Search

Abstract The infantile neuronal ceroid lipofuscinosis, also called CLN1 disease, is a fatal neurodegenerative disease caused by mutations in the CLN1 gene encoding palmitoyl protein thioesterase 1 (PPT1). Identifying the depalmitoylation substrates of PPT1 is crucial for understanding CLN1 disease. In this study, we found that GABAAR, the critical synaptic protein essential for inhibitory neurotransmission, is a substrate of PPT1. PPT1 depalmitoylates GABAAR α1 subunit at Cystein-260, while binding to Cystein-165 and -179. Mutations of PPT1 or its GABAAR α1 subunit binding site enhanced inhibitory synaptic transmission and strengthened oscillations powers but disrupted phase coupling in CA1 region and impaired learning and memory in 1- to 2-months-old PPT1-deficient and Gabra1 em1 mice. Our study highlights the critical role of PPT1 in maintaining GABAAR palmitoylation homeostasis and reveals a previously unknown molecular pathway in CLN1 diseases induced by PPT1 mutations.

Abstract Background Ambient particulate matter (PM) exposure is recognized as a risk factor for cardiovascular disease (CVD). However, the extent to which PM exposure is associated with CVD via triglyceride glucose (TyG)-related indicators remains unknown. This study examines the relationship between long-term PM exposure and CVD events, further assessing whether TyG-related indicators mediate this association. Methods This cohort study involved 7,532 individuals aged at least 45 years who were not diagnosed with CVD in 2011 from the China Longitudinal Study of Health and Retirement (CHARLS) and were followed up for the occurrence of CVD until 2020. The annual PM concentration data at the city level, with aerodynamic diameters ≤ 1 μm (PM1), ≤ 2.5 μm (PM2.5), and ≤ 10 μm (PM10), were obtained from the ChinaHighAirPollutants (CHAP). The average concentration of PM in the 3 years before the baseline survey in 2011 was defined as the long-term exposure level of the individual. The relationship between PM exposure and CVD incidence was examined via Cox proportional hazards models, with a focus on probing the role of TyG-related indicators through mediation analysis. Results A total of 1,865 individuals with CVD were diagnosed over the span of a 7.4-year follow-up period. The 3-year average concentrations before baseline were 31.29 µg/m³ for PM1, 56.03 µg/m³ for PM2.5, and 95.73 µg/m³ for PM10. In fully adjusted model, the Cox proportional hazards models revealed that an increase of 10 µg/m³ in the PM1, PM2.5, and PM10 exposure concentrations corresponded to elevated CVD risk, with HRs (95% CI) of 1.135 (1.078–1.195), 1.092 (1.062–1.123), and 1.075 (1.059–1.090), respectively. Mediation analyses further suggested that the correlation between PM exposure and CVD could be partly mediated via TyG-BMI, TyG-WC, and TyG-WHtR, with mediation proportions varying from 5.54 to 15.30%. Conclusion A significant correlation was observed between long-term PM exposure and increased CVD risk, with TyG-related indicators, such as TyG-BMI, TyG-WC, and TyG-WHtR, partially mediating this relationship.

ABSTRACT Background 7‐Hydroxymethotrexate (7‐OHMTX) is the main metabolite in plasma following high‐dose MTX (HD‐MTX), which may result in activity and toxicity of the MTX. Moreover, 7‐OHMTX could produce crystalline‐like deposits within the renal tubules under acidic conditions or induce renal inflammation, oxidative stress, and cell apoptosis through various signaling pathways, ultimately leading to kidney damage. The objectives of this study were thus to explore the exposure–safety relationship of two compounds and search the most reliable marker for predicting HDMTX nephrotoxicity. Method A total of 280 plasma concentration data (140 for MTX and 140 for 7‐OHMTX) for 60 pediatric patients with non‐Hodgkin lymphoma (NHL) were prospectively collected. Plasma MTX and 7‐OHMTX concentrations were determined using a high‐performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) method. A nonlinear mixed effect model approach was used to build a joint population pharmacokinetic (PopPK) model. After validation, the model estimated the peak concentration (Cmax) and area under the curve within the initial 48 h (AUC0‐48h) of the patients after drug administration by Bayesian feedback. The receiver operating characteristic (ROC) curves were generated to identify an exposure threshold associated with nephrotoxicity. Results A three‐compartment chain model (central and peripheral compartments for MTX and central compartment 7‐OHMTX) with the first‐order elimination adequately characterized the in vivo process of MTX and 7‐OHMTX. The covariate analysis identified that the aspartate aminotransferase (AST) was strongly associated with the peripheral volume of distribution of MTX. Moreover, the Cmax of MTX and 7‐OHMTX showed significant differences (p

Abstract Background Mesenchymal stromal cell (MSC)-derived exosomes (MSC-Exo) have been recognized for their significant role in regulating macrophage polarization, a process crucial to the pathogenesis of abdominal aortic aneurysm (AAA). However, the therapeutic effects of MSC-Exo on AAA remain largely unexplored. Therefore, this study aimed to investigate the functional and mechanistic aspects of MSC-Exo in the progression of AAA. Methods The MSC-derived exosomes were characterized using Transmission Electron Microscopy, Nanoparticle Tracking Analysis, and Western blotting. An experimental mouse model of AAA was established through the administration of angiotensin II (Ang II) in male apoe−/− mice and calcium chloride (CaCl2) in male C57/B6 mice, with subsequent tail vein injection of exosomes to evaluate their efficacy against AAA. Macrophage polarization was assessed using immunofluorescence staining and WB analysis. Mechanistic analysis was performed using 4D Label-free Proteomics analysis. Results We found that intravenous administration of MSC-Exo induced M2 polarization of macrophages within an inflammatory environment, effectively impeding AAA development in Ang II or CaCl2-induced AAA model. The therapeutic efficacy of MSC-Exo treatment was dependent on the presence of macrophages. Mechanistically, MSC-Exo suppressed the levels of cluster of differentiation 74 (CD74), modulating macrophage polarization through the TSC2-mTOR-AKT pathway. These findings highlight the potential of MSC-Exo as a therapeutic strategy for AAA by modulating macrophage polarization.

Abstract This study explores the association between LE8 scores and mortality risks among individuals diagnosed with cardiovascular disease (CVD). Utilizing data from the NHANES conducted between 2005 and 2018, survey-weighted multivariable Cox proportional hazards regression models were utilized. Life’s Essential 8 (LE8) scores dose–response associations were assessed using restricted cubic spline regression. Sub-analyses were performed for different categories of CVD. The study consisted of 2164 participants diagnosed with CVD, ranging in age from 20 to 80 years (weighted mean [SE] age, 61.47 [0.34] years; The average total LE8 was 64.97 [0.54]. 499 participants experienced mortality, with 350 deaths attributed to CVD. After accounting for potential covariates, LE8 score was found to be associated with a decreased both all-cause mortality (OR 0.34, CI 0.22–0.51) and CVD mortality (OR 0.40, CI 0.23–0.68). A survey-weighted multivariable Cox model with restricted cubic splines identified the lowest all-cause mortality (P

A single nanoparticle (NP) capable of simultaneously performing multiple bioimaging and therapeutic functions is an innovative approach to advance the field of cancer diagnostics and treatment. Here we report a facile synthesis approach to produce magnetic-plasmonic core-shell nanostars. These NPs consist of an Fe3O4 core, silica intermediate shell, and outer spiky gold nanostar shell. Remarkably, these core-shell NPs exhibit outstanding magnetisation and tuneable localized surface plasmon resonance (LSPR) spanning from visible to Near Infrared (NIR) wavelengths. Through incorporation of Indocyanine Green (ICG) and subsequent coating with bovine serum albumin (BSA), the obtained NPs demonstrate dual imaging capabilities in the form of magnetic resonance imaging (MRI) which offers high spatial resolution and deep tissue penetration and Surface-Enhanced Raman Scattering (SERS) which can provide the ultrasensitive molecular detection which MRI lacks. More significantly, they also exhibit significant potential to be used in photothermal therapy (PTT). These multi-functional NPs show minimal cytotoxicity when exposed to cells even at high concentrations, positioning them as promising candidates for future in vivo studies centred around imaging-guided photothermal therapy.

