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This is an article in the field of mineral processing engineering. Comprehensive utilization of coal gasification fine slag is a major development direction at present. Coal gasification fine slag has developed pores and rich oxygen groups, which makes it difficult for kerosene and other traditional collectors to recover the residual carbon. Flotation experiments were carried out on the compound MO of methyl oleate and kerosene, and the mechanism was discussed by means of laser particle size analyzer, FTIR, contact angle, and XPS. The results show that when the dosage of MO is increased to 16 kg/t, the loss on ignition of tailings is reduced to 7.12%, and the recovery of combustible is more than 95.63%. MO introduced polar group ester group, which can reduce the interfacial tension of kerosene surface, enhance the dispersing effect of collector in water, so as to increase the contact area and collision probability of carbon residue particles and collector droplet, and improve the hydrophobicity and floatability of carbon residue particles. The hydrophobicity of carbon residue was analyzed by contact angle and the relationship between the hydrophobicity and the rate of fine mineral was explained. XPS shows that the interaction between MO and oxygen-containing functional groups on the surface of the carbon residue can form an effective covering layer at the hydrophilic water level point of the carbon residue, which makes the hydrophobic part outward, reduces the hydration, increases the contact probability, and increases the surface hydrophobicity of the coal gasification fine slag. The use of MO agent provides a new way for comprehensive utilization of solid waste from coal gasification.

Abstract This study was aimed to investigate the impact of intracytoplasmic sperm injection (ICSI) on reproductive outcomes in couples with non-male factor infertility and frozen-thawed embryo transfer (FET) treatment. This retrospective cohort study involved a total of 10,143 cycles from 6206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Patients were categorized into two groups based on the insemination methods of transferred embryos. Clinical and neonatal outcomes were compared between ICSI and conventional in vitro fertilization (cIVF) groups. The results showed that ICSI was not associated with improved clinical outcomes compared to cIVF. However, ICSI was associated with lower birthweight when twins were born. In conclusion, although subgroup analysis showed that ICSI was associated with slightly improved live birth rate for infertile couples with non-male factor infertility compared to cIVF, the regression analysis showed that ICSI did not demonstrate any improvement of the reproductive outcomes. The infertile women with twin pregnancies should be further informed of the lower birthweight and lower birth length when their oocytes were inseminated with ICSI. The findings of this study provide valuable insights for clinicians when discussing the benefits and risks of ICSI in patients with non-male factor infertility.

Abstract Background Studies have found that the ratio of total cholesterol to high‐density lipoprotein cholesterol (TC/HDL‐C) was associated with the development of chronic kidney disease (CKD). However, the relationship in different genders was rarely discussed. The aim of this study was to explore this relationship and assess its predictive power for both males and females. Methods Based on a prospective cohort platform in northwest China, 32,351 participants without CKD were collected in the baseline and followed up for approximately 5 years. Cox proportional hazard model and restricted cubic spline regression analysis were performed to investigate the association between TC, HDL‐C, TC/HDL‐C and CKD in adult female and male. The clinical application value of the indicators in predicting CKD was evaluated by the receiver operator characteristic curve. Results During a mean follow‐up of 2.2 years, 484 males and 164 females developed CKD. After adjusted for relevant confounders, for every one standard deviation increase in TC, HDL‐C and TC/HDL‐C, the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for CKD were 1.17 (1.05–1.31), 0.84 (0.71–0.99), and 1.15 (1.06–1.25) for males, 0.94 (0.78–1.13), 0.58 (0.35–0.95), and 1.19 (1.01–1.40) for females, respectively. The results also showed that TC, HDL‐C, and TC/HDL‐C were associated with CKD in a linear dose–response relationship. The TC/HDL‐C had the largest area under the curve (AUC) compared to TC and HDL‐C, and the AUC among the females was larger than that among males. Conclusions The TC/HDL‐C was significantly associated with CKD in adult males and females and has better clinical value in predicting CKD than TC and HDL‐C, especially in females.

Abstract In the process of tumor treatment, systemic drug administration is hindered by biological barriers, leading to the retention of a large number of drug molecules in healthy tissues and causing unavoidable side effects. The precise deployment of drugs at the tumor site is expected to alleviate this phenomenon. Here, we take endostatin and Her2 (+) tumors as examples and develop an intelligent drug with simple “wisdom” by endowing mesenchymal stem cells (MSCs) with an intelligent response program (iMSCEndostatin). It can autonomously perceive and distinguish tumor cells from non-tumor cells, establishing a logical connection between tumor signals and drug release. Enable it to selectively deploy drugs at the tumor site, thereby locking the toxicity of drugs at the tumor site. Unlike traditional aggressive targeting strategies that aim to increase drug concentration at the lesion, intelligent drugs are more inclined to be defensive strategies that prevent the presence of drugs in healthy tissues.

Abstract Non-direct antimicrobial cationic peptides (NDACPs) are components of the animal innate immune system. But their functions and association with antimicrobial peptides (AMPs) are incompletely understood. Here, we reveal a synergistic interaction between the AMP AW1 and the NDACP AW2, which are co-expressed in the frog Amolops wuyiensis. AW2 enhances the antibacterial activity of AW1 both in vitro and in vivo, while mitigating the development of bacterial resistance and eradicating biofilms. AW1 and AW2 synergistically damage bacterial membranes, facilitating cellular uptake and interaction of AW2 with the intracellular target bacterial genomic DNA. Simultaneously, they trigger the generation of ROS in bacteria, contributing to cell death upon reaching a threshold level. Moreover, we demonstrate that this synergistic antibacterial effect between AMPs and NDACPs is prevalent across diverse animal species. These findings unveil a robust and previously unknown correlation between AMPs and NDACPs as a widespread antibacterial immune defense strategy in animals.

Abstract Background and aims Inflammation is initiates the propagation phase of aortic valve calcification. The activation of NLRP3 signaling in macrophages plays a crucial role in the progression of calcific aortic valve stenosis (CAVS). IFN-γ regulates NLRP3 activity in macrophages. This study aimed to explore the mechanism of IFN-γ regulation and its impact on CAVS progression and valve interstitial cell transdifferentiation. Methods and results The number of Th1 cells and the expression of IFN-γ and STAT1 in the aortic valve, spleen and peripheral blood increased significantly as CAVS progressed. To explore the mechanisms underlying the roles of Th1 cells and IFN-γ, we treated CAVS mice with IFN-γ-AAV9 or an anti-IFN-γ neutralizing antibody. While IFN-γ promoted aortic valve calcification and dysfunction, it significantly decreased NLRP3 signaling in splenic macrophages and Ly6C+ monocytes. In vitro coculture showed that Th1 cells inhibited NLPR3 activation in ox-LDL-treated macrophages through the IFN-γR1/IFN-γR2-STAT1 pathway. Compared with untreated medium, conditioned medium from Th1-treated bone marrow–derived macrophages reduced the osteogenic calcification of valvular interstitial cells. Conclusion Inhibition of the NLRP3 inflammasome by Th1 cells protects against valvular interstitial cell calcification as a negative feedback mechanism of adaptive immunity toward innate immunity. This study provides a precision medicine strategy for CAVS based on the targeting of anti-inflammatory mechanisms. Graphical Abstract

Abstract Employing deep learning techniques for the semantic segmentation of remote sensing images has emerged as a prevalent approach for acquiring information about water bodies. Yet, current models frequently fall short in accurately extracting water bodies from high-resolution remote sensing images, as these images often present intricate details of terrestrial objects and complex backgrounds. Vegetation, shadows, and other objects close to water boundaries have increased similarity to water bodies. Moreover, water bodies in high-resolution images have different boundary complexities, shapes, and sizes. This situation makes it somewhat challenging to accurately distinguish water bodies in high-resolution images. To overcome these difficulties, this paper presents a novel network model named EU-Net, specifically designed to extract water bodies from high-resolution remote sensing images. The proposed EU-Net model, with U-net as the backbone network, incorporates improved residual connections and attention mechanisms, and designs multi-scale dilated convolution and multi-scale feature fusion modules to enhance water body extraction performance in complex scenarios. Specifically, in the proposed model, improved residual connections are introduced to enable the learning of more complex features; the attention mechanism is employed to improve the model's discriminative ability by focusing on important channels and spatial areas. The implemented multi-scale dilated convolution technique enhances the model's receptive field while maintaining the same number of parameters. The designed multi-scale feature fusion module is capable of processing both small-scale details and large-scale structures in images, while simultaneously modeling the spatial context relationships of features at different scales. Experimental results validate the superior performance of EU-Net in accurately identifying water bodies from high-resolution remote sensing images, outperforming current models in terms of water extraction accuracy.

