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Abstract This study introduces a novel self-supervised learning method for single-frame subtraction and vessel segmentation in coronary angiography, addressing the scarcity of annotated medical samples in AI applications. We pretrain a U-Net model on a large dataset of unannotated coronary angiograms using an image-to-image translation framework, then fine-tune it on a limited set of manually annotated samples. The pretrained model excels at comprehensive single-frame subtraction, outperforming existing DSA methods. Fine-tuning with just 40 samples yields a Dice coefficient of 0.828 for vessel segmentation. On the public XCAD dataset, our model sets a new state-of-the-art benchmark with a Dice coefficient of 0.755, surpassing both unsupervised and supervised learning approaches. This method achieves robust single-frame subtraction and demonstrates that combining pretraining with minimal fine-tuning enables accurate coronary vessel segmentation with limited manual annotations. We successfully apply this approach to assist physicians in visualizing potential vascular stenosis sites during coronary angiography. Code, dataset, and a live demo will be available available at: https://github.com/newfyu/DeepSA .

Abstract With the gradual liberalization of the three-child policy and the development of assisted reproductive technology in China, the number of women with high-risk pregnancies is gradually increasing. In this study, 4211 fetuses who underwent chromosomal microarray analysis (CMA) with high-risk prenatal indications were analysed. The results showed that the overall prenatal detection rate of CMA was 11.4% (480/4211), with detection rates of 5.82% (245/4211) for abnormal chromosome numbers and 5.58% (235/4211) for copy number variants. Additionally, the detection rates of clinically significant copy number variants were 3.78% (159/4211) and 1.8% (76/4211) for variants of uncertain significance. The detection rates of fetal chromosomal abnormalities were 6.42% (30/467) for pregnant women with advanced maternal age (AMA), 6.01% (50/832) for high-risk maternal serum screening (MSS) results, 39.09% (224/573) with abnormal non-invasive prenatal testing (NIPT) results, 9.21% (127/1379) with abnormal ultrasound results, and 5.1% (49/960) for other indications. Follow-up results were available for 4211 patients, including 3677 (3677/4211, 87.32%) whose infants were normal after birth, 462 (462/4211, 10.97%) who terminated their pregnancy, 51 (51/4211, 1.21%) whose infants were abnormal after birth, and 21 (21/4211, 0.50%) who refused follow-up. The results of this study demonstrate significant variation in the diagnostic rate of chromosomal microarray analysis across different indications, providing valuable guidance for clinicians to assess the applicability of CMA technology in prenatal diagnosis.

Abstract Background Little is known about the link between the fungal community and phosphorus fractions when land use is converted from cropland to grassland in saline-alkali soil in northeastern China. Therefore, in this study, the diversity, composition, and function of fungi, as well as phosphorus fractions including Olsen-P and inorganic phosphorus (Pi), were investigated under land use conversions from maize cropland (MC) to alfalfa (Medicago sativa L.) (AG), Leymus chinensis (LG), and natural restored grasslands (RG). Results The results showed that the Pi fractions of Ca8-P, Fe-P, Ca2-P, and Ca10-P were closely related with Olsen-P. Significantly increased Olsen-P content was found in 0–10 cm soil layer in the AG treatment, relative to LG and RG treatments (P

Benzene is a common environmental pollutant and significant health hazard. Low-dose benzene exposure is common in most industrial settings, and some workers exhibit hematotoxicity characterized by impaired hematopoietic function. Consequently, understanding the early hematopoietic damage and biomarkers associated with low-dose benzene exposure is of critical importance for health risk assessment. Using data from a 5-year prospective cohort study on benzene exposure and the National Center for Biotechnology Information's Gene Expression Omnibus database, we detected significant downregulation of the ubiquitin-conjugating enzyme UBE2L3 (E2) in benzene-exposed subjects compared to control subjects. Liquid chromatography tandem mass spectrometry and co-immunoprecipitation experiments illustrated the binding interaction between UBE2L3 and the ubiquitin-protein ligase ZNF598 (E3). We applied deep learning algorithms to predict candidate interacting proteins and then conducted validation via co-immunoprecipitation experiments, which showed that ZNF598 engages in binding with the autophagy protein LAMP-2. Subsequent overexpression and knockdown of UBE2L3 coupled with immunofluorescence experiments and transmission electron microscopy revealed that UBE2L3 disrupts the ubiquitination-degradation of LAMP-2 by ZNF598, reduces GPX4 expression levels, and activates an autophagy-dependent ferroptosis pathway. It also leads to increased lipid peroxidation, thereby promoting ferroptosis and contributing to the hematotoxicity induced by benzene. In summary, our results suggest that UBE2L3 may be involved in early hematopoietic damage by modulating the autophagy-dependent ferroptosis signaling pathway in benzene-induced hematotoxicity.

Abstract Trace elements are the essential mineral nutrients in grassland, however, we still know little about the distributions of trace elements in grassland with long‐term grazing exclusion. The contents, stocks, and proportions of iron (Fe), aluminum (Al), manganese (Mn), and boron (B) in green plant‐litter‐root‐soil were evaluated by enclosing for 18, and 39 years inside the fence (F18 and F39) and grazing outside the fence (F0) in Inner Mongolia grassland. The results showed that F18 and F39 decreased the stocks of Fe, Al, and Mn in green plant and root compared to F0 (p

The global scarcity of high-quality solid wood resources has propelled efforts towards developing high value-added products utilizing fast-growing wood. However, the inherent low quality of fast-growing wood poses a significant challenge for its use in engineered wood products. In response to this challenge, this study focuses on the transformation of larch logs into a novel engineering wood product termed cross-laminated-thick veneers (CLTV). The process involves rotary cutting larch logs into 7.5 mm thick veneers, followed by hygrothermal treatment to alleviate stress, and ultimately assembling layers of thick veneers oriented at right angles, securely bonded to form structural panels. The investigation into the mechanical properties of CLTV reveals promising results. The static bending strength and modulus of a 15-layer CLTV with a thickness of 105 mm exhibit noteworthy values of 62.29 MPa and 10986 MPa, respectively. These values stand in comparison to the performance metrics of cross-laminated-timber (CLT) with only 3 layers, indicating the viability of CLTV as a competitive alternative. Additionally, the formaldehyde emission from CLTV measures at a minimal 0.010 mg/m3, while total volatile organic compounds are limited to 47 μg/m3. The development of CLTV emerges as a sustainable solution to the shortage of high-quality solid wood resources. Its comparable performance to traditional materials such as CLT positions CLTV as an eco-friendly alternative for engineered wood products applicable in diverse global building systems. The minimal formaldehyde emission and low volatile organic compounds further emphasize the potential positive impact of CLTV on both the construction industry and broader environmental sustainability initiatives worldwide. This study sets the stage for advancing engineered wood products, addressing resource constraints, and contributing to sustainable practices in the global construction sector.

Abstract Background International experience shows that the suitability of a high-performance healthcare system for its given purposes is reflected in its ability to provide a continuum of services that match the changing health status of the given population. Although many low- and middle-income countries have sought to bring movement away from hospital-centered and towards patient-centered healthcare, such efforts have often had poor results, and one of the major reasons for this is the inability to accurately identify which inpatients need continuing care and what kind of continuing of care is needed. Objectives To measure and assess the continuing care needs of discharged patients and its influencing factors in rural China. Methods Data were obtained from the hospital database of Medical Center M in County Z from May to July 2022. County Z is a county of 1 million people in central China. The database includes basic patient information, disease-related information, and information on readiness for hospital discharge. Factors related to the need for continuing care were included in the analysis. The Readiness for Hospital Discharge Scale was used to assess the need for continuing care. The statistical data are expressed in terms of both frequency and composition ratio. Finally, linear regression was used to analyze the factors influencing the need for continuing care. Results The analysis included a total of 3,791 patients, 123 of whom (3.25%) had continuing nursing needs. The need of continuing nursing was related to patients’ age group, mode of admission, occupation and major diagnostic categories (P

The selection of the finest possible embryo in in-vitro fertilization (IVF) was crucial and revolutionary, particularly when just one embryo is transplanted to lessen the possibility of multiple pregnancies. However, practical usefulness of currently used methodologies may be constrained. Here, we established a novel non-invasive embryo evaluation method that combines non-invasive chromosomal screening (NICS) and Timelapse system along with artificial intelligence algorithms. With an area under the curve (AUC) of 0.94 and an accuracy of 0.88, the NICS-Timelapse model was able to predict blastocyst euploidy. The performance of the model was further evaluated using 75 patients in various clinical settings. The clinical pregnancy and live birth rates of embryos predicted by the NICS-Timelapse model, showing that embryos with higher euploid probabilities were associated with higher clinical pregnancy and live birth rates. These results demonstrated the NICS-Timelapse model's significantly wider application in clinical IVF due to its excellent accuracy and noninvasiveness.