ObjectiveThis study compared the effects of Flywheel Resistance Squat Training (FRST) vs. Traditional Resistance Squat Training (TRST) on lower body strength in female collegiate basketball players.MethodsNineteen participants were randomly assigned to either the FRST group (n = 9) or the TRST group (n = 10) through a random number draw. Both groups underwent a 6-week intervention with training sessions conducted twice a week. The FRST group utilized an inertia of 0.075 kg ·m2, while another group trained at 80% of their one-repetition maximum (1RM). Each training session consisted of 4 sets of 8 repetitions with a 3-minute rest between sets. Both groups performed standardized warm-ups and stretches before and after each training session. The effectiveness of the training methods was assessed through the Countermovement Jump (CMJ), Reactive Strength Index (RSI), Eccentric Utilization Ratio, Running Vertical Jump, and 1RM squat.ResultsThe FRST and TRST groups showed differences within groups in both CMJ and 1RM squat (p < 0.01), with the FRST group demonstrating moderate effect sizes in CMJ (Hedges’ g = 0.59) and 1RM (Hedges’ g = 1.01). However, there were no differences between groups (p > 0.05). The Eccentric Utilization Ratio showed a small effect size (p = 0.78; ηp2=0.01). Additionally, Reactive Strength Index and Running Vertical Jump exhibited low test-retest reliability.ConclusionThe two groups did not exhibit a statistically significant difference. Nonetheless, both FRST and TRST demonstrated positive effects on 1RM squat and CMJ performance compared to baseline values for each method. Therefore, flywheel resistance training can be considered an effective alternative to traditional resistance training for enhancing strength levels in female basketball players.

Abstract Background With the development of pathophysiology, cardiorenal syndrome (CRS), a complex and severe disease, has received increasing attention. Monocyte to high-density lipoprotein-cholesterol ratio (MHR) and body mass index (BMI) are independent risk factors for cardiovascular diseases, but their association with CRS remains unexplored. This study aims to explore the independent and joint effects of MHR and BMI on CRS. Methods We included 42,178 NHANES participants. The determination of CRS referred to the simultaneous presence of cardiovascular disease (identified through self-report) and chronic kidney disease (eGFR

Abstract Numerous observational studies have elucidated a connection between leukocyte telomere length (LTL) and sepsis, yet its fundamental cause remains enigmatic. Thus, the current study’s objective is to employ a bidirectional Mendelian randomization (MR) approach to scrutinize the causality between LTL and sepsis. We selected single nucleotide polymorphisms (SNPs) associated with LTL (n = 472,174) and sepsis from a genome-wide association study (GWAS), including Sepsis (n = 486,484, ncase = 11,643), Sepsis (28 day death in critical care) (n = 431,365, ncase = 347), Sepsis (under 75) (n = 462,869, ncase = 11,568), Sepsis (28 day death) (n = 486,484, ncase = 1896), and Sepsis (critical care) (n = 431,365, ncase = 1380), as instrumental variables (IVs). The inverse variance weighted (IVW) MR method was employed as the primary approach, and various sensitivity analyses were conducted to assess the validity of this instrument and potential pleiotropy. Using the IVW method, we uncovered a potential causal relationship between genetically predicted LTL reduction and increased susceptibility to sepsis, with an odds ratio (OR) of 1.161 [95% confidence interval (CI) 1.039–1.297, p = 0.008]. However, reverse MR analysis did not indicate any impact of sepsis on LTL. Our forward MR study highlights a potential causal relationship between LTL as an exposure and increased susceptibility to sepsis. Specifically, our findings suggest that individuals with genetically determined shorter LTL may be at an increased risk of developing sepsis. This may contribute to the development of novel diagnostic and therapeutic strategies for the prevention, diagnosis, and treatment of sepsis.

Boron (B), an essential micronutrient for fruit development, also plays a crucial role in maintaining the shelf life of strawberries (Fragaria ananassa Duch.) by affecting cell wall structure and components. We investigated the distribution pattern of B within cells and cell walls in strawberry fruits under different B levels and revealed the relationship between the B distribution in cell walls and fruit firmness after harvesting. Foliar spraying of 0.1% H3BO3 promoted the growth of strawberry seedlings and improved fruit yield and flesh firmness by 45.7% and 25.6%. During the fruit softening and decay process, the content of bound B and cell wall-B decreased while more B was allocated to the protoplast and apoplast. The changes in B distribution in cells were attributed to cell damage during fruit decay, and B extended the freshness period of the fruits by alleviating the decrease of B distribution in cell walls. After leaving the fruits at room temperature for 10 h, the B content in different cell wall components significantly decreased, while foliar spraying of B alleviated the reduction of B content in covalently bound pectin (CBP), cellulose, and hemicellulose. Meanwhile, B spraying on fruit decreased the activity of cell wall degradation enzymes, including polygalacturonase (PG) and pectin lyase (PL), by 20.2% and 38.1%, while enhancing the demethylation of pectin by increasing pectin methylesterase (PME) activity from 21.6 U/g to 25.7 U/g. Thus, foliar spraying of 0.1% H3BO3 enhances the cross-linking of B with cell wall components and maintains cell wall structure, thereby prolonging the shelf life of strawberry fruits.

The incidence of melanoma is increasing year by year and is highly malignant, with a poor prognosis. Its treatment has always attracted much attention. Among the more clinically applied immunotherapies are immune checkpoint inhibitors, bispecific antibodies, cancer vaccines, adoptive cell transfer therapy, and oncolytic virotherapy. With the continuous development of technology and trials, in addition to immune monotherapy, combinations of immunotherapy and radiotherapy have shown surprising efficacy. In this article, we review the research progress of immune monotherapy and combination therapy for advanced melanoma, with the aim of providing new ideas for the treatment strategy for advanced melanoma.

Abstract As a subserie of the dental ceramic material family, glass–ceramics are favored for their excellent aesthetic properties. The feasibility of current commercially available dental glass–ceramics applications has been proven, while the assurance and development of more functional properties for them are still being explored. Effective utilization of various modification mechanisms by adjusting the chemical composition and microstructure is essential to improve the mechanical properties, aesthetic properties, and other properties such as biocompatibility of dental restorative materials. Among them, the mechanical properties of restorations should take into account the mechanical properties of glass ceramics and the final restoration (restoration and tooth set) in the mechanical behavior. This paper provides an overview of the chemical composition design, classification of microstructure, property requirements, and strengthening methods applied to dental glass–ceramics, including ion exchange, chain effects, heat treatment modulation, and strengthening mechanisms. In addition, research on traditional hot pressing, subtractive manufacturing, and newly developed additive manufacturing in glass–ceramics are systematically presented. Finally, the tendency of dental glass–ceramics was forecasted by analyzing the relationship between glass–ceramic composition, process, and mechanical properties.

