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OBJECTIVES Ascending to altitudes >2500 m may lead to acute mountain sickness (AMS). METHODS The demographics, height, weight, body mass index (BMI), smoking, and alcohol consumption of 104 healthy controls were collected in Chengdu (500 m). Heart rate (HR), saturation of pulse oxygen (SpO2), and AMS-related symptoms were collected in Hoh Xil (4200 m). A headache with Lake Louise score ≥3 was defined as AMS. RESULTS The incidence of AMS was 60.58%. AMS group had a lower SpO2 and higher HR than non-AMS group. Alcohol consumption seemed a risk factor for AMS. There was no difference in the BMI, age, height, weight, and smoking between AMS and non-AMS groups. The most common AMS symptom was headache, followed by dyspnea, insomnia, dizziness, lassitude, and anorexia. Women were prone to suffer from dizziness. The value of SpO2 and HR was improved both in AMS and non-AMS groups after hypoxia acclimatization, and the value showed greater improvement in AMS group. Oxygen therapy decreased the AMS-induced tachycardia, which had no any effect on SpO2 and symptom alleviating time. CONCLUSION Lower SpO2 and higher HR following exposure to high altitude were associated with AMS susceptibility. The anthropometric data changes were larger in AMS group than non-AMS group before and after hypoxia acclimatization.

ABSTRACT: Bile acids are cholesterol-derived molecules that are primarily produced in the liver. In nonruminants with fatty liver, overproduction of bile acids is associated with liver injury. During the transition period, fatty liver is a metabolic disorder that can affect up to 50% of high-producing dairy cows. The purpose of this study was to provide a comprehensive evaluation of hepatic bile acid metabolism in dairy cows with fatty liver by assessing the expression changes of genes involved in bile acid synthesis, export, and uptake. The serum activities of aspartate aminotransferase, alanine aminotransferase, and glutamate dehydrogenase and the concentration of total bile acids were all greater, whereas the serum concentration of total cholesterol was lower in cows with fatty liver than in healthy cows. The content of total bile acids was higher, but total cholesterol was slightly lower in liver tissues from fatty liver cows than from healthy cows. The hepatic mRNA abundance of cholesterol 7a-hydroxylase (CYP7A1); hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid delta-isomerase 7 (HSD3B7); and sterol 12α-hydroxylase (CYP8B1), enzymes involved in the classic pathway of bile acid synthesis, was higher in fatty liver cows than in healthy cows. Compared with healthy cows, the hepatic mRNA abundance of alternative bile acid synthesis pathway-related genes sterol 27-hydroxylase (CYP27A1) and oxysterol 7α-hydroxylase (CYP7B1) did not differ in cows with fatty liver. The protein and mRNA abundances of bile acid transporter bile salt efflux pump (BSEP) were lower in the liver of dairy cow with fatty liver. Compared with healthy cows, the hepatic mRNA abundance of bile acid transporters solute carrier family 51 subunit α (SLC51A) and ATP binding cassette subfamily C member 1 (ABCC1) and 3 (ABCC3) was greater in cows with fatty liver, whereas the solute carrier family 51 subunit β (SLC51B) did not differ. The expression of genes involved in bile acid uptake, including solute carrier family 10 member 1 (NTCP), solute carrier organic anion transporter family member 1A2 (SLCO1A2) and 2B1 (SLCO2B1) was upregulated in dairy cows with fatty liver. Furthermore, the hepatic protein and mRNA abundance of bile acid metabolism regulators farnesoid X receptor (FXR) and small heterodimer partner (SHP) were lower in cows with fatty liver than in healthy cows. Overall, these data suggest that inhibition of the FXR signaling pathway may lead to increased bile acid synthesis and uptake and decreased secretion of bile acids from hepatocytes to the bile, which elevates hepatic bile acid content in dairy cows with fatty liver. Because the hepatotoxicity of bile acids has been demonstrated on nonruminant hepatocytes, it is likely that liver injury is induced by increased hepatic bile acid content in dairy cows with fatty liver.

Background: With the prevalence of dietary supplements, the use of combinations of herbs and drugs is gradually increasing, together with the risk of drug interactions. In our clinical work, we unexpectedly found that the combination of Panax notoginseng and warfarin, which are herbs that activate blood circulation and remove blood stasis, showed antagonistic effects instead. The purpose of this study was to evaluate the drug interaction between Panax notoginseng saponins (PNS) and warfarin, the main active ingredient of Panax notoginseng, and to explore the interaction mechanism. Methods: The effects and mechanisms of PNS on the pharmacodynamics and pharmacokinetics of warfarin were explored mainly in Sprague–Dawley rats and HepG2 cells. Elisa was used to detect the concentrations of coagulation factors, HPLC-MS to detect the blood concentrations of warfarin in rats, immunoblotting was employed to examine protein levels, qRT-PCR to detect mRNA levels, cellular immunofluorescence to detect the localization of NR1I3, and dual luciferase to verify the binding of miR-214-3p and NR1I3. Results: PNS significantly accelerated warfarin metabolism and reduced its efficacy, accompanied by increased expression of NR1I3 and CYP2C9. Interference with NR1I3 rescued the accelerated metabolism of warfarin induce by PNS co-administration. In addition, we demonstrated that PNS significantly reduced miR-214-3p expression, whereas miR-214-3p overexpression reduced NR1I3 and CYP2C9 expression, resulting in a weakened antagonistic effect of PNS on warfarin. Additionally, we found that miR-214-3p bound directly to NR1I3 3′-UTR and significantly downregulated NR1I3 expression. Conclusion: Our study demonstrated that PNS accelerates warfarin metabolism and reduces its pharmacodynamics by downregulating miR-214-3p, leading to increased expression of its target gene NR1I3, these findings provide new insights for clinical drug applications to avoid adverse effects.

