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Abstract This study aims to assess the global prevalence of kinesiophobia and the potential influencing factors among patients with heart disease. A comprehensive search was conducted in PubMed, Embase, Web of Science, PsycINFO, and Scopus databases to identify studies reporting on the prevalence of kinesiophobia and its influencing factors in heart disease patients up to January 2024. A random-effects model was employed to aggregate prevalence rates. Heterogeneity sources were investigated through subgroup analysis, while differences in the prevalence of kinesiophobia across regions, types of heart disease, and gender were evaluated. Additionally, a qualitative analysis of the factors influencing kinesiophobia was performed. This research incorporated 15 studies from six countries, with 14 providing data on the prevalence of kinesiophobia and nine exploring its potential influencing factors. The findings indicated that the overall prevalence of kinesiophobia among heart disease patients was 61.0% (95% CI 49.4–72.6%). Subgroup analysis revealed that the prevalence in upper-middle-income countries was 71.8% (95% CI 66.2–77.4%), while it stands at 49.9% (95% CI 30.2–69.5%) in high-income countries. The prevalence rates among patients with coronary artery disease, heart failure, and atrial fibrillation were 63.2% (95% CI 45.2–81.3%), 69.2% (95% CI 57.6–80.8%), and 71.6% (95% CI 67.1–76.1%), respectively. Gender-wise, no significant difference was observed in the prevalence of kinesiophobia between men and women (52.2% vs. 51.8%). A total of 24 potential influencing factors of kinesiophobia were identified, with education level, monthly income, anxiety, and exercise self-efficacy being the most recognized. The prevalence of kinesiophobia in patients with heart disease is notably high and is influenced by a multitude of factors. Early implementation of targeted preventive measures is imperative to mitigate the incidence of kinesiophobia in this population.

Abstract Rhein, a component derived from rhubarb, has been proven to possess anti-inflammatory properties. Here, we show that rhein mitigates obesity by promoting adipose tissue thermogenesis in diet-induced obese mice. We construct a macrophage-adipocyte co-culture system and demonstrate that rhein promotes adipocyte thermogenesis through inhibiting NLRP3 inflammasome activation in macrophages. Moreover, clues from acetylome analysis identify SIRT2 as a potential drug target of rhein. We further verify that rhein directly interacts with SIRT2 and inhibits NLRP3 inflammasome activation in a SIRT2-dependent way. Myeloid knockdown of SIRT2 abrogates adipose tissue thermogenesis and metabolic benefits in obese mice induced by rhein. Together, our findings elucidate that rhein inhibits NLRP3 inflammasome activation in macrophages by regulating SIRT2, and thus promotes white adipose tissue thermogenesis during obesity. These findings uncover the molecular mechanism underlying the anti-inflammatory and anti-obesity effects of rhein, and suggest that rhein may become a potential drug for treating obesity.

Abstract Purpose This study aimed to identify and quantify the association and investigate whether serum vitamin B12 alone or vitamin B12 combined with folate and plasma total homocysteine (tHcy) levels could be used to predict the risk of acute ischemic stroke. Materials and methods This retrospective case-control study was conducted in the Department of Neurology, First Affiliated Hospital of Chongqing Medical University. It included 259 inpatients experiencing their first-ever acute ischemic stroke and 259 age-matched, sex-matched healthy controls. Patients were categorized into groups based on the etiology of their stroke: large-artery atherosclerosis (LAAS, n = 126), cardio embolism (CEI, n = 35), small vessel disease (SVD, n = 89), stroke of other determined etiology (ODE, n = 5), and stroke of undetermined etiology (UDE, n = 4). The associations of serum vitamin B12, folate, and plasma tHcy levels with the risk of ischemic stroke were evaluated using multivariable logistic regression analysis. Receiver operator characteristic (ROC) curves were used to assess the diagnostic power of vitamin B12, folate, and tHcy levels for ischemic stroke. Results Serum vitamin B12 and folate levels were significantly lower in ischemic stroke patients compared to controls, while plasma tHcy levels were significantly higher. The first quartile of serum vitamin B12 levels was significantly associated with an increased risk of LAAS (aOR = 2.289, 95% CI = 1.098–4.770), SVD (aOR = 4.471, 95% CI = 1.110–4.945) and overall ischemic stroke (aOR = 3.216, 95% CI = 1.733–5.966). Similarly, the first quartile of serum folate levels was associated with an increased risk of LAAS (aOR = 3.480, 95% CI = 1.954–6.449), CEI (aOR = 2.809, 95% CI = 1.073–4.991), SVD (aOR = 5.376, 95% CI = 1.708–6.924), and overall ischemic stroke (aOR = 3.381, 95% CI = 1.535–7.449). The fourth quartile of tHcy levels was also significantly associated with an increased risk of LAAS (aOR = 2.946, 95% CI = 1.008–5.148), CEI (aOR = 2.212, 95% CI = 1.247–5.946), SVD (aOR = 2.957, 95% CI = 1.324–6.054), and overall ischemic stroke (aOR = 2.233, 95% CI = 1.586–4.592). For predicting different types of ischemic stroke, vitamin B12 alone demonstrated the best diagnostic value for SVD, evidenced by a sensitivity of 71.0% and negative predictive value of 90.3%, along with the highest positive likelihood ratio (+ LR) for SVD. Vitamin B12 + tHcy + folate are valuable in predicting different types of ischemic stroke, with the most significant effect observed in SVD, followed by LAAS, and the weakest predictive effect in CEI. Additionally, vitamin B12 alone in combination with other indicators, such as folate alone, tHcy alone, and folate + tHcy could reduce negative likelihood ratio (-LR) and improve + LR. Conclusions Vitamin B12 was an independent risk factor for acute ischemic stroke. The risk calculation model constructed with vitamin B12 + tHcy + folate had the greatest diagnostic value for SVD.

Introduction: The aims of this study are to explore the factors affecting mild cognitive impairment in patients with chronic kidney disease (CKD) who are not undergoing dialysis and to construct and validate a nomogram risk prediction model. Methods: Using a convenience sampling method, 383 non-dialysis CKD patients from two tertiary hospitals in Chengdu were selected between February 2023 and August 2023 to form the modeling group. The patients were divided into a mild cognitive impairment group (n = 192) and a non-mild cognitive impairment group (n = 191), and factors such as demographics, disease data, and sleep disorders were compared between the two groups. Univariate and multivariate binary logistic regression analyses were used to identify independent influencing factors, followed by collinearity testing, and construction of the regression model. The final risk prediction model was presented through a nomogram and an online calculator, with internal validation using Bootstrap sampling. For external validation, 137 non-dialysis CKD patients from another tertiary hospital in Chengdu were selected between October 2023 and December 2023. Results: In the modeling group, 192 (50.1%) of the non-dialysis CKD patients developed mild cognitive impairment, and in the validation group, 56 (40.9%) patients developed mild cognitive impairment, totaling 248 (47.7%) of all sampled non-dialysis CKD patients. Age, educational level, Occupation status, Use of smartphone, sleep disorders, hemoglobin, and platelet count were independent factors influencing the occurrence of mild cognitive impairment in non-dialysis CKD patients (all p < 0.05). The model evaluation showed an area under the ROC curve of 0.928, 95% CI (0.902, 0.953) in the modeling group, and 0.897, 95% CI (0.844, 0.950) in the validation group. The model's Youden index was 0.707, with an optimal cutoff value of 0.494, sensitivity of 0.853, and specificity of 0.854, indicating good predictive performance; calibration curves, Hosmer-Lemeshow test, and clinical decision curves indicated good calibration and clinical benefit. Internal validation results showed a consistency index (C-index) of 0.928, 95% CI (0.902, 0.953). Conclusion: The risk prediction model developed in this study shows excellent performance, demonstrating significant predictive potential for early screening of mild cognitive impairment in non-dialysis CKD patients. The application of this model will provide a reference for healthcare professionals, helping them formulate more targeted intervention strategies to optimize patient treatment and management outcomes.

