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Abstract Background At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China. Methods A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed. One neonatologist per hospital was randomly selected. The primary outcome was the key care of RDS management. Results Among the 394 participating hospitals, 88·3% were birthing centres. The number of doctors and nurses per bed were 0·27 and 0·72, respectively. Antenatal corticosteroids (any dose) were administered to 90% of the women at risk of preterm birth at 32 weeks. T-piece resuscitators were available in 77·8% of delivery rooms (DRs) (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p

Abstract Toll-like receptor (TLR) 4 contributes to be the induction of neuroinflammation by recognizing pathology-associated ligands and activating microglia. In addition, numerous physiological signaling factors act as agonists or antagonists of TLR4 expressed by non-immune cells. Recently, TLR4 was found to be highly expressed in cerebellar Purkinje neurons (PNs) and involved in the maintenance of motor coordination through non-immune pathways, but the precise mechanisms remain unclear. Here we report that mice with PN specific TLR4 deletion (TLR4PKO mice) exhibited motor impairments consistent with cerebellar ataxia, reduced PN dendritic arborization and spine density, fewer parallel fiber (PF) – PN and climbing fiber (CF) – PN synapses, reduced BK channel expression, and impaired BK-mediated after-hyperpolarization, collectively leading to abnormal PN firing. Moreover, the impaired PN firing in TLR4PKO mice could be rescued with BK channel opener. The PNs of TLR4PKO mice also exhibited abnormal mitochondrial structure, disrupted mitochondrial endoplasmic reticulum tethering, and reduced cytosolic calcium, changes that may underly abnormal PN firing and ultimately drive ataxia. These results identify a previously unknown role for TLR4 in regulating PN firing and maintaining cerebellar function.

Abstract The widespread use of polymers has made our lives increasingly convenient by offering a more convenient and dependable material. However, the challenge of efficiently decomposing these materials has resulted in a surge of polymer waste, posing environment and health risk. Currently, landfill and incineration treatment approaches have notable shortcomings, prompting a shift towards more eco-friendly and sustainable biodegradation approaches. Biodegradation primarily relies on microorganisms, with research focusing on both solitary bacterial strain and multi-strain communities for polymer biodegradation. Furthermore, directed evolution and rational design of enzyme have significantly contributed to the polymer biodegradation process. However, previous reviews often undervaluing the role of multi-strain communities. In this review, we assess the current state of these three significant fields of research, provide practical solutions to issues with polymer biodegradation, and outline potential future directions for the subject. Ultimately, biodegradation, whether facilitated by single bacteria, multi-strain communities, or engineered enzymes, now represents the most effective method for managing waste polymers. Graphical Abstract

Abstract Background 2-Phenylethanol (2-PE) is one of the most widely used spices. Recently, 2-PE has also been considered a potential aviation fuel booster. However, the lack of scientific understanding of the 2-PE biosynthetic pathway and the cellular response to 2-PE cytotoxicity are the most important obstacles to the efficient biosynthesis of 2-PE. Results Here, metabolic engineering and tolerance engineering strategies were used to improve the production of 2-PE in Komagataella phaffii. First, the endogenous genes encoding the amino acid permease GAP1, aminotransferase AAT2, phenylpyruvate decarboxylase KDC2, and aldehyde dehydrogenase ALD4 involved in the Ehrlich pathway and the 2-PE stress response gene NIT1 in K. phaffii were screened and characterized via comparative transcriptome analysis. Subsequently, metabolic engineering was employed to gradually reconstruct the 2-PE biosynthetic pathway, and the engineered strain S43 was obtained, which produced 2.98 g/L 2-PE in shake flask. Furthermore, transcriptional profiling analyses were utilized to screen for novel potential tolerance elements. Our results demonstrated that cells with knockout of the PDR12 and C4R2I5 genes exhibited a significant increase in 2-PE tolerance. To confirm the practical applications of these results, deletion of the PDR12 and C4R2I5 genes in the hyper 2-PE producing strain S43 dramatically increased the production of 2-PE by 18.12%, and the production was 3.54 g/L. Conclusion This is the highest production of 2-PE produced by K. phaffii via l-phenylalanine conversion. These identified K. phaffii endogenous elements are highly conserved in other yeast species, suggesting that manipulation of these homologues might be a useful strategy for improving aromatic alcohol production. These results also enrich the understanding of aromatic compound biosynthetic pathways and 2-PE tolerance, and provide new elements and strategies for the synthesis of aromatic compounds by microbial cell factories.

Abstract China’s higher education system is shifting from quantitative expansion to connotative development to advance its quality. Since 2015, Chinese governments have been implementing a strategic policy for higher education called “double first-class”, which aims to promote a number of Chinese top universities to construct world-class universities or to establish world-class disciplines. “Double first-class” universities have received a large amount of educational resources through this policy. Taking advantage of resources efficiently is an important element in promoting the development of higher quality higher education. However, research on resource allocation in China’s “double first-class” universities is incomplete. Current research has not clarified the level of resource allocation efficiency or the factors affecting China’s “double first-class” universities. With the help of the superefficient data envelopment analysis (DEA)-Malmquist–Tobit model, this study actively explores the current status of the resource allocation efficiency of China’s “double first-class” universities to fill this gap in the field. Specifically, the development level and change trend of the resource allocation efficiency of 13 “double first-class” universities in China from 2015 to 2019 were measured with the help of the superefficient DEA-Malmquist model. The internal and external factors affecting the resource allocation efficiency of “double first-class” universities are also analysed with the help of the Tobit model. The overall level of resource allocation efficiency of “double first-class” universities is high, but the internal variability is large. From the perspective of efficiency decomposition, it is found that both technical efficiency change (EFch) and technical progress efficiency (TEch) play important roles in improving the total factor productivity (TFP) of resource allocation. Compared with TEch, EFch plays a more significant pulling role. This study confirms that the factors affecting resource allocation efficiency are complex. Among them, the regional economic environment, faculty title structure, and degree of international exchange have significant roles in promoting the resource allocation efficiency of “double first-class” universities, but local financial support and the time of policy implementation have certain negative effects.

