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Abstract Background The congenital ventricular outflow tract malformations (CVOTMs) is a major congenital heart diseases (CHDs) subtype, and its pathogenesis is complex and unclear. Lipid metabolic plays a crucial role in embryonic cardiovascular development. However, due to the limited types of detectable metabolites in previous studies, findings on lipid metabolic and CHDs are still inconsistent, and the possible mechanism of CHDs remains unclear. Methods The nest case-control study obtained subjects from the multicenter China Teratology Birth Cohort (CTBC), and maternal serum from the pregnant women enrolled during the first trimester was utilized. The subjects were divided into a discovery set and a validation set. The metabolomics of CVOTMs and normal fetuses were analyzed by targeted lipid metabolomics. Differential comparison, random forest and lasso regression were used to screen metabolic biomarkers. Results The lipid metabolites were distributed differentially between the cases and controls. Setting the selection criteria of P value 1.2 or

Abstract Purpose of review There are significant differences in the transmission rate and mortality rate of COVID-19 under environmental conditions such as seasons and climates. However, the impact of environmental factors on the role of the COVID-19 pandemic and the transmission mechanism of the SARS-CoV-2 is unclear. Therefore, a comprehensive understanding of the impact of environmental factors on COVID-19 can provide innovative insights for global epidemic prevention and control policies and COVID-19 related research. This review summarizes the evidence of the impact of different natural and social environmental factors on the transmission of COVID-19 through a comprehensive analysis of epidemiology and mechanism research. This will provide innovative inspiration for global epidemic prevention and control policies and provide reference for similar infectious diseases that may emerge in the future. Recent findings Evidence reveals mechanisms by which natural environmental factors influence the transmission of COVID-19, including (i) virus survival and transport, (ii) immune system damage, (iii) inflammation, oxidative stress, and cell death, and (iiii) increasing risk of complications. All of these measures appear to be effective in controlling the spread or mortality of COVID-19: (1) reducing air pollution levels, (2) rational use of ozone disinfection and medical ozone therapy, (3) rational exposure to sunlight, (4) scientific ventilation and maintenance of indoor temperature and humidity, (5) control of population density, and (6) control of population movement. Our review indicates that with the continuous mutation of SARS-CoV-2, high temperature, high humidity, low air pollution levels, and low population density more likely to slow down the spread of the virus.

Abstract Purpose To evaluate the dosimetric characteristics of ZAP-X stereotactic radiosurgery (SRS) for single brain metastasis by comparing with two mature SRS platforms. Methods Thirteen patients with single brain metastasis treated with CyberKnife (CK) G4 were selected retrospectively. The prescription dose for the planning target volume (PTV) was 18–24 Gy for 1–3 fractions. The PTV volume ranged from 0.44 to 11.52 cc.Treatment plans of thirteen patients were replanned using the ZAP-X plan system and the Gamma Knife (GK) ICON plan system with the same prescription dose and organs at risk (OARs) constraints. The prescription dose of PTV was normalized to 70% for both ZAP-X and CK, while it was 50% for GK. The dosimetric parameters of three groups included the plan characteristics (CI, GI, GSI, beams, MUs, treatment time), PTV (D2, D95, D98, Dmin, Dmean, Coverage), brain tissue (volume of 100%-10% prescription dose irradiation V100%-V10%, Dmean) and other OARs (Dmax, Dmean),all of these were compared and evaluated. All data were read and analyzed with MIM Maestro. One-way ANOVA or a multisample Friedman rank sum test was performed, where p

Synthetic Aperture Radar (SAR) has the advantage of noncontact monitoring around the clock and is an important tool for closed space security monitoring. However, when SAR is employed in complex closed spaces, it is susceptible to multipath effects, resulting in a considerable number of virtual images in the image, which has a detrimental impact on interpretation. Existing methods require scene priors for multipath estimation or subaperture weighted fusion to suppress multipath; however, accurately distinguishing multipath virtual images from target images is challenging. This paper proposes a novel multi-angle dual-layer deviation measurement method that effectively distinguishes multipath virtual images from targets. The proposed method employs a large viewing angle difference to conduct multi-angle observation of the target scene, capitalizing on the fact that the position of the multipath virtual image varies with the observation angle, whereas the actual target position remains constant; this is followed by applying a dual-layer deviation measurement algorithm. The algorithm calculates the deviation between the sequence amplitude value and mean twice based on the sparsity of multipath in the multiangle sequence. The proposed method accurately detects and removes sparse and unstable multipath components, whereas the remaining stable components are averaged. This effectively suppresses multipath while retaining target information. Finally, the simulation and actual millimeter wave radar data processing verified the effectiveness of the proposed method.

Abstract Background Sheep manure and mushroom residue are common agricultural waste which threaten environment but rich in mineral elements and organic matter. Even though fermentation and adding it to soil for crop growth is a commonly used approach, there are concerns about how efficient the fermentation process is and whether the microbial community remains safe for both the crops and those working in agriculture. We have discovered a composite microbial agent, previously known as CMA, that demonstrates significant efficacy in the fermentation of mushroom residue and sheep manure. Despite its high activity, the impact of this microbial agent on soil nutrient release, soil microbial composition, and plant growth remains still uncertain. Results After fermenting sheep manure and mushroom residue with Bacillus CMA, this study investigated the fermentation products mixed with vermiculite and perlite for the cultivation of tomato. The results demonstrate that the composite substrate align closely within the ideal range for seedling substrates. Notably, compounded with CMA compost products and vermiculite in a 2:1 ratio, yields the most favorable growth for tomato, which may be attributed to the increased nutrient release and most favorable microbial conditions. Moreover, it significantly decreased the abundance of pathogenic bacteria harmful to human and animal health, thereby reducing the risk to individuals engaged in field labor, and mitigating the threat of plant pathogenic bacteria. Conclusions Sheep manure and mushroom residue fermentation with CMA added significantly promoted tomatoes growth and reduced the risk of diseases in crops, animals, and people. These findings hold significant implications also for the reuse of agricultural biowaste and residues, besides the crop growth and safety of humans and animals in agricultural environments. Graphical Abstract

Abstract Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.

Abstract Tulips (Tulipa gesneriana) are one of the most widely cultivated bulbous plants with substantial ornamental value. However, the lack of well-documented reference genomes has limited the research progress and molecular breeding of tulips. In the present study, a full-length transcriptome of a commercial tulip cultivar was obtained using single-molecule long-read sequencing (PacBio Iso-Seq). In total, 244,357 full-length transcripts were identified, which had an average length of 2,044 bp and an N50 value of 3,861; 67,350 of these were annotated to databases. An inaugural integrated analysis of the transcriptome and phytohormone profiles during flower opening and petal senescence was performed using Illumina RNA-seq, coupled with Mfuzz (an R pakage, http://mfuzz.sysbiolab.eu ) and weighted gene coexpression network analysis (WGCNA). A total of 16 gene coexpression and six transcription factor (TF) modules were constructed. Additionally, 26 hormone analogs were comprehensively profiled. Finally, a prominently novel gene, Tulipa gesneriana Homeobox12-like (TgHB12-like), which encodes an homeodomain–leucine zipper (HD-zip) TF, was identified as a pivotal regulator of petal senescence. Overall, this work facilitates the identification of hormones and TFs in plants related to flower opening and senescence in tulips. It also provides an important and valuable genetic basis for further research in them.

