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Abstract Background CD74 is a non-polymorphic type II transmembrane glycoprotein. It is involved in the regulation of T and B cell development, and dendritic cell (DC) motility. Numerous studies have found that CD74 exerts an essential role in tumor immunity, but the expression profile of CD74 is still not systematically reported, and its value in human pan-cancer analysis is unknown. In this study, we analyzed the expression pattern of CD74 in 33 cancers, and evaluated the significance of CD74 in prognosis prediction and cancer immunity. Methods Pan-cancer dataset from UCSC Xena.We used the Sangerbox website combined with R software’ Timer, CIBERSORT method and IOBR package to analyze and plot the data. Survival was assessed using the Kaplan—Meier method and log—rank test for 33 cancer types (p

Abstract Background Gut microbiota exert an immense effect on host health and host environmental adaptation. Furthermore, the composition and structure of gut microbiota are determined by the environment and host genetic factors. However, the relative contribution of the environment and host genetic factors toward shaping the structure of gut microbiota has been poorly understood. Methods In this study, we characterized the fecal microbial communities of the closely related voles Neodon fuscus, Lasiopodomys brandtii, and L. mandarinus after caged feeding in the laboratory for 6 months, through high‐throughput sequencing and bioinformatics analysis. Results The results of pairwise comparisons of N. fuscus vs. L. brandtii and L. mandarinus vs. L. brandtii revealed significant differences in bacterial diversity and composition after domestication. While 991 same operational taxonomic units (OTUs) were shared in three voles, there were 362, 291, and 303 species‐specific OTUs in N. fuscus, L. brandtii, and L. mandarinus, respectively. The relative abundances of Proteobacteria and Prevotella, which are reported to be enriched in high‐altitude populations, were significantly higher in high‐altitude N. fuscus than in low‐altitude L. brandtii after domestication. Firmicutes, which produce various digestive enzymes for energy metabolism, and Spirochaetes, which can degrade cellulose, were found in higher abundance in subterranean L. mandarinus than that in L. brandtii which dwells on the earth surface. Conclusion Our findings showed that some components of gut microbiota still maintained dominance even when different host species are reared under the same environmental conditions, suggesting that these bacteria are substantially influenced by host factors.

BackgroundHuman papillomavirus (HPV) is a main pathogenic factor for cervical carcinoma. The prevalence and genotypes distribution of HPV vary in different regions. Thus, our study aimed to investigate the epidemiology of HPV in Huizhou, China.MethodsHPV tests were detected in 5,325 female outpatients, we focused on the overall HPV prevalence, genotypes distribution, and the correlation of HPV genotypes with cervical cytology.ResultsThe overall HPV prevalence was 27.53%, HPV52, HPV58, HPV39, HPV16 and HPV51 were predominant genotypes with single infection rate of 70.80%. HPV infection rate showed a U-shaped age distribution, statistical differences were observed among 5 age groups (χ2 = 50.497, p < 0.01), and the higher positive rate was aged under 30 (34.42%) and above 60 (34.74%). Among high-risk HPV (hrHPV) infections, 60.69% involved NILM, 0.99% HSIL. The degrees of cervical lesions in multiple hrHPV infections were worse than those in single infection (p

A six-week feeding trial was conducted to investigate the effects of dietary starch levels on growth performance, glucose and lipid metabolism and insulin signaling pathway of juvenile Scylla paramamosain. Three isonitrogenous (41.51% ± 0.31%) and isolipidic (8.68% ± 0.53%) experimental diets were formulated to contain 10%, 20% and 30% starch levels, respectively. A total 96 crabs were divided into 3 treatment groups. There were 4 replicates per treatment group and 8 crabs per replicate (initial weight 5.12 ± 0.05 g). The crabs fed the diet with 20% starch showed the best growth performance, with higher weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER), and feed efficiency (FE) compared to the other diets. Increasing starch levels in the diet resulted in higher levels of glycogen and lipid in the muscles and hepatopancreas. The levels of glucose (GLU), triglyceride (TG), and free fatty acid (FFA) displayed a significant increase in both hemolymph and hepatopancreas with the escalating dietary starch concentrations. In contrast, as the dietary starch levels increased, the concentrations of crustacean hyperglycemic hormone (CHH) and insulin-like peptides (ILPs) in hemolymph and hepatopancreas demonstrated a notable decline. The glycolysis and pentose phosphorylation pathways were significantly promoted, while the gluconeogenic pathway was significantly inhibited, with dietary starch levels increasing from 10% to 30%. Additionally, increasing dietary starch levels led to a significant down-regulation of genes related to the lipid synthesis, lipolysis and insulin signaling pathway. Histological results showed that hepatopancreas fat accumulation increased with the increase of dietary starch level. Overall, the findings of this study suggest that adding 20% starch to the diet can promote growth and improve nutrient utilization. In addition, the level of dietary starch had significant effects on the glucose and lipid metabolism and insulin signaling pathway of mud crabs, thus affecting the deposition of lipid reserves in hepatopancreas.

