EW), breast muscle weight (BMW), drumstick weight (DW), abdominal fat weight (AFW), abdominal fat percentage (AFP), gizzard weight (GW), and intestine length (IL). A total of 1,338 broiler chickens with phenotypic and pedigree information were included in this study. Of these, 435 chickens were genotyped using a 600K single nucleotide polymorphism chip for association analysis. The results indicate that the most significant regions for 9 traits explained 2.38% to 5.09% of the phenotypic variation, from which the region of 194.53 to 194.63Mb on chromosome 1 with the gene RELT and FAM168A identified on it was significantly associated with CW, EWG, EW, BMW, and DW. Meanwhile, the 5 traits have a strong genetic correlation, indicating that the region and the genes can be used for further research. In addition, some candidate genes associated with skeletal muscle development, fat deposition regulation, intestinal repair, and protection were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that the genes are involved in processes such as vascular development (CD34, FGF7, FGFR3, ITGB1BP1, SEMA5A, LOXL2), bone formation (FGFR3, MATN1, MEF2D, DHRS3, SKI, STC1, HOXB1, HOXB3, TIPARP), and anatomical size regulation (ADD2, AKT1, CFTR, EDN3, FLII, HCLS1, ITGB1BP1, SEMA5A, SHC1, ULK1, DSTN, GSK3B, BORCS8, GRIP2). In conclusion, the integration of phenotype, genotype, and pedigree information without creating pseudo-phenotype will facilitate the genetic improvement of carcass traits in chickens, providing valuable insights into the genetic architecture and potential candidate genes underlying carcass traits, enriching our understanding and contributing to the breeding of high-quality broiler chickens.

Vegetation evolution is an important indicator of regional ecosystems and sea–land interactions. In this study, we investigated the evolution of coastal wetland vegetation, focusing on the core area of Yancheng City National Rare Bird Nature Reserve. Using high-precision classification based on phenological characteristics, we delineated the evolutionary process of three predominant wetland vegetation types: Spartina alterniflora, Suaeda salsa, and Phragmites australis. Spatial and temporal patterns were analyzed using the generalized additive model to identify drivers of evolution. From 1990 to 2022, a three-stage shift in vegetation distribution from land to sea was observed. Notably, S. salsa’s distribution area consistently shrank since 2000, whereas P. australis continued to grow. Throughout the entire period, S. alterniflora consistently maintained growth and tended toward stability. The vegetation distinctly showcased zonal patterns along the coastal gradient, revealing a clear inclination to migrate toward the seaside. Specifically, S. alterniflora displayed a centroid migration rate of 195.28 m/year, shifting northward, whereas P. australis and S. salsa migrated eastward (toward the seaside) at rates of 111.84 and 70.88 m/year, respectively. Environmental factors, such as downward irradiance, sea surface salinity, and significant wave height, significantly influenced vegetation patterns. Human activities, particularly aquaculture pond construction, emerged as the primary anthropogenic factor causing the reduction in P. australis distribution. Additionally, the competition for ecological niches among vegetation emerged as a pivotal factor contributing to the alterations in the landscape pattern within the study area.

Abstract Although hard carbon (HC) demonstrates superior initial Coulombic efficiency, cycling durability, and rate capability in ether‐based electrolytes compared to ester‐based electrolytes for sodium‐ion batteries (SIBs), the underlying mechanisms responsible for these disparities remain largely unexplored. Herein, ex situ electron paramagnetic resonance (EPR) spectra and in situ Raman spectroscopy are combined to investigate the Na storage mechanism of HC under different electrolytes. Through deconvolving the EPR signals of Na in HC, quasi‐metallic‐Na is successfully differentiated from adsorbed‐Na. By monitoring the evolution of different Na species during the charging/discharging process, it is found that the initial adsorbed‐Na in HC with ether‐based electrolytes can be effectively transformed into intercalated‐Na in the plateau region. However, this transformation is obstructed in ester‐based electrolytes, leading to the predominant storage of Na in HC as adsorbed‐Na and pore‐filled‐Na. Furthermore, the intercalated‐Na in HC within the ether‐based electrolytes contributes to the formation of a uniform, dense, and stable solid–electrolyte interphase (SEI) film and eventually enhances the electrochemical performance of HC. This work successfully deciphers the electrolyte‐dominated Na+ storage mechanisms in HC and provides fundamental insights into the industrialization of HC in SIBs.

Important progress has been made on the standard Laplacian case with mixed partial dissipation and diffusion. The stability problem of the 3D incompressible magnetohydrodynamic (MHD) equations without vertical dissipation but with the fractional velocity dissipation $ (-\Delta)^\alpha u $ and magnetic diffusion $ (-\Delta)^\beta b $ is unfortunately not often well understood for many ranges of fractional powers. This paper discovers that there are new phenomena with the case $ \alpha, \beta \leq 1 $. We establish that, if an initial datum ($ u_0, b_0 $) in the Sobolev space $ H^3(\mathbb{R}^3) $ is close enough to the equilibrium state, and we replace the terms $ (-\Delta)^\alpha u $ and $ (-\Delta)^\beta b $ by $ (-\Delta_h)^\alpha u $ and $ (-\Delta_h)^\beta b $, respectively, the resulting equations with $ \alpha, \beta \in(\frac{1}{2}, 1] $ then always lead to a steady solution, where $ \Delta_h = \partial_{x_1}^2+\partial_{x_2}^2 $.

An integrated model that considers multiphysics is necessary to accurately analyze the time-dependent response of hydraulic structures on soft foundations. This study develops an integrated superstructure–foundation–backfills model and investigates the time-dependent displacement and stress of a lock head project on a soft foundation during the construction period. Finite element analyses are conducted, incorporating a transient thermal creep model for concrete and an elasto-plastic consolidation model for the soil. The modified Cam-clay model is employed to describe the elasto-plastic behavior of the soil. Subsequently, global sensitivity analyses are conducted to determine the relative importance of the model parameters on the system’s response, using Garson’s and partial derivative algorithms based on the backpropagation (BP) neural network. The results indicate that the integrated system exhibits pronounced time-dependent displacement and stress, with dangerous values appearing during specific periods. These values are easily neglected, highlighting the importance of integrated time-dependent analysis. Construction activities, particularly the backfilling process, could cause a sudden change in stress and significantly impact the stress redistribution of the superstructure. Additionally, the mechanical properties of concrete have a significant impact on the stress on the superstructure, while the mechanical properties of the soil control the settlement of the integrated system.