Abstract Background Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. Methods Elderly patients aged 65–80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1–15 min after administration. Results HR was significantly lower in group G compared to group A at 2–8 min after administration (P

Antibiotics are widely used in the breeding production of Bamei pigs, affecting the quality and safety of pork and causing enormous harm to human health, the environment, and public health. The use of probiotic fermented feed to replace antibiotic feed is one of the solutions, which has the potential to improve the intestinal microbiota, promote animal growth, and enhance immunity. The purpose of this study was to evaluate the effect of fermented feed with Lactiplantibacillus (L.) plantarum QP28-1a or Bacillus (B.) subtilis QB8a on feed, growth performance, gut microbiota, and immunity of weaned piglets. A total of 60 freshly weaned piglets from the Tibetan Plateau were randomly divided into five groups and fed basal feed, L. plantarum fermented feed, B. subtilis fermented feed, mixed fermented feed, and antibiotic fermented feed for 60 days, respectively. The results showed fermented feed supplemented with L. plantarum QP28-1a or B. subtilis QB8a significantly lowered the pH of the feed (P < 0.05), produced lactic acid and acetic acid, inhibited the growth of harmful bacteria in the feed, and reduced the feed conversion rate in the group fed mixed fermented feed (P < 0.05). The fermented feed increased the α-diversity and prominently altered the β-diversity of the intestinal microbiota, increasing the relative abundance of beneficial bacteria such as Lactobacillus and Turicibacter and decreasing the relative abundance of conditional pathogens such as Streptococcus and Clostridium, improving the intestinal microbiota of the Bamei piglets. Notably, the mixed fermented feed improved the immunity of Bamei piglets by modulating the production of pro-inflammatory cytokines, anti-inflammatory cytokines, and inflammatory-related signaling pathways. Spearman’s correlation analysis revealed that the increased expression of immune-related cytokines may be associated with a significant enrichment of Lactobacillus, Prevotellaceae, Erysipelotrichaceae, and Ruminococcaceae in the gut. In conclusion, the probiotic fermented feed maintained an acidic environment conducive to suppressing pathogens, reduced the feed conversion ratio, optimized the intestinal microbiota, improved immunity, and alleviated intestinal inflammation that may be caused by weaning, demonstrating the excellent application prospects of L. plantarum QP28-1a and B. subtilis QB8a fermented feed in the feeding of Bamei piglets.

In crisis management, quickly identifying and helping affected individuals is key, especially when there is limited information about the survivors’ conditions. Traditional emergency systems often face issues with reachability and handling large volumes of requests. Social media has become crucial in disaster response, providing important information and aiding in rescues when standard communication systems fail. Due to the large amount of data generated on social media during emergencies, there is a need for automated systems to process this information effectively and help improve emergency responses, potentially saving lives. Therefore, accurately understanding visual scenes and their meanings is important for identifying damage and obtaining useful information. Our research introduces a framework for detecting damage in social media posts, combining the Bidirectional Encoder Representations from Transformers (BERT) architecture with advanced convolutional processing. This framework includes a BERT-based network for analyzing text and multiple convolutional neural network blocks for processing images. The results show that this combination is very effective, outperforming existing methods in accuracy, recall, and F1 score. In the future, this method could be enhanced by including more types of information, such as human voices or background sounds, to improve its prediction efficiency.

BackgroundChinese patent medicines are specialty preparations in China that are produced using traditional prescriptions processed by modern pharmaceutical technology. They contain complex ingredients and much attention is paid to their clinical safety. Demonstrating the clinical safety of Chinese patent medicines containing toxic ingredients in modern pharmacological studies has become one of the urgent issues to be solved for the safe use of clinical medicines.ObjectivesThe aim of this research is to evaluate the safety of Chinese patent medicines containing toxic ingredients by applying the risk-benefit assessment method. Additionally, a database of ‘toxic ingredients–toxic Chinese herbal medicines-adverse reactions’ will be established to explore the relationship between toxic ingredients and adverse reactions. This will lay the foundation for the rational clinical use of Chinese patent medicines containing toxic ingredients.Methods1) Establish a database of ‘toxic Chinese herbal medicines–toxic ingredients–toxic Chinese patent medicines’ to count the Chinese patent medicines containing toxic ingredients in the 2020 edition of Chinese Pharmacopoeia. 2) Filtered the clinical studies, extracted the drug-related ADEs, and analyzed the characteristics and correlations of these ADEs. 3) Finally, this section summarizes the causes of ADEs related to Chinese patent medicines containing toxic ingredients and extracts the main risk factors to provide a reference for further study.Outcomes1) There are four main types of Chinese patent medicines containing toxic ingredients. These include medicines with diester aconitine metabolites, mineral composition, Araceae metabolites, and hydrogen cyanide. 2) Digestive system, skin and its appendages, and allergic reactions were the main types of ADEs related to four types of Chinese patent medicines containing toxic ingredients. 3) There are four primary risk factors associated with the clinical use of Chinese patent medicines containing toxic ingredients: medicine, medication, individual and regulatory factors.

IntroductionSeveral studies indicated that depression is associated with liver injury. The role of probiotics in alleviating depression is focused on improving the abnormalities of the central nervous system through the gut-brain axis, while the effect on liver injury is still unclear. The aim of this study was to elucidate the potential link between the antidepressant effect of a potential probiotic strain Bifidobacterium pseudocatenulatum W112 and its effect on alleviating liver injury.MethodsThe 4-week-old Kunming mice were exposed to chronic stress for 4 weeks to establish a depression model.ResultsThe depression-like behavior and related biomakers in chronic unpredictable mild stress (CUMS) mice were altered by supplemented with W112 for 2 weeks. Meanwhile, the modulation effect of W112 the gut microbiota in CUMS mice also result in an increase in the abundance of beneficial bacteria and a decrease in the abundance of harmful bacteria. Significantly, liver injury was observed in CUMS model mice. W112 improved liver injury by reducing AST/ALT in serum. Quantitative PCR results indicated that the mechanism of action of W112 in ameliorating liver injury was that the altered gut microbiota affected hepatic phospholipid metabolism and bile acid metabolism.DiscussionIn short, W112 could significantly improve the depressive and liver injury symptoms caused by CUMS. The gut-liver-brain axis is a potential connecting pathway between the antidepressant effects of W112 and its alleviation of liver injury.

Summary: Background: Whether hepatitis B virus (HBV) infection of women prior to pregnancy can influence risk of congenital malformations in offspring remains controversial. We assessed the association between them by considering congenital malformations in the aggregate as well as risk of organs systems using a large national sample of Chinese women. Methods: We performed a record-linkage cohort study of women who participated in National Free Preconception Health Examination Project, between January 1, 2010, and December 31, 2019 for whom data on congenital malformations in their offspring were available from the National Population-Based Birth Defects Surveillance Network. A total of 498,968 linked records were obtained, of which 127,371 were excluded because HBV status before pregnancy was unknown, the records involved multiple pregnancies, or pre-pregnancy examinations were conducted after conception. Based on pre-pregnancy status, mothers were assigned to two categories of HBsAg− or HBsAg+ and, in certain analyses, to three categories of HBsAg−, HBsAg+/HBeAg− or HBsAg+/HBeAg+. Potential associations of serological status with risk of congenital malformations, considered separately or in aggregate, were explored using multilevel logistic regression. Factors that might influence such associations were also explored. Findings: Among the 371,597 women analyzed, 21,482 (5.78%) were HBsAg+ before pregnancy, and 8333 (2.24%) had a fetus or child diagnosed with congenital malformations, composed of 7744 HBsAg− women and 589 HBsAg+ women. HBsAg+ status was associated with increased risk of congenital malformations in the aggregate (OR 1.14, 95% CI 1.03–1.25) and of cardiovascular malformations specifically (OR 1.18, 95% CI 1.03–1.35). HBsAg+/HBeAg− status was associated with significantly higher risk of cardiovascular malformations (OR 1.19, 95% CI 1.01–1.39) as well as reproductive malformations (OR 1.51, 95% CI 1.02–2.23). Associations between HBsAg+ status before pregnancy and risk of congenital malformations was modified by alanine aminotransferase activity (Pinteraction < 0.05). Interpretation: Prepregnancy HBV infection might be associated with fetal malformations. This association needs further investigation to confirm whether it is a causal association, and assess whether antiviral therapy of women with HBsAg+ planning to conceive might reduce the risk of fetal malformations. Funding: The National Health Commission of the People's Republic of China, China; Science and Technology Department of Sichuan Province, China; and the Ministry of Science and Technology of the People's Republic of China.