To solve the problems of poor forming and low corrosion resistance of 316L stainless steel laser cladding layer, the forming, microstructure and properties of single-layer and multi-layer samples prepared at different laser powers were detected and analyzed by microstructure observation, hardness testing, impact testing and electrochemical testing. The results show that the height of the laser cladding layer initially increases and subsequently decreases with the increase of laser power. The content of precipitates and the dilutionrate increase with the increase of laser power. Cracks occur in the laser cladding layer under the condition of low laser power, and it can cause the grains to grow abnormally under the condition of high laser power. Meanwhile, the hardness value of the laser cladding layer increases with the increase of laser power. The hardness value at the interface reach a maximum value of 475 HV when the laser power is 450 W. However, the impact toughness and corrosion resistance of the laser cladding layer decreases as the laser power increases. The maximum impact toughness is 92 J of the laser cladding layer prepared with the laser power of 300 W. Meanwhile, the laser cladding layer prepared with the laser power of 300 W has the best corrosion resistance, with its highest corrosion potential (Ecorr) of -0.3 V and lowest corrosion current density (Icorr) of 0.165 A/cm2, respectively. Therefore, the laser cladding layer prepared at 300 W laser power can obtain excellent impact and corrosion resistance when the laser cladding speed is 3 mm/s, the powder feeding rate is 14 g/min, and the overlap rate is 50%. The research results can provide a reference for the parameter control and performance improvement of laser cladding 316L layer.

Abstract Increasing extreme climate events driven by climate change raise the question of their impacts on the power production system, and implications for renewable versus fossil power supply. Here, using climate reanalysis data and daily electricity generation (2018–2023), we systematically quantify the impact of extreme climate events, specifically extreme cold events and extreme hot events on United States state-level carbon emissions and on the carbon intensity of electricity. We find that extreme climate events increase the carbon intensity of the energy production, increasing the reliance on fossil-based sources of energy and reducing the capacity of renewables. The states with more renewable electricity generation were also more affected by extreme temperatures. Our results reveal the extent to which the reliability and resilience of the current United States electricity system depends on fossil energy during extreme climate events, and suggest a need for adaptation measures as the country will transition to higher shares of renewable energy while extreme events will become more frequent.

It is fundamental to obtain accurate land surface temperature (LST) to study surface energy process. Infrared thermal imagers are commonly used for deriving LST on the basis of radiance measurements. However, when deriving LST from brightness temperature of a blackbody in thermal imagers, thermal imagers only allow setting a fixed land surface emissivity (LSE). This causes uncertainty in retrieving thermal infrared (TIR) temperature from heterogeneous surfaces with varied LSE, such as those covered in vegetation. Corrections can be made using the Normalized Vegetation Index (NDVI). However, commercial thermal imagers provide only red (R), green (G), and blue (B) bands without a near infrared band so NDVI cannot be calculated on the same instrument and is commonly not available. We propose an alternative method to estimate LSE using RGB-based vegetation index. Thereafter the estimated LSE was used to correct the TIR temperature derived from the fixed LSE. An experiment was conducted to validate the proposed correcting method. The results show that 1) the corrected LST values were closer to the ground truth, with a mean absolute error (MAE) of 0.41 ± 0.34 °C, whereas the MAE was 0.75 ± 0.56 °C for the uncorrected LST; 2) the more heterogeneous the surface, the greater the difference between the corrected and uncorrected LST values, indicating the necessity of LST correction when applying thermal imagers over heterogeneous surface.

Abstract The α-molybdenum trioxide has attracted much attention for proton storage owing to its easily modified bilayer structure, fast proton insertion kinetics, and high theoretical specific capacity. However, the fundamental science of the proton insertion mechanism in α-molybdenum trioxide has not been fully understood. Herein, we uncover a three-proton intercalation mechanism in α-molybdenum trioxide using a specially designed phosphoric acid based liquid crystalline electrolyte. The semiconductor-to-metal transition behavior and the expansion of the lattice interlayers of α-molybdenum trioxide after trapping one mole of protons are verified experimentally and theoretically. Further investigation of the morphology of α-molybdenum trioxide indicates its fracture behavior upon the proton intercalation process, which creates diffusion channels for hydronium ions. Notably, the observation of an additional redox behavior at low potential endows α-molybdenum trioxide with an improved specific discharge capacity of 362 mAh g−1.

Cadmium (Cd) is a major pollutant in water, and long-term Cd exposure seriously threatens aquatic organisms. This study evaluated the effects of dietary Cd on growth performance, tissue Cd accumulation, oxidative stress, endoplasmic reticulum (ER) stress, inflammation, apoptosis, and anti-stress response in juvenile black seabream (Acanthopagrus schlegelii). Six experimental diets containing different concentration of Cd were formulated: 0.02 (Control, Cd0.02), 1.60 (Cd1.60), 24.29 (Cd24.29), 49.04 (Cd49.04), 117.26 (Cd 117.26), and 289.65 (Cd289.65) mg/kg. A feeding experiment was performed on 540 juvenile black seabreams (initial weight, 1.42 ± 0.01 g), which were conducted for ten weeks. The findings revealed that Cd in the diet lowered weight gain (WG) and specific growth rate (SGR), but had no effect on survival. Dramatically positive linear trends were found between increasing dietary Cd contents and tissue Cd accumulation, including liver, kidney, and muscle. Dietary Cd exposure increased malondialdehyde (MDA) production in both serum and liver, hence, caused oxidative stress. The endoplasmic reticulum (ER) stress-related genes, including grp78, atf6, and xbp1, were markedly increased with increased dietary Cd levels, showing ER stress was triggered. Likewise, transcriptional expression levels of genes related to anti-stress response mt2, hsp70, and hsp90 were linearly up-regulated with increased dietary Cd contents. Regarding apoptosis, the transcriptional expression levels of pro-apoptosis genes caspase7, caspase9, and bax and anti-apoptosis gene bcl-2 were all significantly promoted with the increasing dietary Cd levels. Similar patterns were found for gene expression levels linked to inflammatory response, as the dietary Cd contents increased, nuclear transcription factor nf-κb, pro-inflammatory cytokines tnfα and il-1β, and anti-inflammatory il-10 and tgfβ were dramatically elevated. In conclusion, dietary Cd supplementation suppressed growth performance, increased Cd deposition in tissues, induced oxidative stress, ER stress, apoptosis, and inflammation. In contrast, black seabream juveniles also showed substantial tolerance for dietary Cd exposure by promoting anti-stress ability.