Unnecessary exposure to ionizing radiation (IR) often causes acute and chronic oxidative damages to normal cells and organs, leading to serious physiological and even life-threatening consequences. Amifostine (AMF) is a validated radioprotectant extensively applied in radiation and chemotherapy medicine, but the short half-life limits its bioavailability and clinical applications, remaining as a great challenge to be addressed. DNA-assembled nanostructures especially the tetrahedral framework nucleic acids (tFNAs) are promising nanocarriers with preeminent biosafety, low biotoxicity, and high transport efficiency. The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity. We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection (tFNAs@AMF, also termed nanosuit). By establishing the mice models of accidental total body irradiation (TBI) and radiotherapy model of Lewis lung cancer, we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress. In the accidental total body irradiation (TBI) mice model, the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents, and functional recovery of hematopoietic system, reducing IR-induced pathological damages of multi-organ and safeguarding mice from lethal radiation. More importantly, the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer. Based on a conveniently available DNA tetrahedron-based nanocarrier, this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs. Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.

Abstract Background Although WD repeat domain 45 (WDR45) mutations have been linked to $$\upbeta$$ β -propeller protein-associated neurodegeneration (BPAN), the precise molecular and cellular mechanisms behind this disease remain elusive. This study aims to shed light on the impacts of WDR45-deficiency on neurodegeneration, specifically axonal degeneration, within the midbrain dopaminergic (DAergic) system. We hope to better understand the disease process by examining pathological and molecular alterations, especially within the DAergic system. Methods To investigate the impacts of WDR45 dysfunction on mouse behaviors and DAergic neurons, we developed a mouse model in which WDR45 was conditionally knocked out in the midbrain DAergic neurons (WDR45 cKO ). Through a longitudinal study, we assessed alterations in the mouse behaviors using open field, rotarod, Y-maze, and 3-chamber social approach tests. We utilized a combination of immunofluorescence staining and transmission electron microscopy to examine the pathological changes in DAergic neuron soma and axons. Additionally, we performed proteomic and lipidomic analyses of the striatum from young and aged mice to identify the molecules and processes potentially involved in the striatal pathology during aging. Further more, primary midbrain neuronal culture was employed to explore the molecular mechanisms leading to axonal degeneration. Results Our study of WDR45 cKO mice revealed a range of deficits, including impaired motor function, emotional instability, and memory loss, coinciding with the profound reduction of midbrain DAergic neurons. The neuronal loss, we observed massive axonal enlargements in the dorsal and ventral striatum. These enlargements were characterized by the accumulation of extensively fragmented tubular endoplasmic reticulum (ER), a hallmark of axonal degeneration. Proteomic analysis of the striatum showed that the differentially expressed proteins were enriched in metabolic processes. The carbohydrate metabolic and protein catabolic processes appeared earlier, and amino acid, lipid, and tricarboxylic acid metabolisms were increased during aging. Of note, we observed a tremendous increase in the expression of lysophosphatidylcholine acyltransferase 1 (Lpcat1) that regulates phospholipid metabolism, specifically in the conversion of lysophosphatidylcholine (LPC) to phosphatidylcholine (PC) in the presence of acyl-CoA. The lipidomic results consistently suggested that differential lipids were concentrated on PC and LPC. Axonal degeneration was effectively ameliorated by interfering Lpcat1 expression in primary cultured WDR45-deficient DAergic neurons, proving that Lpcat1 and its regulated lipid metabolism, especially PC and LPC metabolism, participate in controlling the axonal degeneration induced by WDR45 deficits. Conclusions In this study, we uncovered the molecular mechanisms underlying the contribution of WDR45 deficiency to axonal degeneration, which involves complex relationships between phospholipid metabolism, autophagy, and tubular ER. These findings greatly advance our understanding of the fundamental molecular mechanisms driving axonal degeneration and may provide a foundation for developing novel mechanistically based therapeutic interventions for BPAN and other neurodegenerative diseases.

The factors influencing the external corrosion rate of buried oil pipelines are extremely complex, and the interactions between these factors make accurate prediction of the pipeline corrosion rate challenging.Response surface methodology can analyze the interactions between various influencing factors.Therefore, this study considered four affecting factors: pH value of the soil surrounding buried oil pipelines, Clconcentration, NO3－ concentration and SO42－ concentration.Experiments were designed using response surface methodology to establish a prediction model for pipeline corrosion rates in soil environments.Regression and variance analyses were performed to evaluate the model’s effectiveness and accuracy.The established response surface methodology prediction model was compared with linear regression and PSO-BP prediction models.Results showed that the difference of lack-of-fit terms in the prediction model based on response surface methodology was not significant, and the model itself passed the significance test, demonstrating its reliability.Compared to the other two models, the response surface methodology model had the highest coefficient of determination (R2) of 0.941 8, and the smallest mean absolute error, mean relative error and root mean square error,which were 0.0205,4.53%and 0.027 7,respectively.These results verified the accuracy of the response surface methodology prediction model, showing that it could accurately assess the external corrosion rate of pipelines and provide a reliable basis for developing protection measures and maintenance plans for pipelines.

Abstract As we know, valley-Hall kink states or pseudospin helical edge states are excited by polarized-momentum-locking [left-handed circular polarization (LCP) and right-handed circular polarization (RCP)] because the valley-Hall kink modes or pseudospin polarized modes have intrinsic and local chirality, which is difficult for these states to achieve phase modulation. Here we theoretically design and study a compatible topological photonic system with coexistence of photonic quantum Hall phase and pseudospin Hall phase, which is composed of gyromagnetic photonic crystals with a deformed honeycomb lattice containing six cylinders. A typical kind of hybrid topological waveguide states with pseudospin-characteristic, magnetic field-dependent, and strong robustness against backscattering and perfect electric conductor (PEC) is realized in the present system. Furthermore, we re-design a structure with intersection-liked, achieve splitting for one-way pseudospin quantum Hall edge states by using phase modulation. Robustness of the one-way pseudospin-quantum Hall edge states in splitting has been demonstrated as well. Additionally, PEC inserted in transport channel brings optical path difference in waveguide transmission, which would influence splitting for hybrid topological waveguide states in phase difference modulation. This work not only provides a new way for manipulation (i.e., phase modulation) of hybrid topological waveguide states in compatible topological photonic system from distinct topological classes but also has potential in various applications, such as sensing, signal processing, and on-chip communications.