Abstract Background A knowledge of gouty arthritis could help in the primary prevention of the disease development and lead to an early diagnosis if it occurs. This study investigated the knowledge, attitudes, and practices (KAP) toward gouty arthritis in the general population > 30 years old. Methods This web-based cross-sectional study was conducted among the general population > 30 years old between January and March 2023 in Chengdu, Sichuan. The questionnaire was designed by the investigators based on the available guidelines (Cronbach’s α = 0.846). A score above 70% indicated good knowledge, a positive attitude, and proactive practice. Multivariable and structural equation modeling (SEM) analyses were performed to analyze the factors influencing KAP. Results A total of 537 questionnaires were included. The knowledge, attitudes, and practices scores were 13.12 ± 6.41, 25.28 ± 3.97, and 45.25 ± 5.77, respectively. Female (OR = 0.47, 95%CI: 0.31–0.71, P 10,000 yuan (OR = 2.07, 95%CI: 1.12–3.81, P = 0.020) were independently associated with attitudes. Attitude (OR = 1.31, 95%CI: 1.23–1.40, P

Abstract Background Globally, HCC presents a significant health burden, characterized by high incidence and mortality rates. Epidemiological studies have increasingly suggested a link between dietary patterns and the risk of hepatocellular carcinoma (HCC), yet consensus on this relationship remains elusive. Objective This study aims to synthesize existing literature and provide a comprehensive analysis of the association between dietary patterns and HCC risk through meta-analytical methods. Methods A systematic search of PubMed, Embase, and the Cochrane Library databases was conducted to identify studies examining common dietary patterns in relation to HCC, published up to August 2023. Study quality was rigorously evaluated using the Newcastle–Ottawa Scale. We employed a random effects model to synthesize effect sizes, calculating hazard ratios (HRs) and 95% confidence intervals (CIs). Results We identified 13 papers, of these 10 investigating a priori dietary patterns(index-based dietary patterns) and 3 focusing on a posterior dietary patterns (data-driven dietary patterns). Analysis of a priori dietary patterns revealed that higher scores in the Healthy Eating Index (HEI) & alternative HEI (HR = 0.67, 95% CI: 0.54–0.85), Dietary Approaches to Stop Hypertension (DASH) (HR = 0.77, 95% CI: 0.66–0.91), and the Mediterranean diet (HR = 0.65, 95% CI: 0.56–0.75) were associated with a reduced risk of HCC. Conversely, pro-inflammatory dietary patterns were linked with an increased risk (HR = 2.21, 95% CI: 1.58–3.09). In a posterior dietary patterns, a vegetable-based diet was negatively correlated with HCC risk (HR = 0.63, 95% CI: 0.49–0.81). Conclusion This meta-analysis underscores a significant association between dietary patterns and the risk of HCC. Adherence to healthy dietary patterns characterized by high in vegetables, whole grains, legumes, nuts, and low in red and processed meats may confer a protective effect against HCC, whereas inflammatory diets appear to elevate risk.

Abstract Free-floating bike sharing (FFBS) attracts increasing research focusing on usage patterns, determining factors, and integrated transportation. However, existing researchers tend to overlook the variation in usage characteristics over various time ranges, particularly the usage pattern at night. This paper is conducted to fill the gap through a series of analysis approaches on FFSB in Beijing. The characteristics of the usage pattern, including time-varying usage and traveling distance distributions, are initially illustrated. Subsequently, the spatial patterns of FFBS are visualized and thoroughly analyzed in different time ranges and origin-destination (O-D) flows. A statistical model evaluating the environmental effects of FFBS trips revealed the source of FFBS usage. In addition to focusing on the nighttime, the usage patterns varying day and night are compared through the analysis. The findings explain the usage pattern variation and the unique pattern at night, providing valuable insight for improving the management of the FFBS system.

Abstract Background Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent–offspring trios and proband only analysis. Methods We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. Results Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. Conclusion CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Fungi have been identified as a prolific source of structurally unique secondary metabolites, many of which display promising biological and pharmacological properties. This review provides an overview of the structures of new natural products derived from fungi and their biological activities along with the research strategies, which focuses on literature published in the representative journals in 2023. In this review, a total of 553 natural products including 219 polyketides, 145 terpenoids, 35 steroids, 106 alkaloids, and 48 peptides are presented. By summarising the latest findings, this review aims to provide a guide and inspire further innovation in the fields of the discovery of fungal natural products and pharmaceutical development.

ABSTRACTThe rising prevalence and detrimental impact of inflammatory diseases have spurred the exploration of novel therapeutic approaches to tackle these conditions. Fuzi, lateral root of Aconitum carmichaelii Debx. has been used as a traditional Chinese medicine (TCM) for the treatment of inflammatory diseases for a long time. This article provides a comprehensive review of the medicinal applications, anti-inflammatory constituents, analytical techniques for detecting anti-inflammatory components, molecular mechanisms, and anti-inflammatory effects of Fuzi and its formulas. The information on Fuzi was collected from a variety of resources including classical works on Chinese herbal medicine, scientific databases (PubMed, Google Scholar, ACS, Web of Science, Science Direct, CNKI), TCMSP, NCBI, PubChem databases and others. About 122 compounds were isolated and identified from Fuzi, with alkaloids constituting the primary constituents that demonstrate potent anti-inflammatory activity. Specifically, among the identified compounds, there was one C-18 type, nineteen C-19 type, four C-20 type diterpenoid alkaloids, one other alkaloid, and 6 non-alkaloid constituents, all of which exhibited noteworthy anti-inflammatory and pain-alleviating properties in both in vivo and in vitro models of inflammation. These effects were mainly attributed to the reduction of pro-inflammatory cytokines, including IL-1, TNF-α, NO, IL-Iβ, and IL-6, as well as the inhibition of MAPK, NF-κB or PI3K/Akt signaling pathways, which effectively suppressed the inflammatory response and alleviated pain. Additionally, the anti-inflammatory effects were also achieved through the regulation of TLR4 expression and its downstream factors, or by modulating the homeostasis of the gut microbiota.

Green synthesis of gold nanoparticles (AuNPs) using Ginkgo biloba leaf aqueous extract was optimized by response surface methodology to yield monodispersed, crystalline nanoparticles of 18 ± 4 nm diameter. Fourier transform infrared spectroscopy confirmed capping by flavonoids, terpenoids and polyphenols providing stability for over 6 months. The biosynthesized AuNPs exhibited promising in vitro dose and time-dependent antiproliferative effects against human nasopharyngeal carcinoma CNE1 cells with IC50 reducing from 65.7 to 39.2 μg/mL over 24–72 hrs. Distinct cytoplasmic damage was observed under microscope. Treatment with 50 μg/mL AuNPs for 48 hrs dramatically upregulated pro-apoptotic Bax, Caspase-3 and p53 by 8.7, 6.5 and 4.3 fold respectively while downregulating anti-apoptotic Bcl-2 by 11.2 fold, indicating apoptosis induction via mitochondrial intrinsic pathway. The green fabricated G. biloba AuNPs displayed preferential toxicity towards carcinoma cells compared to normal fibroblasts, indicating potential for targeted nasopharyngeal cancer therapy.