Abstract Quantifying flood risk depends on accurate probability estimation, which is challenging due to non‐stationarity and the combined effects of multiple factors in a changing environment. The threat of compound flood risks may spread from coastal areas to inland basins, which have received less attention. In this study, a framework based on time‐varying copulas was introduced for the treatment of compound flood risk and bivariate design in non‐stationary environments. Archimedean copulas were developed to diagnose the non‐stationary trends of flood risk. Return periods, average annual reliabilities, and bivariate designs were estimated. Model uncertainty was analyzed by comparing the results for stationary and non‐stationary conditions. The case study investigated the extreme rainfall and water level series from the Qinhuai River Basin and the Yangtze River in China. The results showed that marginal distributions and correlations are non‐stationary in all bivariate combinations. Ignoring composite effects may lead to inappropriate quantification of flood risk. Excluding non‐stationarity may lead to risk over or underestimation. It showed the limitations of the 1‐day scale and quantified the uncertainty of non‐stationary models. This study provided a flood risk assessment framework in a changing environment and a risk‐based design technique, which is essential for climate change adaptation and water management.

Study region: Beijing-Tianjin-Hebei urban agglomeration in China Study focus: The prediction of water resources carrying capacity (WRCC) can provide an effective reference for the rational allocation and efficient utilization of water resources. Traditional prediction methods obtained a definite WRCC value but fail to reflect the uncertainty of WRCC changes and limit reference for the optimal allocation of water resources. To ensure the accuracy, availability and comprehensiveness of prediction, this paper adopts the improved principal component analysis (PCA) to screen indicators, and predicts the WRCC through the coupled model of Monte Carlo and Grey Wolf Optimization-Support Vector Machine(GWO-SVM), addressing single result issues and computational complexity. At the same time, various regulation schemes for sensitive indicators are designed to provide an effective guidance for the optimal allocation and sustainable use of water resources. New hydrological insights for the region: In 2025, the probability of WRCC in Tianjin, Handan, Xingtai, Hengshui, Cangzhou, Langfang to maintain grade III is more than 80 %, and that in Beijing, Baoding, Tangshan, Qinhuangdao, Zhangjiakou, Chengde to reach grade IV is more than 50 %. The sensitivity analysis shows that the sensitive indicators mainly focus on water supply and consumption, water use efficiency and pollutant gas emissions. The WRCC can be further improved under different schemes. The results can provide effective guidance for the optimal allocation of water resources and maintain sustainable economic and social development in Beijing-Tianjin-Hebei urban agglomeration.

ABSTRACTObjectives Cognitive-behavioral stress management (CBSM) is an effective psychological intervention to relieve psychological and symptomatic distress. This study aimed to investigate the effect of CBSM in anxiety, depression, and post-traumatic stress disorder (PTSD) in parents of pediatric acute myeloid leukemia (AML) patients.Methods Totally, 56 pediatric AML patients and 100 parents were randomized into the CBSM group (28 patients and 49 parents) and the normal control (NC) group (28 patients and 51 parents) to receive corresponding interventions for 10 weeks. The questionnaire scores were assessed at month M0, M1, M3, and M6.Results In parents of pediatric AML patients, self-rating anxiety scale score at M1 (p = 0.034), M3 (p = 0.010), and M6 (p = 0.003), as well as anxiety at M3 (p = 0.036) and M6 (p = 0.012) were decreased in the CBSM group versus the NC group. Self-rating depression scale score at M3 (p = 0.022) and M6 (p = 0.002), as well as depression at M6 (p = 0.019) were declined in the CBSM group versus the NC group. Symptom checklist-90 (a psychotic status questionnaire) score at M3 (p = 0.031) and M6 (p = 0.019) were declined in the CBSM group versus the NC group. Regarding PTSD, the impact of the events scale-revised score at M3 (p = 0.044) and M6 (p = 0.010) were decreased in the CBSM group versus the NC group. By subgroup analyses CBSM (versus NC) improved all outcomes in parents with anxiety at M0 and depression at M0 (all p 0.050).Conclusion CBSM reduces anxiety, depression, and PTSD in parents of pediatric AML patients.

IntroductionFatty liver syndrome (FLS) is a prevalent nutritional and metabolic disease that mainly occurs in caged laying hens, causing substantial losses in the poultry industry. The study was carried out to explore the protective effect and potential mechanism of betaine on early FLS.MethodsThere were three groups: Con group (basal diet), FLS group (Dexamethasone injection + basal diet) and betaine group (Dexamethasone injection + basal diet with 8 g/kg betaine). Birds in FLS and betaine groups were treated with subcutaneous dexamethasone injection once a day at a dosage of 4.50 mg/kg body weight for 7 days.ResultsThe results revealed that DXM treatment significantly increased the liver index, serum aspartate aminotransferase (AST), total protein (TP), total bilirubin (TBIL), total biliary acid (TBA), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), and glucose (GLU) (p

ABSTRACT: Oxidative stress is a frequent concern in the breeding of laying hens, and limit the healthy development of poultry. Dexamethasone (DXM) has been demonstrated to induce oxidative stress. Conversely, betaine is an alkaloid with a potent antioxidant activity. The study was designed to investigate the ameliorative effect of betaine on DXM-induced oxidative stress in laying hens. The results revealed that DXM treatment significantly decreased laying rate, shell strength, albumen height, Haugh unit, egg weight, folk weight and albumen weight, alongside increased malondialdehyde (MDA) and decreased total antioxidant capacity (T-AOC) in serum and liver (P < 0.05). In contrast, dietary betaine addition reversed those parameters mentioned above (P < 0.05). Hepatic RNA-seq analysis showed that there existed 110 up- and 88 down-regulated genes in DXM group when compared with the control. Meanwhile there were 117 upregulation and 169 downregulation genes in BT group when compared with DXM group. Besides, we found that dietary betaine addition significantly down-regulated cell adhesion molecules, glycerolipid metabolism and glycolysis gluconeogenesis pathways. In addition, a total of 44 and 94 differential metabolites were identified respectively from Con vs. DXM and DXM vs BT. More importantly, dietary betaine addition significantly increased the levels of pantothenic acid, gamma-Aminobutyric acid, equol and choline, all of which were related to antioxidant and anti-inflammatory properties. Furthermore, gut microbiota analysis indicated that the Chao and Observed_species indexes were remarkably higher in BT group (P

ABSTRACT: The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to investigate the effect of butyric acid on the proliferation and differentiation of the immortalized chicken preadipocyte 2 (ICP2). ICP2 were treated respectively with 12mM butyric acid for 48h in proliferation trial and 4mM butyric acid plus 200 μM oleic acid for 3 d in differentiation trial. For the proliferation trial, RNA-seq analysis revealed that 2039 genes were significantly up-regulated and 780 genes were significantly down-regulated with 12 mM butyric acid after 48 h treatment. Concurrently, Cell cycle, DNA replication and p53 signaling pathways were down-regulated in Butyric acid group. More importantly, 12 mM butyric acid restrained the expression of cell proliferation genes such as PCNA, CDK1 and CDK2 in Butyric acid group (P < 0.05), and the protein expression levels of PCNA and CDK1 were also significantly decreased (P < 0.05). The Oil red staining revealed a fewer presence of red fat droplets in ICP2 following treatment with 4 mM butyric acid, accompanied by decreased levels of total cholesterol (TC) and triglycerides (TG). RNA-seq analysis shown that the number of up and down-regulated genes were 2095 and 1042 respectively in OAB group (oleic acid+butyric acid) when compared with OA group (oleic acid). Meanwhile the AMPK signaling pathway, FOXO signaling pathway and focal adhesion were significantly enriched in OAB group. Additionally, 4 mM butyric acid inhibited the expression of lipid differentiation genes including FABP4, C/EBPα, PPARγ and LPL in OAB group (P < 0.05), as well as lipogenesis proteins such as FABP4, C/EBP-α and PPARγ (P < 0.05). In conclusion, 12 mM butyric acid effectively inhibited the proliferation of ICP2 by slowing down cell cycle progression, while 4 mM butyric acid alleviated lipid deposition by reducing the production of lipid droplets through inhibiting the expression of lipid differentiation marker genes and proteins.