Abstract Background The diagnosis of ICU-acquired weakness (ICUAW) may be delayed due to the complexity of critically ill patients. This study aimed to investigate the value of ultrasound measurements of rectus femoris cross-sectional area (RFCSA) in predicting ICUAW in patients undergoing invasive mechanical ventilation. Methods This was a prospective cohort study of patients undergoing mechanical ventilation for at least 48 h. RFCSA was measured using ultrasound in patients upon ICU admission and followed until discharge. Using the Medical Research Council score as the gold standard, we evaluated the diagnostic value of ultrasound measurements in predicting ICUAW. Kaplan–Meier curves were constructed to evaluate and compare the length of ICU stay and duration of invasive mechanical ventilation between patients with and without ICUAW. Results Among the 76 patients, 34 (44.7%) were diagnosed with ICUAW using the Medical Research Council score as the gold standard. The RFCSA atrophy rate between day 1 and day 3 was significantly higher in the ICUAW group (7.9 ± 2.8% vs. 4.3 ± 2.1%, p

Alfalfa (Medicago sativa L.) plays an important role in the development of animal husbandry in the karst region of southwestern China, and karst environmental stress has a significant impact on the germination of alfalfa seeds. This study subjected alfalfa seeds to calcium salt stress (0–100 mM), drought stress (0–0.53 MPa), and pH stress (pH 3–9). Germination indicators (germination rate, germination potential, germination index, and vigor index), seedling morphological indicators (shoot length and root length), and biomass indicators were measured to assess seed stress resistance. The results showed that mild drought stress (5% PEG solution) and weak alkaline stress (pH 8) promoted seed germination, and a 20 mM CaCl2 solution significantly increased the germination rate. The root system of seedlings was more sensitive to the three types of stress. Under moderate calcium stress (40 mM), only a slight decrease in tissue water content was observed. Under moderate drought stress (10% PEG), fresh weight and tissue water content decreased, but dry weight significantly increased. Under alkaline stress (pH 9), both biomass indicators and tissue water content increased. This study provides a theoretical reference for selecting plants suitable for cultivation in karst environments.

ABSTRACT: Lactic acid bacteria (LAB) play a key role in regulating the balance of gut microbiota and serve as a suitable alternative to antibiotics. This study aims to evaluate the characteristics of 2 LAB isolates Lactiplantibacillus plantarum Lp71 (L. plantarum Lp71) and Enterococcus faecium Ef72 (E. faecium Ef72), and their roles in alleviating Salmonella Enteritidis infection. Sixty 1-day-old chicks were randomly divided into 4 groups which treated with or without L. plantarum Lp71 and E. faecium Ef72 mixture for 21 d, and then intestinal samples were collected for gut microbiota analysis, pathological and immunohistochemical analysis at 24 h post infection with or without Salmonella Enteritidis on the 22nd d. The results showed that L. plantarum Lp71 and E. faecium Ef72 had the ability to anti-acid and anti-bile salt. Salmonella Enteritidis infection damaged the intestinal epithelial barrier and reduced the expression level of tight junction proteins (ZO-1, Claudin-1, Occludin). Oral supplementation with L. plantarum Lp71 and E. faecium Ef72 mixture could alleviated the damages to intestinal epithelial barrier by Salmonella Enteritidis infection. Salmonella Enteritidis could cause abnormal Akkermansia muciniphila proliferation and decrease the diversity of cecal microbiota in chicks. These conditions could have further led to reduce gut microbiota health index (GMHI), and improve microbial dysbiosis index (MDI). Moreover, oral supplementation with L. plantarum Lp71 and E. faecium Ef72 mixture could effectively prevent the aforementioned infection outcomes and increase the abundance proportions of the several key functions in metabolic pathways metabolic pathways such as transcription and signal transduction mechanisms. In summary, L. plantarum Lp71 and E. faecium Ef72 could be the probiotics candidates that used to prevent the damage from enteric pathogens such as Salmonella Enteritidis in broiler chicks.

BackgroundThe use of enzymes within pig feed can reduce the challenges associated with antibiotic-free animal feeding. However, this enzymatic effect is often limited by the internal and external gut environment. This study aimed to improve diet quality and assess the impact of an enzymatically hydrolyzed diet (EHD) on growth performance, meat quality, and intestinal health in growing pigs.MethodsThe EHD was prepared by treating a liquid basal diet with a compound enzyme preparation (5 non-starch polysaccharides (NSP) enzymes: cellulase, pectinase, xylanase, β- glucanase, α-galactosidase; 3 exogenous digestive enzymes: amylase, lipase, protease; lysozyme, and glucose oxidase) in a 1:2.5 ratio with water and heated at 40°C for 1 h. Thirty-six growing pigs (average body weight 25 ± 0.5 kg; age 75 ± 3 days) from the Duroc × Landrace × Yorkshire crossbreed were randomly divided into three dietary groups: solid basal diet (S-CON), liquid basal diet (L-CON), and EHD.ResultsEnzymatic pre-treatment reduced the anti-nutritional factors (ANFs) in the diets (p