BackgroundTargeted agents are widely utilized in the treatment of ulcerative colitis (UC). Hence, a comprehensive understanding of comparative drug efficacy in UC is of great importance for drug development and clinical practice. Our objective was the quantitative evaluation of the comparative efficacy of targeted agents for UC.MethodsThree mathematical models were developed based on data from randomized controlled trials in patients with moderate-to-severe UC to describe the time-course and dose-response of efficacy defined as clinical remission, clinical response, and endoscopic improvement, as well as the placebo effect. The covariate effects were further evaluated. Model simulation was performed in a hypothetical population to compare the efficacies across different drugs.ResultsThe analysis dataset was composed of data from 35 trials of 12 drugs in UC. Time–response relationships were evaluated that indicated a gradual onset of drug efficacy in adalimumab, ozanimod, and Janus kinase (JAK) inhibitors. The dose-response relationships were estimated for each drug respectively. Patient age, disease duration, baseline weight, prior tumor necrosis factor (TNF) inhibitor exposure, and current treatment with corticosteroid showed an impact on efficacy, suggesting that younger patients with shorter UC duration without prior anti-TNF treatment and current corticosteroids therapy tend to display greater treatment effects.ConclusionThis study developed three longitudinal models for UC to quantitatively describe the efficacy of targeted agents, as well as the influencing factors of efficacy. Infliximab and upadacitinib were determined to be the most effective biological and small targeted molecules, respectively. These findings may provide valuable implications for guiding future decision-making in clinical practice and drug development for UC.

BackgroundGastric cancer (GC) and type 2 diabetes (T2D) contribute to each other, but the interaction mechanisms remain undiscovered. The goal of this research was to explore shared genes as well as crosstalk mechanisms between GC and T2D.MethodsThe Gene Expression Omnibus (GEO) database served as the source of the GC and T2D datasets. The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were utilized to identify representative genes. In addition, overlapping genes between the representative genes of the two diseases were used for functional enrichment analysis and protein–protein interaction (PPI) network. Next, hub genes were filtered through two machine learning algorithms. Finally, external validation was undertaken with data from the Cancer Genome Atlas (TCGA) database.ResultsA total of 292 and 541 DEGs were obtained from the GC (GSE29272) and T2D (GSE164416) datasets, respectively. In addition, 2,704 and 336 module genes were identified in GC and T2D. Following their intersection, 104 crosstalk genes were identified. Enrichment analysis indicated that “ECM-receptor interaction,” “AGE-RAGE signaling pathway in diabetic complications,” “aging,” and “cellular response to copper ion” were mutual pathways. Through the PPI network, 10 genes were identified as candidate hub genes. Machine learning further selected BGN, VCAN, FN1, FBLN1, COL4A5, COL1A1, and COL6A3 as hub genes.Conclusion“ECM-receptor interaction,” “AGE-RAGE signaling pathway in diabetic complications,” “aging,” and “cellular response to copper ion” were revealed as possible crosstalk mechanisms. BGN, VCAN, FN1, FBLN1, COL4A5, COL1A1, and COL6A3 were identified as shared genes and potential therapeutic targets for people suffering from GC and T2D.

Abstract Background N7-methylguanosine (m7G) is one of the most conserved modifications in nucleosides impacting mRNA export, splicing, and translation. However, the precise function and molecular mechanism of internal mRNA m7G methylation in adult hippocampal neurogenesis and neurogenesis-related Alzheimer’s disease (AD) remain unknown. Results We profiled the dynamic Mettl1/Wdr4 expressions and m7G modification during neuronal differentiation of neural stem cells (NSCs) in vitro and in vivo. Adult hippocampal neurogenesis and its molecular mechanisms were examined by morphology, biochemical methods and biological sequencing. The translation efficiency of mRNA was detected by polysome profiling. The stability of Sptbn2 mRNA was constructed by RNA stability assay. APPswe/PS1ΔE9 (APP/PS1) double transgenic mice were used as model of AD. Morris water maze was used to detect the cognitive function. Methods We found that m7G methyltransferase complex Mettl1/Wdr4 as well as m7G was significantly elevated in neurons. Functionally, silencing Mettl1 in neural stem cells (NSCs) markedly decreased m7G modification, neuronal genesis and proliferation in addition to increasing gliogenesis, while forced expression of Mettl1 facilitated neuronal differentiation and proliferation. Mechanistically, the m7G modification of Sptbn2 mRNA by Mettl1 enhanced its stability and translation, which promoted neurogenesis. Importantly, genetic defciency of Mettl1 reduced hippocampal neurogenesis and spatial memory in the adult mice. Furthermore, Mettl1 overexpression in the hippocampus of APP/PS1 mice rescued neurogenesis and behavioral defects. Conclusion Our findings unravel the pivotal role of internal mRNA m7G modification in Sptbn2-mediated neurogenesis, and highlight Mettl3 regulation of neurogenesis as a novel therapeutic target in AD treatment.

Abstract Background Diabetic foot ulcers (DFUs) represent a significant foot-related concern for patients with multiple co-morbidities, and surgical intervention is often employed. Notably, peripheral nerve block anesthesia (PNB) has emerged as a new approach for the surgical management of DFUs, providing sustained hemodynamic stability and superior postoperative pain control compared to general anesthesia (GEA). Methods The present study utilized a retrospective analysis of hospitalized patients who met the inclusion criteria for DFUs over a period of 7 years. Patients were categorized into two groups based on the type of anesthesia employed during the procedure: GEA or PNB. Extensive patient information was gathered and analyzed, such as demographics, intraoperative hemodynamic parameters, numeric rating scale (NRS) scores, and healing outcomes. The preliminary results assessed in this study were intraoperative hemodynamic stability and postoperative analgesic efficacy. Results During the study period, 117 patients received surgical therapy based on GEA, while 145 patients received PNB. Notably, the mean intraoperative blood pressure was significantly lower in the GEA group, and this difference remained statistically significant even after Bonferroni adjustment using linear mixed models. Additionally, the frequency of hypotensive episodes was higher in the GEA group (P

Wastewater treatment plants (WWTP) are important sources of aerosol-derived dissolved organic matter (ADOM) which may threaten human health via the respiratory system. In this study, aerosols were sampled from a typical WWTP to explore the chemical molecular diversity, molecular ecological network, and potential toxicities of the ADOM in the aerosols. The high fluorescence index (>1.9) and biological index (0.66–1.17) indicated the strong autogenous microbial source characteristics of the ADOM in the WWTP. DOM and microbes in the wastewater were aerosolized due to strong agitation and bubbling in the treatment processes, and contributed to 74 % and 75 %, respectively, of the ADOM and microbes in the aerosols. The ADOM was mainly composed of CHO and CHOS accounting for 35 % and 29 % of the total number of molecules, respectively, with lignin-like (69 %) as the major constituent. 49 % of the ADOM transformations were thermodynamically limited, and intragroup transformations were easier than intergroup transformations. Bacteria in the aerosols involved in ADOM transformations exhibited both cooperative and divergent behaviors and tended to transform carbohydrate-like and amino sugar/protein-like into recalcitrant lignin-like. The microbial compositions were affected by atmosphere temperature and humidity indirectly by modulating the properties of ADOM. Tannin-like, lignin-like, and unsaturated hydrocarbon-like molecules in the ADOM were primary toxicity contributors, facilitating the expression of inflammatory factors IL-β (2.2–5.4 folds), TNF-α (3.5–7.0 folds), and IL-6 (3.5–11.2 folds), respectively.

Targeted drug therapy plays an important role in the clinical application of non-small cell lung cancer, especially adenocarcinoma. However, for patients with advanced disease, drug resistance after targeted therapy, unclear target, and other reasons that cannot or do not want surgery, the combination of chemotherapy, radiotherapy, immunity, etc. is often used. The synergistic effect of targeted drugs and radiotherapy in non-small cell lung cancer has shown good clinical efficacy. This article reviews the clinical progress of targeted drug therapy combined with radiotherapy in advanced non-small cell lung cancer in recent years, in order to provide new ideas for further clinical research of this treatment mode.

