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Fatty acid ethyl esters are important flavor chemicals in strong-flavor Baijiu. Monascus purpureus YJX-8 is recognized as an important microorganism for ester synthesis in the fermentation process. Enzyme LIP05 from YJX-8 can efficiently catalyze the synthesis of fatty acid ethyl esters under aqueous phase, but the key catalytic sites affecting esterification were unclear. The present work combined homology modeling, molecular dynamics simulation, molecular docking and site-directed mutation to analyze the catalytic mechanism of LIP05. Protein structure modeling indicated LIP05 belonged to α/β fold hydrolase, contained a lid domain and a core catalytic pocket with conserved catalytic triad Ser150-His215-Asp202, and the oxyanion hole composed of Gly73 and Thr74. Ile30 and Leu37 of the lid domain were found to affect substrate specificity. The π-bond stacking between Tyr116 and Tyr149 played an important role in stabilizing the catalytic active center of LIP05. Tyr116 and Ile204 determined the substrate spectrum by composing the substrate-entrance channel. Residues Leu83, Ile204, Ile211 and Leu216 were involved in forming the hydrophobic substrate-binding pocket through steric hindrance and hydrophobic interaction. The catalytic mechanism for esterification in aqueous phase of LIP05 was proposed and provided a reference for clarifying the synthesis of fatty acid ethyl esters during the fermentation process of strong-flavor Baijiu.

5-Methylcytosine (m5C) is an important post-transcriptional modification that has been extensively found in multiple types of RNAs. Many studies have shown that m5C plays vital roles in many biological functions, such as RNA structure stability and metabolism. Computational approaches act as an efficient way to identify m5C sites from high-throughput RNA sequence data and help interpret the functional mechanism of this important modification. This study proposed a novel species-specific computational approach, Staem5, to accurately predict RNA m5C sites in Mus musculus and Arabidopsis thaliana. Staem5 was developed by employing feature fusion tactics to leverage informatic sequence profiles, and a stacking ensemble learning framework combined five popular machine learning algorithms. Extensive benchmarking tests demonstrated that Staem5 outperformed state-of-the-art approaches in both cross-validation and independent tests. We provide the source code of Staem5, which is publicly available at https://github.com/Cxd-626/Staem5.git.

Baobaoqu (BBQ) is a traditional fermenting power, which is widely applied in Nong-flavor Baijiu brewing. There are two different types of BBQ (premium BBQ and normal BBQ) used in industrial manufacture, but the reasons for the significant differences between two kinds of BBQ have not been clearly illuminated. In this study, the combination of metagenomics and metabolomics was performed to compare the differences in the composition of microbial communities and the components of flavors between premium BBQ and normal BBQ. The results showed that the glycosidase-producing microorganisms are the biomarkers of premium BBQ, contributing a better ability of carbon source utilization than normal BBQ. In addition, several important flavors (ethyl hexanoate, phenylethanol, ethyl acetate) were rich in normal BBQ, which have a significant positive correlation with the biomarkers (Lactobacillus and Pichia kudriavzevii) of normal BBQ. It suggests that the microbial community has an advantage in utilizing raw materials in premium BBQ, while the community was inclined to form flavors in normal BBQ. The differences between two types of BBQ at the microbial and flavor level have theoretical and practical guiding significance in the application of premium and normal BBQ and in the further improvements of taste and quality of Baijiu.

Ferulic acid (FA) is a bioactive compound found in traditional Chinese herbal medicine; for example, it is present in Xinjiang Ferula, but also in strong-flavor Chinese baijiu. FA has been shown to play a crucial role in treating oxidative stress, skin whitening, and eye diseases. In this study, the potential role of FA as a means of inducing apoptosis and inhibiting colon cancer induced by the transplantation of CT26 cells was investigated. The results show that FA adjuvant treatment caused an upregulation in the expression of genes related to autophagy while simultaneously suppressing the expression of inflammatory response elements and improving the bodyweight, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST) in vivo. Furthermore, FA inhibited the proliferation of CT26 cells and induced apoptosis, specifically by activating the phosphorylation of ERK and JNK to enhance the essential proteins BCL-2 and BAX in the apoptosis pathway. These results suggest that FA could be a promising auxiliary therapeutic agent for the treatment of colon cancer. Further research is needed to better understand the mechanisms underlying the beneficial effects of FA and its synergistic effects with other compounds.

Peanut seeds are susceptible to Aspergillus flavus infection, which has a severe impact on the peanut industry and human health. However, the molecular mechanism underlying this defense remains poorly understood. The aim of this study was to analyze the changes in differentially expressed genes (DEGs) and differential metabolites during A. flavus infection between Zhonghua 6 and Yuanza 9102 by transcriptomic and metabolomic analysis. A total of 5768 DEGs were detected in the transcriptomic study. Further functional analysis showed that some DEGs were significantly enriched in pectinase catabolism, hydrogen peroxide decomposition and cell wall tissues of resistant varieties at the early stage of infection, while these genes were differentially enriched in the middle and late stages of infection in the nonresponsive variety Yuanza 9102. Some DEGs, such as those encoding transcription factors, disease course-related proteins, peroxidase (POD), chitinase and phenylalanine ammonialyase (PAL), were highly expressed in the infection stage. Metabolomic analysis yielded 349 differential metabolites. Resveratrol, cinnamic acid, coumaric acid, ferulic acid in phenylalanine metabolism and 13S-HPODE in the linolenic acid metabolism pathway play major and active roles in peanut resistance to A. flavus. Combined analysis of the differential metabolites and DEGs showed that they were mainly enriched in phenylpropane metabolism and the linolenic acid metabolism pathway. Transcriptomic and metabolomic analyses further confirmed that peanuts infected with A. flavus activates various defense mechanisms, and the response to A. flavus is more rapid in resistant materials. These results can be used to further elucidate the molecular mechanism of peanut resistance to A. flavus infection and provide directions for early detection of infection and for breeding peanut varieties resistant to aflatoxin contamination.

Pichia kudriavzevii is one of the major non-Saccharomyces cerevisiae yeasts in Chinese baijiu brewing, which has shown a substantially higher tolerance to acid, heat, and ethanol. Exploring the mechanism of P. kudriavzevii could have a positive effect on the artificially controlled production of baijiu. In this study, an efficient acetic-acid-tolerant P. kudriavzevii strain, Y2, was isolated from the yellow water of strong-flavored baijiu brewing waste, and its molecular mechanism of acetic acid tolerance was investigated through a comparative transcriptomic analysis. The strain Y2 could tolerate 12 g/L of acetic acid. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, differentially expressed genes (DEGs) were mainly enriched in oxidative phosphorylation, the citrate cycle, glycolysis/gluconeogenesis, and carbon metabolism under low (AL group) and high (AH group) concentrations of acetic acid. However, the DEG enrichment was more profound in the AH group when compared to the control. Compared with the AL group, the expression of genes related to oxidative phosphorylation was more significantly upregulated, while in terms of the TCA cycle, phosphoenolpyruvate carboxykinase was significantly upregulated in both the AH and AL groups and was positively correlated with tolerance to acetic acid. This was followed by citrate synthase, isocitrate dehydrogenase, malate dehydrogenase, and succinate dehydrogenase. These results illustrated a possible mechanism of acid tolerance by regulating the metabolism-related pathways in P. kudriavzevii and provided a basis for the further investigation of the acid tolerance mechanism.