ABSTRACTStaphylococcus aureus, a representative gram-positive bacterium, is a common infectious pathogen widely present in the natural environment. The increasing application of antibiotics is witnessing an increment in the number of clinically resistant strains (such as methicillin-resistant S. aureus [MRSA]), which has posed a great challenge to antimicrobial therapy. In this study, a novel MRSA phage, SauPS-28, was isolated from the lake water of the Guangxi Zhuang Autonomous Region. This phage has an incubation period of approximately 30 min, a lysis period of approximately 40 min, and a burst size of approximately 25 PFU/cell. The isolated phage exhibited good biological stability at a pH range of 6.0–9.0 and temperature range of 4°C–37°C. In addition, the identification of an elongated tail using transmission electron microscopy confirmed that SauPS-28 belongs to the long-tailed phage family. Whole-genome sequencing analysis revealed that SauPS-28 has a 43,286-bp-long genome with 31.03% G + C content. Moreover, SauPS-28 exhibited 95.69% sequence identity with ECel-2020k, while the query coverage was only 66%, which is a newly discovered phage. Whole-genome functional annotation results revealed that SauPS-28 had 68 open reading frames (ORFs). Of these, 30 ORFs are unknown proteins. The results suggest that SauPS-28 could be a lysogenic phage strain. This study thus provides preliminary data to conduct further in-depth analysis of the mechanism of phage–host interaction and provides a reference value for phage therapy.IMPORTANCEIn recent years, drug-resistant bacterial infections have become increasingly serious. As a kind of virus with the ability to infect and lyse drug-resistant bacteria, phage is expected to be a new therapeutic method. In this study, we isolated and purified a new methicillin-resistant Staphylococcus aureus bacteriophage SauPS-28, studied a series of biological characteristics of the bacteriophage, analyzed the genome and structural proteome data of the bacteriophage, and provided reference data for further study of the interaction mechanism between bacteriophage and host bacteria and promoted new antibacterial strategies.

The quality of crustacean aquatic products is affected by feed. Cholesterol (CHO), an essential element for crustacean growth, has been widely supplemented in diet, but its food quality regulation remains unclear. The study aimed to investigate the effects of different dietary CHO levels (0.12%, 1.00%, and 2.50%) on the nutritional value and flavor quality in the edible parts of female swimming crabs (Portunus trituberculatus). Results showed that dietary CHO levels significantly increased lipid content in the hepatopancreas and promoted the accumulation of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in the hepatopancreas and muscle by activating the gene expression related to biosynthesis pathways. However, with dietary CHO levels increased, protein content in muscle decreased significantly. This may be related to dietary CHO supplementation (especially 2.50% CHO level) suppressed amino acid accumulation in the hepatopancreas and muscle by downregulating the target of the rapamycin pathway and upregulating amino acid catabolism-related genes. Moreover, 1.00% CHO treatment had higher relative levels of volatiles, producing grassy, fruity, and fatty odors in muscle, which may be due to the upregulation of the branched-chain amino acid transaminase (bcat) expression level. Dietary CHO weakened nucleotide and free amino acid accumulation in hepatopancreas and muscle. Overall, this study suggests that dietary 1.00% CHO level had higher LC-PUFA and pleasing flavor substances in muscle but was not conducive to hepatopancreatic protein and flavor nucleotide deposition of swimming crab.

Abstract We constructed a frequently updated, near-real-time global power generation dataset: CarbonMonitor-Power since January, 2016 at national levels with near-global coverage and hourly-to-daily time resolution. The data presented here are collected from 37 countries across all continents for eight source groups, including three types of fossil sources (coal, gas, and oil), nuclear energy and four groups of renewable energy sources (solar energy, wind energy, hydro energy and other renewables including biomass, geothermal, etc.). The global near-real-time power dataset shows the dynamics of the global power system, including its hourly, daily, weekly and seasonal patterns as influenced by daily periodical activities, weekends, seasonal cycles, regular and irregular events (i.e., holidays) and extreme events (i.e., the COVID-19 pandemic). The CarbonMonitor-Power dataset reveals that the COVID-19 pandemic caused strong disruptions in some countries (i.e., China and India), leading to a temporary or long-lasting shift to low carbon intensity, while it had only little impact in some other countries (i.e., Australia). This dataset offers a large range of opportunities for power-related scientific research and policy-making.

The physiological processes involved in adaptation to osmotic pressure in euryhaline crustaceans are highly energy demanding, but the effects of dietary lipids (fat) on low salinity adaptations have not been well evaluated. In the present study, a total of 120 mud crabs (Scylla paramamosain, BW = 17.87 ± 1.49 g) were fed control and high-fat (HF) diets, at both medium salinity (23‰) and low salinity (4‰) for 6 wk, and each treatment had 3 replicates with each replicate containing 10 crabs. The results indicated that a HF diet significantly mitigated the reduction in survival rate, percent weight gain and feed efficiency induced by low salinity (P

Neuromedin U receptor 2 is an emerging attractive target for treating obesity. Here, a Cryo-EM structure of NmU-25–NMU2–Gi1 provides the structural basis for the designation of highly selective drugs.

Canopy rainfall interception (E i ) is a key component of global water cycle. Here, the authors quantify E i using flux tower data and machine learning, and find that rainfall gets less partitioned into E i as it gets more intense and less frequent.