The molecular weight is an important indicator for assessing the aging of polymers. However, existing methods for characterizing the molecular weight of polymers involve complex procedures and destructive tests. Therefore, efficient, rapid, and non-destructive testing methods would be a key development in material degradability evaluation. In this paper, we studied the thermo-oxidative aging process of polybutylene adipate terephthalate (PBAT) using a low-field nuclear magnetic resonance (LF-NMR) analysis method. The degradation mechanism of PBAT during thermo-oxidative aging is characterized by its low-field nuclear magnetic resonance decay curve and inversion curve. A two-component LF-NMR fitting analysis reveals that the thermo-oxidative degradation of PBAT conforms to a random fracture mechanism. Furthermore, a correlation between number average molecular weight and LF-NMR relaxation time during thermo-oxidative degradation of PBAT was constructed, with a correlation coefficient R2 greater than 0.97. The error between the correlation equation used in the molecular weight detection of PBAT and the actual test is less than 10%, indicating that it is feasible and reliable to characterize the number average molecular weight of materials by applying the LF-NMR relaxation time.

Abstract To analyze the morphology of paired fibula and mandible aiming to choose optimal fibular segments for mandibular reconstruction in a Chinses population. A total of 118 cases of paired mandible and fibula was collected. All patients were received preoperative cone beam CT (CBCT) scans for mandibular evaluation and CT-angiographical (CTA) examination of the bilateral lower legs, respectively. The cross-sectional morphological differences between proximal (Side P), middle (Side M) and distal (Side D) segments of fibula and anterior, premolar and molar areas of mandible were compared. The most frequent cross-sectional shape at Side D, Side M and Side P portion of fibula was circular (75.4%), triangular (67.8%) and circular (49.2%), respectively. In anterior, premolar and molar areas of mandible, the most of the cross-section was s-shape (90.82%), straight (83.64%) and oblique (91.89%), respectively. The height and width of upper one third (W1) at Side M were significantly larger than those of Side D and Side P (p

Abstract This study mainly studied sensory and metabolite migration from the skin to the soup in the boiling process of tilapia skin using content analysis, electronic nose technique, electronic tongue technique, and metabolomics technique based on ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry and gas chromatography-time-of-flight-mass spectrometry. The content changes, flavor changes, taste changes, metabolite numbers and differential metabolite numbers for both tilapia skin and soup mainly occurred in the initial 30 min. Moreover, the initial 10 min was the key period for the metabolite changes in the boiling process. Further, the differential metabolites in these three periods (0–10, 10–30, and 30–60 min) were identified to show the metabolites migration process. Six (adenine, gingerol, terephthalic acid, vanillin, pentanenitrile, and 2-pyrrolidinonede) and seven (butyramide, lysope(0:0/20:4(5z,8z,11z,14z)), lysope(22:6(4z,7z,10z,13z,16z,19z)/0:0), linoleic acid, N-acetylneuraminic acid, L-threose, and benzoin) chemicals were screened out in the differential metabolites of tilapia skin and soup, respectively, with Variable Importance in the Projection of >1 and p value of

Recent HIV-1 vaccine development has centered on "near native" soluble envelope glycoprotein (Env) trimers that are artificially stabilized laterally (between protomers) and apically (between gp120 and gp41). These mutations have been leveraged for use in membrane-expressed Env mRNA vaccines, although their effects in this context are unclear. To address this question, we used virus-like particle (VLP) produced in 293T cells. Uncleaved (UNC) trimers were laterally unstable upon gentle lysis from membranes. However, gp120/gp41 processing improved lateral stability. Due to inefficient gp120/gp41 processing, UNC is incorporated into VLPs. A linker between gp120 and gp41 neither improved trimer stability nor its antigenic profile. An artificially introduced enterokinase cleavage site allowed post-expression gp120/gp41 processing, concomitantly increasing trimer stability. Gp41 N-helix mutations I559P and NT1-5 imparted lateral trimer stability, but also reduced gp120/gp41 processing and/or impacted V2 apex and interface NAb binding. I559P consistently reduced recognition by HIV+ human plasmas, further supporting antigenic differences. Mutations in the gp120 bridging sheet failed to stabilize membrane trimers in a pre-fusion conformation, and also reduced gp120/gp41 processing and exposed non-neutralizing epitopes. Reduced glycan maturation and increased sequon skipping were common side effects of these mutations. In some cases, this may be due to increased rigidity which limits access to glycan processing enzymes. In contrast, viral gp120 did not show glycan skipping. A second, minor species of high mannose gp160 was unaffected by any mutations and instead bypasses normal folding and glycan maturation. Including the full gp41 cytoplasmic tail led to markedly reduced gp120/gp41 processing and greatly increased the proportion of high mannose gp160. Remarkably, monoclonal antibodies were unable to bind to this high mannose gp160 in native protein gels. Overall, our findings suggest caution in leveraging stabilizing mutations in nucleic acid-based immunogens to ensure they impart valuable membrane trimer phenotypes for vaccine use.

Objective: The aim of this study was to compare the variances in-game loads exhibited by Chinese women’s 3 × 3 basketball team across different stages of the preparation cycle for the Tokyo Olympic Games, and to summarize the fundamental regulations governing Chinese women’s 3 × 3 basketball training and games, in order to establish a theoretical research foundation for the team’s new preparation cycle.Methods: This study measured load-related data during the preparation and main competition periods of the 2019–2021 Tokyo Olympics, from April to August 2019 and from April to June 2021. The aim was to compare the changes and differences in a load of competition during different stages and to explore patterns of load changes during the preparation period. This study used wearable devices authorized by FIFA and NBA, along with the Catapult GPS performance monitoring system from Australia (Catapult&Polar Team) as instruments for collecting sports load data. The OptimEye S5 device was worn around the athlete’s neck to collect data prior to the game, while the Open Field™ system was utilized for data editing and report generation post-game.Results: Compared to the primary competition load during the 2019 preparation period, the 2021 preparation period exhibited significant increases and decreases (p < 0.05) in competition load, high-intensity load, the number of explosive moves, the number of high-intensity acceleration, several changes to the left and right, and the number of explosive jumps. During the 2021 preparation period, the mean heart rate, mean heart rate percentage, and mean speed of the race demonstrated significant decreases in comparison to the race during the 2019 preparation period (p < 0.05). Throughout the training period spanning from 2019 to 2021, no significant differences were observed in running distance and maximum speed (p > 0.05).Conclusion: The findings of this study reveal that the national training team has fostered positive adaptive changes in athletes, resulting in a significant enhancement in both load and sports performance science data during competition from 2019 to 2021.

This work studied the physicochemical properties and odor profiles of tilapia muscles after exposure to four types of thermal processing methods: microwaving, roasting, boiling, or steaming. The effect of thermal processing on textural properties followed a pH–water state–water content–tissue microstructure–mass loss–textural properties route, expressed in the following manner: microwaving > roasting > steaming ≈ boiling. After processing, muscle pH increased from 6.59 ± 0.10 to 6.73 ± 0.04–7.01 ± 0.06, and hardness changed from 1468.49 ± 180.77 g to 452.76 ± 46.94–10723.66 ± 2898.46 g. Gas chromatography-based E-nose analysis confirmed that these methods had significant odor fingerprint effects on the tilapia muscles. Finally, the combined analysis of headspace solid-phase microextraction–gas chromatography–mass spectrometry, statistical MetaboAnalyst, and odor activity value showed that the microwaved, roasted, steamed, and boiled tilapia muscles had, respectively, three (hexanal, nonanal, and decanal), four (2-methyl-butanal, 3-methyl-butanal, decanal, and trimethylamine), one (2-methyl-butanal), and one (decanal) relatively important volatile compounds.