Abstract It is unclear whether there are different body mass index (BMI) trajectories among a population with normal BMI levels, and the association between BMI patterns and incident hypertension is not well characterized. This prospective cohort study includes surveys conducted at baseline and three follow‐ups. 3939 participants who are free of hypertension at baseline or first two follow‐ups were enrolled. At baseline, the age of participants ranged from 35 to 82 years and the mean age was 45.9 years. The BMI trajectories were identified using latent mixture modeling with data from the baseline and first two follow‐ups. The effects of different BMI trajectories on the development of hypertension were analyzed using a Cox proportional hazard model. Four distinct BMI trajectories were identified over the study period (2004‐2010): normal‐stable (n = 1456), normal‐increasing (n = 2159), normal‐fluctuated (n = 166), and normal‐sharp‐increasing (n = 158). Relative to the normal‐stable BMI group, the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjustment for confounding factors of the normal‐increasing, normal‐fluctuated, and normal‐sharp‐increasing groups were 1.244 (1.103‐1.402), 1.331 (1.008‐1.756), and 1.641 (1.257‐2.142), respectively. Additionally, subgroup analysis showed that the normal‐fluctuated BMI trajectory was associated with a significantly higher risk of hypertension only in women (HR = 1.362; 95% CI = 1.151‐1.611). The BMI trajectories were significant predictors of hypertension incidence, and increasing BMI trajectories within the currently designated normal range were associated with an increased hypertension risk, especially in women.

Osteoarthritis (OA) is a multifactorial disease that affects the entire joint, often resulting in severe pain, disability, psychological distress, and a lower quality of life. Patient self-management is emphasized in OA clinical recommendations. Currently, the clinical treatment of OA mainly focuses on pain relief and the improvement of joint function, with few options for regenerating degenerative cartilage or slowing the progression of OA. Therefore, we first reviewed the current treatment of OA, and then summarized the research advances of nanotechnology in OA treatment, including nano drug delivery systems for small molecule drugs, nucleic acids and proteins, nano-scaffolds for cartilage regeneration, and nanoparticle lubricants. Finally, we discussed the opportunities and potential challenges of nanotechnology in OA treatment.

BackgroundTo demonstrate the real-word situation of burdens that are attributed to the risk factor of high low-density lipoprotein cholesterol (LDL-C) at the global, regional, national levels, among different age groups and between genders.MethodsWe analyzed data from the Global Burden of Disease study 2019 related to global deaths, disability-adjusted life years (DALYs), summary exposure value (SEV), average annual percentage change (AAPC), and observed to expected ratios (O/E ratios) attributable to high LDL-C from 1990 to 2019.ResultsGlobally, in 2019, the total numbers of deaths and DALYs attributed to high LDL cholesterol were 1.47 and 1.41 times higher than that in 1990. The age-standardized deaths and DALYs rate was 1.45 and 1.70 times in males compared to females, while the age-standardized SEVs rate was 1.10 times in females compared to males. The deaths, DALYs, and SEV rates increased with age. In 2019, the highest age-standardized rates of both deaths and DALYs occurred in Eastern Europe while the lowest occurred in high-income Asia Pacific. High-income North America experienced a dramatic reduction of risk related to high LDL-C. Correlation analysis identified that the age-standardized SEV rate was positively correlated with Socio-demographic Index (SDI; r = 0.7753, P < 0.001). The average annual percentage change (AAPC) of age-standardized SEV rate decreased in the high SDI and high-middle SDI regions but increased in the middle SDI, low-middle SDI, and low SDI regions. High LDL-C mainly contributed to ischemic heart diseases.ConclusionHigh LDL-C contributed considerably to health burden worldwide. Males suffered worse health outcomes attributed to high LDL-C when compared to females. The burden attributed to high LDL-C increased with age. Lower SDI regions and countries experienced more health problem challenges attributed to high LDL-C as the result of social development and this should be reflected in policymaking.

Dysbiosis of gut microbiota can contribute to the progression of diabetes and obesity. Previous studies have shown that maternal high-fat (HF) diet during the perinatal period can alter the microbiota and induce metabolic disorders at weaning. However, whether dysbiosis of gut microbiota and metabolism could be recovered by a normal diet after weaning and the dynamic changes of gut microbiota have not been fully studied. In this study, C57BL/6J female mice were fed with a normal chow (NC) or HF diet for 4 weeks preconception, during gestation, and until pup weaning. After weaning, male offspring were fed with an NC diet until 9 weeks of age. The microbiota of offspring at weaning and 9 weeks of age was collected for 16S rRNA gene amplicon sequencing. We found that dams fed with an HF diet showed glucose intolerance after lactation. Compared with the offspring from NC dams, the offspring from HF dams exhibited a higher body weight, hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia, and leptin resistance and lower adiponectin at weaning. Fecal analysis indicated altered microbiota composition between the offspring of the two groups. The decrease in favorable bacteria (such as norank f Bacteroidales S24-7 group) and increase in unfavorable bacteria (such as Lachnoclostridium and Desulfovibrio) were strongly associated with a disturbance of glucose and lipid metabolism. After 6 weeks of normal diet, no difference in body weight, glucose, and lipid profiles was observed between the offspring of the two groups. However, the microbiota composition of offspring in the HF group was still different from that in the NC group, and microbiota diversity was lower in offspring of the HF group. The abundance of Lactobacillus was lower in the offspring of the HF group. In conclusion, a maternal HF diet can induce metabolic homeostasis and gut microbiota disturbance in offspring at weaning. Gut microbiota dysbiosis can persist into adulthood in the offspring, which might have a role in the promotion of susceptibility to obesity and diabetes in the later life of the offspring.

Osteoarthritis (OA) is the most common joint disease, usually occurring in middle-aged and elderly people. However, current treatment for OA in its early stages is ineffective, and drug therapy is often ineffective in slowing the progression of the disease. In fact, a deeper understanding of the underlying molecular mechanisms of OA could help us to better develop effective therapeutic measures. N6-methyladenosine (m6A) is a methylation that occurs at the adenosine N6-position, which is the most common internal modification on eukaryotic mRNAs. The role and mechanisms of m6A in mammalian gene regulation have been extensively studied. The “Writer”, “eraser”, and “reader” proteins are key proteins involved in the dynamic regulation of m6A modifications. Recent studies on post-transcriptional regulation alone have shown that m6a modification has an important role in the development of OA. This paper summarizes the specific regulatory processes of M6A in disease and reviews the role of m6A in OA, describing its pathophysiological role and molecular mechanisms, as well as its future research trends and potential clinical applications in OA.