Metal chalcogenides have shown promising performances for renewable hydrogen evolution and such activities are sensitive to the material electronic structures. Here, authors modulate the electronic properties of molybdenum sulfide in 1T'''-MoS2 for hydrogen evolution electrocatalysis.

Background: To establish a canine model of aortic arch aneurysm that is suitable for research on new devices and techniques applied to the aortic arch. Materials and methods: Fifteen mongrel dogs underwent surgery. The autologous pericardial patch was sewn on the aortotomy site in the anterior wall of the aortic arch. The animals were followed up for 3 months postoperatively. Computed tomography angiography was used to visualize and measure the aneurysm model. Hematoxylin and eosin staining was used to observe the histological characteristics of the aneurysm model. Changes in aneurysm diameter over time were analyzed using analysis of variance. Results: One dog died of hemorrhage during surgery. Fourteen dogs survived the surgical procedure. Two of them died on the first postoperative day because of ruptures at the suturing margin. The diameter of the aneurysm model was twice as large as that of the aortic arch. There was no significant change in the maximum diameter of the aneurysm model during the follow-up period. Conclusions: We established a controllable and stable aortic arch aneurysm model created with an autologous pericardium patch. The aneurysm model can be used to research endoleaks after thoracic endovascular aortic repair and new endovascular techniques can be applied to the aortic arch.

Three isonitrogenous diets (41% crude protein) with 4.87%, 10.75% and 16.10% lipid were designed to evaluate the effects of dietary lipid levels growth, antioxidant capacity, expression levels of genes related to lipid and glucose metabolism of juvenile Scylla paramamosain. Each diet was fed to four replicates of 32 crabs with initial weight 5.10 ± 0.05 g for 6 weeks. The results indicated that crabs fed diet with 10.75% lipid exhibited significantly higher percent weight gain (PWG) and specific growth rate (SGR) than those fed diet with 4.87% lipid (P

As a functional fatty acid, Arachidonic acid (ARA) plays an important role in immunity due to its metabolites in mammals, which have been extensively studied in mammals. However, studies on the function of metabolites produced by dietary ARA in aquatic animals are not comprehensive and in-depth. Hence, an eight-week feeding trial was conducted to evaluated the regulatory effects of dietary ARA and its metabolites-eicosanoids on inflammation, oxidative stress and apoptosis in the liver of Acanthopagrus schlegelii with an initial weight of 0.99 ± 0.10 g. Six isonitrogenous and isolipidic (41% protein, 14% lipid) diets were formulated with gradient levels of ARA: 0% (ARA0.10), 0.5% (ARA0.59), 1.0% (ARA1.04), 1.5% (ARA1.42), 2.0% (ARA1.94), 2.5% (ARA2.42), respectively, and palmitic acid was used to regulate lipid levels. Results showed that the key enzyme contents of ARA metabolic pathway such as phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), lipoxygenase (LOX) cytochrome P450 (CYP450), prostaglandin E2 (PGE2), leukotriene C4 (LTC4) and 20-hydroxyeicosatetraenoic acid (20-HETE) in the liver were increased with dietary ARA levels increased. High levels of dietary ARA (1.94% and 2.42%) activated the gene expression levels of nuclear factor kappa B (nf-κb), which were confirmed by the results of immunofluorescence assay. Likewise, the expression levels of pro-inflammatory cytokines (tnf-α and il-1β) were up-regulated by ARA1.94 and ARA2.42 groups. Fish fed with excess ARA level has significantly low antioxidant capacity by decreasing the activity of related antioxidant parameters and down-regulating the expression level of related genes. The pro-apoptotic related genes (bax and caspase 7/9) were markedly up-regulated as dietary ARA levels increased from 1.04% to 2.42%. Collectively, excess dietary ARA levels (1.92% and 2.42%) produced excess eicosanoids, triggering inflammation via activating NF-κB expression and promoting its nuclear translocation, resulting in oxidative stress by reducing antioxidant parameters (SOD, GSH and GPX), inducing cell apoptosis through up-regulating pro-apoptotic gene expression levels.

Vegetable oil (VO) is increasingly replacing fish oil (FO) in the commercial diet of crustaceans, partly due to a global shortage of FO. But little is known about how different amounts of substitution affect the health and metabolism of crustaceans. A six-week feeding trial was conducted to evaluated the effects of different replacement levels of FO with linseed oil (LO) on growth performance, antioxidant and digestive capacity and fatty acid metabolism in swimming crab, Portunus trituberculatus. Five isonitrogenous and isolipidic diets (480 g kg−1 protein and 120 g kg−1 lipid) were formulated to contain graded levels of LO, and FO was replaced with LO at 0%, 25%, 50%, 75% and 100%, respectively. The results showed that 50% of FO could be replaced by LO without affecting the growth performance and feed utilization for juvenile swimming crab. In hemolymph, 100% dietary replacement of FO with LO, the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) exhibited significantly higher than those fed the other diets, the concentrations of triacylglycerol (TAG), total cholesterol (T-CHO) and high-density lipoprotein cholesterol (HDL-C) significantly increased with increase of dietary replacement of FO with LO, which may lead to hyperlipidemia in swimming crabs. The number of R cells and their lipid droplets in hepatopancreas gradually increased with increase of replacement of FO with LO, the results confirmed the occurrence of lipid accumulation in the hepatopancreas. The activities of glutathione (GSH), and glutathione peroxidase (GPX) in hepatopancreas significantly decreased with increase of replacement of FO with LO, and crabs fed diet with 50% replacement of FO with LO had higher activities of trypsin and lipase (LPS) than those fed the other diets. Long-chain polyunsaturated fatty acids (LC-PUFA), n-3/n-6 PUFA in hepatopancreas and muscle significantly decreased with the increase of substitution level of FO with LO. Moreover, the expression of genes related to LC-PUFA synthesis as well as fatty acid β-oxidation, such as elongase 4 (elovl4), hepatocyte nuclear factor 4-α (hnf4α), retinoid X receptor (rxr), carnitine palmitoyltransferase 2 (cpt2) and acyl-CoA oxidase (acox2), were down-regulated with increase of dietary replacement of FO with LO. In conclusion, it is suggested that the optimal substitution ratio of LO for FO should be less than 50% in the diet of Portunus trituberculatus.