Fine particulate matter (PM2.5) exposure is strongly associated with vascular endothelial senescence, a process implicated in cardiovascular diseases. While there is existing knowledge on the impact of Lycium barbarum polysaccharide (LBP) on vascular endothelial damage, the protective mechanism of LBP against PM2.5-induced vascular endothelial senescence remains unclear. In this study, we investigated the impact of PM2.5 exposure on vascular endothelial senescence and explored the intervention effects of LBP in human umbilical vein endothelial cells (HUVECs). We found that PM2.5 exposure dose-dependently reduced cell viability and proliferation in HUVECs while increasing the production of reactive oxygen species (ROS), malondialdehyde (MDA), and hydrogen peroxide (H2O2). Additionally, PM2.5 exposure inhibited the activity of superoxide dismutase (SOD). Notably, PM2.5 exposure induced autophagy impairments and cellular senescence. However, LBP mitigated PM2.5-induced cell damage. Further studies demonstrated that correcting autophagy impairment in HUVECs reduced the expression of the senescence markers P16 and P21 induced by PM2.5. This suggests the regulatory role of autophagy in cellular senescence and the potential of LBP in improving HUVECs senescence. These findings provide novel insights into the mechanisms underlying PM2.5-induced cardiovascular toxicity and highlight the potential of LBP as a therapeutic agent for improving vascular endothelial health.

Abstract Gamma-butyrobetaine hydroxylase 1 antisense RNA 1 (BBOX1-AS1), located on human chromosome 11 p14, emerges as a critical player in tumorigenesis with diverse oncogenic effects. Aberrant expression of BBOX1-AS1 intricately regulates various cellular processes, including cell growth, epithelial–mesenchymal transition, migration, invasion, metastasis, cell death, and stemness. Notably, the expression of BBOX1-AS1 was significantly correlated with clinical-pathological characteristics and tumor prognoses, and it could also be used for the diagnosis of lung and esophageal cancers. Through its involvement in the ceRNA network, BBOX1-AS1 competitively binds to eight miRNAs in ten different cancer types. Additionally, BBOX1-AS1 can directly modulate downstream protein-coding genes or act as an mRNA stabilizer. The implications of BBOX1-AS1 extend to critical signaling pathways, including Hedgehog, Wnt/β-catenin, and MELK/FAK pathways. Moreover, it influences drug resistance in hepatocellular carcinoma. The present study provides a systematic review of the clinical significance of BBOX1-AS1’s aberrant expression in diverse tumor types. It sheds light on the intricate molecular mechanisms through which BBOX1-AS1 influences cancer initiation and progression and outlines potential avenues for future research in this field.

Abstract Background The establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the development of multiple malignancies. However, its role in hypopharyngeal carcinoma (HPC) progression remains uncharacterized. Methods This study employed bioinformatics to determine the ESCO2 expression in head and neck squamous cell carcinoma (HNSC) and normal tissues. In vitro cell proliferation, migration, apoptosis, and/or cell cycle distribution assays were used to determine the function of ESCO2 and its relationship with STAT1. Xenograft models were established in nude mice to determine ESCO2 in HPC growth in vivo. Co-immunoprecipitation/mass spectrometry (Co-IP/MS) was conducted to identify the potential ESCO2 binding partners. Results We found that ESCO2 expression was elevated in HNSC tissues, and ESCO2 depletion suppressed tumor cell migration in vitro and inhibited tumor growth in vitro and in vivo. Co-IP/MS and immunoblotting assays revealed the interaction between ESCO2 and STAT1 in HPC cells. STAT1-overexpression compromised ESCO2-mediated suppressive effects on HPC cell proliferation, viability, and migration. Conclusions These findings suggest that ESCO2 is crucial in promoting HPC malignant progression through the STAT1 pathway and provides novel therapeutic targets for HPC treatment.

Straw returning has gradually been adopted as an effective approach to address the serious degradation of farmland. However, the carbon/nitrogen (C/N) ratio of rice straw is generally too high for microorganisms to decompose the organic materials and release nutrients, which may minimize the benefits of straw returning to the agricultural production system. This study aimed to investigate the effects of straw returning on rice production and propose optimum nitrogen (N) management for early rice production under a straw returning system. The total N fertilizer that was evaluated was 165 kg N ha-1, urea (46% N), applied in different proportions in three stages of rice cultivation: basal, tillering, and panicle. Using no straw returning with the N fertilizer ratio of basal:tillering:panicle = 5:2:3 treatment (T1) as the control, four different N fertilizer ratios of basal:tillering:panicle, including 5:2:3 (T2), 5:2:2 (T3), 5:4:1 (T4), and 5:5:0 (T5) were set under straw returning. The return of straw decreased the available N in the soil at the tillering stage, and impeded root growth and the crop canopy from establishing, which decreased the effective panicles by 10.1% compared with that of T1, limiting the increases in rice grain yield. Increasing the N fertilizer ratio 10–20% (T3 and T4) at the tillering stage effectively increased the content of soil ammonium and nitrate nitrogen, improved the root growth, and increased the root activities by 16.0–40.5% at the tillering stage. As a result, the effective panicle number increased by 5.1–16.2%. Among these, T4 treatment maximized the benefits of straw returning the most. Additionally, increasing the N fertilizer ratio at the tillering stage increased the shoot uptake across the early rice growing season and synchronized crop N uptake with the accumulation of carbon assimilates, which enhanced the crop growth rate and increased the rice yield by 13.5–25.1%. It is concluded that increasing the N fertilizer ratio by 20% at the tillering stage is a promising strategy to increase the availability of N in the phases of high demand for this nutrient.

IntroductionThe rhizomes of Coptis plants have been used in traditional Chinese medicine over 2000 years. Due to increasing market demand, the overexploitation of wild populations, habitat degradation and indiscriminate artificial cultivation of Coptis species have severely damaged the native germplasms of species in China.MethodsGenome-wide simple-sequence repeat (SSR) markers were developed using the genomic data of C. chinensis. Population genetic diversity and structure of 345 Coptis accessions collected from 32 different populations were performed based on these SSRs. The distribution of suitable areas for three taxa in China was predicted and the effects of environmental variables on genetic diversity in relation to different population distributions were further analyzed.Results22 primer pairs were selected as clear, stable, and polymorphic SSR markers. These had an average of 16.41 alleles and an average polymorphism information content (PIC) value of 0.664. In the neighbor-joining (N-J) clustering analysis, the 345 individuals clustered into three groups, with C. chinensis, C. chinensis var. brevisepala and C. teeta being clearly separated. All C. chinensis accessions were further divided into four subgroups in the population structure analysis. The predicted distributions of suitable areas and the environmental variables shaping these distributions varied considerably among the three species.DiscussionOverall, the amount of solar radiation, precipitation and altitude were the most important environmental variables influencing the distribution and genetic variation of three species. The findings will provide key information to guide the conservation of genetic resources and construction of a core reserve for species.