Neurological injury, as a major pathogenic mechanism in depression, holds significant importance in the research and development of antidepressant drugs. Hemerocallis citrina Baroni (H. citrina), referred to as “Forgetting Sadness Grass,” has been confirmed to possess remarkable neuroprotective effects. Studies have identified that the total phenolics in H. citrina Baroni leaves (HLTP) consist of flavonoids and phenolic acids and numerous studies have substantiated the neuroprotective effects of them. Based on this, we propose that HLTP may possess neuroprotective properties. To confirm this hypothesis, we initially employed network pharmacology techniques to predict potential targets for the neuroprotective effects of HLTP based on the Swiss Target Prediction database. GO and KEGG analyses were conducted to predict potential pathways, and a component-target-pathway network was constructed. Molecular docking experiments were then performed to analyze the binding abilities of the selected active components with the main targets. Furthermore, we validated the neuroprotective effects of HLTP and key targets selected through network pharmacology using a corticosterone-induced PC12 neuronal cell damage model. Network pharmacology research has identified that in the HLTP, Quercetin, Rutin, Apigenin, and Isoquercitrin are potential active components that may exert neuroprotective effects by modulating key targets such as AKT1, TNF, TP53, and CASP3 through crucial pathways including PI3K/AKT and apoptosis. Molecular docking revealed that 4-O-Caffeoylquinic acid, 5-O-Caffeoylshikimic acid, 4-p-Coumaroylquinic acid, and 5-O-Feruloylquinic acid exhibit low binding energies with key targets. Particularly, 4-O-Caffeoylquinic acid forms stable binding through hydrogen bonding with residues such as LYS389, GLU49, GLN47, LYS30, ASP44, and GLU40 in AKT1. PC12 cells were stimulated with 200 μmol/L Corticosterone (Cort) for 24 h, and then treated with 50, 100 and 200 μg/mL of HLTP for 24 h. The cell viability of damaged cells were significantly increased in a dose-dependent manner by 9.50%, 10.42% and 21.25%, respectively (P < 0.01). Western blot analysis confirmed that HLTP significantly (P < 0.01) increased the protein expression of PI3K and AKT by 15.24%, 30.44%, 41.03%, and 21.78%, 43.63%, 12.86%, respectively. In addition, through biochemical method, flow cytometry and WB analysis, we found that different concentrations of HLTP can all improve cell damage by reducing ROS, MDA, Ca2+, Cyt-C, Caspase-3, TNF-α and IL-1β, and increasing SOD, CAT, MMP, Bcl-2/Bax and IL-10. In particular, the HLTP at 200 μg/mL, compared with the Model group, decreased by 140.2%, 54.66%, 51.34%, 65.26%, 40.32%, 63.87%, and 55.38%, and increased by 39.65%, 35.45%, 38.38%, 28.54%, and 39.98%, respectively. Through the above experiments, we verified that HLTP may exert neuroprotective effects by mediating the PI3K/AKT signaling pathway to counteract oxidative stress damage, improve mitochondrial dysfunction, and alleviate inflammatory injury.

Abstract With the application of new technologies for coal mine gas control, it has been increasingly urgent to apply the fixed‐point closed sampling (FPCS) technology for accurate measurement of coal seam gas content. In this study, gas desorption during FPCS was analyzed. In addition, gas desorption experiments and COMSOL simulations were conducted on coal particles. Furthermore, the gas desorption law during FPCS was compared with that under atmospheric pressure. The results show that Sun's formula can effectively characterize the gas desorption law during FPCS, and the i value remains unchanged when the gas desorption curve is fitted with Sun's formula. On this basis, a specific method for calculating gas loss during FPCS by using Sun's formula was proposed. The research findings are expected to provide a theoretical basis for accurate measurement of coal seam gas content by means of FPCS.

Abstract Background The majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring. Methods A multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–phthalates exposure interactions. Results There was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28–2.37; dominant: aOR = 1.86, 95% CI:1.25–2.78; recessive: aOR = 2.50, 95% CI: 1.26–4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54–121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed. Conclusions The polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.

Abstract Cross-border neighboring areas could be particularly vulnerable to biological invasions due to short geographic distances and frequent interactions, although the invasion risk remains unevaluated worldwide. Here, based on global datasets of distributions of established alien vertebrates as well as vectors of introduction and establishment, we show that more than one-third of the world’s transboundary neighboring areas are facing high invasion risk of alien vertebrates, especially in Europe, North America, South Asia, and Southeast Asia. The most important predictors of high introduction and establishment risk are bilateral trade, habitat disturbance and the richness of established alien vertebrates. Interestingly, we found that border fences may have limited effects in reducing the risk, as only 7.9% of border fences spatially overlap with hotspots of biological invasion even in the Eurasia areas (13.7% overlap) where physical border barriers are mainly located. We therefore recommend the implementation of immediate and proactive prevention and control measures to cope with cross-border invasions in response to continued globalization.

Abstract. Background:. With an increasing proportion of multiparas, proper interpregnancy intervals (IPIs) are urgently needed. However, the association between IPIs and adverse perinatal outcomes has always been debated. This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages. Methods:. We used individual data from China's National Maternal Near Miss Surveillance System between 2014 and 2019. Multivariable Poisson models with restricted cubic splines were used. Each adverse outcome was analyzed separately in the overall model and stratified models. The stratified models included different categories of fertility policy periods (2014-2015, 2016-2017, and 2018-2019) and infant gestational age in previous pregnancy (

Blade wrap angle is one of the main parameters of centrifugal pump, which has an important influence on the internal flow characteristic and pump performance. In this work, five impeller models with different blade wrap angles (85°, 95°, 105°, 115°, and 125°) are established on the condition of other impeller parameters remain unchanged, whose external characteristic, internal flow, and wear were analyzed by numerical simulation method. The results show that the influence of blade wrap angle on efficiency is more significant than head, has a certain effect on the internal flow field of the centrifugal pumps and effects the wear position of pressure surface. With the increasing of blade wrap angle, the pump efficiency increases companied by the pump head decreases slightly, the area of higher speed at the outlet of the impeller tends to decrease, the higher speed wake area at the end of the blade pressure surface breaks and shrinks, the vortex in the impeller passage is fewer and smaller, the turbulent kinetic energy and morphology of vortex inside the pump decreases gradually, and the wear rate of the flow passage components shows a pattern of first decreasing and then increasing.