Background: Systematic evaluation of the effects of vitamin D supplementation in heart failure (HF) patients. Methods: Searches were conducted on National Library of Medicine, Web of Science, Cochrane Library, Google Scholar, China National Knowledge Infrastructure, and WANFANG databases. We analyzed data by using Review Manager 5.4 software. All are from the earliest records to March 2023. Outcome indicators analyzed the left ventricular ejection fraction (LVEF), the left ventricular end-diastolic internal diameter (LVEDD), the B-type brain natriuretic peptide (BNP) level and the 25-hydroxy vitamin D (25(OH)D) level. Results: Ten studies with 1099 patients were included. LVEF (mean difference (MD) = 0.74, 95% CI: –0.29 to 1.76, p = 0.41), LVEDD (MD = –0.59, 95% CI: –1.83 to 0.66, p = 0.25), BNP (MD = –0.08, 95% CI: –0.24 to 0.08, p = 0.34), 25(OH)D (MD = 0.41, 95% CI: –0.28 to 1.11, p = 0.25) are not statistically significant. And there is no heterogeneity in the results of LVEF, LVEDD and BNP indicators. Conclusions: Vitamin D supplementation may not be helpful in the clinical management of patients with HF.

Background and purposeClinical outcome in patients who received thrombectomy treatment is time-dependent. The purpose of this study was to evaluate the efficacy of the one-stop stroke management (OSSM) platform in reducing in-hospital workflow times in patients receiving thrombectomy compared with the traditional model.MethodsThe data of patients who received thrombectomy treatment through the OSSM platform and traditional protocol transshipment pathway were retrospectively analyzed and compared. The treatment-related time interval and the clinical outcome of the two groups were also assessed and compared. The primary efficacy endpoint was the time from door to groin puncture (DPT).ResultsThere were 196 patients in the OSSM group and 210 patients in the control group, in which they were treated by the traditional approach. The mean DPT was significantly shorter in the OSSM group than in the control group (76 vs. 122 min; P < 0.001). The percentages of good clinical outcomes at the 90-day time point of the two groups were comparable (P = 0.110). A total of 121 patients in the OSSM group and 124 patients in the control group arrived at the hospital within 360 min from symptom onset. The mean DPT and time from symptom onset to recanalization (ORT) were significantly shorter in the OSSM group than in the control group. Finally, a higher rate of good functional outcomes was achieved in the OSSM group than in the control group (53.71 vs. 40.32%; P = 0.036).ConclusionCompared to the traditional transfer model, the OSSM transfer model significantly reduced the in-hospital delay in patients with acute stroke receiving thrombectomy treatment. This novel model significantly improved the clinical outcomes of patients presenting within the first 6 h after symptom onset.

Summary: Background: Determining the origin of bone metastatic cancer (OBMC) is of great significance to clinical therapeutics. It is challenging for pathologists to determine the OBMC with limited clinical information and bone biopsy. Methods: We designed a regional multiple-instance learning algorithm to predict the OBMC based on hematoxylin-eosin (H&E) staining slides alone. We collected 1041 cases from eight different hospitals and labeled 26,431 regions of interest to train the model. The performance of the model was assessed by ten-fold cross validation and external validation. Under the guidance of top3 predictions, we conducted an IHC test on 175 cases of unknown origins to compare the consistency of the results predicted by the model and indicated by the IHC markers. We also applied the model to identify whether there was tumor or not in a region, as well as distinguishing squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumor. Findings: In the within-cohort, our model achieved a top1-accuracy of 91.35% and a top3-accuracy of 97.75%. In the external cohort, our model displayed a good generalizability with a top3-accuracy of 97.44%. The top1 consistency between the results of the model and the immunohistochemistry markers was 83.90% and the top3 consistency was 94.33%. The model obtained an accuracy of 98.98% to identify whether there was tumor or not and an accuracy of 93.85% to differentiate three types of cancers. Interpretation: Our model demonstrated good performance to predict the OBMC from routine histology and had great potential for assisting pathologists with determining the OBMC accurately. Funding: National Science Foundation of China (61875102 and 61975089), Natural Science Foundation of Guangdong province (2021A15-15012379 and 2022A1515 012550), Science and Technology Research Program of Shenzhen City (JCYJ20200109110606054 and WDZC20200821141349001), and Tsinghua University Spring Breeze Fund (2020Z99CFZ023).

Abstract We consider N $$ \mathcal{N} $$ = (2, 2) AdS3/CFT2 dualities proposed in the large central charge limit (c → ∞) by Eberhardt. Here we propose the associated D1-D5 systems to be orbifolds of the standard N $$ \mathcal{N} $$ = (4, 4) systems, thereby elevating the dualities to the finite-c level on the boundary and to the quantum level in the bulk. In particular, we show that our brane systems yield low-energy sigma models whose subleading central charges match earlier predictions from bulk one-loop supergravity computations. In the case involving the Enriques surface, the finite-c sigma model has a non-trivial elliptic genus which we use to microscopically explain both the Bekenstein-Hawking entropy and the subleading logarithmic correction to it for the associated macroscopic black brane.