Background: Improper cleaning is one of the main causes of sub-optimal levels of sterilization, and also a risk factor in terms of nosocomial infections. We aimed to investigate the factors associated with the cleaning quality of the reusable medical devices and prescribe improvement measures for ensuring the safe use of the devices and for iatrogenic infection control. Methods: An expert consultation was conducted to identify the factors associated with the cleaning quality of reusable medical devices. A self-designed quality inspection form for reusable medical device cleaning was used to collect the data concerning the factors associated with the cleaning quality of the reusable medical devices cleaned at our hospital's central sterile supply department (CSSD) during January to June 2022. We also investigated the cleaning personnel's perceptions and knowledge of medical devices cleaning by means of a self-designed questionnaire. Results: Statistically significant differences (P

Objective To explore the feasibility of using autoregressive moving average model (ARIMA) to predict the dosage of suspended red blood cells in children, and to provide a basis for the development of clinical blood reserve plans in children's hospitals. Methods ARIMA model was constructed using the total blood consumption of clinical suspended red blood cells from March 2016 to May 2022 at the Children's Hospital of Chongqing Medical University as the data source by SPSS26.0 software. The optimal model was used to predict the clinical suspended red blood cell consumption from June to October 2022, and the predictive effect of the model was tested. Results ARIMA(0, 1, 1) (0, 1, 1)12 was the optimal model for predicting the consumption of suspended red blood cells in pediatrics. The autocorrelation function and partial autocorrelation function of the residual sequence basically fell within the 95% confidence interval. At the same time, Ljung-Box Q statistical results showed that there was no correlation between the residual (P>0.05), indicating that the residual was white noise, which met the randomicity hypothesis. The average relative error between the predicted values of the model and the actual clinical red blood cell usage from June to October 2022 was 5%, indicating high prediction accuracy. Conclusion The blood usage of children has obvious seasonal and periodic patterns, and the optimal model ARIMA (0, 1, 1) (0, 1, 1)12 can better fit the trend of changes in pediatric suspended red blood cell usage, thus providing a basis for the development of clinical blood reserve plans in children's hospitals.

Abstract Background The exact mechanisms of type 2 diabetes mellitus (T2DM) remain largely unknown. We intended to authenticate critical genes linked to T2DM progression by tandem single-cell sequencing and general transcriptome sequencing data. Methods T2DM single-cell RNA-sequencing data were submitted by the Gene Expression Omnibus (GEO) database and ArrayExpress (EBI), from which gene expression matrices were retrieved. The common cell clusters and representative marker genes were ascertained by principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), CellMarker, and FindMarkers in two datasets (GSE86469 and GSE81608). T2DM-related differentially expressed marker genes were defined by intersection analysis of marker genes and GSE86468-differentially expressed genes. Receiver operating characteristic (ROC) curves were utilized to assign representative marker genes with diagnostic values by GSE86468, GSE29226 and external validation GSE29221, and their prospective target compounds were forecasted by PubChem. Besides, the R package clusterProfiler-based functional annotation was designed to unveil the intrinsic mechanisms of the target genes. At last, western blot was used to validate the alternation of CDKN1C and DLK1 expression in primary pancreatic islet cells cultured with or without 30mM glucose. Results Three common cell clusters were authenticated in two independent T2DM single-cell sequencing data, covering neurons, epithelial cells, and smooth muscle cells. Functional ensemble analysis disclosed an intimate association of these cell clusters with peptide/insulin secretion and pancreatic development. Pseudo-temporal trajectory analysis indicated that almost all epithelial and smooth muscle cells were of neuron origin. We characterized CDKN1C and DLK1, which were notably upregulated in T2DM samples, with satisfactory availability in recognizing three representative marker genes in non-diabetic and T2DM samples, and they were also robustly interlinked with the clinical characteristics of patients. Western blot also demonstrated that, compared with control group, the expression of CDKN1C and DLK1 were increased in primary pancreatic islet cells cultured with 30 mM glucose for 48 h. Additionally, PubChem projected 11 and 21 potential compounds for CDKN1C and DLK1, respectively. Conclusion It is desirable that the emergence of the 2 critical genes indicated (CDKN1C and DLK1) could be catalysts for the investigation of the mechanisms of T2DM progression and the exploitation of innovative therapies.

Abstract Background Galla chinensis is a traditional Chinese medicine (TCM) produced due to the interaction between the Fordinae aphids and the Rhus plant species. Horned galls with high tannin content are the most widely cultivated gall type, and Wufeng county of Hubei province in China is the center of cultivation. However, long-term artificial cultivation and domestication of horned galls to meet the increasing production demand have led to quality degradation. Understanding the reasons underlying quality degradation is urgent for horned gall production and application. The present study used a combination of metabolic, genetic, and ecological analyses to investigate the quality and genetic differentiation of the horned galls under long-term domestication as well as the potential relationships between them. Results Analysis of gallic acid content and other three phenotypic traits (fresh weight, gall size, and wall thickness) revealed quality differentiation of horned galls collected from five locations in Wufeng, in which the cultivated samples from Wang Jiaping (WJP) showed the highest degradation. Genetic differentiation between the cultivated and wild Rhus chinensis trees in WJP, and between WJP and the other populations was detected based on SSR molecular markers, however, no significant difference in genetic structure was seen for the aphid populations. Among the various ecological factors examined, temperature was identified as the primary one affecting the quality of horned galls. Conclusions Both genetic and ecological factors caused quality differentiation of horned galls. The collection of diverse germplasm of host trees and aphids will help reduce the quality degradation of horned galls in Wufeng.

Abstract Background We aimed to examine the reliability and validity of Chengdu pediatric emergency triage criteria in order to provide a reference for the development of pediatric emergency triage within other hospitals. Methods We developed Chengdu pediatric emergency triage criteria based on the conditions/symptom, vital signs, and the Pediatric Early Warning Score system within our hospital using the Delphi method in 2020. The simulation scenario triage and real-life triage which were conducted in our hospital during January - March 2021, and the retrospective study of triage records extracted from our hospital’s health information system in February 2022, were used to measure the agreement in triage decisions between the triage nurses, and between the triage nurses and the expert team. Results For the 20 simulation cases, the Kappa value of triage decisions between the triage nurses was 0.6 (95% CI 0.352–0.849), and the Kappa value of triage decisions between the triage nurses and the expert team was 0.73 (95% CI 0.540–0.911). For the 252 cases in the real-life triage, the Kappa value of triage decisions between the triage nurses and the expert team was 0.824 (95% CI 0.680–0.962). For the 20,540 cases selected for the retrospective study of triage records, the Kappa value of triage decisions between the triage nurses was 0.702 (95% CI 0.691–0.713); that between Triage Nurse 1 and the expert team was 0.634 (95% CI 0.623–0.647); and that between Triage Nurse 2 and the expert team was 0.725 (95% CI 0.713–0.736). The overall agreement rate in triage decisions between the triage nurses and the expert team in the simulation scenario triage was 80%; that between the triage nurses and the expert team in the real-life triage was 97.6%; and that between the triage nurses in the retrospective study was 91.9%. In the retrospective study, the agreement rates in triage decisions between Triage Nurse 1 and the expert team, and between Triage Nurse 2 and the expert team, were 88.0% and 92.3%, respectively. Conclusion Chengdu pediatric emergency triage criteria that developed within our hospital is reliable and valid, and can promote rapid and effective triage by triage nurses.