Objective To test the significance of serum C‐reactive protein (CRP), the erythrocyte sedimentation rate (ESR), the platelet count/mean platelet volume ratio (PC/MPV), plasma fibrinogen, and D‐Dimer in periprosthetic joint infection (PJI) diagnosis. Methods We retrospectively analyzed the clinical data of 149 patients diagnosed from July 2016 to December 2019 with primary osteoarthritis (OA group, average age 63.18 years [range, 53–82 years] 18 males, 46 females), PJI (PJI group, average age 63.74 years [range, 52–81 years], 16 males, 31 females), and aseptic loosening (aseptic group, average age 63.18 years [range, 53–80 years], 12 male, 26 female) in our department. Demographic data and the sensitivity and specificity of preoperative CRP, ESR, PC/MPV, fibrinogen, and D‐Dimer in PJI diagnosis were compared. Results There were no significant differences when the demographic data of the three groups were compared. The expression level of CRP (50.67 ± 58.98 mg/L), ESR (50.55 ± 25.81 mm/h), PC/MPV (35.79 ± 18.00), and fibrinogen (4.85 ± 1.33 μg/mL) in the PJI group were higher than in the OA group (CRP: 4.09 ± 9.68 mg/L; ESR:13.44 ± 9.32 mm/1 h; PC/MPV: 24.97 ± 7.58; fibrinogen: 3.09 ± 0.55 μg/mL) and the aseptic group (CRP: 7.01 ± 11.83 mg/L; ESR: 22.47 ± 17.53 mm/1 h; PC/MPV: 25.18 ± 11.48; fibrinogen: 3.39 ± 0.80 μg/mL), respectively. The expression level of plasma D‐dimer (1.60 ± 1.29 mg/L) in the PJI group was higher than in the OA group (0.49 ± 0.42 mg/L) but similar to that in the aseptic group (1.21 ± 1.35 mg/L). Receiver operating characteristic (ROC) curve analysis demonstrated that the areas under the ROC curve (AUC) for CRP, ESR, PC/MPV, fibrinogen, and D‐dimer were 0.892 (95% confidence interval, 0.829–0.954), 0.888 (0.829–0.947), 0.686 (0.589–0.784), 0.873 (0.803–0.943), and 0.835 (0.772–0.899), respectively. When PC/MPV > 31.70, fibrinogen >4.01 μg/mL, and D‐dimer >1.17 mg/L were set as the threshold values for the diagnosis of PJI, the sensitivity of PC/MPV in PJI diagnosis was lower than that of ESR and plasma fibrinogen. In contrast, there was no significant difference when comparing the specificity of CRP, ESR, PC/MPV, fibrinogen, and D‐dimer in PJI diagnosis. Conclusion Plasma fibrinogen is a good new auxiliary diagnostic marker for PJI.

Abstract Background Waist circumference (WC) and uric acid (UA) are significantly related. Still, their temporal sequence and how the sequence works on future risk of triglyceride glucose (TyG) are unknown, especially in the Chinese population. Methods Cross-lagged panel model was used to analyze the reciprocal, longitudinal relationships among a set of interrelated variables. The mediation model was constructed to test the effect of the relationship between WC and UA on TyG. Results A total of 5727 subjects were enrolled in our study population, of which 53.5% were women, and the mean age was 59.0 (standard deviation, 8.62) years. After adjusting for traditional confounding factors, the results showed that a higher level of baseline WC was significantly associated with a higher level of follow-up UA (β = 0.003, P = 0.031) and follow-up TyG (β = 0.003, P

As an important sensor of an unmanned surface vehicle (USV), an electro-optical device is usually used to detect ships and obstacles in USV autonomous navigation and collision avoidance. However, the installation perpendicularity error of the electro-optical device greatly impacts the line-of-sight (LOS) stability control. This error is difficult to eliminate through mechanical calibration because the platform inertial navigation axis cannot be led out. This study aims to establish the model for the perpendicularity error of electro-optical devices during circumferential scanning and analyze its impact on the stability of LOS. In addition, we present a measurement technique for perpendicularity errors utilizing sea–sky line images. Through this method, we find an error function of LOS elevation angle, which is a convex function that can quickly search out high-precision perpendicularity errors step by step. Finally, we measured and compensated the perpendicularity error according to experimental data collected by the electro-optical device. The findings of this research demonstrate that the suggested approach can efficiently mitigate low-frequency disruptions and minor amplitude high-frequency vibrations of LOS in the elevation direction. As a result, it considerably enhances the precision of stability and image observation effect of electro-optical devices.

A reinforced concrete shear wall is an important building structure. Once damage occurs, it not only causes great losses to various properties but also seriously endangers people’s lives. It is difficult to achieve an accurate description of the damage process using the traditional numerical calculation method, which is based on the continuous medium theory. Its bottleneck lies in the crack-induced discontinuity, whereas the adopted numerical analysis method has the continuity requirement. The peridynamic theory can solve discontinuity problems and analyze material damage processes during crack expansion. In this paper, the quasi-static failure and impact failure of shear walls are simulated by improved micropolar peridynamics, which provides the whole process of microdefect growth, damage accumulation, crack initiation, and propagation. The peridynamic predictions are in good match with the current experiment observations, filling the gap of shear wall failure behavior in existing research.

High density phase change memory array requires both minimized critical dimension (CD) and maximized process window for the phase change material layer. High in-wafer uniformity of the nanoscale patterning of chalcogenides material is challenging given the optical proximity effect (OPE) in the lithography process and the micro-loading effect in the etching process. In this study, we demonstrate an approach to fabricate high density phase change material arrays with half-pitch down to around 70 nm by the co-optimization of lithography and plasma etching process. The focused-energy matrix was performed to improve the pattern process window of phase change material on a 12-inch wafer. A variety of patternings from an isolated line to a dense pitch line were investigated using immersion lithography system. The collapse of the edge line is observed due to the OPE induced shrinkage in linewidth, which is deteriorative as the patterning density increases. The sub-resolution assist feature (SRAF) was placed to increase the width of the lines at both edges of each patterning by taking advantage of the optical interference between the main features and the assistant features. The survival of the line at the edges is confirmed with around a 70 nm half-pitch feature in various arrays. A uniform etching profile across the pitch line pattern of phase change material was demonstrated in which the micro-loading effect and the plasma etching damage were significantly suppressed by co-optimizing the etching parameters. The results pave the way to achieve high density device arrays with improved uniformity and reliability for mass storage applications.