In the process of coal mining, accidents such as water inrush in mines can not only cause huge economic losses, but also seriously threaten the safety of workers. Hydrogeological parameters play an important role in calculating the amount of water inflow in mines. Therefore, accurately measuring the hydrogeological parameters of aquifers is of great significance for coal mine water prevention and control work. In order to obtain more practical hydrogeological parameters of the thick sandstone aquifer in the Luohe Formation of the mining area roof, based on the pumping test data of the upper and lower sections of the Luohe Formation sandstone aquifer in Xinzhuang Coal Mine, traditional analytical methods such as Theis formula method, Jacob line diagram method, and water level restoration method for unstable flow were used, and combined with the actual site characteristics, the upper and lower sections of the Luohe Formation sandstone aquifer were calculated The permeability coefficients of the lower section are 0.22～0.59 and 0.03～0.35 m/d respectively; The upper section has a hydraulic conductivity coefficient of 128.74-373.67 m2/d, while the lower section has a conductivity coefficient of 5.52-47.07 m2/d; The water storage coefficient of the upper section is 2.22×10−4-6.69×10−3, the lower paragraph is 6.53× 10−5-3.29×10−3. And a numerical model of groundwater flow in the Xinzhuang mining area was established using FEFLOW software to solve the hydrogeological parameters of the Luohe Formation aquifer. The permeability coefficients of the upper and lower sections of the Luohe Formation were obtained to be 0.55 and 0.45m/d, respectively. By comparing and analyzing various methods, it is shown that the hydrogeological parameters obtained through numerical simulation are similar to the results calculated by various analytical methods. On this basis, the mine water inflow was calculated based on the hydrogeological parameters obtained by various methods, and compared with the actual water inflow. The results showed that in the upper section of the aquifer, the hydrogeological parameters calculated using numerical simulation method were closer to the actual water inflow; In the lower section of the Luohe Formation, the hydrogeological parameters calculated using Jacob's line diagram method are closer to the actual water inflow. This further improves the accuracy of hydrogeological parameter calculation, providing a basis for later research on aquifer water abundance, prediction of mine water inflow, and mine water prevention and control work in similar mining areas with thick sandstone aquifers in the Luohe Formation.

Objective(s): Tubal factor infertility (TFI) is common female infertility responsible for a large portion of female factor infertility. This study reveals the effect of the quercetin of Huoxuehuayu Tongluo Decoction with azithromycin on the pregnancy rate and inflammation of TFI female rats.Materials and Methods: Female Sprague Dawley rats were constructed into the TFI model and treated with quercetin, Huoxuehuayu Tongluo Decoction, and combination therapy (quercetin and azithromycin). Pregnancy rate and litter size were measured. Network pharmacology was applied to analyze the interaction between Huoxuehuayu Tongluo Decoction and TFI. The combination of quercetin and IL-6 was analyzed by molecular docking. HE staining and electron microscopy were used to observe the histopathology and ultrastructure of fallopian tube tissues. The TNF-α, IL-1β, IL-6, IL-8, and MPO levels were detected by ELISA. The activation of JAK/STAT, MAPK, and NF-κB p65 pathways was detected by western blot or immunohistochemistry.Results: Quercetin was the main active component of Huoxuehuayu Tongluo Decoction, and could bind to IL-6 in TFI. Target genes were enriched in the IL-17 signaling pathway, JAK-STAT signaling pathway, inflammatory disease, etc. Under the quercetin and azithromycin combination therapy, both rat pregnancy rates and litter sizes increased significantly. quercetin and azithromycin alleviated the symptoms of hydrosalpinx and inflammatory damage in fallopian tube tissues. The phosphorylation of JAK/STAT and MAPK pathways and NF-κB p65 translocation to the nucleus were significantly inhibited by the quercetin and azithromycin therapy.Conclusion: Quercetin and azithromycin combination therapy inhibited inflammation and phosphorylation of JAK/STAT and MAPK pathways to improve TFI inflammation and pregnancy function.

Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.

Abstract Background The therapeutic resistance to ionizing radiation (IR) and angiogenesis inhibitors is a great challenge for clinicians in the treatment of glioblastoma, which is associated with Hepatocyte growth factor (HGF)/MET, VEGF/VEGFR signaling pathway, and the crosstalk between them. In this study, we developed a novel recombinant fusion protein, rE27HGFK1, via HGFK1 tandem with 27 N-terminal residues of Endostatin (E27) and produced a polymeric nanoparticle formed by the co-polymer of PEGylated H1 cationic polymer (PH1) with a plasmid encoding the secreted rE27HGFK1 protein (PH1/pE27HGFK1). We further investigated the anti-tumor effects of rE27HGFK1 and PH1/pE27HGFK1 nanoparticles both in vivo and in vitro. Methods We expressed and purified the rE27HGFK1 protein via E. coli. Then, we performed cellular experiments to determine the antitumoral effects and IR radio-sensitivities of the rE27HGFK1 protein in vitro. Finally, we performed animal studies to determine the tumor-targeted abilities and antitumoral activities of the polymeric nanoparticles, PH1/pE27HGFK1, in an orthotopic U118-Luc-bearing xenografted mouse model. Results We showed that rE27HGFK1 inhibited the proliferation and the angiogenesis and enhanced the senescence and radiosensitivity of GBM via both MET and VEFGR2 signaling mediated-p16 over-expression and the down-regulation of cyclin D1-CDK4-Rb axis activities in vitro. Next, we displayed that systemic administration of the PEGylated H1 cationic polymer (PH1) effectively delivered the reporter genes to the brain tumor of an orthotopic U118-bearing xenografted mouse model. Finally, we showed that PH1/pE27HGFK1 significantly produced antitumor effects with radiosensitivity in the orthotopic U118-Luc-bearing xenografted Blab/c mouse model through inhibiting angiogenesis and tumor cell proliferation, as well as inducing the necrosis of tumor cells in vivo. Conclusions The PH1/pE27HGFK1 nano-drug combined with radiotherapy can be used as a potentially effective therapeutic strategy for Glioblastoma multiforme.

Abstract The effect of low‐FODMAPs diet on irritable bowel syndrome (IBS) in Western China has not been reported. We aimed to investigate the effect of low‐FODMAPs diet on IBS patients in the area and whether low‐FODMAPs diet‐induced alterations of microbiota could be improved through probiotics. IBS patients were randomized to the control group, low‐FODMAPs diet group, probiotics group, or combined group. IBS Symptom Severity Score questionnaire (IBS‐SSS) and IBS Quality of Life Score questionnaire (IBS‐QOL) were completed at baseline, 2 and 4 weeks to evaluate the severity of symptoms. Fresh feces were collected for analyses of gut microbiota and short‐chain fatty acids at baseline and 4 weeks after intervention. Seventy‐three patients were included in the per protocol analysis. After intervention, there was significant improvement in IBS‐SSS in the low‐FODMAPs group (37.5%, 44.2%), probiotics group (51.4%, 62.0%), and combined group (34.1%, 40.4%) at both 2 weeks and 4 weeks, compared with the baseline (p

Abstract The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0–95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Objective The main objective of this study was to determine available energy and nutritional digestibility of extruded cereals and the effect of extrusion on the nutritional value of feed ingredients, aiming to provide scientific basis for efficient application of extrusion in the diets of growing pigs. Methods In Exp. 1, 48 crossbred growing pigs (Duroc×Landrace×Yorkshire) with an initial body weight (BW) of 34.6±2.2 kg were selected and fed with eight diets (non-extrusion or extrusion) to determine the digestible energy (DE), metabolizable energy (ME), and nutrients digestibility. Eight diets included extruded grains (barley, wheat, sorghum, or broken rice), while four had unprocessed grains. In Exp. 2, 9 diets were formulated including 4 cereals with extrusion or non-extrusion and a N-free diet. In addition, 9 growing pigs (BW = 22.3±2.8 kg) were fitted with T-cannula in the distal ileum and arranged in a 9×6 Youden square design. Results Results show that apparent total tract digestibility of gross energy, dry matter, organic meal, ether extract, neutral and acid detergent fiber was not affected by the extrusion process and there was no interaction between cereal type and extrusion treatment on DE, ME. However, the apparent total tract digestibility for crude protein (CP) increased markedly (p