Under industrial conditions, efficient catalytic oxidation of Chlorinated volatile organic compounds is an important challenge, not only because of the poisonous effect of Chlorinated volatile organic compounds on catalysts, but also because of their high reaction temperature, which has an adverse impact on industrialization. In a recent article (The efficient and stable catalytic combustion of chlorobenzene utilizing a cordierite honeycomb ceramic Ru/CeO2 catalyst: Transitioning from laboratory innovation to practical application) [1], we developed a strategy for preparing a simple and efficient monolithic catalyst for the catalytic combustion of chlorobenzene. Ru/CeO2 was loaded on the industrial support cordierite by a Sol-gel method. Characterization was performed by techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), and Brunner-Emmet-Teller(BET) measurements surface area analysis. The Sol-gel method demonstrated superior performance, yielding catalysts with better dispersion, larger surface areas, and consequently, higher catalytic oxidation activity for chlorobenzene, compared to the other two methods. Catalytic tests revealed that the Ru/CeO2 catalyst prepared by the Sol-gel method maintained a 99 % conversion rate of chlorobenzene at 500 °C over 80 h, showcasing remarkable stability and resistance to deactivation. This efficacy is attributed to the enhanced dispersion of Ru and the effective interaction between Ru and CeO2, facilitated by the Sol-gel synthesis process. This method is simple and easy to prepare the catalyst and has broad industrial prospects. The data set is supplemented with XRD, XPS, SEM and SEM-EDS images of the material, providing useful supplementary data; activity evaluation data for dichloromethane, 1,2-chloroethane and chloromethane were measured.

Perennial ryegrass (Lolium perenne L.) is a key forage species in warm temperate to subtropical regions worldwide. Climate change poses significant challenges to agriculture, particularly through drought and heat stress, which adversely affect ryegrass yield and may be further exacerbated by global warming. Despite numerous research achievements in recent years, a comprehensive bibliometric analysis of the literature on drought and heat stress in perennial ryegrass is lacking. This study provides a quantitative analysis of relevant literature published from 1994 to 2024, utilizing the Web of Science database to evaluate global research trends and priorities. The results indicate a consistent annual growth in publication output, with China and the United States being major contributors, and the journal Crop Science publishing the most papers. Keyword analysis shows that “growth,” “endophytic fungi,” and “yield” are most frequently used in drought stress research, while “growth,” “gene,” and “leaf” are common in heat stress research. Over the past 30 years, research has mainly focused on phenotype, response mechanisms, and drought and heat resistance techniques in perennial ryegrass. Endophyte have become a hot topic in drought stress research in recent years and have also gained attention in heat stress research, suggesting future research directions in this area. Furthermore, there is a need to strengthen research on the molecular mechanisms associated with drought stress in ryegrass, as well as to explore molecular responses to heat stress. The research trend shows increasing attention to the interaction between drought and heat stress, indicating it will become an important direction for future studies. The findings of this study offer valuable insights for guiding future research on perennial ryegrass under drought and heat stress conditions and provide useful information for researchers in related fields.

Listeria monocytogenes (L. monocytogenes) is a foodborne intracellular pathogen that causes serious disease in both humans and animals. InlB is the major internalin protein of L. monocytogenes, which anchors to the bacterial surface and mediates its invasion into various host cells. Recent studies have shown that galactosylation of the cell wall polymer wall teichoic acid (WTA) is essential for InlB anchoring on the cell surface of L. monocytogenes serotype 4b strains. Galactosylation of WTA is exerted by the coordinated action of several glycosyltransferases, including GalU, GalE, GtcA, GttA, and GttB. Among these glycosyltransferases, GttA and GttB are specific to serotype 4b strains, whereas GalE, GalU, and GtcA are conserved across all serotypes. The role of GalE in InlB anchoring and L. monocytogenes pathogenicity remains unclear. In this study, we deleted the galE gene, which is involved in galactosylation, from L. monocytogenes strain ScottA. We found that galE deletion reduced InlB anchoring, weakened bacterial adhesion and invasion of Caco-2 cells (human colorectal adenocarcinoma cells) and MGC803 cells (human gastric carcinoma cells), increased phagocytosis but decreased proliferation in RAW264.7 cells (mouse mononuclear macrophage leukaemia cells), and decreased bacteria load, mortality, and tissue damage in infected mice. Taken together, galE deletion significantly reduced the anchoring of InlB and weakened the pathogenicity of L. monocytogenes. This finding provides new insights into the correlation between cell wall modification and pathogenicity of L. monocytogenes.

ABSTRACT Background The effectiveness of ultrasound stimulation in treating Alzheimer's disease (AD) has been reported in previous studies, but the underlying mechanisms remain unclear. This study investigated the effects of ultrasound stimulation on the proportion and function of microglia of different phenotypes, as well as on the levels of inflammatory factors. Additionally, it revealed the alterations in proteomic molecules in the mouse hippocampus following ultrasound stimulation treatment, aiming to uncover potential new molecular mechanisms. Methods Ultrasound stimulation was used to stimulate the hippocampus for 30 min per day for 5 days in the ultrasound stimulation‐treated group. Amyloid plaque deposition was measured using immunofluorescence staining. M1 and M2 type microglia were labeled using immunofluorescent double staining, and the ratio was calculated. The levels of Aβ42, IL‐10, and TNF‐α were determined using ELISA kits. The quantitative proteomics method was employed to explore molecular changes in hippocampal proteins. Results Ultrasound stimulation treatment reduced the average fluorescence intensity of amyloid plaques and the concentration of Aβ42. Compared to the AD group, ultrasound stimulation resulted in a 14% reduction in the proportion of M1 microglia and a 12% increase in the proportion of M2 microglia. The concentration of the anti‐inflammatory factor IL‐10 was significantly increased in the ultrasound stimulation‐treated group. Proteomics analysis revealed 753 differentially expressed proteins between the ultrasound stimulation‐treated and AD groups, with most being enriched in the oxidative phosphorylation pathway of mitochondria. Additionally, the activity of cytochrome c oxidase, involved in oxidative phosphorylation, was increased after ultrasound stimulation treatment. Conclusions Ultrasound stimulation affects microglial polarization, reduces amyloid plaque load, and enhances levels of anti‐inflammatory factors in APP/PS1 mice. Proteomics analysis reveals molecular changes in hippocampal proteins after ultrasound stimulation treatment. The mechanism behind ultrasound stimulation‐induced modulation of microglial polarization may be related to changes in mitochondrial oxidative phosphorylation.