Abstract Ribonucleases (RNases) are responsible for RNA metabolism. RNase J, the core enzyme of the RNA degradosome, plays an essential role in global mRNA decay. Emerging evidence showed that the RNase J of Mycobacterium tuberculosis (Mtb-RNase J) could be an excellent target for treating Mtb infection. Here, crystal structures of Mtb-RNase J in apo-state and complex with the single-strand RNA reveal the conformational change upon RNA binding and hydrolysis. Mtb-RNase J forms an active homodimer through the interactions between the β-CASP and the β-lactamase domain. Knockout of RNase J slows the growth rate and changes the colony morphologies and cell length in Mycobacterium smegmatis, which is restored by RNase J complementation. Finally, RNA-seq analysis shows that the knockout strain significantly changes the expression levels of 49 genes in metabolic pathways. Thus, our current study explores the structural basis of Mtb-RNase J and might provide a promising candidate in pharmacological treatment for tuberculosis.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease of the colon that result in the destruction and inflammation of the colonic mucosa. Current research has established a strong correlation between pyroptosis of colonic epithelial cells and the onset and progression of UC. In addition, miRNAs have been implicated in the development and progression of UC and pyroptosis. This aimed of this study was to identify specific miRNAs that could inhibit pyroptosis in colon epithelial cells and alleviate UC. Lipopolysaccharide (LPS) was used to induce inflammation in FHC normal colonic epithelial cells to construct an enteritis cell model and downregulated expression levels of miRNAs were detected in inflammatory bowel disease mucosal tissue model. Pyroptosis indicators were detected using Cell Counting Kit-8, flow cytometry, ELISA, qPCR, western blot, and immunofluorescence, and miRNA target genes were predicted by miRDB, TargetScan, pyroptosis pathway from KEGG, and double luciferase assay was used for verification. The effect of miR-141-3p on colitis was observed in the mouse DSS colitis model. The results showed that miR-141-3p was the most significantly downregulated miRNA in LPS-induced FHC cells, and promoted the proliferation of LPS-induced FHC cells and suppressed their apoptosis. In addition, miR-141-3p decreased the expression of pyroptosis-related proteins such as NLRP3, caspase-1, N-GSDMD, and the other proteins, as well as the release of IL-18 and IL-1β inflammatory factors. Conversely, the miR-141-3p inhibitor promoted LPS-induced FHC pyroptosis. Dual luciferase experiments confirmed that miR-141-3p could target the HSP90 molecular chaperone SUGT1. Further experiments demonstrated that SUGT1 overexpression could restore the inhibitory effect of miR-141-3p on pyroptosis, while SUGT1 knockdown could alleviate the promotion of pyroptosis induced by miR-141-3p inhibitor. Furthermore, miR-141-3p alleviated the inflammatory phenotype of mouse colonic mucosa in the mouse DSS colitis model. Therefore, miR-141-3p inhibits LPS-induced pyroptosis of colonic epithelial cells by targeting SUGT1. miR-141-3p could also alleviate DSS-induced colitis in mice, suggesting that miR-141-3p may become a nucleic acid drug for the treatment of UC.

Global climate change has significantly increased the frequency and intensity of high temperature and drought stresses. Additionally, the high temperature and drought are often concurred, which make the situation of maize production tougher. However, the influence of the combined stresses of high temperature and drought on summer maize production remains uncertain. The study aimed to investigate the effects of high temperature, drought, and their combined stress at different growth stages on photosynthetic and senescence characteristics of summer maize. Denghai 605 (DH605) was used as the experimental material. High temperature (T), drought (D), and their combined stress (T-D) for 6 days were set at the 3rd leaf stage, 12th leaf stage, and tasseling stage, respectively. The natural temperature and normal water management were used as the control (CK). The results showed that high temperature, drought, and their combined stress at different growth stages decreased the activities of antioxidant enzymes and soluble protein content in leaves, leading to increases in MDA content and damage to cell membranes, which accelerated the senescence of the plant. Accordingly, the activities of RuBPcase and PEPCase were decreased, indicating the abilities of plants to harvest and utilize light energy declined due to high temperature, drought, and combined stresses at different growth stages. As a result, the Pn and thus, the dry matter accumulation rate were decreased by these stresses. In addition, the translocation of dry matter to ears was impeded by stresses, especially by the high temperature at the VT stage. While, high temperatures concurred with drought aggravated the adverse effects on summer maize, compared with single stresses. Significantly, high temperature, drought, and their combined stresses at the VT stage decreased the yield mostly, followed by stresses at the V12 stage, and then by stresses at the V3 stage. Compared with CK, the yield of VT-T-D, V12-T-D, and V3-T-D were decreased by 61.6 %, 13.7 %, and 10.4 %, respectively. As global climate change is unstoppable, the superimposed changes of various meteorological factors make the growth conditions for crop production extreme. Studies to explore the combined effects of two or even more meteorological factors on crop growth are becoming more and more important. This study fulfilled the current knowledge gap of the combined stresses on maize production, however, the underlying mechanisms should be dug out in the future.

Wines in the northwest region of China often suffer from poor color stability, low wine acidity, and inelegant aroma description. The Lachancea thermotolerans yeasts with a high yield of lactic acid and pleasant aroma compounds can ameliorate such wines. In this study, the performances of native L. thermotolerans CVE-LT1 co-inoculated with Saccharomyces cerevisiae in different ratios and strategies (simultaneous and sequential mode) were evaluated in pilot scale fermenter (60 L) and industrial scale fermenter (520 hL) of Cabernet Sauvignon grape must with high sugar/low acidity. Results evidenced that the mixed culture of L. thermotolerans and S. cerevisiae can significantly increase lactic acid level (up to 6.98 g/L) and decrease wine pH (up to 3.57). Meanwhile, the color parameters of a* and C* in mixed culture wines were improved. The higher concentrations of volatile compounds were mainly observed in sequential inoculation treatments, including the enhancement of ethyl lactate and 2-phenylethanol. As for phenolic compounds, L. thermotolerans promoted the formation of anthocyanins derivatives and phenolic acids in pilot and industrial fermentation. In conclusion, these results indicated that L. thermotolerans LT1 can be used in hot winery regions to improve the acidity, color indexes, phenolic compounds, and aroma quality of wines.

Abstract Objective Obesity is an important risk factor for COVID‐19. However, whether obesity affects SARS‐CoV‐2 antibody production is unclear. This study aimed to identify the influence of obesity on neutralizing antibody production of an inactivated SARS‐CoV‐2 vaccine to better guide vaccination strategies. Methods This cross‐sectional study recruited a total of 239 healthcare workers (age, 21–50 years) from Suining Central Hospital during 22–23 April 2021. An electronic questionnaire on basic characteristics was completed by all participants. A general physical exam and fasting blood sampling by venipuncture were performed. Peripheral leukocyte counts and the ratios of leukocyte subsets, hepatorenal function, and the neutralizing antibody titers against SARS‐CoV‐2 were measured. Results Among 239 healthcare workers, the participants with underweight, normal weight, overweight, and obesity accounted for 10.88%, 64.44%, 23.01%, and 1.67%, respectively. The highest peripheral monocyte counts were observed in the group with obesity, whereas the lowest were observed in the group with normal weight. Similar results were obtained with respect to percentage of peripheral monocytes. Participants with obesity had higher peripheral eosinophil counts and percentages than the other three groups. The median neutralizing antibody titer was 12.70 AU/mL, with 85.36% (n = 204) of participants were sufficiently protected against SARS‐CoV‐2. The lowest neutralizing antibody titers were observed in the group with obesity, whereas the highest were observed in the group that was underweight. Additionally, high BMI was significantly associated with high peripheral monocyte counts [B (95% CI) = 0.008 (0.002, 0.013)] and low neutralizing antibody titers [B (95% CI) = −1.934 (−3.663, −0.206)]. Conclusions Obesity could induce chronic inflammation, and associated with lower neutralizing antibody titers against SARS‐CoV‐2 after inactivated SARS‐CoV‐2 vaccination.

Analyzing the effective factors influencing online learning performance is a research topic that has garnered significant attention. Traditional approaches, such as multiple regression and structural equation models, tend to assume linearity, while non-linear machine learning models lack interpretability. To address this gap, we propose a framework that interprets machine learning models to analyze the effective factors of online learning performance. By applying this framework to four benchmark datasets of online learning, we examine the differential impact of various factors on performance, explore the interactions among these factors, and identify the key factors for representative learners. Our findings indicate that: 1) non-linear machine learning models, particularly Decision Regression, offer better representation of the non-linear relationship between effective factors and online learning performance compared to classical multivariate regression; 2) the factor of online learning behavior exerts a greater influence on performance than demographic features, academic background, or online curriculum design; 3) online learning behavior features exhibit additional interaction effects on performance; and 4) learners with medium performance are influenced by diverse effective factors, with active participation in online learning activities emerging as the most crucial means to improve performance. Interpreting machine learning models presents an innovative approach for analyzing the effective factors of online learning performance, which can be extended to other factor analysis studies. The results of this research provide valuable insights for optimizing machine learning models in predicting online learning performance and enhancing learner outcomes.