Low thermal conductivity, compatible thermal expansion coefficient, and good calcium–magnesium–aluminosilicate (CMAS) corrosion resistance are critical requirements for environmental barrier coatings used on silicon-based ceramics. RE2Si2O7 (RE = rare earth) has been widely recognized as one of the most promising candidates for environmental barrier coatings due to its good water vapor corrosion resistance. However, the relatively high thermal conductivity and poor resistance to CMAS corrosion have limited its practical application. Inspired by the high entropy effect, in this work, a novel rare earth disilicate (Lu1/7Yb1/7Sc1/7Er1/7Y1/7Ho1/7Dy1/7)2Si2O7 ((7RE1/7)2Si2O7) has been designed and synthesized by a solid reaction process. (7RE1/7)2Si2O7 showed a low thermal conductivity of 1.81 W·m−1·K−1 at 1273 K. Furthermore, the thermal expansion coefficient of (7RE1/7)2Si2O7 (4.07×10−6 ℃−1 from room temperature (RT) to 1400 ℃) is close to that of the SiC-based ceramic matrix composites (SiC-CMCs) ((4.5–5.5)×10−6 ℃−1). Additionally, (7RE1/7)2Si2O7 exhibited excellent resistance to CMAS corrosion. When exposed to CMAS at 1300 ℃ for 48 h, the reaction layer thickness was 22 μm. The improved performance of (7RE1/7)2Si2O7 highlights its potential as a promising candidate for thermal/environmental barrier coatings.

Abstract Background Acute respiratory distress syndrome (ARDS) is a severe and fatal disease. Although mesenchymal stem cell (MSC)-based therapy has shown remarkable efficacy in treating ARDS in animal experiments, clinical outcomes have been unsatisfactory, which may be attributed to the influence of the lung microenvironment during MSC administration. Extracellular vesicles (EVs) derived from endothelial cells (EC-EVs) are important components of the lung microenvironment and play a crucial role in ARDS. However, the effect of EC-EVs on MSC therapy is still unclear. In this study, we established lipopolysaccharide (LPS) - induced acute lung injury model to evaluate the impact of EC-EVs on the reparative effects of bone marrow-derived MSC (BM-MSC) transplantation on lung injury and to unravel the underlying mechanisms. Methods EVs were isolated from bronchoalveolar lavage fluid of mice with LPS - induced acute lung injury and patients with ARDS using ultracentrifugation. and the changes of EC-EVs were analysed using nanoflow cytometry analysis. In vitro assays were performed to establish the impact of EC-EVs on MSC functions, including cell viability and migration, while in vivo studies were performed to validate the therapeutic effect of EC-EVs on MSCs. RNA-Seq analysis, small interfering RNA (siRNA), and a recombinant lentivirus were used to investigate the underlying mechanisms. Results Compared with that in non-ARDS patients, the quantity of EC-EVs in the lung microenvironment was significantly greater in patients with ARDS. EVs derived from lipopolysaccharide-stimulated endothelial cells (LPS-EVs) significantly decreased the viability and migration of BM-MSCs. Furthermore, engrafting BM-MSCs pretreated with LPS-EVs promoted the release of inflammatory cytokines and increased pulmonary microvascular permeability, aggravating lung injury. Mechanistically, LPS-EVs reduced the expression level of isocitrate dehydrogenase 2 (IDH2), which catalyses the formation of α-ketoglutarate (α-KG), an intermediate product of the tricarboxylic acid (TCA) cycle, in BM-MSCs. α-KG is a cofactor for ten-eleven translocation (TET) enzymes, which catalyse DNA hydroxymethylation in BM-MSCs. Conclusions This study revealed that EC-EVs in the lung microenvironment during ARDS can affect the therapeutic efficacy of BM-MSCs through the IDH2/TET pathway, providing potential strategies for improving the therapeutic efficacy of MSC-based therapy in the clinic.

Abstract Background Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. Methods We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. Results The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. Conclusion Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.

Abstract This cross-sectional study aimed to explore the knowledge, attitudes, and practices (KAP) regarding urinary system stones among the general public in Chengdu, China. Conducted between January and June 2023, this research targeted individuals undergoing physical examinations at the Health Management Center of Sichuan Provincial People's Hospital. Structured questionnaires were administered to collect demographic information and assess KAP related to urinary system stones. Following meticulous scrutiny, 1014 valid questionnaires were retained for analysis. The computed scores for knowledge, attitude, and practice were 9.36 ± 4.23 (possible score range 0–17), 37.75 ± 7.20 (possible score range 11–55), and 30.77 ± 4.00 (possible score range 10–50), respectively. These outcomes suggested insufficient knowledge and moderately positive attitudes and practices among the participants. Structural Equation Modeling (SEM) analysis revealed a direct impact of knowledge on attitude (β = 0.967, P

Abstract This retrospective cohort study aimed to determine the prevalence of anemia among patients with gynecological cancer prior to any treatment and to identify contributing factors associated with anemia in this group. We retrospectively analyzed data from female patients aged 18 and above, diagnosed with various forms of gynecological cancer at The Affiliated Hospital of Southwest Medical University between February 2016 and March 2021. Anemia was assessed based on the most recent CBC results before any cancer treatment. Eligibility was based on a definitive histopathological diagnosis. Key variables included demographic details, clinical characteristics, and blood counts, focusing on hemoglobin levels. Statistical analysis was conducted using logistic regression models, and anemia was defined as hemoglobin levels below 12 g/dL for women, according to WHO criteria. Of the 320 participants, a significant prevalence of anemia was found. Correlations between anemia and factors like age, educational level, and biological markers (iron, folic acid, and vitamin B12 levels) were identified. In our study, we found that the prevalence of anemia among patients with gynecological cancer prior to any treatment was 59.06%, indicating a significant health concern within this population. The study highlights a significant prevalence of anemia in patients with gynecological cancer, emphasizing the need for regular hemoglobin screening and individualized management. These findings suggest the importance of considering various characteristics and clinical variables in anemia management among this patient group. Further studies are needed to explore the long-term effects of these factors on patient outcomes and to develop targeted interventions.

The application of platelet-rich plasma (PRP) in wound repair is progressively garnering attention. However, certain patients, owing to relative or absolute contraindications, encounter impediments in the acquisition or application of autologous PRP. The utilization of homologous allogeneic PRP, sourced through rigorous donor selection and standardized preparation methodologies, as a substitute for autologous PRP, may hold favorable implications for such individuals. This article endeavors to succinctly delineate and forecast the mechanisms, advantages, limitations, efficacy and safety of allogeneic PRP in the context of wound healing, furnishing a foundation for its implementation in wound repair.