Abstract Structural annotation of small molecules in tandem mass spectrometry has always been a central challenge in mass spectrometry analysis, especially using a miniaturized mass spectrometer for on-site testing. Here, we propose the Transformer enabled Fragment Tree (TeFT) method, which combines various types of fragmentation tree models and a deep learning Transformer module. It is aimed to generate the specific structure of molecules de novo solely from mass spectrometry spectra. The evaluation results on different open-source databases indicated that the proposed model achieved remarkable results in that the majority of molecular structures of compounds in the test can be successfully recognized. Also, the TeFT has been validated on a miniaturized mass spectrometer with low-resolution spectra for 16 flavonoid alcohols, achieving complete structure prediction for 8 substances. Finally, TeFT confirmed the structure of the compound contained in a Chinese medicine substance called the Anweiyang capsule. These results indicate that the TeFT method is suitable for annotating fragmentation peaks with clear fragmentation rules, particularly when applied to on-site mass spectrometry with lower mass resolution.

Abstract Background Medical students are known to be at a greater risk of psychological disorders compared to the general population. However, their rate of help-seeking behavior is low. The purpose of this study was to explore the influencing factors of attitudes towards psychological help-seeking among Chinese medical students and to examine its gender differences. Methods A total of 3,453 medical students from three medical colleges in Hainan Province, China, completed anonymous questionnaires that included socio-demographic attributes, the Family APGAR Index, the General Health Questionnaire (GHQ-20), and the Attitudes Towards Seeking Professional Psychological Help Short Form (ATSPPH-SF). Associations between predictor variables and attitudes towards help-seeking were explored using multivariate linear regression, and regression models with interaction terms were employed to test gender difference. Results The mean score on ATSPPH-SF Scale was 15.04 ± 3.45, with males scoring significantly lower than females (14.34 vs. 15.64, P

Abstract Efficient milk production in mammals confers evolutionary advantages by facilitating the transmission of energy from mother to offspring. However, the regulatory mechanism responsible for the gradual establishment of milk production efficiency in mammals, from marsupials to eutherians, remains elusive. Here, we find that mammary gland of the marsupial sugar glider contained milk components during adolescence, and that mammary gland development is less dynamically cyclic compared to that in placental mammals. Furthermore, fused in sarcoma (FUS) is found to be partially responsible for this establishment of low efficiency. In mouse model, FUS inhibit mammary epithelial cell differentiation through the cyclin-dependent kinase inhibitor p57Kip2, leading to lactation failure and pup starvation. Clinically, FUS levels are negatively correlated with milk production in lactating women. Overall, our results shed light on FUS as a negative regulator of milk production, providing a potential mechanism for the establishment of milk production from marsupial to eutherian mammals.

Interstitial free (IF) steels are characterized by their interstitial free ferritic matrix due to addition of micro-alloying elements that draw carbon and nitrogen out of matrix to form carbonitrides. The IF steels typically have excellent deep drawing ability, certain mechanical strength, and high plastic deformation performance. In this paper, the microstructure evolution and carbides precipitation behavior during the hot rolling, cold rolling and annealing processes have been studied using both experimental and thermodynamic and kinetic modeling approaches. The strengthening mechanism of Nb–Ti microalloyed IF steel has been investigated. The results of the thermodynamic simulation indicates that the addition of Nb into Ti bearing IF steel promotes recrystallization at 900 °C, leading to fine recrystallized grains. Due to the recrystallization of austenite during the final rolling process, Nb–Ti microalloyed hot rolled plates exhibit finer grain size, fewer substructures, and lower dislocation density compared to the hot rolled plates containing only Ti. Building upon the initial fine and uniform structure, Nb–Ti microalloyed steel maintains a refined structure after undergoing cold rolling and annealing. The study of the carbides precipitation behavior suggests that TiN precipitates at high temperature above 1100 °C, while a substantial amount of (Nb,Ti)C and TiC precipitate at about 900 °C in Nb–Ti and Ti bearing steels, respectively. There is no significantly difference between the amount of carbides in steels hot deformed at 900 °C and in the hot rolled plates, indicating that the carbides mainly precipitate during the hot rolling process. There are negligible carbides precipitated during the coiling process at 600 °C. In Nb–Ti containing steel, Nb and Ti in solid solution are significantly reduced due to the large amount precipitation of (Nb,Ti)C during the final rolling process. The reduction of solid solution Nb effectively promotes the recrystallization of austenite. Therefore, the grains of hot-rolled, cold-rolled, and annealed strips are refined. In addition, there are more small size carbides in Nb–Ti bearing steel than that in Ti bearing steel. Therefore, the higher strength of Nb–Ti steel is mainly from the strengthening effect of grain refinement and carbides precipitation.

Abstract Engineering atom-scale sites are crucial to the mitigation of polysulfide shuttle, promotion of sulfur redox, and regulation of lithium deposition in lithium–sulfur batteries. Herein, a homonuclear copper dual-atom catalyst with a proximal distance of 3.5 Å is developed for lithium–sulfur batteries, wherein two adjacent copper atoms are linked by a pair of symmetrical chlorine bridge bonds. Benefiting from the proximal copper atoms and their unique coordination, the copper dual-atom catalyst with the increased active interface concentration synchronously guide the evolutions of sulfur and lithium species. Such a delicate design breaks through the activity limitation of mononuclear metal center and represents a catalyst concept for lithium–sulfur battery realm. Therefore, a remarkable areal capacity of 7.8 mA h cm−2 is achieved under the scenario of sulfur content of 60 wt.%, mass loading of 7.7 mg cm−2 and electrolyte dosage of 4.8 μL mg−1.

Blueberries are small perennial evergreen or deciduous shrub berries of the genus Vaccinium in Ericaceae family. Pollination with different parental genotypes has significant effects on fruit size, fruit harvest time, fruit firmness, and chemical composition, such as soluble solids, titratable acids, anthocyanins, fructose, sucrose, glucose, flavonoids, and total phenols, showing an evident xenia effect. To understand the molecular mechanism and biosynthetic pathways involved in the xenia effect in rabbiteye blueberry, we employed transcriptome profiling by RNA sequencing to identify differentially expressed genes (DEGs) during fruit development of the variety ‘Premier’ produced by self and cross-pollination with ‘Brightwell’ and ‘Powderblue’. On the basis of the transcriptomic sequences, DEGs related to plant hormone signal transduction were identified through bioinformatics analysis, screening of DEGs, and functional enrichment analysis. The results showed that the single fruit weight and the contents of anthocyanins fructose, glucose, and sucrose showed significant differences between self- and cross-pollinated fruits, demonstrating a distinct xenia effect. High-throughput sequencing was conducted on the transcriptomes of young fruits harvested at six developmental stages (at 10-day intervals from 40 to 90 days after self- and cross-pollination). After screening and identification, 16.37 million to 25.52 million raw reads were generated and 4,937,201,302 to 7,709,896,920 clean bases were obtained. The comparison group of 80-day-old fruits generated through self-pollinated ‘Premier’ and those crossed with ‘Brightwell’ (PBR-80 vs. PPR-80) showed the largest number of DEGs (6377), of which 3052 were upregulated and 3325 were downregulated. Through further screening, 174 DEGs were found related to plant hormone signal transduction, comprising 147 known genes and 27 new genes and that 76 genes were downregulated and 98 genes were upregulated. Of the eight DEGs randomly selected for quantitative real-time polymerase chain reaction verification, their expression patterns were consistent with those revealed by high-throughput sequencing. The results elucidated the underlying mechanism of xenia, thereby providing a solid theoretical foundation for the targeted breeding, quality control, and improvement of economic benefits of blueberry, which are of important theoretical value and practical significance.