This study aimed to identify genetic causes responsible for multiple morphological abnormalities of the sperm flagella (MMAF) in the Han Chinese population. Three primary infertile males with completely immobile sperm and MMAF were enrolled. Whole-exome sequencing and Sanger sequencing were performed to identify disease-causing genes. Subsequently, morphological and ultrastructural analyses of sperm flagella were investigated. The probable impact of genetic variants on protein function was analyzed by online bioinformatic tools and immunofluorescence assay. Three patients with dynein axonemal heavy chain 1 (DNAH1) gene compound heterozygous variations were identified. DNAH1 c.7435C>T, p.R2479X and c.10757T>C, p.F3586S were identified in the patient from Family 1, c.11726_11727delCT, p.P3909fs and c.12154delC, p.L4052fs were found in the patient from Family 2, and c.10627-3C>G and c.11726_11727delCT, p.P3909fs existed in the patient from Family 3. Four of these variations have not been reported, and all the mutations showed pathogenicity by functional effect predictions. The absence of the center pair and disorganization of the fibrous sheath were present in sperm flagella at the ultrastructural level. Moreover, the expression of DNAH1 was absent in spermatozoa from the participants, validating the pathogenicity of the variants. All three couples have undergone intracytoplasmic sperm injection (ICSI), and two couples of them became pregnant after the treatment. In conclusion, the newly identified DNAH1 mutations can expand the mutational and phenotypic spectrum of MMAF genes and provide a theoretical basis for genetic diagnosis in MMAF patients. It is recommended to conduct genetic screening in male infertility patients with MMAF and provide rational genetic counseling, and ICSI might be an optimal strategy to help with fertilization and conception for patients with DNAH1 mutations.

Electrochemical energy storage system play an important role in the reform of the national energy system and the construction of the energy Internet. Whether small or large capacity battery storage converters, the characteristics of their power electronics can generate high frequency common mode voltage that can be potentially harmful to battery storage system. This paper systematically investigates the common-mode interference (CMI) of electrochemical energy storage system. The mechanism of common-mode interference is revealed, a broadband equivalent circuit model of common-mode voltage in electrochemical energy storage system is established, the effect of parasitic capacitance of the battery on common-mode voltage is simulated and analyzed, and the broadband equivalent circuit model is verified based on laboratory data.

Clarifying the spatial and temporal evolution characteristics of the ecological environment quality of World Heritage Karst Sites (WHKSs) and its response to different rocky desertification grades at spatial scales is crucial for the monitoring and protection of WHKSs as well as the implementation of ecological and environmental policies in karst regions. The ecological evaluation model of Remote Sensing Ecological Index (RSEI) was used to evaluate the ecological environment of Libo–Huanjiang World Heritage Karst site and Shibing World Heritage Karst site, and then the spatial autocorrelation and geo-detection model was used to further analyze the ecological environment, and final spatial overlay of RSEI and rocky desertification by year to analyze the linkage relationship between RSEI and rocky desertification. The results showed that (1) in the three-phase ecological environmental quality evaluation of the two heritage sites, the RSEI in 2010, 2016, and 2022 reached 0.60, 0.67, and 0.64 for the Libo–Huanjiang heritage site, and RSEI in 2010, 2016, and 2022 for the Shibing heritage site reached 0.60, 0.74, and 0.70, respectively; (2) the RSEI of both heritage sites show a gradually increasing positive spatial correlation, and has significant spatial aggregation characteristics, with both heritage sites dominated by the high-high and low-low spatial aggregation categories; (3) both heritage sites have the highest degree of explanation of changes in ecological quality by the NDBSI factor, indicating that this factor plays a key role in changes in ecological quality at heritage sites; (4) the response of the RSEI mean value of Libo–Huanjiang in each grade of rocky desertification area is, from high to low, no rocky desertification, non-karst, potential rocky desertification, mild rocky desertification, moderate rocky desertification, intensive rocky desertification, and extreme intensity rocky desertification, and the response of the RSEI mean value of Shibing is, from high to low, non-karst, no rocky desertification, potential rocky desertification, mild rocky desertification, and moderate rocky desertification. The spatial superposition analysis of the RSEI index and rocky desertification index can quantitatively study the changing status of the ecological environment in different rocky desertification areas, and the results of the study can provide theoretical references for the environmental monitoring and the prevention and control of rocky desertification in the karst areas and WHKSs.

The physical properties of Ti6Al4V powder affect the spreadability of the powder and uniformity of the powder bed, which had a great impact on the performance of built parts made by powder bed fusion technology. Micro-computed tomography is a well-established technique used to analyze the non-destructivity of the objects’ interior. Ti6Al4V powders were scanned with micro-CT to show the internal and external information of all the particles. The morphology, particle size distribution, hollow particle ratio, density, inclusion, and specific surface area of the powder samples were quantitatively characterized, and the relationship of flowability with these physical properties was analyzed in this work. The research results of this article showed that micro-CT is an effective way to characterize these items, and can be developed as a standard method of powder physical properties in the future.

Selective laser melting (SLM) has attracted increasing attention all over the world. As an important parameter, hatch spacing, which is the distance between scan lines, however, still needs a more systematic study. In this paper, the relationship between hatch spacing and mechanical properties, including microhardness, wear resistance, and porous density, was studied. The testing results revealed that when hatch spacing decreased, the overlapping rate increased which resulted in an increase in the convection in the molten pool. It led to the formation of pores in the molten pool. However, when hatch spacing was too large, the overlapping zone decreased, while the strength between each welding line was not strong enough. It caused a decrease in the quality of printed parts. Combined with the testing results gained in this work, it can be seen that a 0.06 mm hatch spacing was considered as a relatively optimal condition for part formation under 0.05 μm. Comparison of the morphology of the samples printed under different hatch spacing also confirmed the phenomenon observed here.

Fruit cracking affects both the yield and economic efficiency of citrus; however, the underlying mechanism remains unclear. Therefore, this study focused on resistant and susceptible cultivars to identify the mechanisms underlying fruit cracking. The results showed that in ‘Mingrijian’, pectin morphological transformation and hemicellulose and lignin degradation in the pericarp were important contributing factors. During the critical fruit-cracking period (115–150 days after flowering), the water-soluble pectin, protopectin, and lignin contents in the pericarp of ‘Daya’ presented inverse changes relative to those in ‘Mingrijian’, thus enhancing the mechanical properties and resistance of pericarp. From 115 to 150 days after flowering, the soluble sugar content in the pulp of ‘Mingrijian’ increased rapidly by 97.35%, aiding in pulp water absorption and expansion. Moreover, the soluble protein content in the pericarp of ‘Mingrijian’ exhibited a declining trend and was lower than that of ‘Daya’, thus affecting the overall metabolism. The superoxide dismutase (SOD) activity in the pericarp of ‘Mingrijian’ gradually decreased from 115 to 180 days after flowering, while the peroxidase (POD) activity remained at a low level, resulting in weaker antioxidant capacity and lower environmental resistance. This study provides valuable insights into the mechanisms of citrus fruit cracking, laying the foundation for preventive and control strategies.