Microwave Photonic (MWP) radars have remarkably improved traditional microwave radar hardware architectures using photonics devices. With the exceptional physical properties of photonic devices, MWP radars can emit ultra-wideband, high-linearity, high-quality linear frequency modulation signals, allowing ultra-high-resolution target imaging and detection. Different target regions exhibit distinct responses to different frequency signals during target imaging and detection due to their diverse structures and characteristics. Therefore, MWP radars have the potential to generate pseudo-color images based on scattering differences, further enhancing the information retrieval capability of MWP Synthetic Aperture Radar (MWP-SAR). Pseudo-color images generated using traditional remote sensing techniques cannot achieve centimeter-level resolution. Therefore, we propose a method for generating pseudo-color images while maintaining the resolution of MWP-SAR. The algorithm first determines an optimal sub-band echo search model and subsequently employs the optimal sub-band search algorithm to process the ultra-wideband echoes to obtain sub-band echo channels with the largest scattering characteristic differences. The multi-sub-band images are then color-composited to generate pseudo-color images that best describe the target scattering characteristics. However, to ensure the high resolution of MWP-SAR, a fusion model is established to combine the full-resolution SAR image with the multi-sub-band image. Finally, full-resolution pseudo-color images are successfully synthesized using the measured airborne MWP-SAR data, validating the effectiveness of the algorithm. This algorithm enables MWP-SAR to obtain more target information during imaging, offering assistance in implementing imaging radar and microwave vision.

Background: The dead space fraction (VD/VT) has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome (ARDS). However, its measurement relies on expired carbon dioxide, limiting its widespread application in clinical practice. Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of VD/VT. In this study, we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation. Methods: This retrospective observational study was conducted using data from the Chinese database in intensive care (CDIC). Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021. We collected data during the first 7 days of ventilation to calculate various dead space estimates, including ventilatory ratio (VR), corrected minute ventilation (V˙Ecorr), VD/VT (Harris–Benedict), VD/VT (Siddiki estimate), and VD/VT (Penn State estimate) longitudinally. A time-dependent Cox model was used to handle these time-varying estimates. Results: A total of 392 patients (median age 66 [interquartile range: 55–77] years, median SOFA score 9 [interquartile range: 7–12]) were finally included in our analysis, among whom 132 (33.7%) patients died within 28 days of admission. VR (hazard ratio [HR]=1.04 per 0.1 increase, 95% confidence interval [CI]: 1.01 to 1.06; P=0.013), V˙Ecorr (HR=1.08 per 1 increase, 95% CI: 1.04 to 1.12; P < 0.001), VD/VT (Harris–Benedict) (HR=1.25 per 0.1 increase, 95% CI: 1.06 to 1.47; P=0.006), and VD/VT (Penn State estimate) (HR=1.22 per 0.1 increase, 95% CI: 1.04 to 1.44; P=0.017) remained significant after adjustment, while VD/VT (Siddiki estimate) (HR=1.10 per 0.1 increase, 95% CI: 1.00 to 1.20; P=0.058) did not. Given a large number of negative values, VD/VT (Siddiki estimate) and VD/VT (Penn State estimate) were not recommended as reliable substitutes. Long-term exposure to VR >1.3, V˙Ecorr >7.53, and VD/VT (Harris–Benedict) >0.59 was independently associated with an increased risk of mortality in ARDS patients. These findings were validated in the fluid and catheter treatment trial (FACTT) database. Conclusions: In cases where VD/VT cannot be measured directly, early time-varying estimates of VD/VT such as VR, V˙Ecorr, and VD/VT (Harris–Benedict) can be considered for predicting mortality in ARDS patients, offering a rapid bedside application.

Abstract Aims The combination of haemoglobin, albumin, lymphocytes, and platelets (HALP) is a new metric used to assess patient prognosis in many diseases. This study aimed to assess the relationship between HALP and short‐ and long‐term mortality in patients with heart failure. Methods and results This retrospective cohort study included adult patients with heart failure who were hospitalized between 2019 and 2021. The primary outcomes were 1‐month mortality and 1‐year mortality. The multivariable logistic regression analysis was used to evaluate the association between HALP and the risk of mortality. Stratified analyses were conducted based on New York Heart Association functional classification (NYHA) stage (II/III, IV) and left ventricular ejection fraction (LVEF,

Severe pneumonia (SP) is a prevalent respiratory ailment characterized by high mortality and poor prognosis. Current scoring systems for pneumonia are not only time-consuming but also exhibit limitations in early SP prediction. To address this gap, this study aimed to develop a machine-learning model using inflammatory markers from peripheral blood for early prediction of SP. A total of 204 pneumonia patients from seven medical centers were studied, with 143 (68 SP cases) in the training cohort and 61 (32 SP cases) in the test cohort. Clinical characteristics and laboratory test results were collected at diagnosis. Various models including Logistic Regression, Random Forest, Naïve Bayes, XGBoost, Support Vector Machine, and Decision Tree were built and evaluated. Seven predictors—age, sex, WBC count, T-lymphocyte count, NLR, CRP, TNF-α, IL-4/IFN-γ ratio, IL-6/IL-10 ratio—were selected through LASSO regression and clinical insight. The XGBoost model, exhibiting best performance, achieved an AUC of 0.901 (95 % CI: 0.827 to 0.985) in the test cohort, with an accuracy of 0.803, sensitivity of 0.844, specificity of 0.759, and F1_score of 0.818. Indeed, SHAP analysis emphasized the significance of elevated WBC counts, older age, and elevated CRP as the top predictors. The use of inflammatory biomarkers in this concise predictive model shows significant potential for the rapid assessment of SP risk, thereby facilitating timely preventive interventions.

Ferroptosis is a type of cell death that plays a remarkable role in the growth and advancement of malignancies including hepatocellular carcinoma (HCC). Non-coding RNAs (ncRNAs) have a considerable impact on HCC by functioning as either oncogenes or suppressors. Recent research has demonstrated that non-coding RNAs (ncRNAs) have the ability to control ferroptosis in HCC cells, hence impacting the advancement of tumors and the resistance of these cells to drugs. Autophagy is a mechanism that is conserved throughout evolution and plays a role in maintaining balance in the body under normal settings. Nevertheless, the occurrence of dysregulation of autophagy is evident in the progression of various human disorders, specifically cancer. Autophagy plays dual roles in cancer, potentially influencing both cell survival and cell death. HCC is a prevalent kind of liver cancer, and genetic mutations and changes in molecular pathways might worsen its advancement. The role of autophagy in HCC is a subject of debate, as it has the capacity to both repress and promote tumor growth. Autophagy activation can impact apoptosis, control proliferation and glucose metabolism, and facilitate tumor spread through EMT. Inhibiting autophagy can hinder the growth and spread of HCC and enhance the ability of tumor cells to respond to treatment. Autophagy in HCC is regulated by several signaling pathways, such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs. Utilizing anticancer drugs to target autophagy may have advantageous implications for the efficacy of cancer treatment.