Abstract Background This study investigated whether the Combat compensation method can remove the variability of radiomic features extracted from different scanners, while also examining its impact on the subsequent predictive performance of machine learning models. Materials and methods 135 CT images of Credence Cartridge Radiomic phantoms were collected and screened from three scanners manufactured by Siemens, Philips, and GE. 100 radiomic features were extracted and 20 radiomic features were screened according to the Lasso regression method. The radiomic features extracted from the rubber and resin-filled regions in the cartridges were labeled into different categories for evaluating the performance of the machine learning model. Radiomics features were divided into three groups based on the different scanner manufacturers. The radiomic features were randomly divided into training and test sets with a ratio of 8:2. Five machine learning models (lasso, logistic regression, random forest, support vector machine, neural network) were employed to evaluate the impact of Combat on radiomic features. The variability among radiomic features were assessed using analysis of variance (ANOVA) and principal component analysis (PCA). Accuracy, precision, recall, and area under the receiver curve (AUC) were used as evaluation metrics for model classification. Results The principal component and ANOVA analysis results show that the variability of different scanner manufacturers in radiomic features was removed (P˃0.05). After harmonization with the Combat algorithm, the distributions of radiomic features were aligned in terms of location and scale. The performance of machine learning models for classification improved, with the Random Forest model showing the most significant enhancement. The AUC value increased from 0.88 to 0.92. Conclusions The Combat algorithm has reduced variability in radiomic features from different scanners. In the phantom CT dataset, it appears that the machine learning model’s classification performance may have improved after Combat harmonization. However, further investigation and validation are required to fully comprehend Combat’s impact on radiomic features in medical imaging.

Abstract PTENα/β, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the first crystal structure of PTENα-NTE in complex with WDR5, which reveals that PTENα utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENα/β to specifically bind to the WIN site of WDR5. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as a way of therapeutic intervention of the PTENα/β associated cancers. These findings not only shed light on the important role of the PTENα/β-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway.

Abstract Mechanical overloading can promote cartilage senescence and osteoarthritis (OA) development, but its impact on synovial macrophages and the interaction between macrophages and chondrocytes remain unknown. Here, we found that macrophages exhibited M1 polarization under mechanical overloading and secreted ectosomes that induced cartilage degradation and senescence. By performing miRNA sequencing on ectosomes, we identified highly expressed miR-350-3p as a key factor mediating the homeostatic imbalance of chondrocytes caused by M1-polarized macrophages, this result being confirmed by altering the miR-350-3p level in chondrocytes with mimics and inhibitor. In experimental OA mice, miR-350-3p was increased in synovium and cartilage, while intra-articular injection of antagomir-350-3p inhibited the increase of miR-350-3p and alleviated cartilage degeneration and senescence. Further studies showed that macrophage-derived ectosomal miR-350-3p promoted OA progression by inhibiting nuclear receptor binding SET domain protein 1(NSD1) in chondrocytes and regulating histone H3 lysine 36(H3K36) methylation. This study demonstrated that the targeting of macrophage-derived ectosomal miRNAs was a potential therapeutic method for mechanical overload-induced OA.

Abstract Background Left atrial myxoma during pregnancy is rare. We present three cases in order to aid in the management. Case Presentation Three cases of left atrial myxoma during pregnancy were presented in this article. Three patients all received multidisciplinary team work and acquired good outcomes. The case 1 had no symptoms and delivered before traditional cardiac surgery. The case 2 and case 3 undergone totally endoscopic minimally invasive cardiac surgery during pregnancy. The case 3 maintained pregnancy to term and gave birth to a healthy baby via vaginal delivery. No relapse of the tumor was observed. Conclusions The management of left atrial myxoma during pregnancy ought to be individualized and combined with the gestational age. If the diagnosis was made in the first two trimesters of pregnancy, totally endoscopic minimally invasive cardiac surgery during pregnancy would be an optimal choice. The patients can benefit from the multidisciplinary team work.

The tea plant (Camellia sinensis (L.) O. Kuntze) is an important woody economic crop and often attacked by various insect pests such as tea aphids (Toxoptera aurantii Boyer de Fonscolombe). To reveal tea plant responses to tea aphid infestation, tea aphid-resistant cultivar ‘Taicha13’ and -susceptible one ‘Jingfeng’ were first screened, and then widely targeted metabolomics profiling, biochemical parameter and RT-qPCR analyses were performed in three samples, TCN (tea aphid non-infested ‘Taicha13’), JFN (tea aphid non-infested ‘Jingfeng’) and JFA (tea aphid-infested ‘Jingfeng’). The results showed amnio acid (plus proline) and protein content, and amnio acid: sucrose ratio were significantly less abundant in TCN relative to JFN, suggesting TCN is low nutritional quality for tea aphids. Metabolite profiling revealed that flavonoids and JA-isoleucine (JA-Ile) were more enriched in TCN and JFA compared to JFN, proposing effective roles of flavonoids and JA-Ile in tea plant defense against tea aphid infestation. RT-qPCR results demonstrated that five JA biosynthesis genes (CsLOX2, CsLOX3, CsOPR, CsAOC and CsJAR) in exception of CsAOS, and six flavonoid biosynthesis genes (CsPAL, CsC4H, CsCHS1, CsCHS2, CsFL and CsDFR) shared similarly higher abundance in TCN than in JFN, and exhibited elevated expression levels in JFA relative to JFN, further suggesting flavonoids and JA confer tea plant resistance against tea aphid feeding. Overall, our findings uncovered that tea aphid-infestation activated defensive responses and highlighted involvement of nutritional quality, flavonoids and JA-Ile in tea plant resistance against tea aphid infestation.

ABSTRACT: The late embryonic development of the liver, a major metabolic organ, remains poorly characterized at single cell resolution. Here, we used single-nucleus RNA-sequencing (snRNA-seq) to characterize the chicken liver cells at 2 embryonic development time points (E14 and D1). We uncovered 8 cell types including hepatocytes, endothelial cells, hepatic stellate cells, erythrocytes, cholangiocytes, kupffer cells, mesothelial cells, and lymphocytes. And we discovered significant differences in the abundance of different cell types between E14 and D1. Moreover, we characterized the heterogeneity of hepatocytes, endothelial cells, and mesenchymal cells based on the gene regulatory networks of each clusters. Trajectory analyses revealed 128 genes associated with hepatocyte development and function, including apolipoprotein genes involved hepatic lipid metabolism and NADH dehydrogenase subunits involved hepatic oxidative phosphorylation. Furthermore, we identified the differentially expressed genes (DEGs) between E14 and D1 at the cellular levels, which contribute to changes in liver development and function. These DEGs were significantly enriched in PPAR signaling pathways and lipid metabolism related pathways. Our results presented the single-cell mapping of chick embryonic liver at late stages of development and demonstrated the metabolic changes across the 2 age stages at the cellular level, which can help to further study the molecular development mechanism of embryonic liver.