BackgroundIt is known that 24-hour movement behaviors, including physical activity (PA), sedentary behavior (SB), and sleep, are crucial components affecting older adults’ health. Canadian 24-hour movement guidelines for older adults were launched in 2020, emphasizing the combined role of these 3 movement behaviors in promoting older adults’ health. However, research on the prevalence and correlates of guideline adherence and its associations with health-related outcomes is limited, especially among Chinese older adults. ObjectiveThis study aimed to investigate the prevalence and correlates of meeting 24-hour movement guidelines among Chinese older adults. Furthermore, this study aimed to examine the associations of guideline adherence with older adults’ physical and mental health outcomes. MethodsUsing a stratified cluster random sampling approach, a total of 4562 older adults (mean age 67.68 years, SD 5.03 years; female proportion: 2544/4562, 55.8%) were recruited from the latest provincial health surveillance of Hubei China from July 25 to November 19, 2020. Measures included demographics, movement behaviors (PA, SB, and sleep), BMI, waist circumference, waist-hip ratio (WHR), percentage body fat (PBF), systolic and diastolic blood pressure, physical fitness, depressive symptoms, and loneliness. Generalized linear mixed models were employed to examine the associations between variables using SPSS 28.0 (IBM Corp). ResultsOnly 1.8% (83/4562) of participants met all 3 movement guidelines, while 32.1% (1466/4562), 3.4% (155/4562), and 66.4% (3031/4562) met the individual behavioral guidelines for PA, SB, and sleep, respectively. Participants who were older, were female, and lived in municipalities with lower economic levels were less likely to meet all 3 movement guidelines. Adhering to individual or combined movement guidelines was associated with greater physical fitness and lower values of BMI, waist circumference, WHR, PBF, depressive symptoms, and loneliness, with the exception of the relationship of SB+sleep guidelines with loneliness. Furthermore, only meeting SB guidelines or meeting both PA and SB guidelines was associated with lower systolic blood pressure. ConclusionsThis is the first study to investigate adherence to 24-hour movement guidelines among Chinese older adults with regard to prevalence, correlates, and associations with physical and mental health outcomes. The findings emphasize the urgent need for promoting healthy movement behaviors among Chinese older adults. Future interventions to improve older adults’ physical and mental health should involve enhancing their overall movement behaviors and should consider demographic differences.

Mulberry has also been regarded as a valuable source of forage for ruminants. This study was developed to investigate the impact of four additives and combinations thereof on fermentation quality and bacterial communities associated with whole-plant mulberry silage. Control fresh material (FM) was left untreated, while other groups were treated with glucose (G, 20 g/kg FM), a mixture of Lactobacillus plantarum and L. buchneri (L, 106 CFU/g FM), formic acid (A, 5 mL/kg FM), salts including sodium benzoate and potassium sorbate (S, 1.5 g/kg FM), a combination of G and L (GL), a combination of G and A (GA), or a combination of G and S (GS), followed by ensiling for 90 days. Dry matter content in the A, S, GA, and GS groups was elevated relative to the other groups (p

Background: Constipation is one of the chronic gastrointestinal functional diseases that affects the quality of life. While Qi Lang Formula (QLF) has demonstrated effectiveness in alleviating constipation symptoms, its precise mechanism remains elusive. Methods: QLF was analyzed using UPLC-MS/MS. Targets for QLF were collected from SwissADME, Herb, ITCM databases, and constipation-related targets from scRNA-seq and Genecards databases. Overlapping targets suggested potential QLF therapy targets for constipation. Enrichment analysis used the KOBAS database. A ''drug-ingredient-target'' network was constructed with Cytoscape, and AutoDock verified active ingredient binding. H&E staining assessed colonic mucosa changes, TEM examined ICC structural changes. ELISA measured neurotransmitter levels, and Western blot verified QLF's effect on target proteins. ICC proliferation was observed through immunofluorescence. Results: We identified 89 targets of QLF associated with ICC-related constipation, with c-Kit emerging as the pivotal target. Molecular docking studies revealed that Atractylenolide Ⅲ, Apigenin, Formononetin, Isorhamnetin, Naringenin, and Ononin exhibited strong binding affinities for the c-Kit structural domain. QLF significantly enhanced first stool passage time, fecal frequency, fecal moisture content, and intestinal propulsion rate. Further analysis unveiled that QLF not only restored neurotransmitter levels but also mitigated colon muscular fiber ruptures. ICC ultrastructure exhibited partial recovery, while Western blot confirmed upregulated c-Kit expression and downstream targets. Immunofluorescence results indicated ICC proliferation post QLF treatment in rat colon. Conclusion: Our findings suggest that QLF may promote ICC proliferation by targeting SCF/c-Kit and its downstream signaling pathway, thereby regulating intestinal motility.

Objective: Preeclampsia is a serious pregnancy complication that jeopardizes the health of both the mother and the fetus. Platelet parameters are closely linked to the severity of preeclampsia. This study aimed to assess the diagnostic potential of platelet parameters in the early second trimester for the detection of preeclampsia. Methods: A total of 840 participants from the Affiliated Hospital of Jining Medical College were included in the study, consisting of 327 healthy pregnant women, 209 with mild preeclampsia, and 304 with severe preeclampsia. General clinical data and platelet parameters for these three groups of pregnant women were collected, and differences among them were compared. In addition, univariate analysis and logistic regression were used to identify preeclampsia risk factors, and receiver operating characteristic curve analysis was conducted to assess the predictive value of platelet parameters. Results: Platelet count was not found to significantly differ between the healthy and preeclampsia groups. However, mean platelet volume, platelet distribution width (PDW), and platelet?large cell ratios (P-LCR) were observed to be significantly higher in the preeclampsia group than the healthy group. After adjusting for confounding factors (such as age, gestational week at blood sampling, systolic and diastolic blood pressure, and body mass index during the second trimester), it was determined that PDW and P-LCR could be considered effective predictors of preeclampsia. Conclusion: In clinical practice, P-LCR and PDW hold potential predictive value for preeclampsia.

Determining suitable irrigation technology is of paramount for promoting water-saving agriculture, particularly for winter wheat-summer maize rotation system in well-irrigated regions. To optimize and assess the efficacy of various irrigation technologies (specifically, semi-fixed sprinkler irrigation, walking sprinkler, semi-automatic buried telescopic sprinkler irrigation, thin-soft spray tape irrigation, drip irrigation, self-driven winch sprinkler and manually moving spray gun irrigation, marked as A, B, C, D, E, F and G) applied in south central North China Plain, we first conducted an economic analysis for the winter wheat-summer maize rotation. Subsequently, employing a comprehensive set of 20 indicators spanning economic, societal, technological, ecological, and resource aspects, we employed a TOPSIS model with integrative weighting approach using “AHP + Entropy”. We also employed principal component analysis and the Sankey diagram method to explore characteristics of different irrigation techniques and indexes. Irrigation mode E, conserving energy by 63.19% compared to mode B and offering labor savings five times greater than the mode D. The highest economic benefit for the rotation system was observed with the mode C, resulting in a 25.26% increase compared to the mode G. The top three irrigation modes based on scores were D, G, and E, with scores of 0.532, 0.490, and 0.474, respectively. The Sankey diagram revealed distinct preferences among different agricultural entities for specific irrigation modes. For specific stakeholders, we recommend irrigation modes D, G, F, and B for small farmers, large and specialized family businesses, family farms, and farmer cooperatives, respectively. In conclusion, our findings provide valuable scientific support and recommendations for the practical application of irrigation technology in agricultural production.

Abstract Background The competing interests of the government, smart senior care technology service providers, and older adults have led to a serious fragmentation of governance in China. This study aims to identify the collaboration mechanisms and evolutionary stabilization strategies for these agents. Methods An evolutionary game model is developed to analyze the strategic decisions made by the government, smart senior care technology service providers, and older adults. A sensitivity analysis is conducted using data from Anhui Province, China, to verify the effects of relevant parameters on the strategy decisions of each agent. Results The results of the simulation and sensitivity analysis indicated that, first, despite changes in the initial willingness values of the tripartite agents, the system eventually converges on 1. Second, the collaboration mechanism of the tripartite agents in the smart senior care system is related to government incentives, penalties, and subsidies, smart senior care service costs, and the additional benefits provided to smart senior care technology service providers. Conclusion The strategy decisions of the government, providers, and older adults interact with each other. To promote collaboration among the tripartite agents and improve governance effectiveness, the government should strengthen the regulations for providers, increase penalties for providers that engage in a breach of trust, provide moderate incentives and subsidies, and control smart senior care service costs.