Hydrogels prepared by hydroxypropyl starch have better tensile properties than ordinary starch, but their mechanical properties are relatively poor. In this paper, effect of the heat-moisture treatment on the physical, chemical and the gel properties of hydroxypropyl starch was studied. Compared with the control group, the thermal stability of starch has been improved and the maintenance value decreased from 12.55 J/g to 6.58 J/g. The XRD analysis showed that the crystallicity of the strength from 30.4% to 19.6%. The double helix in strength was first destroyed by heat-moisture treatment. The peak viscosity of hydroxypropyl starch first rose to about 5 000 cp and then dropped to about 3 000 cp. The TPA and the rheological analysis showed that the hardness of the starch increased after the heat treatment of 223.51 g to 463.50 g and the storage elastic module increased, indicating that wet heat treatment improved the mechanical properties of the starch.

BackgroundRegional differences in economic development, natural environment, health care level, and social structure may lead to differences in the provincial distribution of the health status of the elderly population. ObjectiveTo explore the provincial distribution characteristics, regional differences, and influencing factors of the self-assessed health of the elderly population, with the aim of providing a policy basis for improving the health of the elderly population and promoting healthy aging according to local conditions. MethodsUsing 31 provinces (municipalities and autonomous regions) in China as the basicstudy unit and based on the method of Wagstaff, the self-rated health data of the elderly population (aged 60 years and above) in each province from the 2010 and 2020 national censuses and the 2015 1% National Population Sample Survey were converted into ill-health scores as a measure of self-assessed health, and higher scores represented worse health status perception. Global Moran's I was used to evaluate spatial autocorrelation, range [−1, 1], with a value of 1 as a perfect clustered pattern. Local Moran's I was used to evaluate the tendency of local autocorrelation, and high-high aggregation/low-low aggregation indicated that both target province and its neighboring provinces showed higher/lower ill-health scores. Spatial econometric models were selected by Lagrange multiplier test and Hausman test to explore influencing factors of the self-assessed health of the elderly population. ResultsIn 2010, 2015, and 2020, the national ill-health scores of the elderly population were 1.831, 1.873, and 1.547, respectively, and the corresponding Global Moran's I statistics were 0.347, 0.482, and 0.511, respectively (P

Abstract Renewable electricity powered electrochemical CO2 reduction (CO2R) offers a valuable method to close the carbon cycle and reduce our overreliance on fossil fuels. However, high purity CO2 is usually required as feedstock, which potentially decreases the feasibility and economic viability of the process. Direct conversion of flue gas is an attractive option but is challenging due to the low CO2 concentration and the presence of O2 impurities. As a result, up to 99% of the applied current can be lost towards the undesired oxygen reduction reaction (ORR). Here, we show that acidic electrolyte can significantly suppress ORR on Cu, enabling generation of multicarbon products from simulated flue gas. Using a composite Cu and carbon supported single-atom Ni tandem electrocatalyst, we achieved a multicarbon Faradaic efficiency of 46.5% at 200 mA cm-2, which is ~20 times higher than bare Cu under alkaline conditions. We also demonstrate stable performance for 24 h with a multicarbon product full-cell energy efficiency of 14.6%. Strikingly, this result is comparable to previously reported acidic CO2R systems using pure CO2. Our findings demonstrate a potential pathway towards designing efficient electrolyzers for direct conversion of flue gas to value-added chemicals and fuels.

Abstract Liver kinase B1 (LKB1), an evolutionarily conserved serine/threonine kinase, is a master regulator of the AMPK subfamily and controls cellular events such as polarity, proliferation, and energy homeostasis. Functions and mechanisms of the LKB1-AMPK axis at specific subcellular compartments, such as lysosome and mitochondria, have been established. AMPK is known to be activated at the Golgi; however, functions and regulatory mechanisms of the LKB1-AMPK axis at the Golgi apparatus remain elusive. Here, we show that TBC1D23, a Golgi-localized protein that is frequently mutated in the neurodevelopment disorder pontocerebellar hypoplasia (PCH), is specifically required for the LKB1 signaling at the Golgi. TBC1D23 directly interacts with LKB1 and recruits LKB1 to Golgi, promoting Golgi-specific activation of AMPK upon energy stress. Notably, Golgi-targeted expression of LKB1 rescues TBC1D23 deficiency in zebrafish models. Furthermore, the loss of LKB1 causes neurodevelopmental abnormalities in zebrafish, which partially recapitulates defects in TBC1D23-deficient zebrafish, and LKB1 sustains normal neuronal development via TBC1D23 interaction. Our study uncovers a regulatory mechanism of the LKB1 signaling, and reveals that a disrupted Golgi-LKB1 signaling underlies the pathogenesis of PCH.

Tea-oil tree (Camellia oleifera Abel.) is an important edible oil woody plant with a planting area over 3,800,000 hectares in southern China. Species of Diaporthe inhabit a wide range of plant hosts as plant pathogens, endophytes and saprobes. Here, we conducted an extensive field survey in Hainan Province to identify and characterise Diaporthe species associated with tea-oil leaf spots. As a result, eight isolates of Diaporthe were obtained from symptomatic C. oleifera leaves. These isolates were studied, based on morphological and phylogenetic analyses of partial ITS, cal, his3, tef1 and tub2 gene regions. Two new Diaporthe species (D. hainanensis and D. pseudofoliicola) were proposed and described herein.

Abstract. Background:. A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI. Methods:. In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints. Results:. From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA (n = 384) or rt-PA (n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a -15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: -3.4%; 95% confidence interval [CI]: -11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: -0.5%; 95% CI: -5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion:. rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI. Trial registration:. www.ClinicalTrials.gov (No. NCT02835534).

Early diagnosis and intervention of depression promote complete recovery, with its traditional clinical assessments depending on the diagnostic scales, clinical experience of doctors and patient cooperation. Recent researches indicate that functional near-infrared spectroscopy (fNIRS) based on deep learning provides a promising approach to depression diagnosis. However, collecting large fNIRS datasets within a standard experimental paradigm remains challenging, limiting the applications of deep networks that require more data. To address these challenges, in this paper, we propose an fNIRS-driven depression recognition architecture based on cross-modal data augmentation (fCMDA), which converts fNIRS data into pseudo-sequence activation images. The approach incorporates a time-domain augmentation mechanism, including time warping and time masking, to generate diverse data. Additionally, we design a stimulation task-driven data pseudo-sequence method to map fNIRS data into pseudo-sequence activation images, facilitating the extraction of spatial-temporal, contextual and dynamic characteristics. Ultimately, we construct a depression recognition model based on deep classification networks using the imbalance loss function. Extensive experiments are performed on the two-class depression diagnosis and five-class depression severity recognition, which reveal impressive results with accuracy of 0.905 and 0.889, respectively. The fCMDA architecture provides a novel solution for effective depression recognition with limited data.

This paper proposes an unmanned surface vehicles (USVs) formation control method based on distributed average tracking (DAT) with different relative information measurement scale factors. Firstly, the DAT algorithm is designed in the controller to control the time when the system reaches stability. Then, the relative position information of adjacent USVs is measured by installing distance sensors and direction sensors on each USV, and different scale factors are used to control the formation of USVs, and improve the stability and robustness of its control system. Finally, the effectiveness of the method proposed in this paper is verified by numerical simulation experiments.