Hematite as a catalyst for photoelectrochemical water splitting offers huge potential, due to its high chemical stability, great abundance, and low cost. However, the low water oxidation kinetics and poor charge transportation have hindered progress towards the manufacture of practical water splitting devices. To tackle these problems, a visible light responsive metal-organic framework (MOF) polyhedral zeolitic imidazolate (ZIF-67), and optimised plasmonic Ag nanorods were incorporated into hematite nanostructures to form a three-component heterojunction photoelectrode. The designed photoanode showed dramatically improved light harvesting in the visible range and enhanced charge transport. A mechanistic investigation allowed the deconvolution of the enhanced performance pathways. First, the Hematite@ZIF-67 core-shell p-n junction enables facile charge carrier transfer between ZIF-67 and hematite. In addition, ZIF-67 also provides active sites for water oxidation and boosts surface oxygen evolution reaction (OER) kinetics. Guided by finite-difference time-domain (FDTD) modelling, Ag nanorods with optimised aspect ratio were incorporated between ZIF-67 and hematite. The Ag nanorods facilitate broadband light absorption and surface charge injection, induced by near-field excitation enhancement and plasmonic resonance energy transfer (PRET) pathways. The design and addition of ZIF-67 and Ag nanorods result in superior performance for a hematite-based photoanode for photoelectrochemical (PEC) water oxidation.

The Gly-Asp-Ser-Leu (GDSL)-type esterase/lipase proteins (GELP) are one of the most important families of lipolytic enzymes and play prominent roles in seed germination and early seedling establishment through mobilizing the lipids stored in seeds. However, there are no comprehensive studies systematically investigating the GELP gene family in Brassica napus (BnGELP), and their biological significance to these physiological processes are far from understood. In the present study, a total of 240 BnGELP genes were identified in B. napus cultivar “Zhongshuang 11” (ZS11), which is nearly 2.3-fold more GELP genes than in Arabidopsis thaliana. The BnGELP genes clustered into 5 clades based on phylogenetic analysis. Ten BnGELPs were identified through zymogram analysis of esterase activity followed by mass spectrometry, among which five clustered into the clade 5. Gene and protein architecture, gene expression, and cis-element analyses of BnGELP genes in clade 5 suggested that they may play different roles in different tissues and in response to different abiotic stresses. BnGELP99 and BnGELP159 were slightly induced by cold, which may be attributed to two low-temperature responsive cis-acting regulatory elements present in their promoters. An increased activity of esterase isozymes by cold was also observed, which may reflect other cold inducible esterases/lipases in addition to the ten identified BnGELPs. This study provides a systemic view of the BnGELP gene family and offers a strategy for researchers to identify candidate esterase/lipase genes responsible for lipid mobilization during seed germination and early seedling establishment.

In this work, octenyl succinic anhydride (OSA) chemical modification with surfactant physical modification was combined to modify bovine bone gelatin (BBG) for emulsion stabilization at pH 6.0 (to simulate acidic food environment). OSA modification decreased the β-sheet percentage and increased β-turn percentage of BBG. Further, the combination of OSA modification with surfactant physical modification had obvious and different effects on the emulsifying properties of BBG. The creaming stability of gelatin/surfactant-stabilized emulsions was dependent on gelatin structure, surfactant type, and preparation pH. The emulsions stabilized by OBBG/Span 80 and OBBG/soybean lecithin (only blurry creaming at day 28) had significantly better creaming stability than other emulsions. These results demonstrated that the combination of OSA modification with surfactant modification could be applied to improve the emulsifying properties of BBG.

Abstract In this work, lipid profile migration from muscle to juice during the tilapia muscle steaming process was revealed by a transactional analysis of data from ultra-high-performance liquid chromatography coupled with Q Exactive (UHPLC-QE) Orbitrap mass spectrometry (MS) and lipidomics. Firstly, the lipids in tilapia muscles and juices at different steaming time points were extracted and examined by UHPLC-QE Orbitrap mass spectrometry. Secondly, a transactional analysis procedure was developed to analyze the data from UHPLC-QE Orbitrap MS and lipidomics. Finally, the corrected lipidomics data and the normalized MS data were used for lipid migration analysis. The results suggested that the transactional analysis procedure was efficient to significantly decrease UHPLC-QE Orbitrap MS workloads and delete the false-positive data (22.4–36.7%) in lipidomics data, which compensated the disadvantages of the current lipidomics method. The lipid changes could be disappearance, full migration into juice, appearance in juice, appearance in muscle, appearance in both muscle and juice, and retention in the muscle. Moreover, the results showed 9 (compared with 52), 5 (compared with 116), and 10 (compared with 178) of lipid class (compared with individual lipid) variables showed significant differences among the different steaming times (0, 10, 30, and 60 min) in all the muscles, juices, and muscle-juice systems, respectively. These results showed significant lipid profile migration from muscle to juice during the tilapia steaming process.

The exploration of deodorization is important for the application of gelatin in food industry. In this work, the effect of β-cyclodextrin (β-CD) deodorization on the volatile chemicals and functional properties of three types of gelatins (commercial porcine skin gelatin, cold water fish skin gelatin, and Chinese longsnout catfish skin gelatin) were studied. The results suggested the odors of commercial gelatins were significantly less than home-extracted gelatins. The β-CD deodorization efficiency was dependent on both β-CD concentration and volatile chemical. (E)-2-Octenal (C8H14O), 1-octen-3-ol (C8H16O), 2-pentyl-furan (C9H14O), and hentriacontane (C17H36) could be deodorized at low β-CD concentration (even at 2 mg/mL). The best β-CD deodorization concentration for 66.7 mg/mL of Chinese longsnout catfish skin gelatin was 30 mg/mL. β-CD addition could not change the gel forming ability and emulsion activity of gelatins, whereas it had different and concentration-dependent effects on the emulsion stability of gelatins. β-CD addition had no obvious effects on the droplet sizes, droplet coalescence and liquid-gel transition behaviors, but had different effects on the creaming of the emulsions stabilized by three types of gelatins. The encapsulation of β-carotene did not significantly change the droplet trimodal size distribution and liquid-gel transition of fish oil-loaded emulsions. However, β-carotene might delay the droplet coalescence. The creaming stability of β-carotene/fish oil-loaded gelatin/β-CD-stabilized emulsions was dependent on the gelatins, β-CD, and β-carotene. Finally, the β-carotene retention in the emulsions was dependent not on β-CD addition but on the nature of the gelatins. These results provided useful information to understand the molecular deodorization behaviors and explore the deodorization of emulsifiers for food emulsions.