The blood–brain barrier (BBB) impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases (AAND). Meanwhile, circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity of neurological diseases in the accelerated aging population. Importantly, circadian rhythms disruption and gut microbiota dysbiosis are also known to induce the generation of toxic metabolites and pro-inflammatory cytokines, resulting in disruption of BBB integrity. Collectively, this provides a new perspective for exploring the relationship among circadian rhythms, gut microbes, and the BBB in aging-accompanied neurological diseases. In this review, we focus on recent advances in the interplay between circadian rhythm disturbances and gut microbiota dysbiosis, and their potential roles in the BBB disruption that occurs in AAND. Based on existing literature, we discuss and propose potential mechanisms underlying BBB damage induced by dysregulated circadian rhythms and gut microbiota, which would serve as the basis for developing potential interventions to protect the BBB in the aging population through targeting the BBB by exploiting its links with gut microbiota and circadian rhythms for treating AAND.

Abstract In an era of increasing need for precision medicine, machine learning has shown promise in making accurate acute myocardial infarction outcome predictions. The accurate assessment of high-risk patients is a crucial component of clinical practice. Type 2 diabetes mellitus (T2DM) complicates ST-segment elevation myocardial infarction (STEMI), and currently, there is no practical method for predicting or monitoring patient prognosis. The objective of the study was to compare the ability of machine learning models to predict in-hospital mortality among STEMI patients with T2DM. We compared six machine learning models, including random forest (RF), CatBoost classifier (CatBoost), naive Bayes (NB), extreme gradient boosting (XGBoost), gradient boosting classifier (GBC), and logistic regression (LR), with the Global Registry of Acute Coronary Events (GRACE) risk score. From January 2016 to January 2020, we enrolled patients aged > 18 years with STEMI and T2DM at the Affiliated Hospital of Zunyi Medical University. Overall, 438 patients were enrolled in the study [median age, 62 years; male, 312 (71%); death, 42 (9.5%]). All patients underwent emergency percutaneous coronary intervention (PCI), and 306 patients with STEMI who underwent PCI were enrolled as the training cohort. Six machine learning algorithms were used to establish the best-fit risk model. An additional 132 patients were recruited as a test cohort to validate the model. The ability of the GRACE score and six algorithm models to predict in-hospital mortality was evaluated. Seven models, including the GRACE risk model, showed an area under the curve (AUC) between 0.73 and 0.91. Among all models, with an accuracy of 0.93, AUC of 0.92, precision of 0.79, and F1 value of 0.57, the CatBoost model demonstrated the best predictive performance. A machine learning algorithm, such as the CatBoost model, may prove clinically beneficial and assist clinicians in tailoring precise management of STEMI patients and predicting in-hospital mortality complicated by T2DM.

Cerebral ischemia is currently the third leading cause of death worldwide. Among its complications, cerebral ischemia-reperfusion (I/R) is considered the most inevitable problem. To address this condition, there is a need for the development of more drugs. Wedelolactone, the main active chemical component extracted from dried lotus leaves, exhibits a wide range of pharmacological effects. Here we constructed an oxygen-glucose deprivation/reperfusion (OGD/R) model. Cell counting kit-8 (CCK-8) assays evaluated the impact of Wedelolactone on cell growth. Real-time quantitative polymerase chain reaction (RT-qPCR) assessed its effects on inflammation. We employed 2′,7′-Dichlorofluorescein (DCF) staining and an iron detection kit to measure ferroptosis. Flow cytometry (FCM) and immunoblot assays were utilized to investigate cell apoptosis. The results showed that Wedelactone promoted OGD-induced HT-22 cell viability and alleviated OGD/R-induced cellular inflammation, OGD/R-stimulated ferroptosis and OGD/R-induced apoptosis. Mechanically, Wedelactone inhibited OGD/R-stimulated ferroptosis via mediating glutathione peroxidase 4 (GPX4) expression. In conclusion, Wedelolactone may attenuate cerebral ischemia-reperfusion (CIR)/I by blocking GPX4-mediated ferroptosis.

Small UAV target detection and tracking based on cross-modality image fusion have gained widespread attention. Due to the limited feature information available from small UAVs in images, where they occupy a minimal number of pixels, the precision required for detection and tracking algorithms is particularly high in complex backgrounds. Image fusion techniques can enrich the detailed information for small UAVs, showing significant advantages under extreme lighting conditions. Image registration is a fundamental step preceding image fusion. It is essential to achieve accurate image alignment before proceeding with image fusion to prevent severe ghosting and artifacts. This paper specifically focused on the alignment of small UAV targets within infrared and visible light imagery. To address this issue, this paper proposed a cross-modality image registration network based on deep learning, which includes a structure preservation and style transformation network (SPSTN) and a multi-level cross-attention residual registration network (MCARN). Firstly, the SPSTN is employed for modality transformation, transferring the cross-modality task into a single-modality task to reduce the information discrepancy between modalities. Then, the MCARN is utilized for single-modality image registration, capable of deeply extracting and fusing features from pseudo infrared and visible images to achieve efficient registration. To validate the effectiveness of the proposed method, comprehensive experimental evaluations were conducted on the Anti-UAV dataset. The extensive evaluation results validate the superiority and universality of the cross-modality image registration framework proposed in this paper, which plays a crucial role in subsequent image fusion tasks for more effective target detection.

For modern radar systems, small unmanned aerial vehicles (UAVs) belong to a typical types of targets with ‘low, slow, and small’ characteristics. In complex combat environments, the functional requirements of radar systems are not only limited to achieving stable detection and tracking performance but also to effectively complete the recognition of small UAV targets. In this paper, a multi-dimensional feature fusion framework for small UAV target recognition utilizing a small-sized and low-cost high-resolution radar is proposed, which can fully extract and combine the geometric structure features and the micro-motion features of small UAV targets. For the performance analysis, the echo data of different small UAV targets was measured and collected with a millimeter-wave radar, and the dataset consists of high-resolution range profiles (HRRP) and micro-Doppler time–frequency spectrograms was constructed for training and testing. The effectiveness of the proposed method was demonstrated by a series of comparison experiments, and the overall accuracy of the proposed method can reach 98.5%, which demonstrates that the proposed multi-dimensional feature fusion method can achieve better recognition performance than that of classical algorithms and higher robustness than that of single features for small UAV targets.

Neuronopathy, distal hereditary motor, type VIII is an exceedingly rare autosomal dominant genetic disorder, also known as congenital non-progressive distal spinal muscular atrophy. It is characterized by progressive weakness in distal motor function and atrophy of muscles, without accompanying sensory impairment. Presently, there is limited literature on this condition, and accurate epidemiological data regarding its incidence remains unavailable. We report a paediatric case of distal hereditary motor, type VIII that is caused by a heterozygous missense mutation in the TRPV4 gene (NM_021625): c.805C>T. The proband is a 7-year-old male child. During pregnancy, his mother had prenatal ultrasound revealing “inward turning of the feet”, a condition persisting after birth. The proband is currently unable to stand independently, exhibiting bilateral clubfoot deformity. Although possessing normal cognitive function, he cannot walk unaided. Computed radiography findings reveal pelvic tilt, bilateral knee joint valgus, and bilateral clubfoot. The patient underwent familial exome sequencing, revealing a mutation in the TRPV4 gene (NM_021625): c.805C>T (p.Arg269Cys). Considering the patient’s medical history, clinical manifestations, imaging studies, and genetic test results, the diagnosis for this individual is Neuronopathy, distal hereditary motor, type VIII. This report documents a case involving the TRPV4 gene mutation associated with Neuronopathy, distal hereditary motor, type VIII, contributing valuable case reference for the early diagnosis of this condition.