Abstract This study aimed to examine the impact of China’s political openness index and foreign direct investment on its ecotourism index from 1985 to 2019. The findings revealed that a 1% rise in foreign direct investment had a long-term effect, increasing China’s sustainable tourism index by 0.01%. Furthermore, the political openness index played a significant role in boosting ecotourism in China over both short and long periods. A 1% increase in the political openness index corresponded to a 0.32 and 0.53% increase in China’s ecotourism index in the short and long term, respectively. Additionally, the financial openness index had a positive impact in the short and long term, with a 1% improvement resulting in approximately 0.24 and 0.23% increases in China’s ecotourism index. Key policies to advance eco-tourism in China include ensuring political stability, enhancing green financial markets through fintech and blockchain, and implementing poverty alleviation measures.

Abstract While canonical Wnt signaling is well recognized for its crucial regulatory functions in cell fate decisions, the role of non-canonical Wnt signaling in adult stem cells remains elusive and contradictory. Here, we identified Mcam, a potential member of the non-canonical Wnt signaling, as an important negative regulator of mammary gland epithelial cells (MECs) by genome-scale CRISPR-Cas9 knockout (GeCKO) library screening. Loss of Mcam increases the clonogenicity and regenerative capacity of MECs, and promotes the proliferation, differentiation, and ductal morphogenesis of mammary epithelial in knockout mice. Mechanically, Mcam knockout recruits and polarizes macrophages through the Il4-Stat6 axis, thereby promoting secretion of the non-canonical Wnt ligand Wnt5a and its binding to the non-canonical Wnt signaling receptor Ryk to induce the above phenotypes. These findings reveal Mcam roles in mammary gland development by orchestrating communications between MECs and macrophages via a Wnt5a/Ryk axis, providing evidences for non-canonical Wnt signaling in mammary development.

In this paper, we propose a novel RSU-assisted hybrid road-aware routing algorithm, RHRA-DRL, designed for urban vehicular networks to optimize real-time data delivery considering dynamic road conditions. The algorithm minimizes broadcast overhead and efficiently determines optimal routing paths by incorporating two key components. Firstly, a multihop road-segment reward-based ad-hoc (RRAH) routing algorithm is introduced to adaptively respond to changing vehicle topologies within road segments. Rewards are calculated based on performance metrics, and the segment reward integrates into RSU-to-RSU (R2R) routing. Secondly, a distributed Q-learning-based road-aware (DQRA) routing algorithm determines RSUs traversed during data transmission using a decentralized agent reinforcement learning approach. The combination of these algorithms in RHRA-DRL ensures effective and consistent path establishment with a unified reward system. Simulation results demonstrate the superiority of RHRA-DRL over AODV in Internet of Vehicles (IoV) networks, showcasing enhanced communication, prolonged link lifetime, rapid establishment and repair of routing paths, and reduced overhead.

A systematic review and meta-analysis were conducted, aiming to establish a scientifically grounded understanding of trichloroethylene (TCE)-induced hepatotoxicity. Relevant studies published prior to February 29, 2024 were meticulously searched. The standardized mean difference (SMD) was employed to assess the correlation between the control group and the TCE exposure group, while heterogeneity was quantified using the I2 index. After a thorough screening and exclusion process, a total of 57 articles met the eligibility criteria. Important parameters pertaining to liver health, such as ALT, AST, TNF-α, IL-1β, and others, were analyzed, resulting in the identification of 40 parameters related to liver injury. The results revealed that GLB, ALP, CYP2E1, GR, IL-6 (mRNA), and TGF-β (mRNA) did not exhibit statistically significant differences (P > 0.05). However, high heterogeneity was observed in indicators other than F4/80, EGR1 (mRNA), and MDA-protein adducts (P 50%). Notably, TCE exposure significantly increased the activity of ALT, AST, LDH, as well as the expression levels of TNF-α, IL-1β, TNFR1, IL-6, P65, P-P65, F4/80, IFN-γ, iNOS, C3a, TNF-α (mRNA), IL-1β (mRNA), IL-6R (mRNA), GP130 (mRNA), EGR1 (mRNA), CCL2 (mRNA), CCL5 (mRNA), iNOS (mRNA), liver coefficient, MDA, anti-dsDNA, MDA protein adduct, anti-MDA protein adduct antibody, and ANA. Conversely, TCE exposure decreased the activities of CAT, GPx, SOD, as well as the expression levels of Nrf2, TP, ALB, and GSH. Additionally, this study provided a comprehensive review of the two mechanisms underlying liver injury following TCE exposure. In conclusion, our findings furnish compelling evidence that TCE exposure induces liver injury, as manifested by alterations in various physiological indicators, including cytokines and oxidative stress-related markers, among others.

Objective Intradialytic hypotension (IDH) is a common and serious complication in patients with Maintenance Hemodialysis (MHD). The purpose of this study is to externally verify three IDH risk prediction models recently developed by Ma et al. and recalibrate, update and present the optimal model to improve the accuracy and applicability of the model in clinical environment.Methods A multicenter prospective cohort study of patients from 11 hemodialysis centers in Sichuan Province, China, was conducted using convenience sampling from March 2022 to July 2022, with a follow-up period of 1 month. Model performance was assessed by: (1) Discrimination: Evaluated through the computation of the Area Under Curve (AUC) and its corresponding 95% confidence intervals. (2) Calibration: scrutinized through visual inspection of the calibration plot and utilization of the Brier score. (3) The incremental value of risk prediction and the utility of updating the model were gauged using NRI (Net Reclassification Improvement) and IDI (Integrated Discrimination Improvement). Decision Curve Analysis (DCA) was employed to evaluate the clinical benefit of updating the model.Results The final cohort comprised 2235 individuals undergoing maintenance hemodialysis, exhibiting a 14.6% occurrence rate of IDH. The externally validated Area Under the Curve (AUC) values for the three original prediction models were 0.746 (95% CI: 0.718 to 0.775), 0.709 (95% CI: 0.679 to 0.739), and 0.735 (95% CI: 0.706 to 0.764) respectively. Conversely, the AUC value for the recalibrated and updated columnar plot model reached 0.817 (95% CI: 0.791 to 0.842), accompanied by a Brier score of 0.081. Furthermore, Decision Curve Analysis (DCA) exhibited a net benefit within the threshold probability range of 15.2% to 87.1%.Conclusion Externally validated, recalibrated, updated, and presented IDH prediction models may serve as a valuable instrument for evaluating IDH risk in clinical practice. Furthermore, they hold the potential to guide clinical providers in discerning individuals at risk and facilitating judicious clinical intervention decisions.

Background The high prevalence of mild cognitive impairment (MCI) in non-dialysis individuals with chronic kidney disease (CKD) impacts their prognosis and quality of life.Objective This study aims to investigate the variables associated with MCI in non-dialysis outpatient patients with CKD and to construct and verify a nomogram prediction model.Methods 416 participants selected from two hospitals in Chengdu, between January 2023 and June 2023. They were categorized into two groups: the MCI group (n = 210) and the non-MCI (n = 206). Univariate and multivariate binary logistic regression analyses were employed to identify independent influences (candidate predictor variables). Subsequently, regression models was constructed, and a nomogram was drawn. The restricted cubic spline diagram was drawn to further analyze the relationship between the continuous numerical variables and MCI. Internally validated using a bootstrap resampling procedure.Results Among 416 patients, 210 (50.9%) had MCI. Logistic regression analysis revealed that age, educational level, occupational status, use of smartphones, sleep disorder, and hemoglobin were independent influencing factors of MCI (all p

Berry fruits produced by Vaccinium (Ericaceae) plants are small but have a signature flavor and have become increasingly popular in the 21st century. However, self-incompatibility (SI) results in a relatively low fruit-set ratio and reduced fruit quality in Vaccinium. In this study, using Vaccinium ashei (V. ashei) styles after cross-pollination (CP) and self-pollination (SP) as material, transcriptomics and gene expression analyses were performed using high-throughput RNA sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, evolutionary analysis and conserved sequences analysis of candidate genes were conducted. Among the 135,324 unigenes, 30,863 were shown to be differentially expressed, and eight randomly selected differentially expressed genes were expressed in the styles at 96 hours after SP and CP. The transcriptomics and qRT-PCR results were significantly correlated, which confirmed the reliability of the differentially expressed genes obtained in our study. Compared with SP96, six differentially expressed ribonuclease T2 family genes were obtained in CP96, which were considered candidates for S-RNase. Additionally, the spatiotemporal and organizational expression trends of six candidates for S-RNase were confirmed by qRT-PCR, and the evolutionary and conservative sequence analysis indicated six candidate S-RNases with the typical S-RNase structure. The spatiotemporal and organizational expression results and evolutionary and conservative sequence analyses of the six candidate S-RNases suggest that SI in V. ashei is likely an S-RNase-mediated gametophytic one. This finding suggests the involvement of novel, previously undiscovered components involved in the V. ashei SI system. These findings help elucidate the molecular mechanisms of SI in rabbiteye blueberry and may also benefit breeding, production, and genomics research in V. ashei and other Vaccinium species.