BackgroundPosttransplant lymphoproliferative disorders (PTLDs) are uncommon but serious complications in patients following solid organ transplantation. Primary Epstein-Barr virus (EBV) infection is a risk factor for the development of PTLD, especially early-onset PTLD, in EBV-negative recipients. To date, however, there are no specific guidelines on the threshold of EBV-DNA load for therapeutic intervention, the source for measurement (e.g., blood, bronchoalveolar fluid), or the use of antiviral agents as prophylaxis for early PTLD prevention in EBV-mismatched patients.MethodsThe present study describes a 56-year-old male lung transplant recipient diagnosed with EBV-associated PTLD.ResultsThis patient had a history of invasive fungal disease and Mucor and Aspergillus fumigatus infections in the early post-transplant period, necessitating antifungal therapy throughout the course of the disease. The patient was EBV-positive 15 days after transplantation, with lung CT showing multiple bilateral nodules of varying sizes beginning 98 days after transplantation. A lung biopsy showed PTLD, and next-generation sequencing (NGS) revealed EBV. This patient, however, did not receive any antiviral therapy for early PTLD prevention or any PTLD-related treatment. He died 204 days after lung transplantation.ConclusionThe present study describes a lung transplant recipient who developed EBV-associated PTLD, a non-negligible disease, after solid organ transplantation. Monitoring EBV-DNA load is important, as a sudden increase may be a sensitive indicator of PTLD. An earlier diagnosis may increase the likelihood of successful treatment.

Abstract Predicting students' performance is one of the most important issue in educational data mining. In order to investigate the state‐of‐the‐art research development in predicting students' performance by using artificial neural networks (ANN), we conducted a survey on 39 important studies on this issue from 2016 to 2021. The results show that: (1) objectives of most prediction model is the performance of learners on the program and course; (2) datasets used for training prediction model are collected from logs of the learning management system; (3) the most commonly used ANN is feedforward neural network; (4) researchers use stochastic gradient descent and Adam algorithm to optimizes the parameters in ANN and configure hyper parameters of ANN manually; (5) feature selection is not necessary because ANN can automatically adjust the weights of artificial neurons; and (6) ANN has better performance than the classical classifiers in predicting student performance. The challenges in previous studies were comprehensively analyzed, suggestions for future research were put forward.

BackgroundComplications, including arrhythmia, following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection continue to be of concern. Omicron is the mainstream SARS-CoV-2 mutant circulating in mainland China. At present, there are few epidemiological studies concerning the relationship between arrhythmia and Omicron variant infection in mainland China.ObjectivesTo investigate the risk factors of arrhythmia in patients infected with the SARS-CoV-2 Omicron variant and the factors influencing prognosis.MethodsData from 192 Omicron infected patients with symptoms of arrhythmia (AH group) and 100 Omicron infected patients without arrhythmia (Control group) were collected. Patients in the AH group were divided into the good and poor prognosis groups, according to the follow-up results 4–6 weeks after infection. The general and clinical data between the AH and Control groups, and between the good and poor prognosis groups were compared. The variables with differences between the groups were included in the multivariate logistic regression analysis, and the quantitative variables were analyzed by receiver operating characteristic curve to obtain their cut-off values.ResultsCompared with the control group, the body mass index (BMI), proportion of patients with a history of arrhythmia, proportion of antibiotics taken, heart rate, moderate disease severity, white blood cell (WBC) count, and the aspartate aminotransferase, creatine kinase (CK), CK isoenzyme (CK-MB), myoglobin (Mb), high-sensitive troponin I (hs-cTnI), lymphocyte ratio and high sensitivity C-reactive protein (hs-CRP) levels in the AH group were significantly higher (p

Background Gastrodia elata is widely used in China as a valuable herbal medicine. Owing to its high medicinal and nutrient value, wild resources of G. elata have been overexploited and its native areas have been severely damaged. Understanding the impacts of climate change on the distribution of this endangered species is important for the conservation and sustainable use of G. elata. Methods We used the optimized maximum entropy model to simulate the potential distribution of G. elata under contemporary and future time periods (1970–2000, 2050s, 2070s, and 2090s) and different climate change scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). Under these conditions, we investigated the key environmental factors influencing the distribution of G. elata as well as the spatial and temporal characteristics of its niche dynamics. Results With high Maxent model accuracy (AUCmean = 0.947 ± 0.012, and the Kappa value is 0.817), our analysis revealed that annual precipitation, altitude, and mean temperature of driest quarter are the most important environmental factors influencing the distribution of G. elata. Under current bioclimatic conditions, the potentially suitable area for G. elata in China is 71.98 × 104 km2, while the highly suitable region for G. elata growth is 7.28 × 104 km2. Our models for three future periods under four climate change scenarios indicate that G. elata can maintain stable distributions in southern Shaanxi, southwestern Hubei, and around the Sichuan basin, as these areas are highly suitable for its growth. However, the center of the highly suitable areas of G. elata shift depending on different climatic scenarios. The values of niche overlap for G. elata show a decreasing trend over the forecasted periods, of which the niche overlap under the SSP3-7.0 scenario shows the greatest decrease. Discussions Under the condition of global climate change in the future, our study provides basic reference data for the conservation and sustainable utilization of the valuable and endangered medicinal plant G. elata. It is important to carefully choose the protection area of G. elata wild resources according the suitable area conditions modeled. Moreover, these findings will be valuable for providing insights into the breeding and artificial cultivation of this plant, including the selection of suitable areas for planting.

Abstract Background In mammals, normal fertilization depends on the structural and functional integrity of the zona pellucida (ZP), which is an extracellular matrix surrounding oocytes. Mutations in ZP may affect oogenesis, fertilization and early embryonic development, which may cause female infertility. Methods A PubMed literature search using the keywords ‘zona pellucida’, ‘mutation’ and ‘variant’ limited to humans was performed, with the last research on June 30, 2022. The mutation types, clinical phenotypes and pregnancy outcomes were summarized and analyzed. The naive Bayes classifier was used to predict clinical pregnancy outcomes for patients with ZP mutations. Results A total of 29 publications were included in the final analysis. Sixty-nine mutations of the ZP genes were reported in 87 patients with different clinical phenotypes, including empty follicle syndrome (EFS), ZP-free oocytes (ZFO), ZP-thin oocytes (ZTO), degenerated and immature oocytes. The phenotypes of patients were influenced by the types and location of the mutations. The most common effects of ZP mutations are protein truncation and dysfunction. Three patients with ZP1 mutations, two with ZP2 mutations, and three with ZP4 mutations had successful pregnancies through Intracytoplasmic sperm injection (ICSI) from ZFO or ZTO. A prediction model of pregnancy outcome in patients with ZP mutation was constructed to assess the chance of pregnancy with the area under the curve (AUC) of 0.898. The normalized confusion matrix showed the true positive rate was 1.00 and the true negative rate was 0.38. Conclusion Phenotypes in patients with ZP mutations might be associated with mutation sites or the degree of protein dysfunction. Successful pregnancy outcomes could be achieved in some patients with identified ZP mutations. Clinical pregnancy prediction model based on ZP mutations and clinical characteristics will be helpful to precisely evaluate pregnancy chance and provide references and guidance for the clinical treatment of relevant patients.

Abstract Pseudostellaria heterophylla, also called Tai-zi-shen (TZS) in Traditional Chinese Medicine (TCM), is always used clinically to treat spleen deficiency symptoms. Polysaccharides in TZS have various pharmacological activities, including anti-diabetic, immune regulation, and myocardial protection. However, the relationship between the spleen-invigorating effects of TZS or its polysaccharides and intestinal flora are not clear. This study investigated the effects of TZS decoction (PHD) and polysaccharide (PHP) on immune function and intestinal flora in a rat model of spleen deficiency syndrome (SDS) induced by a decoction of raw rhubarb (RRD). PHD and PHP increased immune organ index, alleviated inflammatory cell filtration, and reduced the levels of pro-inflammatory cytokines in rats with spleen deficiency syndrome. In addition, the production of butyric acid was promoted in PHD and PHP groups. Moreover, 16S rRNA gene sequencing showed that PHD and PHP reduced the relative abundance of Firmicutes while increasing the one of Bacteroidetes; significantly increased the abundance of Lactobacillus and decreased the abundance of Rombutsia; and PHP significantly increased the abundance of Alloprevotella. And there was a significant positive correlation between the alleviation of SDS and short-chain fatty acids (SCFAs)-producing bacteria. These findings suggested PHD and PHP, especially PHP, has a potential to relieve spleen deficiency by reducing intestinal inflammation, modulating structure and composition of gut microbiota, and promoting the production of butyric acid.