ABSTRACT: Increased consumption of folic acid is prevalent due to its beneficial effects, but growing evidence emphasizes the side effects pointing to excessive dietary folate intake. The effects of excessive paternal folic acid consumption on offspring and its transgenerational inheritance mechanism have not been elucidated. We hypothesize that excessive folic acid consumption will alter sperm DNA N6-methyladenine (6mA) and 5-methylcytosine (5mC) methylation and heritably influence offspring metabolic homeostasis. Here, we fed roosters either folic acid-control or folic acid-excess diet throughout life. Paternal chronic folic acid excessive supplementation increased hepatic lipogenesis and lipid accumulation but reduced lipolysis both in the roosters and their offspring, which was further confirmed to be induced by one-carbon metabolism inhibition and gene expression alteration associated with the Peroxisome proliferator-activated receptor pathway. Based on the spermatozoal genome-wide DNA methylome identified by Nanopore sequencing, multi-omics association analysis of spermatozoal and hepatic DNA methylome, transcriptome, and metabolome suggested that differential spermatozoal DNA 6mA and 5mC methylation could be involved in regulating lipid metabolism-related gene expression in offspring chickens. This model suggests that sperm DNA N6-methyladenine and 5-methylcytosine methylation were involved in epigenetic transmission and that paternal dietary excess folic acid leads to hepatic lipid accumulation in offspring.

BackgroundPrematurity presents a significant life crisis for families, often exceeding their expectations. Fathers of premature infants face the burden of multiple caregiving roles and undergo psychological changes. When confronted with such crises, individuals often engage in self-evaluation and may experience positive transformations. This study aims to employ a qualitative research methodology to explore the experiences of fathers of preterm infants.Materials and methodsA phenomenological approach design will be utilized, drawing upon semi-structured in-depth interviews informed by existing literature. Thematic analysis will be employed, adhering to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. In-depth individual interviews, lasting 40-60 minutes, will be conducted with fathers of preterm infants to understand their experiences. The thematic analysis process will facilitate a comprehensive understanding of the factors contributing to post-traumatic growth among these fathers. This methodology provides a structured approach to investigating the experiences and influences on post-traumatic growth in fathers of preterm infants.ResultsThis study will highlight changes in post-traumatic growth among fathers of preterm infants.DiscussionResearch on the post-traumatic growth (PTG) of fathers of preterm infants is crucial to understanding the unique challenges and psychological transformations they experience. This study aims to explore the factors contributing to PTG in these fathers and how cultural contexts in China influence this process. By elucidating these aspects, the findings can inform targeted interventions and support systems tailored to the needs of fathers of preterm infants. The results may also contribute to developing guidelines and policies to promote psychological well-being and resilience among this population in the healthcare system.Ethics and disseminationThis study adheres to the International Ethical Guidelines for Biomedical Research and the Declaration of Helsinki. Approval has been obtained from the People’s Hospital of Deyang Human Research Ethics Committee (No: 2019-04-150-K01). The research follows the principles of open science, and the findings will be published while ensuring participants’ confidentiality.

Drip irrigation and the application of controlled-release fertilizers are two effective and important technical measures to conserve water and fertilizer resources and promote the growth and development of maize. However, the underlying physiological mechanism of how drip irrigation combined with controlled release potassium chloride affects maize production and soil properties remains unknown. In different soil water conditions, pot experiments were conducted during the summer maize growing season in 2022 and 2023 to measure maize grain yield, irrigation water productivity, apparent recovery efficiency of potassium, plant physiological characteristics, and soil enzyme activities under the coupling of two irrigation methods (flood irrigation and drip irrigation) and three potassium fertilizer types (potassium chloride (KCl), controlled release potassium chloride (CRK), and 70 % CRK mixed with 30 % KCl). The results revealed that drip irrigation had 6.5–8.1 % and 6.7–9.4 % higher average soil volumetric water content and 3.8–8.1 % and 4.5–13.0 % higher irrigation water productivity than flood irrigation in the two maize growth seasons, respectively. Under the drought conditions, the treatments of 70 % CRK-30 % KCl application led to a significant increase in maize yield by 9.5–10.7 % and 12.2–16.8 % and apparent recovery efficiency of potassium by 8.3–14.2 % and 10.7–10.8 % compared to CRK application treatments in 2022 and 2023, respectively. Compared with the other treatments, the treatment of drip irrigation coupled with 70 % CRK-30 % KCl application under drought conditions (DIDMK) resulted in 4.5–28.7 % and 1.1–31.9 % higher grain yield, 8.2–64.4 % and 8.6–66.8 % higher irrigation water productivity, and 5.9–28.0 % and 6.7–18.9 % higher apparent recovery efficiency of potassium in 2022 and 2023, respectively. Meanwhile, the leaf net photosynthetic rate, rubisco, catalase, peroxidase, and soil enzyme activities of DIDMK treatment were also maintained at a high level. Our results indicated that drip irrigation coupled with 70 % CRK-30 % KCl application were the optimal water and potassium supply modes for maize production. This study can provide useful information regarding summer maize sustainable production and provide theoretical and technical support for summer maize irrigation and potassium fertilizer application technologies in water-scarce regions of China and other similar regions around the world.

Pneumococcal disease is caused by Streptococcus pneumoniae, including pneumonia, meningitis and sepsis. Capsular polysaccharides (CPSs) have been shown as effective antigens to stimulate protective immunity against pneumococcal disease. A major step in the production of pneumococcal vaccines is to prepare CPSs that meet strict quality standards in immunogenicity and safety. The major impurities come from bacterial proteins, nucleic acids and cell wall polysaccharides. Traditionally, the impurity level of refined CPSs is reduced by optimization of purification process. In this study, we investigated new aeration strategy and advanced sterilization methods by formaldehyde or β-propiolactone (BPL) to increase the amount of soluble polysaccharide in fermentation supernatant and to prevent bacterial lysis during inactivation. Furthermore, we developed a simplified process for the CPS purification, which involves ultrafiltration and diafiltration, followed by acid and alcohol precipitation, and finally diafiltration and lyophilization to obtain pure polysaccharide. The CPSs prepared from formaldehyde and BPL sterilization contained significantly lower level of residual impurities compared to the refined CPSs obtained from traditional deoxycholate sterilization. Finally, we showed that this novel approach of CPS preparation can be scaled up for polysaccharide vaccine production.

Objective: The present investigation aimed to analyze the in vivo study in support with in silico molecular docking mechanism of natural phenolic compounds Syringic acid (SA), Resveratrol (RV), Gallic acid (GA) and combination (COMB) with SA + RV against Isoproterenol (ISO) in myocardial necrotic rats. Methods: The compounds were tested for in vivo and in silico lipid metabolism enzymes HMG-CoA reductase and lipoprotein lipase (LPL) regulatory activities. Rats were orally pretreated with 50 mg/ kg of each compounds SA, RV, GA and COMB (SA 25 mg/ kg + RV 25 mg/ kg) for 30 days. GA has taken as positive control. After the treatment period, ISO (50 mg/ kg) in sub-cutaneous route was administered to the rats for two consecutive days. Then the rats sacrificed and the cardiac tissues were used for enzyme inhibitory analysis. Results: SA, RV, GA and COMB exhibited HMG-CoA reductase enzyme inhibitory activity. Also, the compounds augmented the LPL enzyme activity in the rats administered with ISO. Furthermore, in silico molecular docking reports also supported to the activity of SA, RV, GA and COMB compounds towards the enzymes HMG-CoA reductase and LPL. Conclusion: This report for the first time indicates the potential of phenolic compounds SA, RV, GA and COMB as excellent natural compounds in the therapeutic treatment of lipid metabolism disorders.

The Tibetan Plateau (TP) is the headwater of the Yangtze, Yellow, and the transboundary Yarlung Zangbo, Lancang, and Nujiang Rivers, providing essential and pristine freshwater to around 1.6 billion people in Southeast and South Asia. However, the temperature rise TP has experienced is almost three times that of the global warming rate. The rising temperature has resulted in glacier retreat, snow cover reduction, permafrost layer thawing, and so forth. Here we show, based on the longest observed streamflow data available for the region so far, that changing climatic conditions in the TP already had significant impacts on the streamflow in the headwater basins in the area. Our analysis indicated that the annual average temperature in the headwater basins of these five major rivers has been rising on a trend averaging 0.38 °C·decade−1 since 1998, almost triple the rate before 1998, and the change of streamflow has been predominantly impacted by precipitation in these headwater basins. As a result, streamflow in the Yangtze, Yarlung Zangbo, Lancang, and Nujiang River headwater areas is on a decreasing trend with a reduction of flow ranging from 3.0 ×109–5.9 ×109 m3·decade−1 (−9.12% to −16.89% per decade) since 1998. The increased precipitation in the Tangnahai (TNH) and Lanzhou (LZ) Basins contributed to the increase of their streamflows at 8.04% and 14.29% per decade, respectively. Although the increased streamflow in the headwater basins of the Yellow River may ease some of the water resources concerns, the decreasing trend of streamflow in the headwater areas of the southeastern TP region since 1998 could lead to a water crisis in transboundary river basins for billions of people in Southeast and South Asia.