As a crucial component of the oil transportation system, the oil terminal (or oil tank farm) may often pose some serious threats and damage to the ecological environment and production safety for the oil leakage. An effective emergency management strategy is particularly significant, involving the accurate assessment of leakage time, oil migration path, volume distribution, etc. Therefore, the volume of fluid (VOF) and liquid phase leakage model were applied to investigate the migration and distribution characteristic after the accidental hole occurs in the tank wall, and influence factors including height and diameter of the hole were considered in our study. Results show that the lower the leaking hole position is, the faster the horizontal injection rate of the leakage hole, the increase of the accumulation area of the oil on the ground, and the difference in the overall pressure value at the leakage hole is nearly four times. Under different leakage diameters, the oil spill is symmetrical. The larger the leakage diameter, the higher the amount of oil leakage and the initial leakage speed, the maximum speed is 1.5 times the minimum speed, causing harm to safety and environmental pollution. These results can quickly locate the leakage location of the tank and provide valuable references for emergency management of the oil pipeline transportation system.

BackgroundThis study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS.MethodsA total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied.ResultsThe male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8–13.1 years), the disease duration was 1.0 month (IQR, 0.5–2.0 months), and follow-up was 36.5 months (IQR, 25.7–50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)—these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001).ConclusionEndothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.

The seven major river basins (the Yangtze River, the Yellow River, the Pearl River, the Songhua River, the Huai River, the Hai River and the Liao River) are the most important surface water resources in China, but there is a lack of quantitative analyses of water quality change trends, horizontal comparisons of governance effects, and systematic review of effective policies since the 21st century. Based on the water resources bulletin and environmental status bulletin issued by government departments, the changes in water quality, pollutant indicators and treatment effectiveness of seven major basins from 2001 to 2020 have been scientifically analyzed using mathematical and statistical methods. (1) Over the period 2001 to 2020, the overall water quality in the seven major river basins exhibited a gradual improvement. Different basins demonstrated varied growth values for Grade I-III water, reduction values for Grade IV-V, and inferior Grade V water. (2) Between 2001 and 2020, changes in sewage discharge volume and types led to adjustments in the main pollutant indicators of the seven basins. (3) The ranking of the pollution degree in the seven major basins exhibited dynamic changes but also remained relatively stable during specific periods or years. (4) Assessing the average annual growth rate of Grade I-III water and the average annual reduction rate of Grade IV-V and inferior Grade V water, the Huai River basin demonstrated the most outstanding governance effectiveness, while the Liao River basin, the Yellow River basin, and the Songhua River basin also achieved notable treatment results. (5) The improvement in water quality across the seven major river basins can be attributed to scientific planning, enhanced policies and regulations, surge in investment in water conservancy infrastructure, heightened environmental protection awareness, application of green production technology. To sum up, the research findings not only provide a scientific foundation for the governance and protection of the seven major basins but also offer a valuable reference for other developing countries to strike a balance between economic development and environmental protection.

Development of the mammalian oocyte requires physical contact with the surrounding granulosa cells of the follicle, which provide it with essential nutrients and regulatory signals. This contact is achieved through specialized filopodia, termed transzonal projections (TZPs), that extend from the granulosa cells to the oocyte surface. Transforming growth factor (TGFβ) family ligands produced by the oocyte increase the number of TZPs, but how they do so is unknown. Using an inducible Cre recombinase strategy together with expression of green fluorescent protein to verify Cre activity in individual cells, we examined the effect of depleting the canonical TGFβ mediator, SMAD4, in mouse granulosa cells. We observed a 20–50% decrease in the total number of TZPs in SMAD4-depleted granulosa cell-oocyte complexes, and a 50% decrease in the number of newly generated TZPs when the granulosa cells were reaggregated with wild-type oocytes. Three-dimensional image analysis revealed that TZPs of SMAD4-depleted cells were longer than controls and more frequently oriented towards the oocyte. Strikingly, the transmembrane proteins, N-cadherin and Notch2, were reduced by 50% in SMAD4-depleted cells. SMAD4 may thus modulate a network of cell adhesion proteins that stabilize the attachment of TZPs to the oocyte, thereby amplifying signalling between the two cell types.

Abstract Background The PI3K/AKT pathway transduces the majority of the metabolic actions of insulin. In addition to cytosolic targets, insulin-stimulated phospho-AKT also translocates to mitochondria in the myocardium. Mouse models of diabetes exhibit impaired mitochondrial AKT signaling but the implications of this on cardiac structure and function is unknown. We hypothesized that loss of mitochondrial AKT signaling is a critical step in cardiomyopathy and reduces cardiac oxidative phosphorylation. Methods To focus our investigation on the pathophysiological consequences of this mitochondrial signaling pathway, we generated transgenic mouse models of cardiac-specific, mitochondria-targeting, dominant negative AKT1 (CAMDAKT) and constitutively active AKT1 expression (CAMCAKT). Myocardial structure and function were examined using echocardiography, histology, and biochemical assays. We further investigated the underlying effects of mitochondrial AKT1 on mitochondrial structure and function, its interaction with ATP synthase, and explored in vivo metabolism beyond the heart. Results Upon induction of dominant negative mitochondrial AKT1, CAMDAKT mice developed cardiac fibrosis accompanied by left ventricular hypertrophy and dysfunction. Cardiac mitochondrial oxidative phosphorylation efficiency and ATP content were reduced, mitochondrial cristae structure was lost, and ATP synthase structure was compromised. Conversely, CAMCAKT mice were protected against development of diabetic cardiomyopathy when challenged with a high calorie diet. Activation of mitochondrial AKT1 protected cardiac function and increased fatty acid uptake in myocardium. In addition, total energy expenditure was increased in CAMCAKT mice, accompanied by reduced adiposity and reduced development of fatty liver. Conclusion CAMDAKT mice modeled the effects of impaired mitochondrial signaling which occurs in the diabetic myocardium. Disruption of this pathway is a key step in the development of cardiomyopathy. Activation of mitochondrial AKT1 in CAMCAKT had a protective role against diabetic cardiomyopathy as well as improved metabolism beyond the heart.