The intricate relationship between resistant starch (RS) and the gut microbiome presents a dynamic frontier in nutrition science. This review synthesizes current understandings of how RS, an indigestible form of starch found naturally in certain foods and also enhanced through various modification methods, interacts with the gut microbiome. We particularly focus on how RS fermentation in the colon contributes to the production of beneficial volatile fatty acids (VFAs) such as butyrate, acetate, and propionate. These VFAs have been recognized for their vital roles in maintaining gut barrier integrity, modulating inflammation, and potentially influencing systemic health. Additionally, we discuss the dietary implications of consuming foods rich in RS, both in terms of gut health and broader metabolic outcomes. By consolidating these insights, we emphasize the significance of RS in the context of dietary strategies aimed at harnessing the gut microbiome's potential to impact human health.

Objective: To systematically review the efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD).Methods: We systematically searched six databases to identify randomized controlled trials (RCTs) about nonsteroidal MRAs for CKD, from inception to 22 August 2023. Two reviewers independently screened the retrieved articles, extracted data, and assessed the risk of bias of included RCTs using the Cochrane risk of bias tool. We then conducted meta-analysis of the data using Stata 17.0 software.Results: 11 RCTs (n = 15,817) were included in this meta-analysis. Compared with placebo, nonsteroidal MRAs significantly reduced the proportion of patients with ≥40% decline in estimated glomerular filtration rate (eGFR) from baseline [RR = 0.85, 95% CI (0.78, 0.92), p < 0.001], although the magnitude of eGFR reduction was greater [WMD = −2.83, 95% CI (−3.95, −1.72), p < 0.001]. The experimental group also had lower incidence of composite renal outcome [RR = 0.86, 95% CI (0.79, 0.93), p < 0.001] and greater reduction in urine albumin-to-creatinine ratio (UACR) from baseline [WMD = −0.41, 95% CI (−0.49, −0.32), p < 0.001], as well as reduced cardiovascular events [RR = 0.88, 95% CI (0.80, 0.95), p = 0.003]. MRAs did not increase any adverse events compared to placebo [RR = 1.00, 95% CI (0.99, 1.01), p = 0.909], but had higher incidence of hyperkalemia [RR = 2.05, 95% CI (1.85, 2.280), p < 0.001]. Compared with eplerenone, there was no significant difference in the proportion of patients with ≥40% decline in eGFR [RR = 0.57, 95% CI (0.18, 1.79), p = 0.335] or hyperkalemia [RR = 0.95, 95%CI (0.48, 1.88), p = 0.875].Conclusion: Nonsteroidal MRAs can reduce the incidence of end-stage renal disease and cardiovascular adverse events in patients. Although there was still a risk of hyperkalemia compared to placebo, there was no significant difference in any adverse events compared to either placebo or eplerenone. It has become a new option for drug treatment of CKD patients, but more clinical trials are still needed to verify its efficacy and safety. Especially further direct comparison of the nonsteroidal MRAs to eplerenone in view of the relatively small number of patients reviewed are needed.

''Fruitless Lycium barbarum leaf (FLBL) are the leaves of a new variety of Lycium barbarum in Ningxia, which exhibit higher content of various nutrients, trace elements, and bioactive substances compared to Lycium barbarum fruits and leaves. However, the health and medicinal value as well as the by-products derived from FLBL have not received sufficient attention, and the contents of main components vary at different harvesting periods. Therefore, for the first time this study aimed to establish high-performance liquid chromatography (HPLC) fingerprints and determine the contents of four phenolic acid bioactive substances during different harvesting periods in order to provide an experimental basis for cultivation, collection, and research on FLBL. The results revealed 17 common peaks among 10 batches samples with a similarity ranging from 0.71 to 0.976. The linear relationships R2 for catechin, epicatechin-catechin, chlorogenic acid, and rutin were determined as 0.9999 each; meanwhile, the average recovery rate ranged from 93.92 % to 120.11 %, with an RSD between 0.91 % and 2.82 %. The precision, repeatability stability (24 h), and recovery rate met the requirements outlined in ''Chinese Pharmacopoeia''. Catechin, epicatechin, and rutin exhibited higher levels from June to August, while chlorogenic acid showed increased levels from July to September. The findings serve as a foundation for quality control measures such as identifying optimal harvest periods or facilitating development and production processes related to Ningxia FLBL.''

Biological specimens are fundamental for taxonomy and flora/fauna research. More importantly, they also play crucial roles in recording environmental impacts on morphology and behavior, which is vital for biodiversity research and conservation. However, there are few systematic studies on the patterns and drivers of bird specimen number at regional scales. This study is the first attempt to examine the relationships between bird specimen number and species traits as well as climate niche breadth in China, aiming to answer two questions: 1) how do species’ temperature niche breadth and precipitation niche breadth influence specimen number? 2) which trait is most associated with bird specimen number? The associations between bird specimen number and explanatory variables were examined using ordinary least squares, generalized linear models, phylogenetic generalized linear mixed models, and multiple comparisons. The results showed that Muscicapidae was the family with the highest specimen number, and Passeriformes was the order with the highest specimen number. Bird specimen number significantly increased with larger temperature niche breadth and precipitation niche breadth. Specimen number was also positively associated with geographic range size, habitat specificity, hunting vulnerability and clutch size, but negatively associated with body size. These findings suggest that future bird specimen collection should pay more attention to birds with limited ecological niches, large body sizes, and small clutch sizes. This research enhances the use of bird specimen data to study and preserve biodiversity.

Introduction: Shizao decoction (SZD) is a traditional Chinese medicine decoction that has therapeutic effects on cirrhotic ascites (CAS). Because of the unclear treatment mechanism, in the current study, the anti-CAS activity of SZD and molecular mechanisms were analyzed by network analysis combined with pharmacokinetics and metabolomics.Methods: Firstly, we assessed the anti-CAS efficacy of SZD by hematoxylin-eosin (H&E), liver function tests, NO and ET-1 levels, and portal venous pressure. Secondly, network analysis was applied to dig out the metabolites, targets, and pathways related to SZD and CAS. Then, the pharmacokinetics of the pharmacokinetically relevant metabolites (PRM) were analyzed. Thirdly, the serum and urine metabolic biomarkers of rats with CAS were identified using metabolomics by comparing them with the SZD treatment group. In addition, MetaboAnalyst was utilized to conduct metabolic pathway analysis. Finally, the correlation analysis established a dynamic connection between absorbed PRM from SZD and CAS-associated endogenous metabolites.Results: Pharmacodynamic analysis indicated that SZD effectively mitigated liver injury symptoms by ameliorating inflammatory cell infiltration in CAS rats. The network analysis results indicated that twelve RPM contribute to the therapeutic efficacy of SZD against CAS; the key signaling pathways involved might be hepatitis B and PI3K-Akt. Pharmacokinetics results showed that the 12 RPM were efficiently absorbed into rat plasma, ensuring desirable bioavailability. The metabolomic analysis yielded 21 and 23 significantly distinct metabolites from the serum and urine, respectively. The 12 bioavailable SZD-PRM, such as luteolin, apigenin, and rutin, may be associated with various CAS-altered metabolites related to tryptophan metabolism, alpha-linolenic acid metabolism, glycine metabolism, etc.Discussion: A novel paradigm was provided in this study to identify the potential mechanisms of pharmacological effects derived from a traditional Chinese medicine decoction.