Abstract Background Ultrasonic measurement has not been utilized to assess the functional recovery of transplanted muscle. This study aimed to investigate the feasibility of using B-ultrasound measurement to assess muscle recovery following free functioning gracilis transfer. Methods From January 2009 to January 2014, 35 patients receiving free functioning gracilis transfer to treat total brachial plexus injury were enrolled. B-ultrasound was adopted to determine the cross-sectional area (CSA) of transplanted gracilis muscle at rest and contraction state. The ratio of pre- to post-transplant CSA value at rest state was defined as muscle bulk ratio (MBR). The ratio of CSA value at contraction state to rest state was defined as contraction ratio (CR). Results Patients with muscle strength M ≥ 4 had significantly higher CR1 (post-transplant), CR2 (pre-transplant), and range of motion (ROM, joint mobility) than those with muscle strength M CR2 group had significantly higher CR1, muscle strength, and ROM than the CR1 ≤ CR2 group. The MBR > 1 group had significantly higher muscle strength than the MBR ≤ 1 group. CR1 value was highly correlated with muscle strength and with ROM. CR2 value was moderately correlated with muscle strength and ROM. Multivariate linear regression analysis showed that a higher CR1/CR2 value was associated with a higher muscle strength and joint mobility. The CR1 > CR2 group had better muscle strength and ROM than the CR1 ≤ CR2 groups. Conclusion B-ultrasound measurement can quantitatively reflect muscle strength following gracilis transfer, and CR value could be a potential indicator for functional recovery of the transplanted gracilis muscle. Level of Evidence: Prognostic studies, Level II.

Abstract This study aimed to assess the impact of the 2017 American College of Cardiology and American Heart Association (ACC/AHA) guideline and the 2018 Chinese hypertension guidelines on the different secular trends for hypertension prevalence. A total of 82 665 eligible individuals aged ≥20 years were selected from nine cross‐sectional study periods (1991‐2015) from the China Health and Nutrition Survey (CHNS). Over the 24‐year period, the long‐term trend for the prevalence of the 2017 ACC/AHA‐defined age‐adjusted hypertension showed an increase from 32.2% (95% confidence interval (CI): 31.0%‐33.3%) in 1991 to 60.0% (95% CI: 58.6%‐61.3%) in 2015 (Ptrend

Abstract Background Short-term exercise training programs that consist of moderate intensity endurance training or high intensity interval training have become popular choices for healthy lifestyle modifications, with as little as two weeks of training being shown to improve cardiorespiratory fitness and whole-body glucose metabolism. An emerging concept in exercise biology is that exercise stimulates the release of cytokines and other factors into the blood that contribute to the beneficial effects of exercise on metabolism, but whether these factors behave similarly in response to moderate and high intensity short term training is not known. Here, we determined the effects of two short-term exercise training programs on the concentrations of select secreted cytokines and Klotho, a protein involved in anti-aging. Methods Healthy, sedentary men (n = 22) were randomized to moderate intensity training (MIT) or sprint intensity training (SIT) treatment groups. SIT consisted of 6 sessions over 2 weeks of 6 × 30 s all out cycle ergometer sprints with 4 min of recovery between sprints. MIT consisted of 6 sessions over 2 weeks of cycle ergometer exercise at 60% VO2peak, gradually increasing in duration from 40 to 60 min. Blood was taken before the intervention and 48 h after the last training session, and glucose uptake was measured using [18F]FDG‐PET/CT scanning. Cytokines were measured by multiplex and Klotho concentrations by ELISA. Results Both training protocols similarly increased VO2peak and decreased fat percentage and visceral fat (P

Abstract Reprogramming glycolysis for directing glycolytic metabolites to a specific metabolic pathway is expected to be useful for increasing microbial production of certain metabolites, such as amino acids, lipids or considerable secondary metabolites. In this report, a strategy of increasing glycolysis by altering the metabolism of inositol pyrophosphates (IPs) for improving the production of S-adenosyl-l-methionine (SAM) for diverse pharmaceutical applications in yeast is presented. The genes associated with the metabolism of IPs, arg82, ipk1 and kcs1, were deleted, respectively, in the yeast strain Saccharomyces cerevisiae CGMCC 2842. It was observed that the deletions of kcs1 and arg82 increased SAM by 83.3 % and 31.8 %, respectively, compared to that of the control. In addition to the improved transcription levels of various glycolytic genes and activities of the relative enzymes, the levels of glycolytic intermediates and ATP were also enhanced. To further confirm the feasibility, the kcs1 was deleted in the high SAM-producing strain Ymls1ΔGAPmK which was deleted malate synthase gene mls1 and co-expressed the Acetyl-CoA synthase gene acs2 and the SAM synthase gene metK1 from Leishmania infantum, to obtain the recombinant strain Ymls1Δkcs1ΔGAPmK. The level of SAM in Ymls1Δkcs1ΔGAPmK reached 2.89 g L−1 in a 250-mL flask and 8.86 g L−1 in a 10-L fermentation tank, increasing 30.2 % and 46.2 %, respectively, compared to those levels in Ymls1ΔGAPmK. The strategy of increasing glycolysis by deletion of kcs1 and arg82 improved SAM production in yeast.

To explore the potential application of non-Saccharomyces yeasts screened from Baijiu fermentation environment in winemaking, the effect of four Baijiu non-Saccharomyces yeasts (two Zygosaccharomyces bailii and two Pichia kudriavzevii) sequentially fermented with Saccharomyces cerevisiae on the physicochemical parameters and volatile compounds of wine was analyzed. The results indicated that there was no obvious antagonism between S. cerevisiae and Z. bailli or P. kudriavzevii in sequential fermentations, and all strains could be detected at the end of alcoholic fermentation. Compare with S. cerevisiae pure fermentation, Z. bailii/S. cerevisiae sequential fermentations significantly reduced higher alcohols, fatty acids, and ethyl esters and increased acetate esters; P. kudriavzevii/S. cerevisiae sequential fermentations reduced the contents of C6 alcohols, total higher alcohols, fatty acids, and ethyl esters and significantly increased the contents of acetate esters (especially ethyl acetate and 3-methylbutyl acetate). Sequential fermentation of Baijiu non-Saccharomyces yeast and S. cerevisiae improved the flavor and quality of wine due to the higher ester content and lower concentration of higher alcohols and fatty acids, non-Saccharomyces yeasts selected from Baijiu fermentation environment have potential applications in winemaking, which could provide a new strategy to improve wine flavor and quality.

Targeted therapy is a groundbreaking innovation for cancer treatment. Among the receptor tyrosine kinases, the fibroblast growth factor receptors (FGFRs) garnered substantial attention as promising therapeutic targets due to their fundamental biological functions and frequently observed abnormality in tumors. In the past 2 decades, several generations of FGFR kinase inhibitors have been developed. This review starts by introducing the biological basis of FGF/FGFR signaling. It then gives a detailed description of different types of small-molecule FGFR inhibitors according to modes of action, followed by a systematic overview of small-molecule-based therapies of different modalities. It ends with our perspectives for the development of novel FGFR inhibitors.