Abstract Background Research has confirmed the importance of workplace social capital in the nursing workforce. Integration of the empirical evidence about nurses’ workplace social capital into a scientific collection can provide a comprehensive presentation of this concept. This scientific collection can be a conduit for further research and advancement of nursing management and leadership. The purpose of this paper, therefore, is to discuss the process of developing a conceptual model of nurses’ workplace social capital, an effective and concise approach to illustrate a scientific phenomenon. Methods The model of nurses’ workplace social capital was developed following Walker and Avant’s strategy of theory synthesis. Empirical evidence relevant to nurses’ workplace social capital was synthesized by systematically examining the existing literature. PubMed, CINAHL, Web of Science and Google Scholar were searched periodically from October 2017 to July 2020. Results Our proposed conceptual model lays out the determinants and outcomes of nurses’ workplace social capital and specifies the relational statements among these concepts. Nurses’ workplace social capital is influenced by the organizational and individual determinants shaped by multiple layers of sub-concepts. The development and implementation of nurses’ workplace social capital has three themes of consequences: 1) nurses’ outcomes; 2) patients’ outcomes; and 3) organizational outcomes. All the concepts and statements have been organized and aligned with the principles of “inventory of determinants or results” and “theoretical blocks”. Conclusion Our theoretical synthesis offers a comprehensive picture of the current knowledge of nurses’ workplace social capital. Efforts should be dedicated to evaluating, revising, and revamping this newly developed model based on future empirical evidence. Our synthesized conceptual model is the segue to more comprehensive studies about nurses’ workplace social capital. Interventional programs for the development of social capital can be structured based on the identified determinants.

Abstract Background Danon disease (DD) is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and mental retardation. It is caused by a defect in the lysosomal-associated membrane protein-2 (LAMP2) gene, which leads to the formation of autophagic vacuoles containing glycogen granule deposits in skeletal and cardiac muscle fibers. So far, more than 50 different mutations in LAMP2 have been identified. Case presentation Here, we report an 18-year-old male patient who was hospitalized for heart failure. Biopsy of the left lateral femoral muscle revealed scattered autophagic vacuoles in the muscle fibers with increased glycogen. Next generation sequencing (NGS) was used to detect gene mutations of the proband sample and a novel frameshift mutation (c.1052delG) has been identified in exon 8 of LAMP2, which leads to truncation of the protein. Conclusion We found a novel frameshift mutation, a hemizygous mutation (c.1052delG) in exon 8 of LAMP2, identified as presenting the hypertrophic cardiomyopathy (HCM) phenotype. Genetic analysis is the gold standard for the diagnosis of DD and is essential to determine appropriate treatment strategies and to confirm the genetic risk of family members.

Abstract Background To evaluate the predictive value of the index of microcirculatory resistance (IMR) for long-term cardiac systolic function after primary percutaneous coronary intervention (pPCI) in patients with acute anterior wall ST-segment elevation myocardial infarction (STEMI). Methods A total of 53 acute anterior wall STEMI patients were included and followed up within 1-year. IMR was measured to evaluate the immediate intraoperative reperfusion. IMR > 40 U was defined as the high IMR group and ≤ 40 U was defined as the low IMR group. Left ventricular ejection fraction (LVEF) was measured by echocardiography at 24 h, 1 month, 3 months, and 1 year after PCI to analyze the correlation between IMR and cardiac systolic function. Heart failure was estimated according to classification within one year. Results The ratio of TMPG (TIMI myocardial perfusion grade) 3 (85.7% vs. 52%, p = 0.015) and STR (ST-segment resolution) > 70% (82.1% vs. 48%, p = 0.019) were significantly higher in the low IMR group. The LVEF in the low IMR group was significantly higher than that in the high IMR group at 3 months (43.06 ± 2.63% vs. 40.20 ± 2.67%, p

Abstract Background Several large clinical trials have confirmed the cardioprotective role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes. However, whether empagliflozin, as an SGLT2i, could alleviate atherosclerosis progression in non-diabetic states remain unknown. Methods ApoE-/- mice were fed a Western diet for 12 weeks to induce atherosclerosis. On the 7th week, a group of mice were treated with drinking water containing empagliflozin (10 mg/kg/day), while another group was given normal water. At the 12th week, the whole aortas of each group were harvested. Oil Red O, HE and Movat staining were performed for atherosclerotic lesion area and size. Mouse serum lipid profiles (total cholesterol [TC], triglyceride [TG], low-density lipoprotein-c [LDL], and high-density lipoprotein-c [HDL]), systemic inflammation levels (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) components and sympathetic activity (norepinephrine and neuropeptide Y) indicators were measured by ELISA. Results Empagliflozin reduced the atherosclerotic lesion burden (-8.6 %, P = 0.004) at aortic root in ApoE-/- mice. In addition, empagliflozin decreased body weight (-3.27 g, P = 0.002), lipid profiles (TC: [-15.3 mmol/L, P = 0.011]; TG: [-2.4 mmol/L, P

Abstract Background Immune escape is an immunological mechanism underlying tumorigenesis, and T cells play an important role in this process. In this study, immune-related genes were evaluated in tumor-infiltrating CD4+ and CD8+ T cells in colon cancer. Methods ESTIMATE was used to calculate stromal and immune scores for tumor datasets downloaded from The Cancer Genome Atlas–Colon Cancer (COAD). Differentially expressed genes (DEGs) between samples with high and low stromal and immune scores were screened, followed by a functional enrichment analysis of the overlapping DEGs. The DEGs related to CD4+ and the CD8+ T cells were then screened. Predicted miRNA–mRNA and lncRNA–miRNA pairs were used to construct a competing endogenous RNA (ceRNA) network. Furthermore, chemical–gene interactions were predicted for genes in the ceRNA network. Kaplan–Meier survival curves were also plotted. Results In total, 83 stromal-related DEGs (5 up-regulated and 78 down-regulated) and 1270 immune-related DEGs (807 up-regulated and 293 down-regulated genes) were detected. The 79 overlapping DEGs were enriched for 39 biological process terms. Furthermore, 79 CD4+ T cell-related genes and 8 CD8+ T cell-related genes, such as ELK3, were screened. Additionally, ADAD1 and DLG3, related to CD4+ T cells, were significantly associated with the prognosis of patients with colon cancer. The chr22-38_28785274–29,006,793.1–miR-106a-5p-DDHD1 and chr22-38_28785274–29,006,793.1–miR-4319-GRHL1 axes obtained from CD4+ and CD8+ T cell-related ceRNAs were identified as candidates for further studies. Conclusion ELK3 is a candidate immune-related gene in colon cancer. The chr22-38_28785274–29,006,793.1–miR-106a-5p-DDHD1 and chr22-38_28785274–29,006,793.1–miR-4319-GRHL1 axes may be related to CD4+ and CD8+ T cell infiltration in colon cancer.

BackgroundInhibition of sympathetic activity and renin–angiotensin system with renal denervation (RDN) was proved to be effective in managing refractory hypertension, and improving left ventricular (LV) performance in chronic heart failure. The inhibition of sustained sympathetic activation prevents or delays the development of cardiac fibrosis and dysfunction that occurs after myocardial infarction and ischemia–reperfusion (I/R) injury. The translational efficiency of RDN remains to be defined in preclinical animal studies.ObjectivesThis study investigated the therapeutic role of RDN in adverse remodeling and intramyocardial inflammation in myocardial ischemia–reperfusion (MI/R) injury.MethodsHerein, 15 minipigs were subjected to 90-min percutaneous occlusion of the left anterior descending artery followed by reperfusion. Eight animals received simultaneous RDN using catheter-based radiofrequency ablation (MI/R-RDN). Cardiac function and infarct volume were measured in vivo, followed by histological and biochemical analyses.ResultsThe infarct volume in I/R-RDN pigs reduced at 30 days postreperfusion, compared to I/R-Sham animals. The levels of catecholamine and cytokines in the serum, kidney cortex, the border, and infarcted regions of the heart were significantly reduced in I/R-RDN group. Moreover, the gene expression of collagen and the protein expression of adrenergic receptor beta 1 in heart were also decreased in I/R-RDN mice. Additionally, RDN therapy alleviated myocardial oxidative stress.ConclusionRDN is an effective therapeutic strategy for counteracting postreperfusion myocardial injury and dysfunction, and the application of RDN holds promising prospects in clinical practice.