Abstract Surgical instrument packaging defects may affect the safety of medical care and patients and waste the hospital workforce, material resources, and financial resources. This study explored the application of healthcare failure mode and effect analysis in controlling surgical instrument packaging defects. We retrospectively evaluated the packaging process of 183,642 surgical instruments packaged in our hospital during January–June 2020 using the healthcare failure mode and effect analysis. Besides, we used a decision tree model to determine the steps requiring improvement and formulate the improvement measures. We applied the improvement measures to 190,231 surgical instrument packs packaged in our hospital during July–December 2020. Based on the healthcare failure mode and effect analysis, we compared the packaging defect rates before and after adopting the improvement measures. Of the 183,642 packs selected before adopting the improvement measures, 98 defects occurred, with a defect rate of 0.053%. However, of the 190,231 packs selected after adopting the improvement measures, 22 defects occurred, with a defect rate of 0.012%. The defect rate of surgical instrument packaging handled by the central sterile supply department staff was significantly reduced (χ2 = 50.822, P = 0.001) after adopting the improvement measures. Using the medical failure mode and effect analysis method to control the defects in surgical instrument packaging can effectively reduce the packaging defect rate, ensuring patient safety.

Abstract Polysaccharide (PF40) has been recognized as a main bioactive substances in Pseudostellaria heterophylla (Miq.). The current study explored the potential protective effects of PF40 on immune system in mice with cyclophosphamide‐induced immunosuppression. The mice were intragastric administered PF40 at the dosage of 100, 200 or 400 mg/kg once daily for 30 days, On the 24th and 25th day, the additional intraperitoneal injection of PF40 (50 mg/kg) were administered. The results showed that PF40 enhanced the cell‐mediated immunity via improvements in macrophage phagocytosis, splenocyte proliferation, NK cell activity and delayed type hypersensitivity. Equally, it improves humoral immunity through promoting the formation of serum hemolysin. Moreover, PF40 maintain the immune balance of splenic lymphocytes and altered the intestinal physiological status in Cyp‐induced mice. PF40 regulates the intestinal microbiota by restoring the relative abundance of Odoribacter and Mucispirillum and reducing the relative abundance of Sporosarcina, Yaniella, and Jeotgalicoccus in Cyp‐intervened mice. The findings suggested that PF40 might be a promising natural functional foods for reducing chemotherapy‐induced immunosuppression.

Abstract Background The extent of surgery in nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has not well established, partly owing to the dilemma of precise prediction of lymph node metastasis (LNM) preoperatively. This study proposed to develop and validate the value of MRI features for predicting LNM in NF-PNETs. Methods A total of 187 patients with NF-PNETs who underwent MR scan and subsequent lymphadenectomy from 4 hospitals were included and divided into training group (n = 66, 1 center) and validation group (n = 121, 3 centers). The clinical characteristics and qualitative MRI features were collected. Multivariate logistic regression model for predicting LNM in NF-PNETs was constructed using the training group and further tested using validation group. Results Nodal metastases were reported in 41 patients (21.9%). Multivariate analysis showed that regular shape of primary tumor (odds ratio [OR], 4.722; p = .038) and the short axis of the largest lymph node in the regional area (OR, 1.488; p = .002) were independent predictors for LNM in the training group. The area under the receiver operating characteristic curve in the training group and validation group were 0.890 and 0.849, respectively. Disease-free survival was significantly different between model-defined LNM and non-LNM group. Conclusions The novel MRI-based model considering regular shape of primary tumor and short axis of largest lymph node in the regional area can accurately predict lymph node metastases preoperatively in NF-PNETs patients, which might facilitate the surgeons’ decision on risk stratification.

Abstract Background We aimed to establish simplified and quantifiable triage criteria in pediatric emergency care, improving the efficiency of pediatric emergency triage and ensuring patient safety. Methods We preliminarily determined the pediatric emergency triage criteria with references to pediatric emergency department characteristics and internationally recognized triage tools after literature review and discussion. The final determination of the triage criteria was reached after two rounds of Delphi surveys completed by18 experts from 3 hospitals in China. Results Both round 1 and round 2 surveys had a 100% response rate. The overall expert authority coefficient in the two rounds of surveys was 0.872. The experts had 100% enthusiasm for participating in the surveys. Kendall’s coefficients of concordance for conditions/symptoms in patients triaged to level 1, 2, 3, and 4 were 0.149, 0.193, 0.102, and 0.266, respectively. All p-values were less than 0.05. The coefficients of variation in conditions/symptoms, vital signs, and the Pediatric Early Warning Score (PEWS) ranged between 0.00 and 0.205, meeting the inclusion criteria. The pediatric emergency triage criteria containing conditions/symptoms, vital signs, PEWS scores, and other 4 level 1 indicators, 51 level 2 indicators and 23 level 3 indicators were built. The maximum waiting time to treatment for the patients triaged to level 1, 2, 3, and 4 was immediate, within 10 min, within 30 min, and within 240 min, respectively. Conclusion The pediatric emergency triage criteria established in this study was scientific and reliable. It can be used to quickly identify the patients requiring urgent and immediate care, thereby ensuring the priorities for the care of critically ill patients.

This study investigated the chemical composition and biosynthesis pathway of compounds produced by Streptomyces sulphureus DSM 40104. With the guild of molecular networking analysis, we isolated and identified six uncommon structural characteristics of compounds, including four newly discovered pyridinopyrones. Based on genomic analysis, we proposed a possible hybrid NRPS-PKS biosynthesis pathway for pyridinopyrones. Notably, this pathway starts with the use of nicotinic acid as the starting unit, which is a unique feature. Compounds 1–3 exhibited moderate anti-neuroinflammatory activity against LPS-induced BV-2 cell inflammation. Our study demonstrates the diversity of polyene pyrone compounds regarding their chemical structure and bioactivity while providing new insights into their biosynthesis pathway. These findings may lead to the development of new treatments for inflammation-related diseases.

Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported.Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. Sanger sequencing was used to validate the variants identified in the siblings and their parents. In vitro functional study was performed.Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. However, the actual genotype-phenotype relationship needs more study.Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity.

Abstract Background Surgical instrument packaging quality directly affects the safety and performance of surgery. We aimed to investigate the factors causing defects in surgical instrument packaging and recommend strategies to prevent defects in surgical instrument packaging. Methods We collected surgical instrument packaging data regarding age, gender, length of service, educational background, number of staff dealing with packaging, time period of packaging, instrument specification, where the wrap was intact, whether the wrap reached the required quality of cleaning, and whether the instruments were satisfactorily cleaned in compliance with guidelines from 5000 surgical instrument packages during June-December 2018 at Central Sterile Supply Department of the West China Second University Hospital, Sichuan University. Meanwhile, a questionnaire survey completed by the operating room staff using surgical instruments was used to measure the level of their satisfaction with the instruments in the packages. We utilized single-factor analysis to investigate possible factors that might cause defects in surgical instrument packaging, and conducted multivariate logistic regression analysis of the factors associated with defects in packaging. Results Length of service, educational background, number of staff dealing with packaging, time period of packaging, instrument structure, whether the wrap was intact, whether the wrap reached the required quality of cleaning, and whether the surgical instruments were satisfactorily cleaned in compliance with guidelines were the factors significantly (P < 0.05) associated with defects in surgical instrument packaging. Conclusion This study reveals that various factors are associated with defects in surgical instrument packaging. Recommendations for reducing incidences of defects include improved scheduling of packaging workload, greater provision of training in packaging skills, and standardization of packaging procedure.