Abstract Background Fabry disease (FD) is a progressive multisystemic disease characterized by a lysosomal enzyme deficiency. A lack of α-galactosidase A (α-Gal A) activity results in the progressive systemic accumulation of its substrates, including globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3), which results in renal, cardiac, and/or cerebrovascular disease and early death. Enzyme replacement therapy (ERT) is the current standard of care for FD; however, it has important limitations, including a low half-life, limited distribution, and requirement of lifelong biweekly infusions of recombinant enzymes. Methods Herein, we evaluated a gene therapy approach using an episomal adeno-associated viral 2/8 (AAV2/8) vector that encodes the human GLA cDNA driven by a liver-specific expression cassette in a mouse model of FD that lacks α-Gal A activity and progressively accumulates Gb3 and Lyso-Gb3 in plasma and tissues. Results A pharmacology and toxicology study showed that administration of AAV2/8-hGLA vectors (AAV2/8-hGLA) in FD mice without immunosuppression resulted in significantly increased plasma and tissue α-Gal A activity and substantially normalized Gb3 and Lyso-Gb3 content. Conclusions Moreover, the plasma enzymatic activity of α-Gal A continued to be stably expressed for up to 38 weeks and sometimes even longer, indicating that AAV2/8-hGLA is effective in treating FD mice, and that α-Gal A is continuously and highly expressed in the liver, secreted into plasma, and absorbed by various tissues. These findings provide a basis for the clinical development of AAV2/8-hGLA.

Abstract Background Whole-genome doubling (WGD) has been observed in 30% of cancers, followed by a highly complex rearranged karyotype unfavourable to breast cancer's outcome. However, the macro-alterations that characterise liver metastasis in breast cancer(BC) are poorly understood. Here, we conducted a whole-genome sequencing analysis of liver metastases to explore the status and the time frame model of these macro-alterations in pre-treatment patients with metastatic breast cancer. Results Whole-genome sequencing was conducted in 11 paired primary tumours, lymph node metastasis, and liver metastasis fresh samples from four patients with late-stage breast cancer. We also chose five postoperative frozen specimens from patients with early-stage breast cancer before any treatment as control. Surprisingly, all four liver metastasis samples were classified as WGD + . However, the previous study reported that WGD happened in 30% of cancers and 2/5 in our early-stage samples. WGD was not observed in the two separate primary tumours and one lymph node metastasis of one patient with metastatic BC, but her liver metastasis showed an early burst of bi-allelic copy number gain. The phylogenetic tree proves her 4 tumour samples were the polyclonal origin and only one WGD + clone metastasis to the liver. Another 3 metastatic BC patients’ primary tumour and lymph node metastasis experienced WGD as well as liver metastasis, and they all showed similar molecular time-frame of copy number(CN) gain across locations within the same patient. These patients’ tumours were of monoclonal origin, and WGD happened in a founding clone before metastasis, explaining that all samples share the CN-gain time frame. After WGD, the genomes usually face instability to evolve other macro-alterations. For example, a greater quantity and variety of complex structural variations (SVs) were detected in WGD + samples. The breakpoints were enriched in the chr17: 39 Mb-40 Mb tile, which contained the HER2 gene, resulting in the formation of tyfonas, breakage-fusion-bridge cycles, and double minutes. These complex SVs may be involved in the evolutionary mechanisms of the dramatic increase of HER2 copy number. Conclusion Our work revealed that the WGD + clone might be a critical evolution step for liver metastasis and favoured following complex SV of breast cancer.

The improvement in the utilization rate and nutritional value of soybean meal (SBM) represents a significant challenge in the feed industry. This study conducted a 50 kg SBM fermentation based on the 300 g small-scale fermentation of SBM in early laboratory research, to explore the combined effects of lactic acid bacteria (LAB) and acid protease on fermentation quality, chemical composition, microbial population, and macromolecular protein degradation during fermentation and aerobic exposure of SBM in simulated actual production. The results demonstrated that the increase in crude protein content and reduction in crude fiber content were considerably more pronounced after fermentation for 30 days (d) and subsequent aerobic exposure, compared to 3 d. It is also noteworthy that the treated group exhibited a greater degree of macromolecular protein degradation relative to the control and 30 d of fermentation relative to 3 d. Furthermore, after 30 d of fermentation, adding LAB and protease significantly inhibited the growth of undesired microbes including coliform bacteria and aerobic bacteria. In the mixed group, the microbial diversity decreased significantly, and Firmicutes replaced Cyanobacteria for bacteria in both groups’ fermentation.

Whole crop corn silage (WCCS) been an important source of roughage for confined ruminants. However, at the silage feed-out phase, the rise in temperature and relative humidity under aerobic conditions breeds the production of undesirable microorganisms, such as yeast and mold. In order to investigate the conservation characteristics and aerobic stability underlying the effects of additives in whole crop corn silage (WCCS), whole crop corn (WCC) at the milk-ripe stage was ensiled with Lentilactobacillus (L.) buchneri (LB) and different proportions of Artemisia argyi (AA) for 90 days (d) at room temperature, respectively, and aerobic exposure after 90 d fermentation was also conducted. The study found that AA as an additive improved the fermentation quality and enhanced aerobic stability of WCCS, for which the addition of 60% AA increased the lactic acid fermentation rate, with the lactic acid concentration at the end of aerobic exposure significantly higher than in all other treatment groups, at 98.21 g/kg DM (p < 0.01), which decreased the relative abundance of none wanted microorganisms and reduced the content of fungal toxins (p < 0.05). After 90 d of fermentation, LB also increased the organic acids and reduced the pH compared with control, thereby improving fermentation quality. Furthermore, we also discovered that the relative abundance of Candida within the 60% AA was the highest. Candida have the ability to convert WSC into organic acids and lower pH, thus improving the quality of silage. Particularly, 60% AA could improve the fermentation quality and aerobic stability of silage through the biosynthetic pathways of phenylalanine, tyrosine and tryptophan, as well as by participation in the hydrolysis of glycoside hydrolases (GHs). Unexpectedly, the addition of AA was found to reduce the relative abundance of antibiotic resistance genes. WCC, ensiled with 60% AA, exhibited excellent fermentation quality and aerobic stability, providing a theoretical basis for understanding the mechanisms of AA which improve the quality of WCCS during the aeration phase.

In a community, due to the different characteristics of each species, their contributions to community beta diversity may vary. Quantifying the contribution of each species to overall beta diversity (SCBD) is essential for explaining the patterns of beta diversity. However, there is currently limited research linking SCBD with species functional traits, and how species functional traits influence SCBD remains unclear. This study is based on tree census data, species functional traits, and environmental variables from a 15 ha permanent monitoring plot in a tropical karst rainforest in south China. By calculating species-specific SCBD based on abundance and presence–absence data, as well as functional distinctiveness and species ecological niche characteristics (niche position and niche width), we applied structural equation modeling (SEM) to analyze how functional traits, distinctiveness, and niche characteristics jointly influence SCBD. The results revealed that SCBD based on abundance is positively correlated with occupancy and abundance, whereas SCBD based on presence–absence data exhibits a hump-shaped relationship with occupancy and abundance. Species ecological niche characteristics directly influence SCBD, with species occupying central ecological niches having a negative effect on SCBD and niche width having a positive effect. Functional traits and functional distinctiveness indirectly impact SCBD through their influence on species ecological niche characteristics. SEM models based on the presence–absence data provide higher explanatory power. In summary, in the seasonal rainforest communities of northern tropical karst regions in China, the combined effects of species’ functional traits, functional distinctiveness, and ecological niche characteristics determine SCBD. This not only contributes to a deeper understanding of how species traits influence β-diversity, making SCBD a more applicable tool for biodiversity conservation, but also allows for the development of more effective biodiversity protection strategies by elucidating the link between SCBD and ecosystem multifunctionality.