A facile hydrothermal process has been developed to synthesize the α-Fe2O3 nanowire arrays with a preferential growth orientation along the [110] direction. The W/α-Fe2O3/FTO memory device with the nonvolatile resistive switching behavior has been achieved. The resistance ratio (RHRS/RLRS) of the W/α-Fe2O3/FTO memory device exceeds two orders of magnitude, which can be preserved for more than 103s without obvious decline. Furthermore, the carrier transport properties of the W/α-Fe2O3/FTO memory device are dominated by the Ohmic conduction mechanism in the low resistance state and trap-controlled space-charge-limited current conduction mechanism in the high resistance state, respectively. The partial formation and rupture of conducting nanofilaments modified by the intrinsic oxygen vacancies have been suggested to be responsible for the nonvolatile resistive switching behavior of the W/α-Fe2O3/FTO memory device. This work suggests that the as-prepared α-Fe2O3 nanowire-based W/α-Fe2O3/FTO memory device may be a potential candidate for applications in the next-generation nonvolatile memory devices.

In this paper, the effect of nitrogen annealing on the resistive switching characteristics of the rutile TiO2 nanowire-based W/TiO2/FTO memory device is analyzed. The W/TiO2/FTO memory device exhibits a nonvolatile bipolar resistive switching behavior with a high resistance ratio (RHRS/RLRS) of about two orders of magnitude. The conduction behaviors of the W/TiO2/FTO memory device are attributed to the Ohmic conduction mechanism and the Schottky emission in the low resistance state and the high resistance state, respectively. Furthermore, the RHRS/RLRS of the W/TiO2/FTO memory device is obviously increased from about two orders of magnitude to three orders of magnitude after the rapid nitrogen annealing treatment. In addition, the change in the W/TiO2 Schottky barrier depletion layer thickness and barrier height modified by the oxygen vacancies at the W/TiO2 interface is suggested to be responsible for the resistive switching characteristics of the W/TiO2/FTO memory device. This work demonstrates the potential applications of the rutile TiO2 nanowire-based W/TiO2/FTO memory device for high-density data storage in nonvolatile memory devices.

Brassica juncea is an economically important vegetable and oilseed crop. The MYB transcription factor superfamily is one of the largest transcription factor families in plants, and plays crucial roles in regulating the expression of key genes involved in a variety of physiological processes. However, a systematic analysis of the MYB transcription factor genes in Brassica juncea (BjMYB) has not been performed. In this study, a total of 502 BjMYB superfamily transcription factor genes were identified, including 23 1R-MYBs, 388 R2R3-MYBs, 16 3R-MYBs, 4 4R-MYBs, 7 atypical MYBs, and 64 MYB-CCs, which is approximately 2.4-fold larger than that of AtMYBs. Phylogenetic relationship analysis revealed that the MYB-CC subfamily consists of 64 BjMYB-CC genes. The expression pattern of members of PHL2 subclade homologous genes in Brassica juncea (BjPHL2) after Botrytis cinerea infection were determined, and BjPHL2a was isolated from a yeast one-hybrid screen with the promoter of BjCHI1 as bait. BjPHL2a was found to localize mainly in the nucleus of plant cells. An EMSA assay confirmed that BjPHL2a binds to the Wbl-4 element of BjCHI1. Transiently expressed BjPHL2a activates expression of the GUS reporter system driven by a BjCHI1 mini-promoter in tobacco (Nicotiana benthamiana) leaves. Taken together, our data provide a comprehensive evaluation of BjMYBs and show that BjPHL2a, one of the members of BjMYB-CCs, functions as a transcription activator by interacting with the Wbl-4 element in the promoter of BjCHI1 for targeted gene-inducible expression.

Emotional intelligence plays a crucial role in children's development. It has been shown in previous studies that emotional intelligence not only influences academic performance but also benefits children's social and interpersonal lives. This study proposes a new strategy that integrates dialogical reading with visible thinking routines to develop young children's emotional intelligence. Children's books have been shown to benefit the development of young children's emotional skills. This study builds upon past research by utilizing visible thinking routines during dialogic reading of both children's books and self-made books to create an engaging and comfortable environment for young children to demonstrate and practice their emotional knowledge and skills. A mixed class of sixteen kindergarten and first-grade children, mostly immigrants from Central America, participated in this study. Through classroom observations and monitoring of the children's interactions and performance over time, the intervention was found to develop children's performance in these key areas of emotional intelligence: recognition, expression, regulation, and empathy.

C-H diamond metal-oxide-semiconductor field effect transistors with different structures were fabricated on the same polycrystalline diamond plate. Devices A and B with 25-nm-thick high temperature (300°C) atomic layer deposition grown Al2O3 dielectric have the same source-to-drain distance of 6 μm and different gate length of 2 μm and 6 μm, respectively. Both devices show ultra-high on/off ratio of over 1010 and ultra-low gate leakage of below 10-10 A and continuous measurement stability. Device B with the source/drain-channel interspaces eliminated has achieved an on resistance of 46.20 Ω·mm, which is record low in the reported 6-μm H-diamond MOSFETs with the gate dielectric prepared at high temperature (≥ 300 °C). Meanwhile, device B shows larger drain current in a large portion of the linear region at VGS = -6 V, and a just slightly smaller IDmax compared with device A though its LG is three times of that of device A. A simple model of ID was used to explain the physics behind this phenomenon. In addition, the breakdown voltage is 145 V for device A and 27 V for device B, corresponding to the average breakdown field of about 0.72 MV/cm and 10.8 MV/cm, respectively.

Three-dimensional (3D) modeling is an important topic in computer graphics and computer vision. In recent years, the introduction of consumer-grade depth cameras has resulted in profound advances in 3D modeling. Starting with the basic data structure, this survey reviews the latest developments of 3D modeling based on depth cameras, including research works on camera tracking, 3D object and scene reconstruction, and high-quality texture reconstruction. We also discuss the future work and possible solutions for 3D modeling based on the depth camera. Keywords: 3D Modeling, Depth camera, Camera tracking, Signed distance function, Surfel

Response of nitrogen removal efficiency and microbial interactions to organic pollution has been a major issue in wastewater treatment system. However, the nitrogen removal efficiency and interactions among microbial community under antibiotics press is still unclear. Thus, the effect of sulfamethoxazole (SMX) on nitrogen removal and microbial responses of IVCWs was investigated through recorded the nitrogen removal efficiency before and after adding SMX and random matrix theory (RMT)-based network analysis. Results showed that better NH4+-N removal (>90%) after a long period of operation were achieved in IVCWs, but NO3--N was accumulated. However, nitrate removal rates were significantly increased after long-term exposure (60 d) to 100 μgL−1 SMX (from 27.35% to 35.57%) with relatively high SMX removal (53.50%). Surprisingly, the ammonia nitrogen removal rate (90.07−92.70%) were not significantly affected by SMX in IVCWs. Moreover, the bacterial richness was decreased and the bacterial community structures were altered by the presence of SMX, especially those of nitrogen-transforming microorganisms. Molecular ecological network analysis suggested that SMX had positive influences on denitrifying bacteria interactions but reduced the network complexity and microbial interactions on whole molecular network, and among-module connections were weakened obviously at SMX.