Maternal overnutrition can affect fetal growth and development, thus increasing susceptibility to obesity and diabetes in later life of the offspring. Placenta is the central organ connecting the developing fetus with the maternal environment. It is indicated placental fatty acid metabolism plays an essential role in affecting the outcome of the pregnancy and fetus. However, the role of placental fatty acid β-oxidation (FAO) in maternal overnutrition affecting glucose metabolism in the offspring remains unclear. In this study, C57BL/6J female mice were fed with normal chow or high-fat diet before and during pregnancy and lactation. The placenta and fetal liver were collected at gestation day 18.5, and the offspring's liver was collected at weaning. FAO-related genes and AMP-activated protein kinase (AMPK) signaling pathway were examined both in the placenta and in the human JEG-3 trophoblast cells. FAO-related genes were further examined in the liver of the fetuses and in the offspring at weaning. We found that dams fed with high-fat diet showed higher fasting blood glucose, impaired glucose tolerance at gestation day 14.5 and higher serum total cholesterol (T-CHO) at gestation day 18.5. The placental weight and lipid deposition were significantly increased in maternal high-fat diet group. At weaning, the offspring mice of high-fat diet group exhibited higher body weight, impaired glucose tolerance, insulin resistance and increased serum T-CHO, compared with control group. We further found that maternal high-fat diet downregulated mRNA and protein expressions of carnitine palmitoyltransferase 2 (CPT2), a key enzyme in FAO, by suppressing the AMPK/Sirt1/PGC1α signaling pathway in the placenta. In JEG-3 cells, protein expressions of CPT2 and CPT1b were both downregulated by suppressing the AMPK/Sirt1/PGC1α signaling pathway under glucolipotoxic condition, but were later restored by the AMPK agonist 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR). However, there was no difference in CPT2 and CPT1 gene expression in the liver of fetuses and offspring at weaning age. In conclusion, maternal high-fat diet can impair gene expression involved in FAO in the placenta by downregulating the AMPK signaling pathway, and can cause glucose and lipid dysfunction of offspring at weaning, indicating that placental FAO may play a crucial role in regulating maternal overnutrition and metabolic health in the offspring.

Osteoporosis is one of the most frequent skeletal disorders and a major cause of morbidity and mortality in the expanding aging population. Evidence suggests that hesperidin may have a therapeutic impact on osteoporosis. Nevertheless, little is known about the role of hesperidin in the development of osteoporosis. Bioinformatics analyses were carried out to explore the functions and possible molecular mechanisms by which hesperidin regulates osteogenic differentiation. In the present study, we screened and harvested 12 KEGG pathways that were shared by hesperidin-targeted genes and osteoporosis. The p53 signaling pathway was considered to be a key mechanism. Our in vitro results showed that hesperidin partially reversed dexamethasone-induced inhibition of osteogenic differentiation by suppressing the activation of p53, and suggest that hesperidin may be a promising candidate for the treatment against dexamethasone-induced osteoporosis.

The relationship between serum spermidine levels and future cardiovascular disease risk has not yet been well elucidated in the general population based on community studies. Using a nested case-control study, we estimated the association between serum spermidine level and future stroke. New stroke cases had higher baseline levels of spermidine than controls [182.8 (141.8–231.5) vs. 152.0 (124.3–193.0), P < 0.001]. After multivariable adjustment, individuals with spermidine ≥ 205.9 nmol/L (T3) higher risks of stroke (HR 5.02, 95% CI 1.58–16.02) with the lowest quartile (< 136.9 nmol/L) as reference. The association between serum spermidine levels and risk of stroke seemed to be consistent and was reproducible in our cross-sectional studies. In addition, comparisons of the areas under receiver operator characteristics curves confirmed that a model including spermidine had better discrimination than without (0.755 vs. 0.715, P = 0.04). Here we report a close relationship exists between serum spermidine levels and risk of stroke.

BackgroundSorafenib, which can induce ferroptosis, is a multikinase inhibitor for enhancing survival in advanced hepatocellular carcinoma (HCC). However, a considerable challenge for the treatment of HCC is sorafenib resistance. Therefore, targeting the relationship between sorafenib resistance and ferroptosis genes may provide a novel approach for the treatment of HCC.Materials and MethodsWe analyzed the gene expression and clinicopathological factors from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases (GSE109211/GSE62813). The statistical analysis was conducted in R. Cell proliferation was assayed by MTT, cell colony-forming assay, and wound healing assay. Immunofluorescence assay and Western blot were used to evaluate the expression of AKT.ResultsMany ferroptosis-related genes were upregulated in the sorafenib-resistant group. Aldo-keto reductase 1C3 (AKR1C3) was highly expressed in sorafenib-resistant patients, and the high expression of AKR1C3 was associated with the poor prognosis of patients from the TCGA and ICGC databases. MTT and colony-forming assays showing AKR1C3 overexpression enhanced the proliferation of HCC cells and acute sorafenib resistance. Knockdown of AKR1C3 inhibited the proliferation of HCC cells and increased the drug sensitivity of sorafenib. Immunofluorescence assay and Western blot proved that AKR1C3 promoted the phosphorylation of AKT.ConclusionAKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in HCC. AKR1C3 inhibitors may be used in conjunction with sorafenib to become a better therapeutic target for HCC.

Abstract Objectives A role for the type II arginine methyltransferase PRMT5 in various human diseases has been identified. In this study, the potential mechanism underlying the involvement of PRMT5 in the pathological process leading to osteoarthritis (OA) was investigated. Methods PRMT5 expression in cartilage tissues from patients with OA and control individuals was assessed by immunohistochemical staining. The regulatory and functional roles of PRMT5 in the chondrocytes of patients with OA and control individuals were determined by western blotting and reverse transcription polymerase chain reaction. The effects of the PRMT5 inhibitor EPZ on interleukin-1β-induced inflammation were examined in the chondrocytes of patients with OA and in the destabilized medial meniscus (DMM) of a mouse model of OA. Results PRMT5 was specifically upregulated in the cartilage of patients with OA. Moreover, adenovirus-mediated overexpression of PRMT5 in human chondrocytes caused cartilage degeneration. This degeneration was induced by elevated expression levels of matrix-degrading enzymes (matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13)) in chondrocytes. The activation of the MAPK and nuclear factor κB signaling pathways was evidenced by elevated levels of p-p65, p-p38, and p-JNK. These effects were attenuated by inhibiting the expression of PRMT5. In the mouse model, EPZ inhibited PRMT5 expression, thus protecting mouse cartilage from DMM-induced OA. Conclusions Our results demonstrate that PRMT5 is a crucial regulator of OA pathogenesis, implying that EPZ has therapeutic value in the treatment of this cartilage-destroying disease.