The Qinghai-Xizang Plateau, hosting the world’s largest alpine pastures, plays a pivotal environmental role in Asia. These ecosystems face alterations driven by both climate change and anthropogenic activities, resulting in the widespread consideration of grassland degradation. From 2000 to 2020, the northern Xizang Plateau experienced a pronounced escalation in drought conditions, particularly following a management policy aimed at combating grassland degradation, via restricting livestock numbers and implementing fencing enclosures, initiated in 2009. Specially, following the enforcement of this policy (2010–2020), there was a substantial 13.5 % reduction in soil moisture levels compared to the pre-implementation period (2000–2009), accompanied by a 42.8 % increase in drought severity (measured by the Palmer Drought Severity Index, PDSI) and an 11.6 % rise in drought duration. Under these challenging drought conditions, we identified negative trends of potential grassland Net Primary Productivity (NPP) which in absence of anthropogenic influence, as simulated by terrestrial ecosystem model (TEM). Contrary to this simulation, satellite time series observations revealed a widespread increase in actual grassland productivity. Remarkably, despite the challenging drought conditions between 2010 and 2020, we observed a substantial increase of 4.8 % in actual NPP (measured by light use efficiency model), 2.7 % in Normalized Difference Vegetation Index (NDVI), 10 % in solar-induced chlorophyll fluorescence (SIF), and 7.95 % in Gross Primary Productivity (GPP), respectively. Much of this enhancement in grassland productivity occurred in areas where livestock populations had markedly declined. Notably, the percentage of NPP increase mainly caused by degradation-combating actions doubled from 24.8 % during 2000–2009 to 49.8 % during 2010–2020 across the northern Xizang Plateau. In conclusion, our findings highlight the potential of large-scale degradation-combating actions to mitigate the negative impacts of climate change and contribute to a greener Earth.

BackgroundTelemedicine is expanding rapidly, with public direct-to-consumer (DTC) telemedicine representing 70% of the market. A key priority is establishing clear quality distinctions between the public and private sectors. No studies have directly compared the quality of DTC telemedicine in the public and private sectors using objective evaluation methods. ObjectiveUsing a standardized patient (SP) approach, this study aimed to compare the quality of DTC telemedicine provided by China’s public and private sectors. MethodsWe recruited 10 SPs presenting fixed cases (urticaria and childhood diarrhea), with 594 interactions between them and physicians. The SPs evaluated various aspects of the quality of care, effectiveness, safety, patient-centeredness (PCC), efficiency, and timeliness using the Institute of Medicine (IOM) quality framework. Ordinary least-squares (OLS) regression models with fixed effects were used for continuous variables, while logistic regression models with fixed effects were used for categorical variables. ResultsSignificant quality differences were observed between public and private DTC telemedicine. Physicians from private platforms were significantly more likely to adhere to clinical checklists (adjusted β 15.22, P

Abstract Sortilin‐related receptor 1 (SorL1) deficiency is a genetic predisposition to familial Alzheimer’s disease (AD), but its pathology is poorly understood. In SorL1‐null rats, a disorder of the global endosome‐lysosome network (ELN) is found in hippocampal neurons. Deletion of amyloid precursor protein (APP) in SorL1‐null rats could not completely rescue the neuronal abnormalities in the ELN of the hippocampus and the impairment of spatial memory in SorL1‐null young rats. These in vivo observations indicated that APP is one of the cargoes of SorL1 in the regulation of the ELN, which affects hippocampal‐dependent memory. When SorL1 is depleted, the endolysosome takes up more of the lysosome flux and damages lysosomal digestion, leading to pathological lysosomal storage and disturbance of cholesterol and iron homeostasis in the hippocampus. These disturbances disrupt the original homeostasis of the material‐energy‐subcellular structure and reprogram energy metabolism based on fatty acids in the SorL1‐null hippocampus, instead of glucose. Although fatty acid oxidation increases ATP supply, it cannot reduce the levels of the harmful byproduct ROS during oxidative phosphorylation, as it does in glucose catabolism. Therefore, the SorL1‐null rats exhibit hippocampal degeneration, and their spatial memory is impaired. Our research sheds light on the pathology of SorL1 deficiency in AD.

Recent advancements in high-order topological insulators have heralded new opportunities for the innovation and utilization of optical devices. This paper presents a composite asymmetric C4 photonic crystal to achieve multifunctional, robust topological states. Through detailed analysis of the fine changes in the topological bandgap induced by distortion parameters, we facilitate the realization of topological edge states in wavelength division multiplexing applications. We utilize both trivial and nontrivial properties of the topological bandgap to precisely manipulate zero-dimensional angular states, one-dimensional topological boundary states, and two-dimensional body states. Through simulations and experimental results, our advanced asymmetric C4 photonic crystal structure demonstrates superior robustness for the transmission of topological edge states. Our research paves the way for the deployment of more robust topological boundary state transmission systems and advances the application potential of higher-order topological states.

Abstract Background 5-Aminolevulinic acid (ALA) recently received much attention due to its potential application in many fields such as medicine, nutrition and agriculture. Metabolic engineering is an efficient strategy to improve microbial production of 5-ALA. Results In this study, an ALA production strain of Escherichia coli was constructed by rational metabolic engineering and stepwise improvement. A metabolic strategy to produce ALA directly from glucose in this recombinant E. coli via both C4 and C5 pathways was applied herein. The expression of a modified hemA RS gene and rational metabolic engineering by gene knockouts significantly improved ALA production from 765.9 to 2056.1 mg/L. Next, we tried to improve ALA production by RGMS-directed evolution of eamA gene. After RGMS, the ALA yield of strain A2-ASK reached 2471.3 mg/L in flask. Then, we aimed to improve the oxidation resistance of cells by overexpressing sodB and katE genes and ALA yield reached 2703.8 mg/L. A final attempt is to replace original promoter of hemB gene in genome with a weaker one to decrease its expression. After 24 h cultivation, a high ALA yield of 19.02 g/L was achieved by 108-ASK in a 5 L fermenter. Conclusions These results suggested that an industrially competitive strain can be efficiently developed by metabolic engineering based on combined rational modification and optimization of gene expression.