Baseflow plays a crucial role in sustaining the alpine ecosystem during rainless or cold periods. Despite its importance, information on how and why baseflow has changed in the source region of the Yangtze River (SRYR) is sparse. In our study, statistical analysis and the elastic coefficient method were used to identify the dynamic characteristics of baseflow and the underlying causes. The results show that monthly baseflow contributed 62–97% of runoff with a mean value of 75%, and they followed remarkable increasing trends from 1957 to 2020. The contributions of precipitation, temperature, evapotranspiration, and ecological conservation programs (ECPs) on baseflow variations were 86, 53, −15, and −24%, respectively. However, their contributions differed across months. During the warm months of May to September, precipitation played a dominant role, followed by evapotranspiration. In contrast, during other colder months, temperature was dominant; meanwhile, the effect of precipitation was almost absent. Moreover, climatic change had a hysteretic effect on baseflow variation, with a maximum lag time of 10 months. Our results highlighted critical roles of both precipitation and temperature, and indicated that climate change, rather than ECPs, dominated the variation in baseflow in the SRYR. HIGHLIGHTS Monthly baseflow contributed 62–97% of runoff with a mean value of 75%.; Contributions of precipitation, temperature, evapotranspiration, and ecological conservation to the increasing baseflow were 86, 53, −15, and −24%, respectively.; During warm months, precipitation played a dominant role, while during colder months, the impact of temperature was dominant.; Climatic change had a hysteretic effect on baseflow variation.;

Abstract Background Fatty liver disease causes huge economic losses in the poultry industry due to its high occurrence and lethality rate. Three-dimensional (3D) chromatin architecture takes part in disease processing by regulating transcriptional reprogramming. The study is carried out to investigate the alterations of hepatic 3D genome and H3K27ac profiling in early fatty liver (FLS) and reveal their effect on hepatic transcriptional reprogramming in laying hens. Results Results show that FLS model is constructed with obvious phenotypes including hepatic visible lipid deposition as well as higher total triglyceride and cholesterol in serum. A/B compartment switching, topologically associating domain (TAD) and chromatin loop changes are identified by high-throughput/resolution chromosome conformation capture (HiC) technology. Targeted genes of these alternations in hepatic 3D genome organization significantly enrich pathways related to lipid metabolism and hepatic damage. H3K27ac differential peaks and differential expression genes (DEGs) identified through RNA-seq analysis are also enriched in these pathways. Notably, certain DEGs are found to correspond with changes in 3D chromatin structure and H3K27ac binding in their promoters. DNA motif analysis reveals that candidate transcription factors are implicated in regulating transcriptional reprogramming. Furthermore, disturbed folate metabolism is observed, as evidenced by lower folate levels and altered enzyme expression. Conclusion Our findings establish a link between transcriptional reprogramming changes and 3D chromatin structure variations during early FLS formation, which provides candidate transcription factors and folate as targets for FLS prevention or treatment.

Abstract Objective To clarify whether the 3D printing model has auxiliary functions in toto extraction of donor tooth in autotransplantation cases. Methods Two hundred and sixty patients who would have operation of ATT were divided into two groups. In group 1, determination of the tooth extraction in toto was predicted only according to the clinical and imaging examination. In group 2, the prediction was performed according to the clinical and imaging examination as well as the 3D model of donor tooth pre-extraction. A prespctive clinical study was designed on intra-group comparison between the predicted and actual donor teeth situation when extraction in cases of ATT. The consistent rate for the predicted results and the actual results were compared with the two groups. Results A remarkable difference was observed between the predicted results and the actual results of tooth positions and root numbers in group without model (p

In order to meet the needs of consumers for diversified taste and healthy diets, a scientific formula and advanced manufacturing method for a new type of jam with low-sugar and no preservative were developed. By using purslane and purple sweet potato, which are rich in functional factors for human health, as the main raw materials, the formula of purslane and purple sweet potato jam was optimized through single factor experiment and orthogonal test, and the nutritional, physicochemical and sanitary indexes of the final product just produced and stored for a period of time were determined. The results showed that the optimal formula for low-sugar purslane and purple sweet potato jam were as follows: Purslane stem juice and purple sweet potato pulp mass ratio was 5:5, amount of citric acid added was 0.3%, amount of xylitol added was 25%, and amount of thickener addition was 0.4%. Based on this optimized formula, the purslane and purple sweet potato jam produced had purplish-red color, uniform texture, delicate taste, moderate acidity and sweetness, unique aroma of purslane and purple sweet potato, and sensory score of 90.5±0.4 points. The final product had 42.32%±1.43% soluble solid content, 13.41±0.52 g/100 g total sugar content, and pH3.61±0.18, 0.83±0.08 g/100 g crude protein content, 3.77±0.11 mg/100 g VC content, 4.18±0.10 mg/g flavonoids content, 2.05±0.13 mg/g polyphenols content and 37.27±0.84 mg/100 g anthocyanins content, and all the above physicochemical and sanitary indexes met the national standards for jams. The IC50 value of the purslane and purple sweet potato jam on DPPH free radical was 7.071 mg/mL, indicating that it had certain antioxidant activity. After being stored at 25 ℃ and 37 ℃ for 1 month respectively, the sensory score and various nutritional components of the jam decreased to some extent with the total number of bacteria increased, but they still met the national standards for jams. The results of this study could provide reference for the deep processing of purslane and purple sweet potato and the standardized production of purslane-purple sweet potato jam.

In tumor treatment, the deposition of nanoenzymes in normal tissues and cause potential side effects are unavoidable. Here, we designed an intelligent biomimetic nanoenzymes carrier platform (MSCintelligent) that endows the carrier platform with “wisdom” by introducing Affibody-Notch(core)-VP64-GAL4/UAS-HSV-TK artificial signal pathways to mesenchymal stem cells (MSCs). This intelligent nanoenzymes carrier platform is distinguished from the traditional targeting tumor microenvironment or enhancing affinity with tumor, which endue MSCintelligent with tumor signal recognition capacity, so that MSCintelligent can autonomously distinguish tumor from normal tissue cells and feedback edited instructions. In this study, MSCintelligent can convert tumor signals into HSV-TK instructions through artificial signal pathway after recognizing Her2 (+) tumor. Subsequently, the synthesized HSV-TK can rupture MSCintelligent under the mediation of ganciclovir, and release the preloaded Cu/Fe nanocrystal clusters to kill the tumor accurately. Meanwhile, MSCintelligent without recognizing tumors will not initiate the HSV-TK instructions, thus being unresponsive to GCV and blocking the release of nanoenzymes in normal tissues. Consequently, MSCintelligent is the first intelligent biomimetic nanoenzymes carrier platform, which represents a new biomimetic nanoenzymes targeting mode.

Introduction Drivers for remission, relapse and violence-related behaviour among patients with schizophrenia are the most complicated issue.Methods and analysis This study aims to recruit a longitudinal cohort of patients with schizophrenia. Two suburban districts and two urban districts were randomly selected according to health service facilities, population, geographical region and socioeconomic status. Individuals (>18 years old) who received a diagnosis of schizophrenia following the International Classification of Diseases (10th edition) criteria within the past 3 years will be invited as participants. Assessments will be carried out in local community health centres. Data will be used to (1) establish a community-based schizophrenia cohort and biobank, (2) prospectively determine the course of multidimensional functional outcomes of patients with schizophrenia who are receiving community-based mental health treatment, and (3) map the trajectories of patients with schizophrenia and prospectively determine the course of multidimensional outcomes based on the differential impact of potentially modifiable moderators.Ethics and dissemination The study has been reviewed and approved by the Human Research Ethics Committee of Shanghai Mental Health Center (2021-67). Results of the study will be disseminated through peer-reviewed journals. If effective, related educational materials will be released to the public.