In order to explore the efficient use of water and nitrogen for winter wheat under irrigation with micro-sprinkling hose, two-season field experiments were conducted to evaluate the effects of irrigation levels and nitrogen application rate on yield, water productivity (WP) and nitrogen partial factor productivity (NPFP). Three irrigation levels were 60 %, 65 %, and 70 % field capacity (FC) during the reviving to jointing stage, 65 %, 70 %, and 75 % FC after the jointing stage, referred to as W1, W2 and W3, respectively. The irrigating water quota is 30 mm. The five N topdressing period treatments were reviving period + booting stage (N1), jointing + booting stage (N2), reviving period (N3), jointing stage (N4), and booting stage (N5). The results showed that the water consumption, leaf area index, plant height, biomass, grain yield, and NPFP increased with an increase in irrigation amount, and the WP decreased with an increase in irrigation amount. Nitrogen applied during the reviving period was beneficial for increasing grain yield, WP, and NPFP under the irrigation level W1; nitrogen applied during the jointing period was beneficial for increasing grain yield, WP, and NPFP for winter wheat under the W2 and W3 irrigation levels. The W3N2 treatment resulted in the highest grain yield (8.98 t·ha−1), but it was not significant difference from W2N2 (average of 8.92 t·ha−1). After a comprehensive evaluation based on grain yield, WP and NPFP, the appropriate modes of irrigation and nitrogen is the treatment of W2N2 (65 % and 70 % FC irrigation treatments during the reviving to jointing stage and the stages after jointing stage, respectively; the nitrogen topdressing during jointing + booting stage) for winter wheat using micro-sprinkling hose irrigation in North China.

ObjectiveThe aim of this study is to comprehensively investigate the temporal dynamics of faecal gut microbiota and metabonomics in early postnatal with a focus on very low or extremely low birth weight (VLBW/ELBW) infants.MethodsWe collected faecal samples from 157 VLBW/ELBW infants at three time points: days 1, 14, and 28 in a prospective cohort study. The faecal microbial diversity, abundance, composition, and metabolomic analyses were determined using 16S rRNA sequencing and liquid chromatography tandem mass spectrometry (LC-MS/MS). Microbiome functional analyses were conducted utilizing PICRUSt2. The ecological association networks were employed to investigate the interactions between gut microbiota and identify the core genus within 28 days of birth, as well as to unveil correlations between taxa and metabolites.Result(1) The alpha diversity of gut microbiota significantly decreased from D1 to D28, accompanied by an interrupted trajectory lacking obligate anaerobes. At the phylum level, the 16S RNA sequencing results showed an increase in Proteobacteria and a decrease in Firmicutes and Bacteroidota from D1 to D28. At the genus level, there was a decrease in the relative abundance of Staphylococcus, Acinetobacter and Ureaplasma, with Klebsiella and Enterococcus emerging as the most abundant genera. (2) The analysis revealed a total of 561 metabolic markers that exhibited significant and distinct alterations between D1 and D14. (3) Ecological association networks revealed that the gut microbiota in D1 exhibited a significantly higher degree of microbial interactions compared to those in D14 and D28. Additionally, Enterococcus, Klebsiella, and Enterobacter were major contributors to the co-occurring network at these three time points. (4) Steroid hormone biosynthesis, including tetrahydrocortisone, androsterone glucuronide, androstenedione and etiocholanolone glucuronide, decreased within 28 days after birth.ConclusionWe have successfully demonstrated a significant dysbiosis in the gut microbiota and a subsequent decrease in its diversity within 4 weeks postpartum in VLBW/ELBW infants. Monitoring the gut microbiota of VLBW/ELBW infants and promptly rectifying dysbiosis in the early stages may represent a potential therapeutic strategy.

BackgroundLactiplantibacillus plantarum (L. plantarum) is known for its probiotic properties, including antioxidant and anti-inflammatory effects. Recent studies have highlighted the role of extracellular vesicles (EVs) from prokaryotic cells in anti-inflammatory effects.ObjectiveThis study aims to investigate the anti-inflammatory effects of extracellular vesicles derived from a newly isolated strain of L. plantarum (LP25 strain) and their role in macrophage polarization.MethodsThe LP25 strain and its extracellular vesicles were isolated and identified through genomic sequencing, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). RAW 264.7 cells were treated with lipopolysaccharide (LPS) and/or LP25-derived extracellular vesicles (LEV). Morphological changes in the cells were observed, and the expression levels of pro-inflammatory cytokines (TNF-α, IL-6)、iNOS and anti-inflammatory cytokines (IL-10) 、Arg-1 were measured using quantitative real-time PCR (qPCR). Flow cytometry was used to detect the expression of Arg-1 in the treated cells.ResultsTreatment with LP25 EVs led to significant morphological changes in RAW 264.7 cells exposed to LPS. LP25 EVs treatment resulted in increased expression of Arg-1 and anti-inflammatory cytokines IL-10, and decreased expression of iNOS and surface markers protein CD86. Flow cytometry confirmed the increased expression of the M2 macrophage marker Arg-1 in the LP25 EVs-treated group.ConclusionExtracellular vesicles from Lactiplantibacillus plantarum LP25 can suppress inflammatory responses and promote the polarization of macrophages toward the anti-inflammatory M2 phenotype. These findings provide new evidence supporting the anti-inflammatory activity of L. plantarum-derived EVs.

Abstract This study aims to investigate the relationship between casein oxidation and moisture status in the presence of milk fat to clarify the role of fat on water in milk powder. The results showed that at the same water activity (aw), the faster oxidation of whole milk powder (WMP) is attributed to the high proportion of free water and immobilized water in them, indicating that the adsorption of milk fat mainly depended on multilayer water and the entrapped water. In the diffusion‐limited reaction, changes in water state affected more than radicals on casein oxidation. Glass transition temperature (Tg) was also affected by the water state of lipid adsorption. At low aw (

The discovery of an inhibitor for acyl-CoA synthetase long-chain family member 4 (ACSL4), a protein involved in the process of cell injury through ferroptosis, has the potential to ameliorate cell damage. In this study, we aimed to investigate the potential of berberine (BBR) as an inhibitor of ACSL4 in order to suppress endothelial ferroptosis and provide protection against atherosclerosis. An atherosclerosis model was created in ApoE-/- mice by feeding a high fat diet for 16 weeks. Additionally, a mouse model with endothelium-specific overexpression of ACSL4 was established. BBR was administered orally to assess its potential therapeutic effects on atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were exposed to oxidized low density lipoprotein (ox-LDL) to simulate atherosclerotic endothelial damage in vitro. The interaction between ACSL4 and BBR has been confirmed, with BBR playing a role in inhibiting erastin-induced ferroptosis by regulating ACSL4. Additionally, BBR has been found to inhibit lipid deposition, plaque formation, and collagen deposition in the aorta, thereby delaying the progression of atherosclerosis. It also restored the abnormal expression of ferroptosis-related proteins in atherosclerotic vascular endothelial cells both in vivo and in vitro. In conclusion, BBR, acting as an ACSL4 inhibitor, can improve atherosclerosis by inhibiting ferroptosis in endothelial cells. This highlights the potential of targeted inhibition of vascular endothelial ACSL4 as a strategy for treating atherosclerosis, with BBR being a candidate for this purpose.