Abstract Background Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes. Methods Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram. Results This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance. Conclusion Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.

Abstract Limited information is available on the cardiovascular health (CVH) index and risk of high-normal blood pressure (HNBP) in elderly people. Randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used in this study analyze the relationship between CVH index and HNBP in the elderly. 1089 non-hypertensive residents aged 65 years or older completed the study. The positive rate of HNBP was 75.85% (male vs. female: 76.13% vs. 75.64%, P = 0.852); The ideal rate of CVH (ideal CVH index ≥ 5 items) was 14.51% (male vs. female: 15.91% vs. 13.46%, P = 0.256). Compared with people with 0–2 ideal CVH index, the risk of HNBP in people with 4 ideal indexes and ≥ 5 ideal indexes decreased by 50% and 63%, respectively, and their OR (95% CI) were 0.50 (0.31, 0.81) and 0.37 (0.21, 0.66), respectively. The results of the trend test showed that the risk of HNBP decreased by 32% for every increase in the ideal CVH index (trend P

ABSTRACT: The aim of the present study was to investigate the activity of AMPK and mTORC1 as well as TFEB transcriptional activity and autophagy-lysosomal function in the liver of dairy cows with mild fatty liver (FL) and cows with moderate FL. Liver and blood samples were collected from healthy dairy cows (n = 10; hepatic triglyceride content

Merging bound states in the continuum (BICs) and avoided crossing of resonances (ACR) are promising theoretical approaches to greatly enhance the quality (Q) factors of quasi-BICs in reciprocal space. We observe the phenomena of merging BICs and ACR in millimeter-sized C4v symmetry photonic crystal structures. The ACR at Γ point is obtained in the variation of the structural parameter. In off-Γ region, the merging BICs at arbitrary locations are observed in the experimental measurements. The findings offer a pathway to high-performance photonic devices with potential applications in optoelectronics and microwave experimentation.

Extreme droughts can severely impact terrestrial vegetation productivity. In the summer of 2022, approximately 32.7% of China’s land area experienced extreme drought conditions, marked by reduced rainfall both in terms of amount and intensity, prolonged consecutive dry days, minimal rainy days, and accompanied by heat waves. While previous studies have reported productivity losses in over half of China’s vegetated areas in 2022, how vegetation productivity recover from extreme drought remains to be clarified. In this study, we utilized the Enhanced Vegetation Index (EVI), Gross Primary Productivity (GPP) and meteorological data to evaluate the extent and pace of vegetation productivity change from loss in 2022 to post-drought recovery in 2023. We also assessed the contributions of seven meteorological variables and two drought-related variables to variations in vegetation productivity in regions affected by extreme drought using machine-learning techniques. Our findings revealed that, in 2022, the average EVI and GPP in regions affected by extreme drought were 2.3% and 8.0% lower, respectively, compared to the baseline period from 2018 to 2021. Soil water content (SWC) emerged as the primary factor contributing to the decline in EVI/GPP, followed by the number of rainy days for EVI and vapor pressure deficit for GPP. In 2023, we observed a significant vegetation recovery, with the average EVI increasing by 2.6% and the GPP rising by 14.9% within the study area compared to 2022. SWC played a dominant role in this recovery, and both EVI recovery and GPP recovery displayed a non-linear response to SWC. Additionally, we identified a threshold effect for SWC on recovery; once SWC increased above a certain threshold, EVI and GPP would recover largely and rapidly. Furthermore, rainfall intensity and rainfall amount emerged as the second most important factors influencing the recovery of EVI and GPP, respectively. Our study underscores the significance of soil moisture and rainfall seasonality in influencing plant growth.

Apolipoprotein E (APOE)is the gene with greatest genetic risk for Alzheimer’s disease (AD). We successfully established a human induced pluripotent stem cell(iPSC) line from a woman mutated by APOE gene. The cell line was isolated from this woman’s peripheral blood mononuclear cells using a non-integrated Sendai virus, which retained the original genotype, showed a normal karyotype, highly expressed pluripotent markers and could differentiate into three germ layers.

IntroductionLeritrelvir (RAY1216) acts as a main protease inhibitor that hinders the cleavage of viral precursor proteins, thereby inhibiting virus replication of SARS-CoV-2). This antiviral mechanism has shown significant efficacy against the novel coronavirus. Preclinical studies have demonstrated the potent antiviral activity and favorable safety profile of this compound. This study aims to develop a pharmacokinetic model for leritrelvir, with and without ritonavir as a pharmacokinetic enhancer and to evaluate the necessity of co-administration with ritonavir and to investigate different dosage regimens.MethodThe model establishment was based on plasma concentration data from a phase I trial involving 72 subjects in single-ascending dose (SAD), multiple-ascending dose (MAD), and a food effect cohort. Analysis was conducted using a nonlinear mixed-effects model, and clinical trial simulations were carried out.ResultsThe findings of this study demonstrate a favorable safety profile for leritrelvir. With simulation suggests that a 400 mg thrice-daily (TID) regimen may be optimal to maintain the trough concentrations (Ctrough) above levels required for inhibiiting viral replication. While ritonavir was found to enhance exposure, it was deemed unnecessary. Gender and food consumption were identified as significant covariates affecting pharmacokinetic parameters, however, no dose adjustments were deemed necessary.DiscussionThis findings supported by subsequent phase II and phase III trials validated the appropriateness of a 400 mg TID regimen for the administration of leritrelvir.