Abstract Background In recent years, there have been frequent reports of gaming disorder in China, with more focus on young people. We developed and psychometrically tested a Gaming Disorder screening scale (i.e., Gaming Disorder Screening Scale - GDSS) for Chinese adolescents and young adults, based on the existing scales and diagnostic criteria, but also considering the development status of China. Methods For testing content and criterion validity, 1747 participants competed the GDSS and the Internet Addiction Test (IAT). After 15 days, 400 participants were retested with the scales for to assess test-retest reliability. Besides, 200 game players were interviewed for a diagnosis of gaming disorder. Results The Cronbach’s alpha coefficient on the GDSS was 0.93. The test-retest coefficient of 0.79. Principal components analysis identified three factors accounting for 62.4% of the variance; behavior, functioning, cognition and emotion. Confirmatory factor analysis showed a good model fit to the data (χ2 /df = 5.581; RMSEA =0.074; TLI = 0.916, CFI = 0.928). The overall model fit was significantly good in the measurement invariance tested across genders and different age groups. Based on the clinical interview, the screening cut-off point was determined to be ≥47 (sensitivity 41.4%, specificity 82.3%). Conclusions The GDSS demonstrated good reliability and validity aspects for screening online gaming disorder among Chinese adolescents and young adults.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis, is commonly used as an internal reference gene in humans, mice, and insects. However, the function of GAPDH in insect development, especially in metamorphosis, has not been reported. In the present study, Helicoverpa armigera and Spodoptera frugiperda ovarian cell lines (Sf9 cells) were used as materials to study the function and molecular mechanism of GAPDH in larval metamorphosis. The results showed that HaGAPDH was more closely related to GAPDH of S. frugiperda and Spodoptera litura. The transcript peaks of HaGAPDH in sixth instar larvae were 6L-3 (epidermal and midgut) and 6L-1 (fat body) days, and 20E and methoprene significantly upregulated the transcripts of HaGAPDH of larvae in qRT-PCR. HaGAPDH–GFP–His was specifically localized in mitochondria in Sf9 cells. Knockdown of HaGAPDH by RNA interference (RNAi) in sixth instar larvae resulted in weight loss, increased mortality, and decreases in the pupation rate and emergence rates. HaGAPDH is directly bound to soluble trehalase (HaTreh1) physically and under 20E treatment in yeast two-hybrid, coimmunoprecipitation, and colocalization experiments. In addition, knockdown of HaGAPDH increased the Treh1 activity, which in turn decreased the trehalose content but increased the glucose content in larvae. Therefore, these data demonstrated that GAPDH controlled the glucose content within the normal range to ensure glucose metabolism and metamorphosis by directly binding with HaTreh1.

Background This study aims to investigate whether a systematic digital training system can improve the learning efficiency of residents in the first-year orthognathic surgery training course and evaluate its effectiveness in teaching orthognathic surgery. Methods A digital training system was applied, and a comparative research approach was adopted. 24 first-year orthognathic surgery residents participated in the experiment as part of their professional skill training. The Experimental group was required to use a digital training system, and the Control group was trained in lectures without digital technologies. Three indicators, including theoretical knowledge and clinical operation, were assessed in tests, and evaluations from instructors were analyzed to evaluate learning efficiency. Results The results showed that the scores in theoretical tests, practical operations, and teacher evaluations, the Experimental groups were all higher than the Control group (P = 0.002 for anatomy, P = 0.000 for operation theory) after using digital technology, except for the understanding of complications (P = 0.771). In addition, the questionnaire survey results showed that the study interest (P = 0.001), self-confidence (P = 0.001), satisfaction (P = 0.002), and academic performance (P = 0.001) of the residents of the Experimental group were higher than those of the Control group. Conclusions The outcomes indicated that the digital training system could benefit orthognathic residents’ learning efficiency, and learning interest and teaching satisfaction will also improve.

Developing highly selective and efficient bifunctional catalysts is an important issue for the hydroisomerization of long-chain n-alkanes. It is vital to tailor the balance of isomerization and cracking reactions in hydroisomerization. Herein, a bifunctional Pt/hierarchical SSZ-32 catalyst was fabricated with a sequential desilication–dealumination treatment to boost the selective hydroisomerization of n-hexadecane (C16). The pore structure and acid sites of SSZ-32 zeolite were tailored. More mesopore and Brønsted acid sites were generated, and the ratio of weak to strong Brønsted acidity (Bw/Bs) was increased by the sequential desilication–dealumination. The generated hierarchical structure had little effect on the selectivity of the reaction pathways of hydroisomerization versus cracking. The ratio of isomers/cracking products increased almost linearly with the increase in the Bw/Bs ratios. Meanwhile, the synergetic effect of the hierarchical structure and acidity regulation promoted the selectivity of monobranched i-C16 products. Therefore, the resulting Pt/SSZ-0.6AS exhibited the highest activity with a total isomer yield of 71.5% at 255 °C and the enhanced formation mechanism of monobranched isomers occurred via the pore mouth.