Abstract Background The current analysis was performed to estimate the percentage and number of Chinese adults with hypertension and the percentage and number of Chinese adults recommended to receive pharmacological antihypertensive treatment according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline compared with the same parameters according to the 2010 Chinese guideline. Methods We used 2011 data from the China Health and Nutrition Survey (CHNS). A total of 12,499 Chinese adults aged ≥18 years with complete blood pressure (BP) values were selected for the present analysis. Results The crude prevalence rates (95% CI) of hypertension according to the definitions from the 2017 ACC/AHA guideline and the 2010 Chinese guideline were 58.0% (57.2 to 58.9%) and 25.4% (24.7 to 26.2%), respectively. Moreover, the percentage of the participants recommended to take antihypertensive medications were 31.5 and 28.8%, respectively. Among adults who took antihypertensive medications, 88.8% had above-goal BP levels compared to 53.3%. Overall, 613.3 million Chinese adults (aged ≥18 years) met the criteria for hypertension according to the 2017 ACC/AHA guideline, and 267.7 million met the criteria according to 2010 Chinese guideline. An additional 28.4 million (2.7%) Chinese adults were recommended to take antihypertensive medication. Conclusions The present analysis revealed that the 2017 ACC/AHA hypertension guideline will result in a substantial increase in the percentage and number of Chinese adults defined as having hypertension and a small increase in the percentage of adults who are recommended to take antihypertensive medications compared to the same parameters based on the 2010 Chinese guideline. More intensive management and antihypertensive medications use are suggested to improve the control rate of hypertension among Chinese adults.

Abstract. It shows that detrimental exposures and conditions in mothers can lead to the development of obesity and type 2 diabetes in offspring. This can lead to a vicious cycle of metabolic dysfunction, where rising rates of obesity, pre-diabetes, and diabetes in individuals of reproductive age, propagating risks to subsequent generations. It is well established that regular exercise has important health benefits for people with obesity and type 2 diabetes. Recently, increasing studies aim to examine the effects of maternal exercise on metabolic health in offspring. This review aims to demonstrate the evidence linking maternal exercise during critical periods of development and its implications for glucose metabolism in offspring, including intervention timing, sexual dimorphism, different exercise type, and intensity. Then we further examine the potential role of epigenetic modifications in this process.

ContextEye tracking is a technology to measure and determine the eye movements and eye positions of an individual. The eye data can be collected and recorded using an eye tracker. Eye-tracking data offer unprecedented insights into human actions and environments, digitizing how people communicate with computers, and providing novel opportunities to conduct passive biometric-based classification such as emotion prediction. The objective of this article is to review what specific machine learning features can be obtained from eye-tracking data for the classification task.MethodsWe performed a systematic literature review (SLR) covering the eye-tracking studies in classification published from 2016 to the present. In the search process, we used four independent electronic databases which were the IEEE Xplore, the ACM Digital Library, and the ScienceDirect repositories as well as the Google Scholar. The selection process was performed by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) search strategy. We followed the processes indicated in the PRISMA to choose the appropriate relevant articles.ResultsOut of the initial 420 articles that were returned from our initial search query, 37 articles were finally identified and used in the qualitative synthesis, which were deemed to be directly relevant to our research question based on our methodology.ConclusionThe features that could be extracted from eye-tracking data included pupil size, saccade, fixations, velocity, blink, pupil position, electrooculogram (EOG), and gaze point. Fixation was the most commonly used feature among the studies found.

BackgroundDental practitioners and dental students are classified as high-risk exposure to COVID-19 due to the nature of dental treatments, but evidence of their acceptance towards COVID-19 vaccination is still scarce. Hence, this systemic review aims to critically appraise and analyse the acceptability of COVID-19 vaccination among dental students and dental practitioners.Materials and methodsThis review was registered in the PROSPERO database (CRD42021286108) based on PRISMA guidelines. Cross-sectional articles on the dental students' and dental practitioners' acceptance towards COVID-19 vaccine published between March 2020 to October 2021 were searched in eight online databases. The Joanna Briggs Institute critical appraisal tool was employed to analyse the risk of bias (RoB) of each article, whereas the Oxford Centre for Evidence-Based Medicine recommendation tool was used to evaluate the level of evidence. Data were analysed using the DerSimonian-Laird random effect model based on a single-arm approach.ResultsTen studies were included of which three studies focused on dental students and seven studies focused on dental practitioners. Four studies were deemed to exhibit moderate RoB and the remaining showed low RoB. All the studies demonstrated Level 3 evidence. Single-arm meta-analysis revealed that dental practitioners had a high level of vaccination acceptance (81.1%) than dental students (60.5%). A substantial data heterogeneity was observed with the overall I2 ranging from 73.65% and 96.86%. Furthermore, subgroup analysis indicated that dental practitioners from the Middle East and high-income countries showed greater (p < 0.05) acceptance levels, while meta-regression showed that the sample size of each study had no bearing on the degree of data heterogeneity.ConclusionsDespite the high degree of acceptance of COVID-19 vaccination among dental practitioners, dental students still demonstrated poor acceptance. These findings highlighted that evidence-based planning with effective approaches is warranted to enhance the knowledge and eradicate vaccination hesitancy, particularly among dental students.

The solid-state fermentation of Baijiu is complicated by the co-fermentation of many microorganisms. The instability of the composition and abundance of the microorganisms in the fermentation process leads to fluctuations of product quality, which is one of the bottleneck problems faced by the Strong-flavor Baijiu industry. In this study, we established a combination of functional microorganisms for the stable fermentation of the main flavor compounds of Baijiu, including medium and long-chain fatty acid ethyl esters such as hexanoic acid, ethyl ester; butanoic acid, ethyl ester; octanoic acid, ethyl ester; acetic acid, ethyl ester; 9,12-octadecadienoic acid, ethyl ester; and decanoic acid, ethyl ester in the fermented grains. Our study investigated the effects of microbial combinations on the fermentation from three aspects: microbial composition, microbial interactions, and microbial association with flavor compounds. The results showed that the added functional microorganisms (Lactobacillus, Clostridium, Caproiciproducens, Saccharomyces, and Aspergillus) became the dominant species in the fermentation system and formed positive interactions with other microorganisms, while the negative interactions between microorganisms were significantly reduced in the fermentation systems that contained both Daqu and functional microorganisms. The redundancy analysis showed that the functional microorganisms (Lactobacillus, Saccharomyces, Clostridium, Cloacibacterium, Chaenothecopsis, Anaerosporobacter, and Sporolactobacillus) showed strong positive correlations with the main flavor compounds (hexanoic acid, ethyl ester; lactic acid, ethyl ester; butanoic acid, ethyl ester; acetic acid, ethyl ester; and octanoic acid, ethyl ester). These results indicated that it was feasible to produce Baijiu with a functional microbial combination, and that this could promote stable Baijiu production.