BackgroundA combination of standard biomedical treatment and traditional Chinese medicine (TCM) has been suggested as a therapeutic approach for rosacea that may significantly lower the recurrence rate and clinical symptom scores. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of this combination treatment on clinical symptom and TCM syndrome scores, as well as on the scores of the Dermatology Life Quality Index (DLQI), erythema index (EI), and interleukin 37 (IL-37) levels in patients with rosacea.MethodsThe PROSPERO registration number for the study is CRD42023472737. We systematically searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure Wanfang Database, China Biomedical Medicine database (CBM), and the VIP information resource integration service platform (cqvip) databases for RCTs (published from the beginning to September 2023, regardless of the language used) that compared the traditional Chinese medicine and standard biomedical treatment combination treatment to conventional anti-rosacea treatments. Our primary outcomes comprised the clinical symptom and TCM syndrome scores, and the scores of Dermatology Life Quality Index, erythema index, and IL-37 levels. We used a random-effects model to evaluate the pooled data.ResultsWe identified 260 studies. Of these, 13 eligible studies were employed for analysis (N = 1,348 participants). Compared with other anti-rosacea treatments, the TCM and standard biomedical treatment combination treatment yielded an improved mean reduction in the clinical symptom score −2.24% [95% CI (–3.02 to −1.46), p < 0.00001], TCM syndrome score −4.42 [95% CI (–5.33 to −3.50), p < 0.00001], and the score of DLQI of −2.55 [95% CI (–3.73 to −1.36), p < 0.00001], EI of −151.97 [95% CI (–276.59 to −27.36), p < 0.00001], and IL-37 level −4.23 [95% CI (–4.95 to −3.51), p = 0.854], as well as in the overall effective rate risk ratio (RR) = 1.25 [95%CI (1.18, 1.32), p = 0.994] and the recurrence rate = 0.27 [95%CI (0.15, 0.46), p = 0.297].ConclusionThe TCM and standard biomedical treatment combination treatment can provide a better outcome, including a reduction in the TCM syndrome and clinical symptom scores, and in the scores of DLQI, EI, and IL-37. Hence, this combination is a viable and more effective therapeutic approach for rosacea. However, these results should be considered cautiously because of uncertain evidence and the low quality of the study reports considered in this meta-analysis.Systematic Review Registration:website, identifier CRD42023472737.

The guided tissue regeneration (GTR) procedure has become an important process for the treatment of periodontal tissue regeneration, using the membrane as a mechanical barrier to generate a distance across the defect that subsequently allowing bone regeneration. Due to the complexity of periodontal microenvironment caused by bacterial infections, inflammation, and fibrous tissue penetration, the guided tissue regeneration membrane is required to have antibacterial and barrier functions. We developed a loaded methylene blue @ ZIF-8 and hydroxyapatite gradient thermoplastic polyurethane Janus membrane for antibacterial osteogenic and barrier. This Janus membrane with a porous gradient structure was prepared to use phase-conversion method. The rough layer facilitated cell growth and promoted periodontal bone regeneration, whereas the smooth layer isolated the growing fiber tissue.The rapid release of reactive oxygen species in the early stage and continuous release of zinc ions by methylene blue @ZIF-8 can achieve long-term synergistic antibacterial effect, with antibacterial rates of 84 % and 72 % against Escherichia coli and Staphylococcus aureus, respectively, which can effectively reduce the local inflammation caused by bacteria. In summary, we applied the Janus membrane to a rat periodontal bone defect model, and the membrane showed good surgical performance, barrier properties, osteogenic properties, and antibacterial effects, which could have broad application prospects in the treatment of periodontal bone defects.

Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.

Introduction The efficacy of multitarget neuroprotective drug DL-3-n-butylphthalide (NBP) in improving cognitive function has been confirmed in patients with vascular cognitive impairment without dementia. However, its efficacy in patients with symptomatic predementia phase of Alzheimer’s disease remains uncertain. This study aims to evaluate the efficacy and safety of NBP in improving cognitive function in patients with mild cognitive impairment (MCI) through a clinical randomised controlled trail.Methods and analysis This study is a 12-month, randomised, double-blind, placebo-controlled, multicentric trial, involving 270 patients with MCI. Subjects are randomly assigned to receive either NBP soft capsule (200 mg, three times per day) or placebo with an allocation ratio of 1:1. The efficacy and safety of NBP are assessed by comparing the results of neuropsychological, neuroimaging and laboratory tests between the two groups. The primary endpoint is the change in Alzheimer’s Disease Assessment Scale-Cognitive Subscale after 12 months. All patients will be monitored for adverse events.Ethics and dissemination This study involving human participants has been reviewed and approved by Ethics Committee of Xuan Wu Hospital (No.2017058). The participants provide their written informed consent to participate in this study. Results will be published in peer-reviewed medical journals and disseminated to healthcare professionals at local and international conferences.Protocol version V 3.0, 3 September 2022.Trial registration number ChiCTR1800018362.

The electron-phonon (el-ph) and phonon-phonon interactions play a key role in determining electronic and thermal transport properties, respectively, in promising two-dimensional (2D) semiconductor devices. In this study, we investigated el-ph interactions using Wannier-Fourier interpolation method and renormalized phonon scattering considering finite-temperature effects in Bi2TeSe2 monolayer. The results show that the optical phonon modes dominate the carrier scattering, where level repulsion induced by crystal field splitting and spin-orbit coupling (SOC) effect effectively suppresses intervalley scattering, leading to high hole mobility. Moreover, the strong anharmonicity in Bi2TeSe2 monolayer results in the temperature-dependent softening of its optical phonons, along with a corresponding variation in interatomic force constants (IFCs). As a result, the lattice thermal conductivity is remarkably low and exhibits weak temperature dependence. Finally, the predicted dimensionless thermoelectric figure of merit exceeds unity in the range of 200–800 K, indicating the potential of Bi2TeSe2 monolayer for thermoelectric applications. This work provides new insights into the elimination of intervalley scattering by crystal field splitting and SOC effects, and paves the way for the evaluation of thermoelectric properties of materials with complex scattering mechanisms and strong anharmonicity.