In order to develop a new brewing technology of compound fruit wine and analyze its antioxidant activity, the compound fruit wine was prepared from Malus doumeri (Bois) Chevalier and Ziziphus jujube Mill. as main raw material, the medicine-food homologous foods, and fermentation process of it was optimized through single factor experiments and response surface test, as well as its antioxidant capacity in vitro was measured. The results showed that the best fermentation technology parameter were as follows: Malus doumeri (Bois) Chevalier juice and Ziziphus jujube Mill. juice mass ratio was 1:2, with initial sugar content 21°Bx, yeast inoculum 0.3%, fermentation temperature 19 ℃, SO2 addition 55 mg/L, and fermentation time 7 d. On this condition, the compound fruit wine was light yellow with mellow body and no impurities, provided with the unique fragrance of Malus doumeri (Bois) Chevalier and Ziziphus jujube Mill., both refreshing and pleasant. The alcohol content of compound fruit wine was 11.50%vol±0.10%vol, the soluble solid content was 7.80%±0.08%, the sugar content was 3.40±0.13 g/L, the acid content was 7.13±0.03 g/L, the extraction content was 22.40±0.15 g/L, the SO2 content was 0.074±0.006 g/L, the sensory score was 93.80±0.40, and its physicochemical and hygiene indicators reached the national standard of fruit wine. Meanwhile, the maximum scavenging capacity of DPPH· and ABTS+· could reach 85.7% and 88.8%, respectively, and the antioxidant capacity was significantly higher than that of compound juice, but less than that of vitamin C. The compound fruit wine developed by this study has a unique flavor and a good specific antioxidant activity, which would provide a scientific basis for the development and application of Malus doumeri (Bois) Chevalier and Ziziphus jujube Mill.

Abstract The aim of the study is to compare the outcomes between the insemination methods of conventional in vitro fertilization and intracytoplasmic sperm injection in infertile women with thyroid autoimmunity and non-male factor infertility. This was a retrospective cohort study which included women with thyroid autoimmunity and non-male factor infertility. Reproductive outcomes such as embryo development parameters and clinical outcomes were compared between the two groups. The propensity score matching was applied to balance the general characteristics with significant differences between the two groups. Generalized estimating equations were used to explore the impact of ICSI on the embryo development potential of the inseminated oocytes. Sensitivity analysis using E-values was used to account for unknown confounders. After 1:2 propensity score matching, the general characteristics were all comparable. The good cleavage embryo rate, blastocyst utilization rate, and good blastocyst rate were significantly lower in the intracytoplasmic sperm injection group than those in the conventional in vitro fertilization group. After controlling for the confounding factors, intracytoplasmic sperm injection was significantly negatively associated with development of usable blastocysts and good blastocysts, while showed no impact on fertilized oocytes, usable cleavage embryos and good cleavage embryos. Although limited by the limited sample size, there were comparable clinical and obstetrical outcomes between conventional in vitro fertilization and intracytoplasmic sperm injection groups. Intracytoplasmic sperm injection neither improved the embryo development potential nor increased the clinical pregnancy and live birth rates compared to conventional in vitro fertilization in the studied population. Prospective studies that randomly divide the studied population in two the two groups and compare the reproductive outcomes are warranted.

Abstract Chemotherapy can cause ovarian dysfunction and infertility since the ovary is extremely sensitive to chemotherapeutic drugs. Apart from the indispensable role of the ovary in the overall hormonal milieu, ovarian dysfunction also affects many other organ systems and functions including sexuality, bones, the cardiovascular system, and neurocognitive function. Although conventional hormone replacement therapy can partly relieve the adverse symptoms of premature ovarian insufficiency (POI), the treatment cannot fundamentally prevent deterioration of POI. Therefore, effective treatments to improve chemotherapy-induced POI are urgently needed, especially for patients desiring fertility preservation. Recently, mesenchymal stem cell (MSC)-based therapies have resulted in promising improvements in chemotherapy-induced ovary dysfunction by enhancing the anti-apoptotic capacity of ovarian cells, preventing ovarian follicular atresia, promoting angiogenesis and improving injured ovarian structure and the pregnancy rate. These improvements are mainly attributed to MSC-derived biological factors, functional RNAs, and even mitochondria, which are directly secreted or indirectly translocated with extracellular vesicles (microvesicles and exosomes) to repair ovarian dysfunction. Additionally, as a novel source of MSCs, menstrual blood-derived endometrial stem cells (MenSCs) have exhibited promising therapeutic effects in various diseases due to their comprehensive advantages, such as periodic and non-invasive sample collection, abundant sources, regular donation and autologous transplantation. Therefore, this review summarizes the efficacy of MSCs transplantation in improving chemotherapy-induced POI and analyzes the underlying mechanism, and further discusses the benefit and existing challenges in promoting the clinical application of MenSCs in chemotherapy-induced POI.

In order to accurately evaluate the aroma quality of raw Pu'er tea in Lincang City, the aroma components of 16 raw Pu'er teas were systematically analyzed and comprehensively evaluated by multivariate statistical analysis. A total of 48 aroma components were detected, with 11 aroma components were more than 2.00% content. Among them, linalool was the most abundant component and the content was 24.68%. For the aroma types, the alcohols were accounted for the largest proportion with a mean of 46.55%, followed by aldehydes with a mean of 26.81%, while ketones, esters and other components were responsible for little proportion. Multivariate statistical analysis showed that the raw Pu'er teas obtained form in southern region were clearly distinguished from those in northern region. The concentration of alcohols and esters was significantly higher in southern region than those in northern region, whereas aldehyde, ketones and other components were remarkably lower. Altitude may be an important reason for the difference of aroma components of Pu'er raw tea in the south and north regions. Furthermore, 23 aroma components were identified based on variable importance in projection (VIP) score>1, which might be responsible for the discrimination of raw Pu'er teas in southern and northern region. Linalool, isoflolone, ketones, alcohols, aldehydes, β-cyclocitral, α-cyclocitral, 2,2,6-trimethyl-cyclohexanone, nerol and β-ionone play siginificant role in the differentiation of raw Pu'er tea harvested from different regions. This study would provide some theoretical basis for accurately understanding the aroma quality of Lincang Pu'er raw tea, and also provide ideas and methods for the study on the quality evaluation and origin determination of Lincang Pu'er raw tea.

Intestinal microbiota, which contains bacteria, archaea, fungi, protists, and viruses including bacteriophages, is symbiotic and evolves together with humans. The balanced intestinal microbiota plays indispensable roles in maintaining and regulating host metabolism and health. Dysbiosis has been associated with not only intestinal diseases but other diseases such as neurology disorders and cancers. Faecal microbiota transplantation (FMT) or faecal virome or bacteriophage transplantation (FVT or FBT), transfers faecal bacteria or viruses, with a focus on bacteriophage, from one healthy individual to another individual (normally unhealthy condition), and aims to restore the balanced gut microbiota and assist in subduing diseases. In this review, we summarized the applications of FMT and FVT in clinical settings, discussed the advantages and challenges of FMT and FVT currently and proposed several considerations prospectively. We further provided our understanding of why FMT and FVT have their limitations and raised the possible future development strategy of FMT and FVT.

Infrared detection is more and more widely used in the field of non-destructive testing of buildings to detect whether there is a defect on the surface of the building facade. In many cases, it is necessary to obtain more information about the defect, such as the depth of the defect, so as to evaluate the severity of the defect and repair. The theoretical formula of hollowing defect depths was derived in this paper based on the heat transfer characteristics of the intact and defective areas on the building facade, and the influence of defects with different shapes, sizes and cavity thicknesses on the temperature distribution of the building facade was summarized quantitatively. Firstly, the theoretical formula of the hollowing defect depth and the factors affecting the distribution of the temperature gradient on the building facade excited by external thermal source was derived and restricted by the boundary condition. Secondly, three sets of physical building facade models that contained hollowing defects with different shapes, sizes and cavity thicknesses were fabricated and designed, and the experimental platform was built. The infrared thermograms and the temperature characteristic curves of the hollowing defect in a natural light environment were obtained and fitted according to the temperature differences of the defective area, while analyzing the influence of the size, shape and cavity thicknesses on surface temperature distribution. Finally, the theoretical formula of the defect depth that is applicable to the building façade was validated through the experimental simulation of 14 forms of hollowing. The experimental results demonstrated that the revised formula of defect depth is consistent with the actual defect depth, and the three-dimensional positioning of the hollowing defect of the building facade can be effectively carried out and combined with the defect size taken from the obtained infrared thermal image.