Objectives The blood urea nitrogen to creatinine (BUN/Cr) ratio is associated with early neurological deterioration in acute ischaemic stroke (AIS). However, the predictive value of the BUN/Cr ratio for the AIS prognosis remains unclear. Therefore, we evaluated the correlation between the BUN/Cr ratio and the 3-month outcome in patients with AIS, further testing their dose–response relationship.Design This retrospective cohort study enrolled patients with AIS who were admitted between 1 January 2013 and 31 May 2022. Poor clinical outcome was defined as 3-month Modified Rankin Scale (mRS) >2. Cox proportional HR was used to evaluate the correlation between the BUN/Cr ratio and 3-month outcome. Restricted cubic spline and robust locally weighted regression analyses were conducted to determine the dose–response relationship between the BUN/Cr ratio and the 3-month outcome.Results A total of 4952 eligible patients were included in the study. The patients were divided into three groups according to the tertiles of BUN/Cr ratio (T1, 0.093). After logistic regression adjustment for demographic and clinical characteristics, the BUN/Cr ratio was found to be independently associated with the 3-month outcome in patients with AIS. The restricted cubic spline and locally regression smoothing scatterplot graph showed a strong dose–response relationship between the BUN/Cr ratio and the 3-month outcome in patients with AIS.Conclusion A dose–response relationship was observed between the BUN/Cr ratio and the 3-month outcome in patients with AIS, suggesting that the BUN/Cr ratio could serve as a reliable predictor for the AIS prognosis.

The Qinghai-Tibet Plateau stands as one of the most ecologically fragile and biodiversity-rich regions globally. Understanding the distribution of different taxa and their relationship with environmental factors is crucial for effective conservation and sustainable management. Polytrichaceae, a significant bryophyte family widely distributed in Tibet, displays distinct structural, morphological, and phylogenetic traits compared to other mosses. Despite its importance, the distribution of Polytrichaceae in Tibet and its correlation with environmental factors have yet to be explored. In this study, we used an optimized Maximum Entropy (MaxEnt) model to explore the potential suitable habitats of Polytrichaceae in Tibet, aiming to clarify their geographic distribution pattern as well as the key environmental influence factors. The model had high accuracy with an average Area Under the Curve (AUC) of 0.933 and True Skill Statistics (TSS) value of 0.789. The results showed that the potential suitability habitats of Polytrichaceae were mainly located in southeastern Tibet, and the low suitable, moderately suitable, and highly suitable habitats accounted for 12.53 %, 6.84 %, and 3.31 % of the total area of Tibet respectively. Unsuitable habitats were mainly located in northwestern Tibet, accounting for about 77.32 %. In Tibet, temperature factors (Mean Temperature of Coldest Quarter (Bio11) and Annual Mean Temperature (Bio1)) played a pivotal role in determining the potential suitable habitats for Polytrichaceae, and elevation, precipitation, and vegetation coverage also had an important influence. The family preferred warm, moist and densely vegetated habitats in Tibet. This study enriched our ecological understanding of bryophyte ecology in this region and provided data-driven support for biodiversity conservation and ecosystem management in Tibet.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and involves various pathogenic mechanisms, including oxidative stress and neuroinflammation. Niacin, an important cofactor in mitochondrial energy metabolism, may play a key role in the pathogenesis of PD. An in-depth exploration of the relationship between niacin and mitochondrial energy metabolism may provide new targets for the treatment of PD. The present study was designed to examine the association between dietary niacin intake and the risk of PD in US adults. Data from adults aged 40 years and older collected during cycles of the United States (US) National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 were used. A multiple logistic regression model was used to analyze the relationship between dietary niacin intake and the risk of PD. Further linear tests using restricted cubic splines (RCS) were performed to explore the shape of the dose–response relationship. Subgroup stratification and interaction analyses were conducted according to years of education, marital status, smoking, and hypertension to evaluate the stability of the association between different subgroups. A total of 20,211 participants were included in this study, of which 192 were diagnosed with PD. In the fully adjusted multiple logistic regression model, dietary niacin intake was negatively associated with the risk of PD (OR: 0.77, 95%CI: 0.6–0.99; p = 0.042). In the RCS linear test, the occurrence of PD was negatively correlated with dietary niacin intake (nonlinearity: p = 0.232). In stratified analyses, dietary niacin intake was more strongly associated with PD and acted as an important protective factor in patients with fewer years of education (OR: 0.35, 95%CI: 0.13–0.93), married or cohabitating (OR: 0.71, 95%CI: 0.5–0.99), taking dietary supplements (OR: 0.6, 95%CI: 0.37 0.97), non-smokers (OR: 0.57, 95%CI: 0.39–0.85), those with hypertension (OR: 0.63, 95%CI: 0.63–0.95), coronary artery disease (OR: 0.77, 95%CI: 0.6–1), and stroke (OR: 0.75, 95%CI: 0.88–0.98), but the interaction was not statistically significant in all subgroups. Dietary niacin intake was inversely associated with PD risk in US adults, with a 23% reduction in risk for each 10 mg increase in niacin intake.

Introductionmyo7aa, the homolog of the human Usher 1B syndrome pathogenic gene, myo7A, plays an important role in stereociliary development and maintenance, therefore, is critical for hearing and balance. However, the molecular mechanisms that myo7aa regulate hearing and balance still need to be studied.MethodsIn this study, we generated two independent zebrafish myo7aa knockout lines using CRISPR/Cas9 technology. To investigate the effects of myo7aa on hearing, YO-PRO-1 staining and startle response assay were used. To gain insight into the specific molecular mechanisms by which myo7aa affects hearing, transcriptome sequencing and bioinformatics analysis were employed.ResultsOur study showed that hair cells of myo7aa-/- zebrafish can not take up YO-PRO-1 fluorescent dye and are insensitive to acoustic stimulation in myo7aa-/- zebrafish compared to wild type. Genes related to the Rho GTPase signaling pathway, such as arhgap33, dab2ip, and arghef40, are significantly down-regulated in myo7aa-/- zebrafish embryos at 3 dpf. GTP and ATP compensation can partially rescue the hair cell defects in myo7aa knockout zebrafish.DiscussionOur findings suggest that zebrafish myo7aa affects congenital hearing by regulating Rho GTPase signaling, and loss of myo7aa leads to abnormal Rho GTPase signaling and impairs hair cell function. myo7aa, myo7A, arhgap33, dab2ip, arghef40 and myo7aa-/- fonts in the abstract are italicized. -/- is a superscript format.