Abstract Background This study aimed to assess the impacts of closed-off measures with different strictness levels (lockdown, partial lockdown and non-lockdown) and geographic proximity to patients with coronavirus disease 2019 (COVID-19) on prenatal depression during an epidemic rebound of COVID-19. Methods This was a cross-sectional web-based survey including 880 pregnant women. Depressive symptoms were measured by Self-Rating Depression Scale (SDS) and geographic proximity was calculated using Geographic Information Systems. Linear and logistic regression were used to assess the associations of closed-off measures and geographic proximity with SDS scores and depressive symptoms. Restricted cubic splines were used to model non-linear associations between geographic proximity and depression symptoms. Results Compared with those living in non-lockdown areas, women in lockdown areas had higher SDS scores (adjusted β: 3.51, 95% CI: 1.80, 5.21) and greater risk of depressive symptoms (adjusted OR: 4.00, 95% CI: 2.18, 7.35), but evidence for partial lockdown was not obvious. A progressive increase in the risk of depressive symptoms was found with decreasing distance to COVID-19 patients when geographic proximity was

Abstract Landslides cause huge human and economic losses globally. Detecting landslide precursors is crucial for disaster prevention. The small baseline subset interferometric synthetic-aperture radar (SBAS-InSAR) has been a popular method for detecting landslide precursors. However, non-monotonic displacements in SBAS-InSAR results are pervasive, making it challenging to single out true landslide signals. By exploiting time series displacements derived by SBAS-InSAR, we proposed a method to identify moving landslides. The method calculates two indices (global/local change index) to rank monotonicity of the time series from the derived displacements. Using two thresholds of the proposed indices, more than 96% of background noises in displacement results can be removed. We also found that landslides on the east and west slopes are easier to detect than other slope aspects for the Sentinel-1 images. By repressing background noises, this method can serve as a convenient tool to detect landslide precursors in mountainous areas.

High-speed rail express is gradually gaining attention due to its low cost and high on-time performance. This paper studied the optimization of high-speed rail express transportation modes considering passenger capacity loss. A spatio-temporal network was constructed that includes the fixed passenger train schedule and the high-speed rail express transportation status. Based on this network, an optimization model for transportation schemes considering passenger capacity loss with non-splittable freight flows was developed. The model aims to minimize passenger loss and maximize net revenue from express transportation while comprehensively considering practical constraints such as transfer, loading and unloading, and carrying capacity. The Gurobi optimization solver was used to solve numerical cases, and the optimization results and solution effectiveness were comparatively analyzed under scenarios of sufficient and insufficient capacity.

Oat is an important crop widely distributed in temperate zones and is also commonly planted in the karst areas of southwest China. However, due to severe rocky desertification, the complex soil in this area is characterized by high calcium content, alkaline conditions, and drought, which significantly negatively impact the growth of oat seedlings. To study the adaptability of oats to rocky desertification stress at the seedling stage, we investigated the effects of CaCl2 (0–150 mM), the pH (3–9), and drought stress (PEG-6000 solution at 0 to −0.79 MPa) on seed germination and seedling growth. The results showed that (1) calcium stress had dual effects on seed germination within the range of 5–150 mM CaCl2. Low concentrations of CaCl2 (5 mM) promoted the germination potential, germination rate, germination index, and vigor index of oats, as well as the growth and biomass accumulation of radicles in oat seedlings; however, high concentrations of CaCl2 inhibited these germination parameters. (2) Under drought stress, moderate concentrations of a PEG-6000 solution significantly improved the germination potential and germination rate of oat seeds, but the germination index and vigor index decreased with an increasing PEG-6000 concentration. When the PEG-6000 concentration corresponded to −0.06 MPa, the root growth and fresh weight accumulation of oat seedlings were significantly promoted; however, as the concentration increased to −0.53 MPa and –0.79 MPa, seed germination and seedling growth were significantly inhibited. (3) pH treatments had no significant effect on oat seed germination, but all growth indexes of oats showed a downward trend under alkaline conditions. These results suggest that suitable conditions for oat planting in karst rocky desertification areas are 5 mM CaCl2, pH levels of 5–8, and drought stress between 0 and −0.32 MPa. This study provides a theoretical basis for oat introduction, cultivation, and stress-resistant breeding in this area.

Background and aims: The transplacental vertical transfer of maternal antibodies was determined to be a crucial factor in conferring protective immunity to infants following delivery, and this study aimed to evaluate the protective effect of maternal preconception COVID-19 vaccination on infants. Methods: A prospective cohort study was conducted at the National Clinical Medical Research Center for Child Health and Diseases in Chongqing, China, spanning from July 2022 to April 2023. The study included infants from mothers with a preconception COVID-19 vaccination and (or) a SARS-CoV-2 infection during pregnancy. Titers of SARS-CoV-2 immunoglobulin G (IgG) and cross-neutralizing activity against SARS-CoV-2 variants were detected. Results: In this cohort study comprising 158 infants, it was observed that infants born to mothers who experienced a pregnancy-related breakthrough infection following a preconception vaccination had the highest titers of SARS-CoV-2 IgG and cross-neutralizing antibody activity against different variants compared to those with either of these factors alone. The transplacental vertical transmission of anti-SARS-CoV-2 antibodies decreased significantly with increasing age, from 3.16 ODs at birth to 2.29 ODs at two months, and persisted for approximately four months after birth. The predominant subclass of passively transmitted antibodies via the placenta was found to be IgG1, and a positive correlation was observed between the titers of SARS-CoV-2 IgG and IgG1 (R = 0.59, p < 0.001; Slope: 0.49 ± 0.070, p < 0.001). Conclusions: Maternal preconception COVID-19 vaccination represents a promising immunological strategy for conferring postnatal protection to infants, especially during the period of heightened risk of exposure to SARS-CoV-2 infection. It is imperative to underscore the significance of vaccination for women who are preparing to become pregnant or are pregnant, and concerted efforts must be made to promote vaccination among eligible women.