Abstract Background The gastrointestinal tract contains a massive microbiota, and targeting the gut could be a potential intervention for sepsis. However, the interaction between sepsis and the intestinal microbiota is defined as an “incompletely understood bidirectional relationship”. Methods This retrospective observational cohort study investigated the fecal microbiota of sepsis patients admitted to the Department of Critical Care Medicine of the Central Hospital of Wuhan, China, from May 2019 to January 2020. 14 septic patients were divided into the non-severe group and the severe group according to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Herein, fecal samples were serially collected on admission, the third, fourth, and fifth days, and ICU discharge. The fecal microbiota was analyzed by 16S rRNA gene sequencing and its correlation with clinical parameters was evaluated. Results Bacteroidetes, Firmicutes, and Proteobacteria were dominant phyla at ICU admission, and fecal biodiversity was not significantly different between the non-severe group (APACHE II 15). However, the diversity of the gut microbiota was significantly lower at ICU discharge than that at ICU admission with the extension of treatment time. Further significant difference flora analysis (LEfSe) showed that the genera Veillonella and Ruminococcus were the most discriminant biomarkers at ICU admission in non-severe and severe patients, respectively, while Enterococcus was the most discriminant biomarker at ICU discharge in all septic patients. Of note, liver function tests, including ALT, AST, TBIL, and DBIL correlated with the prevalence of various bacterial genera. Conclusions The diversity of the gut microbiota in patients with sepsis decreases dramatically during ICU stay, and there are distinct dynamic changes in gut microbiota among patients with different severity in sepsis.

Abstract Establishing a valid in vitro model to represent tumor heterogeneity and biology is critical but challenging. Tumor organoids are self‐assembled three‐dimensional cell clusters which are of great significance for recapitulating the histopathological, genetic, and phenotypic characteristics of primary tissues. The organoid has emerged as an attractive in vitro platform for tumor biology research and high‐throughput drug screening in cancer medicine. Organoids offer unique advantages over cell lines and patient‐derived xenograft models, but there are no standardized methods to guide the culture of organoids, leading to confusion in organoid studies that may affect accurate judgments of tumor biology. This review summarizes the shortcomings of current organoid culture methods, presents the latest research findings on organoid standardization, and proposes an outlook for organoid modeling.

Abstract Background Radiomic diagnosis models generally consider only a single dimension of information, leading to limitations in their diagnostic accuracy and reliability. The integration of multiple dimensions of information into the deep learning model have the potential to improve its diagnostic capabilities. The purpose of study was to evaluate the performance of deep learning model in distinguishing tuberculosis (TB) nodules and lung cancer (LC) based on deep learning features, radiomic features, and clinical information. Methods Positron emission tomography (PET) and computed tomography (CT) image data from 97 patients with LC and 77 patients with TB nodules were collected. One hundred radiomic features were extracted from both PET and CT imaging using the pyradiomics platform, and 2048 deep learning features were obtained through a residual neural network approach. Four models included traditional machine learning model with radiomic features as input (traditional radiomics), a deep learning model with separate input of image features (deep convolutional neural networks [DCNN]), a deep learning model with two inputs of radiomic features and deep learning features (radiomics‐DCNN) and a deep learning model with inputs of radiomic features and deep learning features and clinical information (integrated model). The models were evaluated using area under the curve (AUC), sensitivity, accuracy, specificity, and F1‐score metrics. Results The results of the classification of TB nodules and LC showed that the integrated model achieved an AUC of 0.84 (0.82–0.88), sensitivity of 0.85 (0.80–0.88), and specificity of 0.84 (0.83–0.87), performing better than the other models. Conclusion The integrated model was found to be the best classification model in the diagnosis of TB nodules and solid LC.

Abstract Aim Nurse‐led transitional care programmes (TCPs) have been shown to facilitate patient recovery in several illness settings, but its role among patients discharged with T‐tubes remains uncertain. The aim of the study was to investigate the effects of a nurse‐led TCP among patients discharged with T‐tubes. Design This retrospective cohort study was conducted at a tertiary medical centre. Methods From January 2018 to December 2020, a total of 706 patients discharged with T‐tubes after biliary surgery were included in the study. Patients were divided into a TCP group (n = 255) and a control group (n = 451) based on whether they participated in a TCP. The baseline characteristics, discharge readiness, self‐care ability, transitional care quality and quality of life (QoL) were compared between the groups. Results Self‐care ability and transitional care quality were significantly higher in the TCP group. Patients in the TCP group also exhibited improved QoL and satisfaction. The results suggest that the incorporation of a nurse‐led TCP among patients discharged with T‐tubes after biliary surgery is feasible and effective. No Patient or Public Contribution.

AbstractThe Saihanba Mechanical Forest is an artificial national forest park with a forest-steppe landscape. The flora and fauna have been extensively studied, but a comprehensive understanding of the bacterial community composition and structure of the natural rainwater lakes present in the area has rarely been reported. In this study, the structure and functional characteristics of bacterial communities in lake sediments and water samples in the Saihanba artificial forest were investigated using 16s rRNA high-throughput sequencing. Microbial diversity analyses revealed that Proteobacteria, Acidobacteria, Bacteroidota and Verrucomicrobiota microbiota dominated. The abundance of Proteobacteria and Actinobacteriota was significantly higher (p

ABSTRACT: Excess abdominal fat reduces carcass yield and feed conversion ratio, thereby resulting in significant economic losses in the poultry industry. Our previous study demonstrated that dietary addition of folic acid reduced fat deposition and changed gut microbiota and short-chain fatty acid. However, whether folic acid regulating abdominal fat deposition was mediated by gut microbiota was unclear. A total of 210 one-day-old broiler chickens were divided into 3 groups including the control (CON), folic acid (FA), and fecal microbiota transplantation (FMT) groups. From 14th day, broiler chickens in CON and FA groups were given perfusion administration with 1 mL diluent daily, while 1 mL fecal microbiota transplantation suspension from FA group prepared before was perfusion in FMT group receiving control diets. The result showed that abdominal fat percentage was significantly lower in FA and FMT groups when compared with CON group (P < 0.05). Morphology analysis revealed that the villus height of jejunum and ileum were significantly higher in FMT group (P < 0.05), and the villus height of jejunum was also significantly higher in FA group (P < 0.05), while the diameter and cross-sectional area (CSA) of adipocytes were significantly decreased in FA and FMT groups when compared with CON group (P < 0.05). Western blot results indicated that the expression levels of FOXO1 and PLIN1 in FMT group were significantly increased (P < 0.05), whereas the expression levels of PPARγ, C/EBPα, and FABP4 were significantly decreased (P < 0.05). Additionally, the Chao1, Observed-species, Shannon and Simpson indexes in FA and FMT groups were significantly higher (P < 0.05), but the microbiota were similar between FMT and FA groups (P < 0.05). LEfSe analysis determined that Lactobacillus, Clostridium and Dehalobacterium were found to be predominant in FA group, while Oscillospira, Shigella, and Streptococcus were the dominant microflora in FMT group. Furthermore, these cecal microbiota were mostly involved in infectious disease, cellular community prokaryotes, cell motility and signal transduction in FA group (P < 0.05), whereas functional capacities involved in signal transduction, cell motility, infectious disease and environment adaptation were enriched significantly of cecal microbiota in FMT group (P < 0.05). In summary, both fecal microbiota transplantation from the broiler chickens of dietary added folic acid and dietary folic acid addition effectively reduced abdominal fat deposition, indicating that the regulatory effect of folic acid on abdominal fat deposition was mediated partly by gut microbiota in broiler chickens.