An eight-week feeding trial was conducted to investigate the effects of dietary lipid sources on growth performance, fatty acids composition in tissue and expression of genes related to lipid metabolism in juvenile largemouth bass (Micropterus salmoides). Four experimental diets were formulated to contain 6% coconut oil (CO), rapeseed oil (RO), linseed oil (LO) and fish oil (FO), respectively. Each diet was fed to triplicate groups of juvenile for 8 weeks. The results indicated that final body weight (FBW), percent weight gain (PWG), specific growth rate (SGR), feed efficiency (FE), survival, hepatopancreas index (HSI), viscerosomatic index (VSI) and intraperitoneal fat ratio (IPF) were not significantly influenced by dietary different lipid sources (P＞0.05). Moreover, proximate composition in whole body, dorsal muscle and liver were also not significantly affected by dietary different lipid sources (P ＞0.05). Fish fed with FO diet was significantly higher MDA concentration in hepatic and serum than those fed with CO, RO and LO diets (P

Metabolic dysfunction plays a key role in the development of diabetic nephropathy (DN). However, the exact effects and mechanisms are still unclear. The pyrin domain-containing protein 3 (NLRP3) inflammasome, a member of the nod-like receptor family, is considered a crucial inflammatory regulator and plays important roles in the progress of DN. A growing body of evidence suggests that high glucose, high fat, or other metabolite disorders can abnormally activate the NLRP3 inflammasome. Thus, in this review, we discuss the potential function of abnormal metabolites such as saturated fatty acids (SFAs), cholesterol crystals, uric acid (UA), and homocysteine in the NLRP3 inflammasome activation and explain the potential function of metabolic dysfunction regulation of NLRP3 activation in the progress of DN via regulation of inflammatory response and renal interstitial fibrosis (RIF). In addition, the potential mechanisms of metabolism-related drugs, such as metformin and sodium glucose cotransporter (SGLT2) inhibitors, which have served as the suppressors of the NLRP3 inflammasomes, in DN, are also discussed. A better understanding of NLRP3 inflammasome activation in abnormal metabolic microenvironment may provide new insights for the prevention and treatment of DN.

Purpose: As a new category proposed in the International Classification of Diseases (11th Revision) (ICD-11), the reliability and clinical utility of ICD diagnostic guidelines for gaming disorder (GD) in the Chinese population have not been studied. The purpose of this field study is to clarify the reliability, clinical utility, and cultural applicability of ICD diagnostic guidelines for GD in China and its comparability with Internet GD (IGD) in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5).Methods: Participants included 21 paired clinical raters consisting of seven psychiatrists and 200 gaming players aged from 15 to 18 years with different risk levels of Internet addiction based on the scores of Young's Internet Addiction Test. Each participant received a semi-structured face-to-face interview by paired clinical raters at the same time. Then clinical raters made the diagnosis and filled the clinical utility questionnaire independently according to the diagnostic guidelines for GD in both ICD-11 and DSM-5.Results: The diagnostic consistency coefficient (kappa value) between the paired clinical raters was 0.545 (0.490–0.600, p < 0.001) and 0.622 (0.553–0.691, p < 0.001) for ICD-11 and DSM-5 diagnostic guidelines, respectively, for GD. The diagnostic consistency was 0.847 (0.814–0.880, p < 0.001) between GD in ICD-11 and IGD in DSM-5. Meanwhile, 86.7% of responses that agreed with the ICD-11 diagnostic guidelines for GD provided enough detailed implementation characteristics and showed good overall clinical applicability (86.0%), specificity (94.4%), usefulness (84.1%), and acceptable cultural adaptation (74.8%). GD in ICD-11 was slightly more accepted than IGD in DSM-5 (p < 0.001), while the clinical efficiency of ICD-11 was inferior to that of DSM-5 (p < 0.001).Conclusion: This study indicates that the ICD-11 diagnostic guidelines for GD have acceptable clinical reliability and high consistency with IGD in DSM-5. Their clinical applicability and cultural adaption are comparable with those of DSM-5. Although the guidelines still need to be adjusted for better implementation in China, this is already a great step committed to reducing the serious consequences caused by excessive gaming behaviors through effective identification and normative diagnosis, especially for adolescents.

Helicoverpa armigera (cotton bollworm) is one of the most destructive pests worldwide. Due to resistance to Bacillus thuringiensis and conventional insecticides, an effective management strategy to control this pest is urgently needed. Spinosad, a natural pesticide, is considered an alternative; however, the mechanism underlying the developmental effects of sublethal spinosad exposure remains elusive. In this study, the mechanism was examined using an insect model of H. armigera. Results confirmed that exposure to sublethal spinosad led to reduced larval wet weight, delayed larval developmental period, caused difficulty in molting, and deformed pupae. Further investigation demonstrated that exposure to sublethal spinosad caused a significant decrease in 20E titer and increase in JH titer, thereby leading to the discordance between 20E and JH titers, and consequently alteration in the expression levels of HR3 and Kr-h1. These results suggested that sublethal spinosad caused hormonal disorders in larvae, which directly affect insect development. Our study serves as a reference and basis for the toxicity evaluation of spinosad on molting and pupation in insect metamorphosis, which may contribute to identifying targets for effective control of cotton bollworm.

Female moths use sex pheromones to attract males, and corresponding regulatory mechanism underlying sex pheromone biosynthesis is species-dependent. However, the detailed mechanism involved in sex pheromone biosynthesis in Ostrinia furnacalis has not yet been fully addressed. In the present study, transcriptome sequencing of O. furnacalis pheromone glands screened a serials of candidate genes involved in sex pheromone biosynthesis. Our analysis showed that sex pheromone release in O. furnacalis females arrives its peak at the 2nd scotophase, consistent with its mating behavior. Pheromone biosynthesis-activating neuropeptide (PBAN) was confirmed to regulate sex pheromone biosynthesis, and Ca2+ is the secondary messenger of PBAN signaling in O. furnacalis. The functional analysis of candidate genes demonstrated that the decreased mRNA levels or activities of calcineurin (CaN) and acetyl-CoA carboxylase (ACC) led to significant decrease in sex pheromone production and female capability to attract males, as demonstrated by RNAi-mediated knockdown and pharmacological inhibitor assay. Most importantly, the activities of CaN and ACC depend on the activation of PBAN/PBANR/Ca2+. Furthermore, fatty-acyl reductase 14 was involved in PBAN-mediated sex pheromone biosynthesis. Altogether, our results demonstrated that PBAN regulates sex pheromone biosynthesis through PBANR/Ca2+/CaN/ACC pathway to promote sex pheromone biosynthesis in O. furnacalis and provided a reference for non-model organism to study neuropeptide signal transduction.