Strengthening the interfacial contact between the reactive components effectively boosts the energy release of energetic materials. In this study, we aimed to create a close-knit interfacial contact condition between aluminum nanoparticles (Al NPs) and Polyvinylidene fluoride-hexafluoropropylene (P(VDF-HFP)) through hydrolytic adsorption and assembling 1H, 1H, 2H, 2H-Perfluorododecyltrichlorosilane (FTCS) on the surface of Al NPs. Leveraging hydrogen bonding between –CF and –CH and the interaction between C–F⋯F–C groups, the adsorbed FTCS directly leads to the growth of the P(VDF-HFP) coating layer around the treated Al NPs, yielding Al@FTCS/P(VDF-HFP) energetic composites. In comparison with the ultrasonically processed Al/P(VDF-HFP) mixture, thermal analysis reveals that Al@FTCS/P(VDF-HFP) exhibits a 57 °C lower reaction onset temperature and a 1646 J/g increase in heat release. Associated combustion tests demonstrate a 52% shorter ignition delay, 62% shorter combustion time, and a 288% faster pressurization rate. These improvements in energetic characteristics stem from the reactivity activation of FTCS towards Al NPs by the etching effect to the surface Al2O3. Moreover, enhanced interfacial contact facilitated by the FTCS-directed growth of P(VDF-HFP) around Al NPs further accelerates the whole reaction process.

Three-dimensional SAR imaging of urban buildings is currently a hotspot in the research area of remote sensing. Synthetic Aperture Radar (SAR) offers all-time, all-weather, high-resolution capacity, and is an important tool for the monitoring of building health. Buildings have geometric distortion in conventional 2D SAR images, which brings great difficulties to the interpretation of SAR images. This paper proposes a novel Rotating SAR (RSAR) mode, which acquires 3D information of buildings from two different angles in a single rotation. This new RSAR mode takes the center of a straight track as its rotation center, and obtains images of the same facade of a building from two different angles. By utilizing the differences in geometric distortion of buildings in the image pair, the 3D structure of the building is reconstructed. Compared to the existing tomographic SAR or circular SAR, this method does not require multiple flights in different elevations or observations from varying aspect angles, and greatly simplifies data acquisition. Furthermore, both simulation analysis and actual data experiment have verified the effectiveness of the proposed method.

Addressing common challenges such as limited indicators, poor adaptability, and imprecise modeling in gas pre-warning systems for driving faces, this study proposes a hybrid predictive and pre-warning model grounded in time-series analysis. The aim is to tackle the effects of broad application across diverse mines and insufficient data on warning accuracy. Firstly, we introduce an adaptive normalization (AN) model for standardizing gas sequence data, prioritizing recent information to better capture the time-series characteristics of gas readings. Coupled with the Gated Recurrent Unit (GRU) model, AN demonstrates superior forecasting performance compared to other standardization techniques. Next, Ensemble Empirical Mode Decomposition (EEMD) is used for feature extraction, guiding the selection of the Variational Mode Decomposition (VMD) order. Minimal decomposition errors validate the efficacy of this approach. Furthermore, enhancements to the transformer framework are made to manage non-linearities, overcome gradient vanishing, and effectively analyze long time-series sequences. To boost versatility across different mining scenarios, the Optuna framework facilitates multiparameter optimization, with xgbRegressor employed for accurate error assessment. Predictive outputs are benchmarked against Recurrent Neural Networks (RNN), GRU, Long Short-Term Memory (LSTM), and Bidirectional LSTM (BiLSTM), where the hybrid model achieves an R-squared value of 0.980975 and a Mean Absolute Error (MAE) of 0.000149, highlighting its top performance. To cope with data scarcity, bootstrapping is applied to estimate the confidence intervals of the hybrid model. Dimensional analysis aids in creating real-time, relative gas emission metrics, while persistent anomaly detection monitors sudden time-series spikes, enabling unsupervised early alerts for gas bursts. This model demonstrates strong predictive prowess and effective pre-warning capabilities, offering technological reinforcement for advancing intelligent coal mine operations.

High-pixel-number synchrotron radiation computed tomography (CT) has the advantages of high sensitivity, high resolution, and a large field of view. It has been widely used in biomedicine, cultural heritage research, non-destructive testing, and other fields. The Nyquist sampling theorem states that when the detector’s pixels per row are increased, it requires more CT projections, resulting in a lengthened CT scan time and increased radiation damage. Sparse-view CT can significantly reduce radiation damage and improve the projection data acquisition speed. However, there is insufficient sparse projection data, and the slices reconstructed show aliasing artifacts. Currently, aliasing artifact correction processes more medical CT images, and the number of pixels of such images is small (mainly 512×512 pixels). This paper presents an aliasing artifact correction algorithm based on deep learning for synchrotron radiation CT with a high pixel number (1728×1728 pixels). This method crops high-pixel-number CT images with aliasing artifacts into patches with overlapping features. During the network training process, a convolutional neural network is utilized to enhance the details of the patches, after which the patches are reintegrated into a new CT slice. Subsequently, the network parameters are updated to optimize the new CT slice that closely approximates the full-view slice. To align with practical application requirements, the neural network is trained using only three samples to optimize network parameters and applied successfully to untrained samples for aliasing artifact correction. Comparative analysis with typical deep learning aliasing artifact correction algorithms demonstrates the superior ability of our method to correct aliasing artifacts while preserving image details more effectively. Furthermore, the effect of aliasing artifact correction at varying levels of projection sparsity is investigated, revealing a positive correlation between image quality after deep learning processing and the number of projections. However, the trade-off between rapid experimentation and artifact correction remains a critical consideration.

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and is notorious for its resistance to both chemotherapy and small-molecule inhibitor targeted therapies. Subcellular targeted cancer therapy may thwart the resistance to produce a substantial effect. Methods We tested whether the resistance can be circumvented by subcellular targeted cancer therapy with DZ-CIS, which is a chemical conjugate of the tumor-cell specific heptamethine carbocyanine dye (HMCD) with cisplatin (CIS), a chemotherapeutic drug with limited use in ccRCC treatment because of frequent renal toxicity. Results DZ-CIS displayed cytocidal effects on Caki-1, 786-O, ACHN, and SN12C human ccRCC cell lines and mouse Renca cells in a dose-dependent manner and inhibited ACHN and Renca tumor formation in experimental mouse models. Noticeably, in tumor-bearing mice, repeated DZ-CIS use did not cause renal toxicity, in contrast to the CIS-treated control animals. In ccRCC tumors, DZ-CIS treatment inhibited proliferation markers but induced cell death marker levels. In addition, DZ-CIS at half maximal inhibitory concentration (IC50) sensitized Caki-1 cells to small-molecule mTOR inhibitors. Mechanistically, DZ-CIS selectively accumulated in ccRCC cells’ subcellular organelles, where it damages the structure and function of mitochondria, leading to cytochrome C release, caspase activation, and apoptotic cancer cell death. Conclusions Results from this study strongly suggest DZ-CIS be tested as a safe and effective subcellular targeted cancer therapy.