A totally endoscopic minimally invasive approach is widely used for cardiac valve surgery in normal adults. However, minimally invasive cardiac surgery during pregnancy is rarely reported. In addition to traditional median thoracotomy, totally endoscopic minimally invasive approaches can now be used for pregnant patients. We describe our experience with totally endoscopic cardiac valve surgery (TECVS) during pregnancy, which is safe for both mothers and fetuses.

Abstract Clinical evidence shows that the mechanical stimulation obtained from occlusion could enhance periodontal ligament (PDL) remodeling. Mechano‐growth factor (MGF) is a growth factor produced specifically following mechanical stimulus Here, we aim to investigate the mechanical enhancement potential and mechanism of the MGF in PDL regeneration. In vivo study found that MGF produced from the PDL under occlusion force could strongly enhance PDL remodeling. In vitro experiments and mathematical modeling further confirmed the mechanical enhancement effect of MGF for PDLSC differentiation toward fibroblasts. A mechanochemical coupling effect of MGF mediated the enhancement of mechanical effect, which was modulated by Fyn‐FAK kinases signaling and subsequent MAPK pathway. Finally, enhanced PDL regeneration under the mechanochemical coupling of MGF and occlusal force was verified in vivo. There exists an additive mechanical effect of MGF mediated by Fyn‐FAK crosstalk and subsequent ERK1/2 and p38 phosphorylation, which could be developed as an MGF‐centered adjuvant treatment to optimize PDL remodeling, especially for patients with weakened bite force or destroyed periodontium.

Abstract To investigate whether there is a relationship between TSH levels on the 14th day post embryo transfer (D14 TSH levels) and the reproductive outcomes in euthyroid women who are free from levothyroxine (LT4) treatment and undergo the first in vitro fertilization /intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET) cycles with the homogeneous ovarian stimulation protocols. This was a prospective study including a total of 599 euthyroid women undergoing the first IVF/ICSI ET cycles. Serum samples were collected and frozen on the 14th day post embryo transfer. TSH levels were measured after the confirmation of clinical pregnancy. The patients were divided into three groups (low-normal ≤ 2.5 mIU/L; high-normal 2.5–4.2 mIU/L; and high > 4.2 mIU/L) based on D14 TSH levels. Reproductive outcomes were compared among the three groups. Binary logistic regression analyses and generalized additive mixed models with smoothing splines were used to investigate the relationship between TSH levels and reproductive outcomes. D14 TSH levels were significantly elevated compared to basal TSH levels, and the degree of TSH elevation was significantly higher in pregnant women compared to that in non-pregnant women. The clinical pregnancy and live birth rates increased significantly in the high-normal D14 TSH groups, and doubled in the high D14 TSH groups compared to the low TSH groups. When adjusted by age, basal TSH, AMH, E2, endometrial thickness, type and causes of infertility, and transferred embryos, the dose-dependent relationships between D14 TSH and clinical pregnancy and live birth were observed. Obstetric outcomes in singleton or twins live birth among the different D14 TSH groups were similar. Elevated D14 TSH levels were associated with better clinical pregnancy and live birth rates, and were not associated with worse obstetric outcomes. The mechanisms to explain the phenomenon remained to be studied.

Evaluating the impact of multi-source uncertainties in complex forecasting systems is essential to understanding and improving the systems. Previous studies have paid little attention to the influence of multi-source uncertainties in complex meteorological and hydrological forecasting systems. In this study, we developed a general ensemble framework based on Bayesian model averaging (BMA) for evaluating the impact of multi-source uncertainties in complex forecast systems. Based on this framework, we used eight numerical weather prediction products from the International Grand Global Ensemble (TIGGE) dataset, four hydrological models with different structures, and 1000 sets of parameters to comprehensively account for the input, structure, and parameter uncertainties. The framework’s application to the Chitan Basin in China revealed that the numerical weather prediction input uncertainty in the forecasting system was more significant than the hydrological model uncertainty. The hydrological model structure uncertainty was more prominent than the parameter uncertainty. The accuracy of the numerical weather prediction dominates the accuracy of the forecast of high flows. In addition, the structures and parameters of the hydrological model and their interactions contributed to the main uncertainty of the low flow forecasts. The streamflow was more realistically represented when the three uncertainty sources were considered jointly. By accounting for the significant uncertainty sources in complex forecast systems, the BMA ensemble forecasting produces more realistic and reliable predictions and reduces the influences of other incomplete considerations. The developed multi-source uncertainty assessment framework improves our understanding of the complex meteorological and hydrological forecasting system. Therefore, the framework is promising for improving the accuracy and reliability of complex forecasting systems.

Abstract Chemotherapy was conventionally applied to kill cancer cells, but regrettably, they also induce damage to normal cells with high-proliferative capacity resulting in cardiotoxicity, nephrotoxicity, peripheral nerve toxicity, and ovarian toxicity. Of these, chemotherapy-induced ovarian damages mainly include but are not limited to decreased ovarian reserve, infertility, and ovarian atrophy. Therefore, exploring the underlying mechanism of chemotherapeutic drug-induced ovarian damage will pave the way to develop fertility-protective adjuvants for female patients during conventional cancer treatment. Herein, we firstly confirmed the abnormal gonadal hormone levels in patients who received chemotherapy and further found that conventional chemotherapeutic drugs (cyclophosphamide, CTX; paclitaxel, Tax; doxorubicin, Dox and cisplatin, Cis) treatment significantly decreased both the ovarian volume of mice and the number of primordial and antral follicles and accompanied with the ovarian fibrosis and reduced ovarian reserve in animal models. Subsequently, Tax, Dox, and Cis treatment can induce the apoptosis of ovarian granulosa cells (GCs), likely resulting from excessive reactive oxygen species (ROS) production-induced oxidative damage and impaired cellular anti-oxidative capacity. Thirdly, the following experiments demonstrated that Cis treatment could induce mitochondrial dysfunction through overproducing superoxide in GCs and trigger lipid peroxidation leading to ferroptosis, first reported in chemotherapy-induced ovarian damage. In addition, N-acetylcysteine (NAC) treatment could alleviate the Cis-induced toxicity in GCs by downregulating cellular ROS levels and enhancing the anti-oxidative capacity (promoting the expression of glutathione peroxidase, GPX4; nuclear factor erythroid 2-related factor 2, Nrf2 and heme oxygenase-1, HO-1). Our study confirmed the chemotherapy-induced chaotic hormonal state and ovarian damage in preclinical and clinical examination and indicated that chemotherapeutic drugs initiated ferroptosis in ovarian cells through excessive ROS-induced lipid peroxidation and mitochondrial dysfunction, leading to ovarian cell death. Consequently, developing fertility protectants from the chemotherapy-induced oxidative stress and ferroptosis perspective will ameliorate ovarian damage and further improve the life quality of cancer patients.

Background: Long COVID, characterized by a persistent symptom spectrum following SARS-CoV-2 infection, poses significant health, social, and economic challenges. This review aims to consolidate knowledge on its epidemiology, clinical features, and underlying mechanisms to guide global responses; Methods: We conducted a literature review, analyzing peer-reviewed articles and reports to gather comprehensive data on long COVID’s epidemiology, symptomatology, and management approaches; Results: Our analysis revealed a wide array of long COVID symptoms and risk factors, with notable demographic variability. The current understanding of its pathophysiology suggests a multifactorial origin yet remains partially understood. Emerging diagnostic criteria and potential therapeutic strategies were identified, highlighting advancements in long COVID management; Conclusions: This review highlights the multifaceted nature of long COVID, revealing a broad spectrum of symptoms, diverse risk factors, and the complex interplay of physiological mechanisms underpinning the condition. Long COVID symptoms and disorders will continue to weigh on healthcare systems in years to come. Addressing long COVID requires a holistic management strategy that integrates clinical care, social support, and policy initiatives. The findings underscore the need for increased international cooperation in research and health planning to address the complex challenges of long COVID. There is a call for continued refinement of diagnostic and treatment modalities, emphasizing a multidisciplinary approach to manage the ongoing and evolving impacts of the condition.