BackgroundPharmaceutical management is a new frontier subject between pharmacy, law and management, and related research involves the whole process of drug development, production, circulation and use. With the development of medical systems and the diversification of patients’ drug needs, research in the field of pharmaceutical management is becoming increasingly abundant. To clarify the development status of this field, this study conducted a bibliometric analysis of relevant literature in the field based on the knowledge graph method for the first time and explored the evolutionary trends of research hotspots and frontiers.MethodsLiterature was obtained from the Web of Science Core Collection database. CiteSpace 6.2.R4 (Advanced), VOSViewer, Scimago Graphica, Pajek and the R programming language were used to visualize the data.ResultsA total of 12,771 publications were included in the study. The publications in the field of pharmaceutical management show an overall increasing trend. In terms of discipline evolution, early research topics tended to involve the positioning of pharmacists and pharmaceutical care and the establishment of a management system. From 2000 to 2005, this period tended to focus on clinical pharmacy and institutional norms. With the development of globalization and the market economy, research from 2005 to 2010 began to trend to the fields of drug markets and economics. From 2010 to 2015, research was gradually integrated into health systems and medical services. With the development of information technology, after 2015, research in the field of pharmaceutical management also began to develop in the direction of digitalization and intelligence. In light of the global pandemic of COVID-19, research topics such as drug supply management, pharmaceutical care and telemedicine services under major public health events have shown increased interest since 2020.ConclusionBased on the knowledge mapping approach, this study provides a knowledge landscape in the field of pharmaceutical management research. The results showed that the reform of pharmacy education, the challenge of drug management under the COVID-19 pandemic, digital transformation and the rise of telemedicine services were the hot topics in this field. In addition, the research frontier also shows the broad prospects of the integration of information technology and pharmaceutical management, the practical value of precision pharmaceutical services, the urgent need of global drug governance, and the ethical and legal issues involved in the application of artificial intelligence technology in drug design, which points out the direction for the future development of pharmaceutical practice.

Background: Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) is associated with strongyloidiasis. Herein, a rare case of severe SIADH secondary to disseminated strongyloidiasis in a kidney transplant recipient is reported. Case presentation: A case involving a 43-year-old male kidney transplant recipient with severe disseminated Strongyloides stercoralis infection is reported. The patient was a construction worker with a history of consuming undercooked yellow eel and sashimi. On admission, the patient presented with poor appetite, nausea, vomiting and diarrhea. Laboratory investigations revealed persistent significant hyponatremia and low serum osmolality, confirming the diagnosis of SIADH. S. stercoralis was detected in the stool and bronchoalveolar lavage fluid. He was treated with empirical albendazole because S. stercoralis was detected in the stool; however, his symptoms and hyponatremia did not improve until ivermectin was administered, after which SIADH resolved quickly. Conclusion: This case suggests that S. stercoralis infection should be included in the differential diagnosis when a kidney transplant recipient presents with gastrointestinal symptoms and SIADH. In such situations, pre- or post-transplant screening for S. stercoralis is needed, and early ivermectin treatment is very important.

Ribosomes mediate protein synthesis, which is one of the most energy-demanding activities within the cell, and mitochondria are one of the main sources generating energy. How mitochondrial morphology and functions are adjusted to cope with ribosomal defects, which can impair protein synthesis and affect cell viability, is poorly understood. Here, we used the fission yeast Schizosaccharomyces Pombe as a model organism to investigate the interplay between ribosome and mitochondria. We found that a ribosomal insult, caused by the absence of Rpl2702, activates a signaling pathway involving Sty1/MAPK and mTOR to modulate mitochondrial morphology and functions. Specifically, we demonstrated that Sty1/MAPK induces mitochondrial fragmentation in a mTOR-independent manner while both Sty1/MAPK and mTOR increases the levels of mitochondrial membrane potential and mitochondrial reactive oxygen species (mROS). Moreover, we demonstrated that Sty1/MAPK acts upstream of Tor1/TORC2 and Tor1/TORC2 and is required to activate Tor2/TORC1. The enhancements of mitochondrial membrane potential and mROS function to promote proliferation of cells bearing ribosomal defects. Hence, our study reveals a previously uncharacterized Sty1/MAPK-mTOR signaling axis that regulates mitochondrial morphology and functions in response to ribosomal insults and provides new insights into the molecular and physiological adaptations of cells to impaired protein synthesis.

Sole biochar addition or exogenous melatonin application can decrease cadmium (Cd) toxicity in polluted soils and improve plant performance and growth. Yet the additive effects of biochar and melatonin application on plant growth, oxidative stress modulation and Cd absorption remain unclear. We conducted a pot experiment to study the combined effects of melatonin, biochar and Cd stress on pea (Pisum sativum L.) seedling growth, antioxidant enzyme activities, photosynthesis parameters and Cd uptake. Results showed that Cd addition significantly decreased pea growth, chlorophyll content, net photosynthesis rate (Pn), transpiration rate (Tr), stomatal conductance (gs), and increased intercellular CO2 concentration (ci) and oxidant enzyme activities when compared to non-Cd contaminated treatment. Exogenous applications of the biochar or melatonin alone significantly decreased the harmful effects of Cd stress and promoted pea seedling growth. Moreover, soil remediation with biochar could more effectively improve pea growth, chlorophyll contents, and photosynthesis parameters and contribute to Cd immobilisation; the melatonin treatment alone could more effectively increase antioxidant enzyme activities. The treatments of biochar and melatonin showed an additive result and had the largest promoting in pea growth, antioxidant enzyme activities, and lowest Cd contents in pea tissue and soil. These results indicate that the combined use of melatonin and biochar is more effective at reducing Cd uptake by pea tissues and alleviating Cd harm to pea plants.

In recent years, the Ordos Basin has undergone a reevaluation, transitioning from a perception of a single block to a focus on understanding the influence of multiple stages and fault systems on hydrocarbon accumulation. This study utilizes the latest 3D seismic and drilling data alongside a theoretical model of strike-slip fault to analyze fault geometry and kinematics in the Xunyi-Yijun area of the basin's southern region. The mechanisms of fault formation are predicted and the related impacts on the formation and accumulation of deep carbonate rocks are also discussed. The results indicate the presence of three fault systems in the Xunyi-Yijun area, with decoupling between deep and shallow layers. The Lower Paleozoic strike-slip faults exhibit distinct characteristics, including high vertical structure, dip swing, and a "flower-shaped" structure in the section. The faults display "compression shear in the northwest, tension shear in the center, and segmental deformation on trunk fractures" on their planes.Moreover, the Lower Paleozoic strike-slip faults experienced two stages of tectonic activities with greater intensity observed from the Late Ordovician to the Silurian, marking the primary period of fault development. The activity intensity during the Middle to Late Permian was relatively weaker, with faults exhibiting inherited strike-slip characteristics. These faults formed two groups, one with a NE strike and the other with a NW strike. Additionally, during the second stage of the Caledonian period, ocean subduction and closure lead to stress being transferred to the basin interior. It is believed that the NE and NW strike basement weak zones existed in the southern Ordos Basin. As a result, the Lower Paleozoic strike-slip fault system likely formed due to the activation of oblique compression. This fault system has the potential to enhance the physical properties of deep carbonate reservoirs and create high-quality karst or tectonic fracture reservoirs in the Xunyi-Yijun area. Moreover, The formation of the "upper source and lower reservoir-lateral source and lateral reservoir" combination along the strike-slip fault belt is an area of interest for deep oil and gas exploration in the Xunyi-Yijun region.

Highlights The recent advances in non-noble-metal bifunctional electrocatalysts for zinc–air batteries are summarized with the design principles. The working mechanism are discussed to provide a comprehensive understanding of the structure-performance relationship of electrocatalysts and the reaction pathways of the oxygen redox reactions. The challenges and prospects related to designing advanced non-noble-metal bifunctional electrocatalysts for high performance zinc–air batteries are provided.