Abstract Background Increasing evidence has shown that the mammalian target of rapamycin (mTOR) pathway plays a critical role in oocyte meiosis and embryonic development, however, previous studies reporting the effects of rapamycin on oocyte IVM showed different or even opposite results, and the specific mechanisms were not clear. Methods The immature oocytes from female mice underwent IVM with rapamycin at different concentrations to select an optimal dose. The maturation rate, activation rate, subsequent cleavage and blastocyst formation rates, spindle assembly, chromosome alignment, mitochondrial membrane potential (MMP), ROS levels, and DNA damage levels were evaluated and compared in oocytes matured with or without rapamycin. In addition, the expression levels of genes associated with mTORC1 pathway, spindle assembly, antioxidant function, and DNA damage repair (DDR) were also assessed and compared. Results Rapamycin at 10 nM was selected as an optimal concentration based on the higher maturation and activation rate of IVM oocytes. Following subsequent culture, cleavage and blastocyst formation rates were elevated in activated embryos from the rapamycin group. Additionally, oocytes cultured with 10 nM rapamycin presented decreased ROS levels, reduced chromosome aberration, and attenuated levels of γ-H2AX. No significant effects on the percentages of abnormal spindle were observed. Correspondingly, the expressions of Nrf2, Atm, Atr, and Prkdc in IVM oocytes were markedly increased, following the inhibition of mTORC1 pathway by 10 nM rapamycin. Conclusion Rapamycin at 10 nM could ameliorate the developmental competence and quality of IVM oocytes of mice, mainly by improving the chromosome alignments. The inhibition of mTORC1 pathway, which involved in activating DDR-associated genes may act as a potential mechanism for oocyte quality improvement by rapamycin.

Stable yield of staple grains must be ensured to satisfy food demands for daily dietary energy requirements against the backdrop of global climate change. Summer maize, a staple crop, suffers severe yield losses due to extreme rainfall events, threatening food security. A randomized block experiment with four treatments: control, no water stress (CK); waterlogging for 6 days at the third leaf, sixth leaf stage, and 10th day after tasseling, was conducted to investigate the mechanism of waterlogging-induced yield losses of summer maize. Waterlogging delayed plant growth and impaired tassel and ear differentiation, leading to high grain yield losses of Denghai 605 (DH605). Waterlogging at third leaf (V3) stage reduced the photosynthesis of DH605, reducing total dry matter weight. Waterlogging at V3 stage reduced sucrose-cleaving enzymes activities in spike nodes and ears, reducing the carbon partitioned to ears (–53.1%), shanks (–46.5%), and ear nodes (–71.5%) but increasing the carbon partitioned to ear leaves (9.6%) and tassels (43.9%) in comparison with CK. The reductions in total carbon assimilate together with the reduced carbon partitioning to ears resulted in poor development of spikes (with respectively 15.2% and 20.6% reductions in total florets and fertilized florets) and lengthened the anthesis–silking interval by around 1 day, leading to high yield losses.

Genetic susceptibility is one of the most important causes of otitis media (OM). Mutant Galnt2 homozygote (Galnt2tm1Lat/tm1Lat) mimics human otitis media in comparable pathology and causes hearing loss. Otitis media is characterized by effusion and dysregulated mucosa proliferation and capillary expansion in the middle ear cavity, which is associated with hearing loss. The mucociliary dysfunction could be seen in the middle ear cavity (MEC) in a patient harboring the disease that develops in severity with age by a scanning electron microscope. Tumor necrosis factor alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), Muc5ac, and Muc5b upregulate the expression in the middle ear, which correlates with inflammation, craniofacial development, and mucin secretion. The mouse model with a mutation in the Galnt2 (Galnt2tm1Lat/tm1Lat) was explored in this study as a novel model of human otitis media.

The rapid evolution of antibiotic resistance and the complicated bacterial infection microenvironments are serious obstacles to traditional antibiotic therapy. Developing novel antibacterial agents or strategy to prevent the occurrence of antibiotic resistance and enhance antibacterial efficiency is of the utmost importance. Cell membrane-coated nanoparticles (CM-NPs) combine the characteristics of the naturally occurring membranes with those of the synthetic core materials. CM-NPs have shown considerable promise in neutralizing toxins, evading clearance by the immune system, targeting specific bacteria, delivering antibiotics, achieving responsive antibiotic released to the microenvironments, and eradicating biofilms. Additionally, CM-NPs can be utilized in conjunction with photodynamic, sonodynamic, and photothermal therapies. In this review, the process for preparing CM-NPs is briefly described. We focus on the functions and the recent advances in applications of several types of CM-NPs in bacterial infection, including CM-NPs derived from red blood cells, white blood cells, platelet, bacteria. CM-NPs derived from other cells, such as dendritic cells, genetically engineered cells, gastric epithelial cells and plant-derived extracellular vesicles are introduced as well. Finally, we place a novel perspective on CM-NPs’ applications in bacterial infection, and list the challenges encountered in this field from the preparation and application standpoint. We believe that advances in this technology will reduce threats posed by bacteria resistance and save lives from infectious diseases in the future.

The mechanism of hepatocellular carcinoma (HCC) development induced by liver fibrosis is obscure. The objective of this study is to establish miRNAs from exosomes associated with liver fibrosis, and to identify potential biomarkers for the prediction of personalized clinical management effectiveness in HCC. Our research focused on miRNAs from exosomes and mRNA from liver fibrosis, which we found in the gene expression omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) evaluated miRNAs from exosomes associated with liver fibrosis, and Wilcoxon analysis assessed differentially expressed mRNAs (DEGs) across liver fibrosis/normal tissues. Following that, DEGs were assessed through gene set enrichment analysis (GSEA), gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, based on the screened targeted genes, including SAMD12 and CADM2, we further elucidated their correlation in HCC patients from the BEST database. The Kaplan-Meier Plotter platform was applied to evaluate the prognostic values of miRNA in HCC. In vitro and vivo experiments validated our findings. Six miRNAs associated with liver fibrosis were evaluated in our investigation. In-depth research presented exosome-derived miR-106a-5p, SAMD12 and CADM2 could exert valuable predictive implications for HCC treatment and illness assessment. Serum miR-106a-5p derived from liver fibrosis was decreased compared with healthy individuals. SAMD12 and CADM2 were diminished in liver cancer cell lines, and their knockdown of them exacerbated the proliferation capacities of liver cells in vitro. Exosome-derived miRNA of liver fibrosis modulated tumorigenesis by targeting SAMD12 and CADM2 in HCC.

IntroductionIt was reported that there were still up to 30% immature retrieved oocyte at germinal vesicle (GV) or metaphase I (MI) stage. Whether the spontaneous maturity competency of immature oocytes associated to the clinical outcome of in vitro fertilization (IVF) cycles remains unclear and unexplored. This study aimed to investigate how the oocyte developmental parameters in in vitro maturation (IVM) affect clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles.MethodsThis retrospective cohort study included couples undergoing ICSI in a university-affiliated hospital. Surplus immature oocytes during ICSI were collected and cultured in vitro. The numbers of germinal vesicle (GV) oocytes undergoing GV breakdown (GVBD) and polar body 1 extrusion within 24 h culture were recorded. The main outcome measurements were demographic baselines and oocyte developmental parameters in IVM associated with pregnancy outcomes.ResultsA total of 191 couples were included with an overall GVBD rate of 63.7% (327/513) and oocyte maturation rate of 46.8% (240/513). 53.4% (102/191) of them had embryos transferred freshly, which originated from metaphase II oocytes that matured spontaneously in vivo, and 60.8% (62/102) got pregnant. Among factors with a P-value < 0.2 in univariate logistic regression analyses of pregnancy correlation, GVBD rate (OR 3.220, 95% CI 1.060-9.782, P=0.039) and progesterone level on human chorionic gonadotropin (HCG) day (OR 0.231, 95% CI 0.056-0.949, P=0.042) remained significant in the multivariate model. The area under the curve (AUC) of the predictive nomogram was 0.729 (95% CI 0.632-0.826) with an acceptable calibration. Moreover, decision curve analyses illustrated the superior overall net benefit of models that included the GVBD rate in clinical decisions within a wide range of threshold probabilities.ConclusionIn conclusion, GVBD rate and progesterone level on HCG day may be associated with pregnancy outcomes in infertile couples during the regular ICSI procedure. An elevated GVBD rate within 24 h may greatly increase the likelihood of pregnancy in infertile couples during ICSI. This preliminary study may optimize clinical pregnancy prediction, which provides support in decision-making in clinical practice.