Salt stress is a critical abiotic factor that adversely affects plant growth and productivity by impairing photosynthesis. This study explores the impact of exogenous ascorbic acid (AsA) on the photosynthetic performance of tomato seedlings (Solanum lycopersicum L. cv. Ligeer 87-5) under salt stress. Hydroponic experiments were conducted in a solar greenhouse, where tomato seedlings were subjected to the following five treatments: Control, NaCl, NaCl + AsA, NaCl + lycorine (LYC), and NaCl + LYC + AsA. Our findings demonstrate that salt stress significantly reduced chlorophyll and carotenoid contents, levels of chlorophyll synthesis precursors (5-aminolevulinic acid (ALA), porphobilinogen (PBG), uroporphyrinogen III (Urogen III), protoporphyrin IX (Proto IX), magnesium protoporphyrin IX (Mg-Proto IX), protochlorophyllide (Pchl)), and essential elements (Mg, Fe, Mn, Zn, Mo, and P) in both roots and leaves. These reductions led to a substantial decline in net photosynthetic rate (Pn) and compromised photosystem II (PSII). In contrast, exogenous AsA application significantly enhanced the content of photosynthetic pigment precursors and essential elements, improved stomatal aperture and gas exchange efficiency, and boosted the photosynthetic performance of tomato seedlings under salt stress. Furthermore, AsA treatment mitigated the negative effects of salt stress by protecting PSII, increased light energy utilization efficiency, and alleviated both stomatal and non-stomatal limitations. The application of the AsA synthesis inhibitor LYC exacerbated the detrimental effects of salt stress, further reducing chlorophyll content and photosynthetic efficiency. In conclusion, exogenous AsA plays a vital role in enhancing the photosynthetic performance and stress tolerance of tomato seedlings under salt stress by stabilizing chlorophyll biosynthesis, facilitating essential element absorption, and optimizing stomatal function. This study provides a new approach and feasible measures for improving tomato resistance and yield, which is significant for enhancing crop productivity, managing saline soils, and promoting sustainable agricultural practices.

Background and purpose: Clinically, the ability to identify individuals at risk of ischemic stroke remains limited. This study aimed to develop a nomogram model for predicting the risk of acute ischemic stroke. Methods: In this study, we conducted a retrospective analysis on patients who visited the Department of Neurology, collecting important information including clinical records, demographic characteristics, and complete hematological tests. Participants were randomly divided into training and internal validation sets in a 7:3 ratio. Based on their diagnosis, patients were categorized as having or not having ischemic stroke (ischemic and non-ischemic stroke groups). Subsequently, in the training set, key predictive variables were identified through multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods, and a nomogram model was constructed accordingly. The model was then evaluated on the internal validation set and an independent external validation set through area under the receiver operating characteristic curve (AUC-ROC) analysis, a Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA) to verify its predictive efficacy and clinical applicability. Results: Eight predictors were identified: age, smoking status, hypertension, diabetes, atrial fibrillation, stroke history, white blood cell count, and vitamin B12 levels. Based on these factors, a nomogram with high predictive accuracy was constructed. The model demonstrated good predictive performance, with an AUC-ROC of 0.760 (95% confidence interval [CI]: 0.736–0.784). The AUC-ROC values for internal and external validation were 0.768 (95% CI: 0.732–0.804) and 0.732 (95% CI: 0.688–0.777), respectively, proving the model’s capability to predict the risk of ischemic stroke effectively. Calibration and DCA confirmed its clinical value. Conclusions: We constructed a nomogram based on eight variables, effectively quantifying the risk of ischemic stroke.

This study aimed to explore the relationship between life events and non-suicidal self-injury (NSSI) in college students, as well as the mediating effect of sleep disturbances and psychotic-like experiences (PLEs). After excluding invalid questionnaires, 5,754 were retained, and the valid efficiency was 75.94%. The subjects were aged 16 to 29 years (M = 19.166; SD = 1.392), with 1,969 males (34.22%) and 3,785 females (65.78%). Life events, sleep disturbances, PLEs, and NSSI were assessed using standard scales. Data were analyzed by Pearson Correlation Analysis and bias-correction percentile Bootstrap method. The results show that (1) life events were significant positive predictors of NSSI, sleep disturbances, and PLEs; (2) sleep disturbances, PLEs, and the chain mediation between the two, were mediators between life events and NSSI. Life events are thus shown to be an important external factor influencing NSSI in university students, and this process is mediated through sleep disturbances, PLEs, and the chain between the two. Interventions for NSSI can therefore be made by improving college students’ sleep quality and reducing PLEs.

BackgroundMandibuloacral dysplasia (MAD) syndrome is a rare genetic disease. Several progeroid syndromes including mandibuloacral dysplasia type A (MADA), mandibuloacral dysplasia type B(MADB), Hutchinson-Gilford progeria (HGPS) and mandibular hypoplasia, deafness, and lipodystrophy syndrome (MDPL) have been reported previously. A novel MAD progeroid syndrome (MADaM) has recently been reported. So far, 7 cases of MADaM diagnosed with molecular diagnostics have been reported in worldwide. In the Chinese population, cases of MAD associated with the MTX2 variant have never been reported.MethodsThe clinical symptoms and the genetic analysis were identified and investigated in patients presented with the disease. In addition, we analyzed and compared 7 MADaM cases reported worldwide and summarized the progeroid syndromes reported in the Chinese population to date.ResultsThe present study reports a case of a novel homozygous mutation c.378 + 1G > A in the MTX2 gene, which has not been previously reported in the literature. Patients present with early onset and severe symptoms and soon after birth are found to have growth retardation. In addition to the progeroid features, skeletal deformities, generalized lipodystrophy reported previously, and other multisystem involvement, e.g. hepatosplenic, renal, and cardiovascular system, this case was also reported to have combined hypogammaglobulinemia. She has since been admitted to the hospital several times for infections. Among 22 previously reported progeroid syndromes, 16/22 were MADA or HGPS caused by LMNA gene mutations, and the homozygous c.1579C > T (p.R527C) mutation may be a hot spot mutation for MAD in the Chinese population. MAD and HGPS mostly present in infancy with skin abnormalities or alopecia, MDPL mostly presents in school age with growth retardation as the first manifestation, and is often combined with an endocrine metabolism disorder after several decades.ConclusionThis is the first case of MAD syndrome caused by mutations in MTX2 gene reported in the Chinese population. MTX2 gene c.378 + 1G > A homozygous mutation has not been previously reported and the report of this patient expands the spectrum of MTX2 mutations. In addition, we summarized the genotypes and clinical characteristics of patients with progeroid syndromes in China.

Floods are a widespread natural disaster with substantial economic implications and far-reaching consequences. In Northern Pakistan, the Hunza-Nagar valley faces vulnerability to floods, posing significant challenges to its sustainable development. This study aimed to evaluate flood risk in the region by employing a GIS-based Multi-Criteria Decision Analysis (MCDA) approach and big climate data records. By using a comprehensive flood risk assessment model, a flood hazard map was developed by considering nine influential factors: rainfall, regional temperature variation, distance to the river, elevation, slope, Normalized difference vegetation index (NDVI), Topographic wetness index (TWI), land use/land cover (LULC), curvature, and soil type. The analytical hierarchy process (AHP) analysis assigned weights to each factor and integrated with geospatial data using a GIS to generate flood risk maps, classifying hazard levels into five categories. The study assigned higher importance to rainfall, distance to the river, elevation, and slope compared to NDVI, TWI, LULC, curvature, and soil type. The weighted overlay flood risk map obtained from the reclassified maps of nine influencing factors identified 6% of the total area as very high, 36% as high, 41% as moderate, 16% as low, and 1% as very low flood risk. The accuracy of the flood risk model was demonstrated through the Receiver Operating Characteristics-Area Under the Curve (ROC-AUC) analysis, yielding a commendable prediction accuracy of 0.773. This MCDA approach offers an efficient and direct means of flood risk modeling, utilizing fundamental GIS data. The model serves as a valuable tool for decision-makers, enhancing flood risk awareness and providing vital insights for disaster management authorities in the Hunza-Nagar Valley. As future developments unfold, this study remains an indispensable resource for disaster preparedness and management in the Hunza-Nagar Valley region.