Terpenes are compounds that include monoterpenes, sesquiterpenes, diterpenes, and terpenes, where isoprene is the basic structural unit of multiple oxygenated hydrocarbons. Terpenes are often found in plants, especially in some Zingiberaceae or tulips, and they have been obtained by direct extraction, chemical synthesis, and microorganisms. They exhibit anti-bacterial, anti-viral, anti-oxidant, and analgesic activity, aid digestion, and have other biological activities. Terpenes are widely used as factors in food health and as anti-cancer treatments. They are used especially as active substances in fermented Chinese baijiu products and gives Chinese baijiu its fruity aroma. To a certain extent, terpenes affect the quality of baijiu. In pharmaceutical products, terpenes, especially limonene and elemene, have strong biological activity that reduces the mitosis of tumor cells, induces tumor cell apoptosis, and inhibits tumor cell growth. However, the low yield of terpenes limits its application. Therefore, we review the sources of terpenes, focus on the biosynthesis pathway of sesquiterpenes, and explore the latest research progress on terpenes that play a biologically active and functional role in fermented products and pharmaceutical products, especially in the development and utilization of the Chinese baijiu industry. We provide new research ideas for the improvement and optimization of terpenes in various industries.

A Lie bialgebra is a vector space endowed simultaneously with the structure of a Lie algebra and the structure of a Lie coalgebra, and some compatibility condition. Moreover, Lie brackets have skew symmetry. Because of the close relation between Lie bialgebras and quantum groups, it is interesting to consider the Lie bialgebra structures on the Lie algebra L related to the Virasoro algebra. In this paper, the Lie bialgebras on L are investigated by computing Der(L, L⊗L). It is proved that all such Lie bialgebras are triangular coboundary, and the first cohomology group H1(L, L⊗L) is trivial.

Graded lattice structures have been paid wide attention in the engineering and biological fields due to their excellent energy absorption capacity and variable porosity characteristics. Based on the size-graded lattice structure, laser powder bed fusion is utilized to manufacture the corresponding Ti-6Al-4 V lattice samples. Then, the quasi-static compression experiment is conducted and a predictive model for its mechanical properties is established accordingly. Also, its dynamic fatigue behavior is studied, and the influence of sandblasting and gradient direction on its mechanical response is evaluated. The results show that excellent mechanical properties and energy absorption capacity is exhibited in the vertical graded (VG) structure. Compared to the uniform structure, its elastic modulus and energy absorption are increased by 17.53% and 59.43%, respectively. The compression response of the radial graded (RG) structure is similar to that of the uniform structure, with minor changes on the mechanical properties and energy absorption capacity. However, the fatigue performance of the RG structure is better than that of the VG structure. With appropriate mechanical properties and changes in pores, this graded structure can simulate the changing physical and chemical properties of natural bone. Therefore, it has great potentiality in the application of bone implants.

The prevalence of obesity has become a threatening global public health issue. The consequence of obesity is abnormal energy metabolism. Unlike white adipose tissue (WAT), brown adipose tissue (BAT) has a unique role in nonshivering thermogenesis. Lipids and glucose are consumed to maintain energy and metabolic homeostasis in BAT. Recently, accumulating evidence has indicated that exposure to excess maternal energy intake affects energy metabolism in offspring throughout their life. However, whether excess intrauterine energy intake influences BAT metabolism in adulthood is not clear. In this study, mouse dams were exposed to excess energy intake by feeding a high-fat diet (HFD) before and during pregnancy and lactation. The histology of BAT was assessed by hematoxylin and eosin staining. The genome-wide methylation profile of BAT was determined by a DNA methylation array, and specific site DNA methylation was quantitatively analyzed by methylated DNA immunoprecipitation (MeDIP) qPCR. We found that intrauterine exposure to a high-energy diet resulted in blood lipid panel disorders and impaired the BAT structure. Higher methylation levels of genes involved in thermogenesis and fatty acid oxidation (FAO) in BAT, such as Acaa2, Acsl1, and Cox7a1, were found in 16-week-old offspring from mothers fed with HFD. Furthermore, the expression of Acaa2, Acsl1, and Cox7a1 was down-regulated by intrauterine exposure to excess energy intake. In summary, our results reveal that excess maternal energy leads to a long-term disorder of BAT in offspring that involves the activation of DNA methylation of BAT-specific genes involved in fatty acid oxidation and thermogenesis.

To explore the effects of microbial community changes on the key flavor substances in base Baijiu, this study analyzed the microbiome of the pre-pit fermentation grains using high-throughput sequencing technology and determined the flavor substances of the base Baijiu by GC-FID. The results showed the microbial community changed dynamically between the different rounds, as well as bacteria and fungi displayed different succession patterns. Next, the variations of skeletal flavor substances in the base Baijiu were analyzed by multiomics, and it was found that alcohols, acids, and esters were the most abundant, accounting for 88.16–98.87% of the total flavor substances, and decreased with the increase of the rounds. By calculating the Spearman coefficient, it was found that microorganisms such as Acinetobacter, Oceanobacillus, Saccharomyces, and Byssochlamys were significantly correlated with the n-Propano and 2,3-Butanediol and other components in the base Baijiu. Finally, 15 flavor substances such as Acetaldehyde, Propionaldehyde, and Isobutyraldehyde were identified as key substances by OAV analysis. This study is the first to reveal the potential association between the microbial community of pre-pit fermentation grains and flavor of base Baijiu and has the benefit of improving the quality of base Baijiu.

The hollow turbine blade plays an important role in the propulsion of the aeroengine. However, due to its complex hollow structure and nickel-based superalloys material property, only industrial computed tomography (ICT) could realize its nondestructive detection with sufficient intuitiveness. The ICT detection precision mainly depends on the segmentation accuracy of target ICT images. However, because the hollow turbine blade is made of special superalloys and contains many small unique structures such as film cooling holes, exhaust edges, etc., the ICT image quality of the hollow turbine blades is often deficient, with artifacts, low contrast, and inhomogeneity scattered around the blade contour, making it hard for traditional mathematical model-based methods to acquire satisfying segmentation precision. Therefore, this paper presents a deep learning-based approach, i.e., the enhanced U-net with multiscale inputs, dense blocks, focal loss function, and residual path in the skip connection to realize the high-precision segmentation of the hollow turbine blade. The experimental results show that our proposed enhanced U-net can achieve better segmentation accuracy for practical turbine blades than conventional U-net and traditional mathematical model-based methods.