Background: β-Hydroxybutyrate (BHB) is produced by fatty acid oxidation in the liver under the fasting state and confirmed to play a cardioprotective role in ischemia and hypertensive settings. Doxorubicin (DOX) is an effective chemotherapeutic drug, but limited by serious irreversible cardiotoxicity. However, whether BHB can protect from DOX-induced cardiotoxicity remains unknown.Methods and Results: C57BL/6 mice were intraperitoneally injected with DOX to induce cardiac toxicity and intragastrically administered into BHB for treatment. They were randomly divided into three groups, namely a sham group (Sham), a doxorubicin group (DOX), and a doxorubicin+β-Hydroxybutyrate group (DOX + BHB). Echocardiography and pathological staining were performed to evaluate cardiac function and fibrosis. H9c2 cardiomyocyte was treated with DOX or BHB for in vitro experiments. Cell apoptosis and ROS were determined by flow cytometry. BHB significantly restored DOX-induced cardiac function decline and partially prevented cardiac reverse remodeling, characterized by increased cell size and decreased fibrosis. In vitro, BHB treatment decreased cellular injury and apoptosis. Also, BHB alleviated oxidative stress level and increased mitochondrial membrane potential.Conclusion: Our results suggested that BHB could protected from DOX-induced cardiotoxicity by inhibiting cell apoptosis and oxidative stress and maintaining mitochondrial membrane integrity.

The performance of hydrogen-terminated diamond MOSFETs with a large gate–drain interspace (LGD) was analyzed on a polycrystalline diamond sample. A 300 °C atomic layer deposition grown (ALD-grown) HfO2 dielectric (28 nm) was used the gate dielectric and device passivation layer. The HfO2/H-diamond interfacial valence band offset of 1.98 eV was determined by x-ray photoelectron spectroscopy, indicating that the high temperature grown HfO2 dielectric has great potential for accommodating a high density of holes on the H-diamond surface, and the high dielectric constant of HfO2 is also useful for improving the control capability of the gate on the device channel. A breakdown voltage of 657 V was achieved on the device. Baliga’s figure of merit of the device was calculated to be ∼2.0 MW/cm2, which is comparable to that of the H-diamond FETs with Al2O3 dielectrics that are more than 200 nm thick. The HfO2 dielectric shows great potential for use in H-diamond power devices.

Ischemic cerebral infarction represents a significant cause of disability and death worldwide. Caspase-1 is activated by the NLRP3/ASC pathway and inflammasomes, thus triggering pyroptosis, a programmed cell death. In particular, this death is mediated by gasdermin D (GSDMD), which induces secretion of interleukin (IL)-1β and IL-18. Accordingly, inhibition of caspase-1 prevents the development and worsening of multiple neurodegenerative diseases. However, it is not clear whether inhibition of caspase-1 can preserve blood-brain barrier (BBB) integrity following cerebral infarction. This study therefore aimed at understanding the effect of caspase-1 on BBB dysfunction and its underlying mechanisms in permanent middle cerebral artery occlusion (MCAO). Our findings in rat models revealed that expression of caspase-1 was upregulated following MCAO-induced injury in rats. Consequently, pharmacologic inhibition of caspase-1 using vx-765 ameliorated ischemia-induced infarction, neurological deficits, and neuronal injury. Furthermore, inhibition of caspase-1 enhanced the encapsulation rate of pericytes at the ischemic edge, decreased leakage of both Evans Blue (EB) and matrix metalloproteinase (MMP) proteins, and upregulated the levels of tight junctions (TJs) and tissue inhibitors of metalloproteinases (TIMPs) in MCAO-injured rats. This in turn improved the permeability of the BBB. Meanwhile, vx-765 blocked the activation of ischemia-induced pyroptosis and reduced the expression level of inflammatory factors such as caspase-1, NLRP3, ASC, GSDMD, IL-1β, and IL-18. Similarly, vx-765 treatment significantly reduced the expression levels of inflammation-related receptor for advanced glycation end products (RAGE), high-mobility family box 1 (HMGB1), mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB). Evidently, inhibition of caspase-1 significantly improves ischemia-associated BBB permeability and integrity by suppressing pyroptosis activation and the RAGE/MAPK pathway.

ObjectiveThis study aimed to characterize the tumor-infiltrating T cells in moderately differentiated colorectal cancer.MethodsUsing single-cell RNA sequencing data of isolated 1632 T cells from tumor tissue and 1252 T cells from the peripheral blood of CRC patients, unsupervised clustering analysis was performed to identify functionally distinct T cell populations, followed by correlations and ligand-receptor interactions across cell types. Finally, differential analysis of the tumor-infiltrating T cells between colon cancer and rectal cancer were carried out.ResultsA total of eight distinct T cell populations were identified from tumor tissue. Tumor-Treg showed a strong correlation with Th17 cells. CD8+TRM was positively correlated with CD8+IEL. Seven distinct T cell populations were identified from peripheral blood. There was a strong correlation between CD4+TN and CD4+blood-TCM. Colon cancer and rectal cancer showed differences in the composition of tumor-infiltrating T cell populations. Tumor-infiltrating CD8+IEL cells were found in rectal cancer but not in colon cancer, while CD8+ TN cells were found in the peripheral blood of colon cancer but not in that of rectal cancer. A larger number of tumor-infiltrating CD8+ Tex (88.94%) cells were found in the colon cancer than in the rectal cancer (11.06%). The T cells of the colon and rectal cancers showed changes in gene expression pattern.ConclusionsWe characterized the T cell populations in the CRC tumor tissue and peripheral blood.

The prefrontal cortex (PFC) plays a central role in executive functions and inhibitory control over many cognitive behaviors. Dynamic changes in local field potentials (LFPs), such as gamma oscillation, have been hypothesized to be important for attentive behaviors and modulated by local interneurons such as parvalbumin (PV) cells. However, the precise relationships between the firing patterns of PV interneurons and temporal dynamics of PFC activities remains elusive. In this study, by combining in vivo electrophysiological recordings with optogenetics, we investigated the activities of prefrontal PV interneurons and categorized them into three subtypes based on their distinct firing rates under different behavioral states. Interestingly, all the three subtypes of interneurons showed strong phase-locked firing to cortical high frequency oscillations (HFOs), but not to theta or gamma oscillations, despite of behavior states. Moreover, we showed that sustained optogenetic stimulation (over a period of 10 s) of PV interneurons can consequently modulate the activities of local pyramidal neurons. Interestingly, such optogenetic manipulations only showed moderate effects on LFPs in the PFC. We conclude that prefrontal PV interneurons are consist of several subclasses of cells with distinct state-dependent modulation of firing rates, selectively coupled to HFOs.

At present, the drug is still difficult to release completely and quickly only with single stimulation. In order to promote the rapid release of polymeric micelles at tumor site, pH/reduction sensitive polymers (PCT) containing disulfide bonds and orthoester groups were synthesized. The PCT polymers can self-assemble in water and entrap doxorubicin to form drug-loaded micelles (DOX/PCT). In an in vitro drug release experiment, the cumulative release of DOX/PCT micelles in the simulated tumor microenvironment (pH 5.0 with GSH) reached (89.7 ± 11.7)% at 72 h, while it was only (16.7 ± 6.1)% in the normal physiological environment (pH 7.4 without GSH). In addition, pH sensitive DOX loaded micellar system (DOX/PAT) was prepared as a control. Furthermore, compared with DOX/PAT micelles, DOX/PCT micelles showed the stronger cytotoxicity against tumor cells to achieve an effective antitumor effect. After being internalized by clathrin/caveolin-mediated endocytosis and macropinocytosis, DOX/PCT micelles were depolymerized in intercellular acidic and a reductive environment to release DOX rapidly to kill tumor cells. Additionally, DOX/PCT micelles had a better inhibitory effect on tumor growth than DOX/PAT micelles in in vivo antitumor activity studies. Therefore, pH/reduction dual sensitive PCT polymers have great potential to be used as repaid release nanocarriers for intercellular delivery of antitumor drugs.