Background Atrial fibrillation (AF) is the most common type of arrhythmia worldwide and is associated with serious complications. This study investigated the metabolic biomarkers associated with AF and the differences in metabolomics and associated metabolic biomarkers between paroxysmal AF (AFPA) and persistent AF. Methods and Results Plasma samples were prospectively collected from patients with AF and patients in sinus rhythm with negative coronary angiography. The patients were divided into 3 groups: AFPA, persistent AF, and sinus rhythm (N=54). Metabolomics (n=36) using ultra‐high‐performance liquid chromatography mass spectrometry was used to detect differential metabolites that were validated in a new cohort (n=18). The validated metabolites from the validation phase were further analyzed by receiver operating characteristic. Among the 36 differential metabolites detected by omics assay, 4 were successfully validated with area under the curve >0.8 (P

Acne vulgaris is a common inflammatory skin disease associated with Propionibacterium acnes (P. acnes), with serious physical and psychological effects on patients. Conventional topical use of antibiotics is not effective due to the skin barrier and oral administration can adversely affect the intestinal flora. Microneedle is a novel type of localized drug delivery system that noninvasively breaks through the stratum corneum barrier and effectively enhances the transdermal absorption of drugs. Here, Bletilla striata polysaccharide (BSP)/Hyaluronic acid (HA) loaded Epigallocatechin gallate (EGCG) was used as the microneedle body to easily penetrate the epidermis and enhance antibacterial ability. Polyvinyl alcohol (PVA) and Diatomaceous earth (DE) are used as the microneedle backing to absorb pus and bacterial debris, prevent re-infection of bacteria and promote skin healing. Compared to traditional antibiotics, the excellent skin permeability of EGCG@BSP/HA MNs studied here can improve the efficacy and solve side effects and drug resistance. In vivo studies in mice models induced by P. acnes showed that this microneedle could effectively reduce skin swelling, inhibit bacterial growth and reduce the levels of TNF-α, IL-8 and MMP-2. In summary, this study provides an ideal antimicrobial drug delivery system for the treatment of acne vulgaris.

Ecological history is crucial in ecosystem restoration, serving as a tool to identify and characterize suitable restoration targets. Pakistan has implemented laws and policies to enhance forest sustainability and preserve biodiversity, as it is becoming a global strategy for future water planning and management. This study seeks to analyze the impact of national park policies and laws on various factors, including biodiversity conservation, ecological processes preservation, water resource protection, consumptive and non-consumptive benefits, research and education, and the promotion of recreation and tourism. To assess the effectiveness of established policies in 19 National Parks in Pakistan, a mixed-mode research design was utilized, combining both quantitative and qualitative approaches. Data was collected from 300 participants through a close-ended questionnaire employing a Likert scale. Analysis of the collected data was conducted using the software Smart Partial Least Squares method. The findings demonstrate that the existing policies and laws have contributed to the preservation of forest sustainability in Pakistan. The policies related to recreation and tourism; consumptive benefits; and research are more effective respectively compared to other sets of regulations. The laws and policies related to preservation of ecological processes are least effective. The study suggests that laws related to national parks need to be revised to preserve biodiversity and ecological processes. The preservation of water resources should be a major concern, and the consumptive benefits of these parks should be rechecked. Awareness campaigns are to be part of the expansionary policy framework, and while tourism opportunities should be created, a check on natural resource misuse should be implemented. The non-consumptive benefits of these parks should also be assessed. Due to its potential limitations, such as limited stakeholder analysis, difficulty in creating legitimacy in national parks due to bureaucratic structures, lack of community sensitization, and long-term trends in sustainable conservation strategies, there are certain future research directions that can address challenges in studying the impact of policies on national park habitats. There is a pressing demand for a more dynamic approach to ecological policymaking. Continuous evaluation and adaptation of policies will be essential in creating an environment conducive to sustainable development.

ObjectivesThe present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China.MethodsA total of 219 new leprosy cases during two periods, 2018–2019 and 2020–2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods.ResultsThere was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January–March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K.ConclusionCOVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

The fundamental research on thermo-mechanical conditions provides an experimental basis for high-performance Mg-Al-Ca-Mn alloys. However, there is a lack of systematical investigation for this series alloys on the hot-deformation kinetics and extrusion parameter optimization. Here, the flow behavior, constitutive model, dynamic recrystallization (DRX) kinetic model and processing map of a dilute rare-earth free Mg-1.3Al-0.4Ca-0.4Mn (AXM100, wt.%) alloy were studied under different hot-compressive conditions. In addition, the extrusion parameter optimization of this alloy was performed based on the hot-processing map. The results showed that the conventional Arrhenius-type strain-related constitutive model only worked well for the flow curves at high temperatures and low strain rates. In comparison, using the machine learning assisted model (support vector regression, SVR) could effectively improve the accuracy between the predicted and experimental values. The DRX kinetic model was established, and a typical necklace-shaped structure preferentially occurred at the original grain boundaries and the second phases. The DRX nucleation weakened the texture intensity, and the further growth caused the more scattered basal texture. The hot-processing maps at different strains were also measured and the optimal hot-processing range could be confirmed at the deformation temperatures of 600∼723 K and the strain rates of 0.018∼0.563 s−1. Based on the optimum hot-processing range, a suitable extrusion parameter was considered as 603 K and 0.1 mm/s and the as-extruded alloy in this parameter exhibited a good strength-ductility synergy (yield strength of ∼ 232.1 MPa, ultimate strength of ∼ 278.2 MPa and elongation-to-failure of ∼ 20.1%). Finally, the strengthening-plasticizing mechanisms and the relationships between the DRXed grain size, yield strength and extrusion parameters were analyzed.

Abstract Due to the complexity and incomplete understanding of the crosstalk between liver and adipose tissue, especially the processes of hepatic lipogenesis and adipogenic differentiation, there are currently no effective drugs for the treatment of nonalcoholic fatty liver disease (NAFLD). Stearoyl-coenzyme A desaturase 1 (SCD1), which is abundantly expressed in liver and adipose tissue, may mediate the cross-talk between liver and adipose tissue. Thus, it is essential to develop specific SCD1 inhibitors that target the liver-adipose axis. Herein, we identified a novel SCD1 inhibitor, E6446, through a high-throughput virtual screen. E6646 significantly inhibited adipogenic differentiation and hepatic lipogenesis via SCD1-ATF3 signaling. The SPR results showed that E6446 had a strong interaction ability with SCD1 (KD:4.61 μM). Additionally, E6646 significantly decreased hepatic steatosis, hepatic lipid droplet accumulation and insulin resistance in high-fat diet (HFD)-fed mice. Taken together, our findings not only suggest that E6446 can serve as a new, safe and highly effective anti-NAFLD agent for future clinical use but also provide a molecular basis for the future development of SCD1 inhibitors that inhibit both adipogenic differentiation and hepatic lipogenesis. Video Abstract

Abstract Background The accumulation of reactive oxygen species (ROS) in tumor microenvironment (TME) is an important player for tumorigenesis and progression. We aimed to explore the outcomes of ROS on tumor vessels and the potential regulated mechanisms. Methods Exogenous H2O2 was adopted to simulate the ROS setting. Immunofluorescence staining and ultrasonography were used to assess the vascular endothelial coverage and perfusions in the tumors inoculated with Lewis lung cancer (LLC) and melanoma (B16F10) cells of C57BL/6 mice, respectively. ELISA and western-blot were used to detect the expression of secreted acidic and cysteine-rich protein (SPARC) and Caveale-1 in human umbilical vein endothelial cells (HUVEC) extra- and intracellularly. Intracellular translocation of SPARC was observed using electron microscopy and immunofluorescence approaches. Result Under the context of oxidative stress, the pericyte recruitment of neovascularization in mouse lung cancer and melanoma tissues would be aberrated, which subsequently led to the disruption of the tumor vascular architecture and perfusion dysfunction. In vitro, HUVEC extracellularly SPARC was down-regulated, whereas intracellularly it was up-regulated. By electron microscopy and immunofluorescence staining, we observed that SPARC might undergo transmembrane transport via caveale-1-mediated endocytosis. Finally, the binding of SPARC to phosphorylated-caveale-1 was also detected in B16F10 tissues. Conclusion In the oxidative stress environment, neovascularization within the tumor occurs structural deterioration and decreased perfusion capacity. One of the main regulatory mechanisms is the migration of extracellular SPARC from the endothelium to intracellular compartments via Caveolin-1 carriers.