Cationic liposome delivery of interfering RNA (shRNA) plays an important role in tumor therapy. The cyclic Arg-Gly-Asp (cRGD) modified cationic liposomes (cRGD-CL) were designed for targeted delivery of ONECUT2 (OC-2) shRNA (pshOC-2) to breast cancer cells. The characterization analysis of cationic liposome showed that the prepared cRGD-CL/pshOC-2 lipoplexes had uniform particle size (150 ± 1.02 nm), moderate zeta potential (19.8 ± 0.249 mV) and high encapsulation efficiency (up to 96%). The results of flow cytometer showed that the introduction of cRGD could significantly promote the liposomes targeting tumor cells. In MCF-7 cells, the pshOC-2 could down-regulate expression of OC-2 and result in cell apoptosis, inhibition of the wound healing, migration and cell colony formation, in which the signal pathways of Bcl-xL, Bcl-2 were inhibited and the signal pathways of Bax and Cleaved Caspase-3 were promoted. In MCF-7 xenograft mice, intravenous administration of cRGD-CL/pshOC-2 lipoplexes could effectively reduce the expression of OC-2 in tumors and result in apparently antitumor effects, which suggested that the lipoplexes might be deeply penetrated into tumor through receptor-mediated transcytosis. The results revealed that the cationic liposome (cRGD-CL) was an effective delivery system for OC-2 shRNA, which might be an effective therapeutic candidate for breast cancer.

Pyruvate kinase (PYK) is a speed-limited enzyme of glycolysis that catalyzes the formation of pyruvate, and plays an important role in acetyl-CoA synthesis. The acetyl-CoA is the precursor of sex pheromone biosynthesis in Helicoverpa armigera. However, the role of PYK in sex pheromone biosynthesis remains elusive. Here, PYK in H. armigera (HaPYK) was found to be highly expressed in the pheromone glands (PGs). The developmental expression profile of HaPYK was consistent with the fluctuation of sex pheromone release. Function analysis revealed that the knockdown of HaPYK led to a decrease in the levels of pyruvic acid and acetyl-CoA in PGs, which in turn caused a significant decrease in cis-11-hexadecenal (Z11-16: Ald) production, female capability to attract males, and mating frequency. Further study demonstrated that sugar feeding (5% sugar) increased the transcription and enzyme activity of HaPYK, thereby facilitating sex pheromone biosynthesis. Moreover, pheromone biosynthesis activating neuropeptide (PBAN) upregulated HaPYK activity through protein kinase C (PKC), as shown by PKC-specific inhibitor analysis. Altogether, our results revealed that PBAN activated HaPYK by Ca2+/PKC, thereby regulating the synthesis of pyruvate and subsequent acetyl-CoA, ensuring the supply of sex pheromone precursor, and finally facilitating sex pheromone biosynthesis and mating behavior.

There is an association between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis, but the genetic risk of atherosclerosis in NAFLD remains unclear. Here, a single-nucleotide polymorphism (SNP) of the heat shock 70 kDa protein 8 (HSPA8) gene was analyzed in 123 NAFLD patients who had been diagnosed using a liver biopsy, and the NAFLD phenotype including the maximum intima–media thickness (Max-IMT) of the carotid artery was investigated. Patients with the minor allele (A/G or G/G) of rs2236659 showed a lower serum heat shock cognate 71 kDa protein concentration than those with the major A/A allele. Compared with the patients with the major allele, those with the minor allele showed a higher prevalence of hypertension and higher Max-IMT in men. No significant associations between the HSPA8 genotype and hepatic pathological findings were identified. In decision-tree analysis, age, sex, liver fibrosis, and HSPA8 genotype were individually associated with severe carotid artery atherosclerosis (Max-IMT ≥ 1.5 mm). Noncirrhotic men aged ≥ 65 years were most significantly affected by the minor allele of HSPA8. To predict the risk of atherosclerosis and cardiovascular disease, HSPA8 SNP genotyping might be useful, particularly for older male NAFLD patients.

Acetyl-CoA, the precursor of sex pheromone biosynthesis in Helicoverpa armigera, is generated from glycolysis. As the first speed-limited enzyme in glycolysis, Hexokinase (HK) plays an important role in acetyl-CoA production. However, the function of HK in sex pheromone production remains unclear. This study employed H. armigera as material to explore the role of HK in sex pheromone production. Results demonstrated that the transcription profile of HaHK in female moth pheromone glands (PGs) was consistent with the release fluctuation of sex pheromone. Interference of HaHK prevented the increase of acetyl-CoA content induced by PBAN. Therefore, knockdown of HaHK in female PGs caused significant decreases in (Z)-11-hexadecenal (Z11-16:Ald) production, female capability to attract males, and mating rate. Furthermore, sugar feeding (5% sugar) increased the transcription and enzymatic activity of HK. Pheromone biosynthesis activating neuropeptide (PBAN) signal phospho-activated HaHK in PGs and Sf9 cells via protein kinase A (PKA), as shown by pharmacological inhibitor analysis. In general, our study confirmed that PBAN/cAMP/PKA signal activated HaHK, in turn promoted glycolysis to ensure the supply of acetyl-CoA, and finally facilitated sex pheromone biosynthesis and subsequent mating behavior.