Myocardial infarction is characterized by cardiomyocyte death, and can be exacerbated by mitochondrial damage and endoplasmic reticulum injury. In the present study, we investigated whether communication between mitochondria and the endoplasmic reticulum contributes to cardiomyocyte death after myocardial infarction. Our data demonstrated that hypoxia treatment (mimicking myocardial infarction) promoted cardiomyocyte death by inducing the c-Jun N-terminal kinase (JNK) pathway. The activation of JNK under hypoxic conditions was dependent on overproduction of mitochondrial reactive oxygen species (mtROS) in cardiomyocytes, and mitochondrial division was identified as the upstream inducer of mtROS overproduction. Silencing mitochondrial division activators, such as B cell receptor associated protein 31 (BAP31) and mitochondrial fission 1 (Fis1), repressed mitochondrial division, thereby inhibiting mtROS overproduction and preventing JNK-induced cardiomyocyte death under hypoxic conditions. These data revealed that a novel death-inducing mechanism involving the BAP31/Fis1/mtROS/JNK axis promotes hypoxia-induced cardiomyocyte damage. Considering that BAP31 is localized within the endoplasmic reticulum and Fis1 is localized in mitochondria, abnormal mitochondria-endoplasmic reticulum communication may be a useful therapeutic target after myocardial infarction.

Substantial evidence indicated that maternal malnutrition could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes in adulthood. It is increasingly apparent that the brain, especially the hypothalamus, plays a critical role in glucose homeostasis. However, little information is known about the mechanisms linking maternal protein restriction combined with post-weaning high-fat (HF) feeding with altered expression of brain neurotransmitters, and investigations into the epigenetic modifications of hypothalamus in offspring have not been fully elucidated. Our objective was to explore the effects of maternal protein restriction combined with post-weaning HF feeding on glucose metabolism and hypothalamic POMC methylation in male offspring mice. C57/BL6 mice were fed on either low-protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the male offspring were randomly weaned to either NC or high-fat (HF) diet until 32 weeks of age. Gene expressions and DNA methylation of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in male offspring. The results showed that birth weights and body weights at weaning were both significantly lower in male offspring mice of the dams fed with a LP diet. Maternal protein restriction combined with post-weaning high-fat feeding, predisposes higher body weight, persistent glucose intolerance (from weaning to 32 weeks of age), hyperinsulinemia, and hyperleptinemia in male offspring mice. POMC and MC4R expressions were significantly increased in offspring mice fed with maternal LP and postnatal high-fat diet (P < 0.05). Furthermore, maternal protein restriction combined with post-weaning high-fat feeding induced hypomethylation of POMC promoter in the hypothalamus (P < 0.05) and POMC-specific methylation (%) was negatively correlated with the glucose response to a glucose load in male offspring mice (r = −0.42, P = 0.039). In conclusion, maternal LP diet combined with post-weaning high-fat feeding predisposed the male offspring to impaired glucose metabolism and hypothalamic POMC hypomethylation. These findings can advance our thinking about hypothalamic POMC gene methylation between maternal LP diet combined with post-weaning high-fat feeding and metabolic health in offspring.

Landslides are widely distributed worldwide and often result in tremendous casualties and economic losses, especially in the Loess Plateau of China. Taking Wuqi County in the hinterland of the Loess Plateau as the research area, using Bayesian hyperparameters to optimize random forest and extreme gradient boosting decision trees model for landslide susceptibility mapping, and the two optimized models are compared. In addition, 14 landslide influencing factors are selected, and 734 landslides are obtained according to field investigation and reports from literals. The landslides were randomly divided into training data (70%) and validation data (30%). The hyperparameters of the random forest and extreme gradient boosting decision tree models were optimized using a Bayesian algorithm, and then the optimal hyperparameters are selected for landslide susceptibility mapping. Both models were evaluated and compared using the receiver operating characteristic curve and confusion matrix. The results show that the AUC validation data of the Bayesian optimized random forest and extreme gradient boosting decision tree model are 0.88 and 0.86, respectively, which showed an improvement of 4 and 3%, indicating that the prediction performance of the two models has been improved. However, the random forest model has a higher predictive ability than the extreme gradient boosting decision tree model. Thus, hyperparameter optimization is of great significance in the improvement of the prediction accuracy of the model. Therefore, the optimized model can generate a high-quality landslide susceptibility map.

The etiology of subacute combined degeneration (SCD) of the spinal cord is closely associated with vitamin B12 (VitB12) deficiency. The clinical manifestations of SCD are complex and vary substantially. Due to some SCD patients with atypical manifestations and concomitant autoimmune disorders, the probability of misdiagnosis and missed diagnosis is still relatively high in the early stage. We report the cases of two patients who were missed or misdiagnosed at another hospital because of the normal initial VitB12 level and partial overlap of clinical manifestations, finally diagnosed as SCD with atypical manifestations and concomitant autoimmune disorders, pharyngeal-cervical-brachial Guillain-Barre syndrome in Case 1 and SCD with autoimmune thyroiditis in Case 2. After undergoing corresponding treatment, death was reported in Case 1 and improvement in Case 2. Analysis of the clinical manifestations and investigation of the underlying pathogenesis in such patients could help improve the rate of early diagnosis and allow timely treatment of SCD, thereby preventing disease progression and poor clinical outcomes.

While a strong literature base exists around undergraduate experiences in Science, Technology, Engineering, and Math (STEM), few studies examine how students approach the question of "what's next" after graduation. This study examines the impact of social ties on STEM college seniors' plans to enter the STEM workforce, and how race/ethnicity and gender impact postgraduation planning in STEM. We interviewed a racially diverse sample of 39 STEM college seniors at a predominantly White research institution. Analysis showed that students relied on weak and strong social ties in obtaining job leads and valued diversity in the workplace. Some students of color and women experienced negative social ties (via racism and sexism) during internship experiences, which shaped their thinking around postgraduate opportunities. We discuss implications for equity, as well as recommendations for research and practice.

Higher education practitioners are a wide-ranging group of professionals often responsible for implementing programs and services that support student success. In this qualitative study, we examine the nature of student-practitioner relationships among a multiracial sample of 39 science, technology, engineering, and mathematics (STEM) college seniors to address three questions: (a) How do STEM students describe their relationships with practitioners on campus? (b) In what ways, if any, do student-practitioner relationships influence STEM students' feelings of marginality and/or mattering in STEM? and (c) To what extent do STEM students have different experiences based on their racial/ethnic identities? We employ a cross-case study analysis approach, contrasting the experiences of majority-status (e.g., White and Asian/Asian American) and minoritized-status (e.g., Black/African American and Latinx) students within STEM contexts. Our findings show clear differences regarding how students describe their interactions with practitioners based on racial/ethnicbackground, as well as how student-practitioner relationships impact students' sense of mattering and marginality in STEM. We conclude with implications for research and practice to address the persistent structural issues affecting STEM college students.