Soybean agglutinin (SBA) is a primary antinutritional factor in soybeans that can inhibit the growth of humans and mammals, disrupt the intestinal environment, and cause pathological changes. Therefore, detecting and monitoring SBA in foods is essential for safeguarding human health. In this paper, M13 phage-displayed nanobodies against SBA were isolated from a naive nanobody library. An M13 phage-displayed nanobody-based competitive enzyme-linked immunosorbent assay (P-cELISA) was then established for SBA analysis using biotinylated anti-M13 phage antibody (biotin-anti-M13) and streptavidin poly-HRP conjugate (SA-poly-HRP). The biotin-anti-M13@SA-poly-HRP probe can easily amplify the detection signal without the chemical modifications of phage-displayed nanobodies. The established P-cELISA presented a linear detection range of 0.56–250.23 ng/mL and a limit of detection (LOD) of 0.20 ng/mL, which was 12.6-fold more sensitive than the traditional phage-ELISA. Moreover, the developed method showed good specificity for SBA and acceptable recoveries (78.21–121.11%) in spiked wheat flour, albumen powder, and whole milk powder. This study proposes that P-cELISA based on biotin-anti-M13@SA-poly-HRP may provide a convenient and effective strategy for the sensitive detection of SBA.

The drug detection technology plays a pivotal role in the domains of pharmaceutical regulation and law enforcement. In this study, we introduce a method that combines thermal desorption corona discharge ionization (TD-CDI) with mass spectrometry for efficient drug detection. The TD-CDI module, characterized by its compact and simple design, enables the separation of analytes within seconds and real-time presentation of one or two analyte peaks on the mass spectrum most of the time, which reduces matrix interference and improves detection performance. Through experimental investigation, we studied the characteristics of TD-CDI for analyte separation and detection, even with the same mass number, and optimized the TD-CDI approach. TD-CDI-MS was employed for the rapid detection of drugs in various traditional medicine, food products, and human samples. Additionally, by utilizing TD-CDI for segmented hair direct analysis, it becomes possible to trace the drug usage cycle of individuals. This underscores the feasibility of the proposed analytical method within the realm of drug detection.

Myocardial infarction (MI), including ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI), is still a leading cause of death worldwide. Metabolomics technology was used to explore differential metabolites (DMs) as potential biomarkers for early diagnosis of STEMI and NSTEMI. In the study, 2531 metabolites, including 1925 DMs, were discovered. In the selected 27 DMs, 14 were successfully verified in a new cohort, and the AUC values were all above 0.8. There were 10 in STEMI group, namely L-aspartic acid, L-acetylcarnitine, acetylglycine, decanoylcarnitine, hydroxyphenyllactic acid, ferulic acid, itaconic acid, lauroylcarnitine, myristoylcarnitine, and cis-4-hydroxy-D-proline, and 5 in NSTEMI group, namely L-aspartic acid, arachidonic acid, palmitoleic acid, D-aspartic acid, and palmitelaidic acid. These 14 DMs may be developed as biomarkers for the early diagnosis of MI with high sensitivity and specificity. These findings have particularly important clinical significance for NSTEMI patients because these patients have no typical ECG changes.

It is currently a challenge to accurately predict the deformation and fracture behavior of metal parts in automobile crashes. Many studies have shown that the deformation and fracture behavior of materials are significantly affected by the stress state during automobile crashes with complex stress state characteristics. In order to further promote the application of die-cast magnesium alloys in automobiles, it is particularly important to study the material deformation and fracture behavior of die-cast magnesium alloys. In this paper, the mechanical properties of the AM60B die-cast magnesium alloy sheet under four stress states (shear, tension, R10 notch tension, and cupping) were designed and tested. Based on the von Mises isotropic constitutive model and Swift weighted Hockett–Sherby hardening model, the plastic constitutive model of die-cast magnesium alloy was established. Based on the plastic model and the fracture model (JC, MMC, and DIEM) considering the influence of three stress states, the deformation and fracture behavior of the AM60B die-cast magnesium alloy front-end members in three-point bending were predicted by experiments and finite element simulation. The experimental results show that the deformation mode and loading–displacement curve trend of the AM60B die-cast magnesium alloy front members are the same, the crack initiation point and crack initiation time are the same, and the crack shape is similar. The results show that the complex stress state constitutive model parameters and the DIEM fracture model obtained in this paper can accurately predict the deformation and fracture failure behavior of the AM60B die-cast magnesium alloy sheet.

Abstract Cardiovascular disease is a high incidence and mortality rate disease worldwide. Exercise training has become an established evidence-based treatment strategy that is beneficial for many cardiovascular diseases. This study aimed to investigate the effects of exercise on hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient (ApoE−/−) mice. Male ApoE−/− mice were randomly divided into the following four groups: normal diet (ND), normal diet + exercise training (ND + E), high-fat diet (HFD), and high-fat diet + exercise training (HFD + E). Exercise training consisted of swimming for 40 min, 5 days/week for 12 weeks. After 12 weeks, histopathological alterations in cardiac tissue and the serum were measured. Furthermore, the NOX4, NRF2, SIRT1, TGF-β, HO-1, collagen III, Smad3, Bax, Bak, Bcl-2, Bcl-xl, IL-1β, IL-6, and IL-18 expression levels were evaluated using immunohistochemistry and western blotting; Results: the serum levels of SIRT1, GSH-Px, and SOD were lower in ApoE−/− HFD mice compared with those in ApoE−/− HFD + E mice. Significant pathological changes were observed in the ApoE−/− HFD + E group compared with those in the ApoE−/− HFD group. Increased levels of oxidative stress, fibrosis, and apoptosis, and decreased antioxidant expression in the ApoE−/− HFD group compared with those in ApoE−/− HFD + E mice. Exercise exerts protective effects against cardiac damage caused by hyperlipidemia.

Abstract Background Femoral neck fracture (FNF) is a very common traumatic disorder and a major cause of blood supply disruption to the femoral head, which may lead to a severe long-term complication, osteonecrosis of femoral head (ONFH). Early prediction and evaluation of ONFH after FNF could facilitate early treatment and may prevent or reverse the development of ONFH. In this review paper, we will review all the prediction methods reported in the previous literature. Methods Studies on the prediction of ONFH after FNF were included in PubMed and MEDLINE databases with articles published before October 2022. Further screening criteria were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This study highlights all the advantages and disadvantages of the prediction methods. Results There were a total of 36 studies included, involving 11 methods to predict ONFH after FNF. Among radiographic imaging, superselective angiography could directly visualize the blood supply of the femoral head, but it is an invasive examination. As noninvasive detection methods, dynamic enhanced magnetic resonance imaging (MRI) and SPECT/CT are easy to operate, have a high sensitivity, and increase specificity. Though still at the early stage of development in clinical studies, micro-CT is a method of highly accurate quantification that can visualize femoral head intraosseous arteries. The prediction model relates to artificial intelligence and is easy to operate, but there is no consensus on the risk factors of ONFH. For the intraoperative methods, most of them are single studies and lack clinical evidence. Conclusion After reviewing all the prediction methods, we recommend using dynamic enhanced MRI or single photon emission computed tomography/computed tomography in combination with the intraoperative observation of bleeding from the holes of proximal cannulated screws to predict ONFH after FNF. Moreover, micro-CT is a promising imaging technique in clinical practice.