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Abstract Smoking is an important modifiable factor in the risk of type 2 diabetes. Type 2 diabetes and hypertension overlap in the population. The present study investigated effects of smoking on glucose metabolism under different blood pressure (BP) levels in occupational population. A smoking survey among occupational groups was conducted in 2018. The general linear model was used to analyze the differences of glucose metabolism indexes and BP indexes influenced by different smoking intensity (never 0, mild

Objective Investigating the associations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with all-cause, cardiovascular disease (CVD) and cancer mortality in a large cohort of community-dwelling patients with type 2 diabetes mellitus (T2DM).Design Community-based prospective cohort study conducted between 2013 and 2014.Setting 44 selected townships in Changshu and Huai’an City, Jiangsu province, China.Participants 20340 participants with T2DM were recruited in Jiangsu province, China.Methods We use Cox proportional hazard models to estimate the HR and 95% CIs of associations of serum ALT and AST levels with all-cause and cause-specific mortality. Restricted cubic splines were used to explore the dose-response relationships between ALT and AST levels with mortality.Results ALT and AST levels were inversely associated with CVD mortality, compared with the lowest quintile (Q1), the multivariable HRs of the highest quintile (Q5) was 0.82 (95% CI: 0.66 to 1.01, p for trend=0.022) and 0.78 (95% CI: 0.63 to 0.96, p for trend=0.022), respectively. Furthermore, the HRs for ALT levels in all-cause mortality were 0.90 (95% CI: 0.79 to 1.01, p for trend=0.018), and the HRs for AST levels in cancer mortality were 1.29 (95% CI: 1.02 to 1.63, p for trend=0.023). Stronger inverse effects of ALT and AST levels on all-cause mortality were observed in the older subgroup and in those with dyslipidaemia (all p for interaction

Theta oscillations in the primary visual cortex (VC) have been observed during running tasks, but the mechanism behind their generation is not well understood. Some studies have suggested that theta in the VC is locally generated, while others have proposed that it is volume conducted from the hippocampus. The present study aimed to investigate the relationship between hippocampal and VC LFP dynamics. Analysis of power spectral density revealed that LFP in the VC was similar to that in the hippocampus, but with lower overall magnitude. As running velocity increased, both the power and frequency of theta and its harmonics increased in the VC, similarly to what is observed in the hippocampus. Current source density analysis triggered to theta did not identify distinct current sources and sinks in the VC, supporting the idea that theta in the VC is conducted from the adjacent hippocampus. Phase coupling between theta, its harmonics, and gamma is a notable feature in the hippocampus, particularly in the lacunosum moleculare. While some evidence of coupling between theta and its harmonics in the VC was found, bicoherence estimates did not reveal significant phase coupling between theta and gamma. Similar results were seen in the cross-region bicoherence analysis, where theta showed strong coupling with its harmonics with increasing velocity. Thus, theta oscillations observed in the VC during running tasks are likely due to volume conduction from the hippocampus.

VPS4 series proteins play a crucial role in the endosomal sorting complexes required for the transport (ESCRT) pathway, which is responsible for sorting and trafficking cellular proteins and is involved in various cellular processes, including cytokinesis, membrane repair, and viral budding. VPS4 proteins are ATPases that mediate the final steps of membrane fission and protein sorting as part of the ESCRT machinery. They disassemble ESCRT-III filaments, which are vital for forming multivesicular bodies (MVBs) and the release of intraluminal vesicles (ILVs), ultimately leading to the sorting and degradation of various cellular proteins, including those involved in cancer development and progression. Recent studies have shown a potential relationship between VPS4 series proteins and cancer. Evidence suggests that these proteins may have crucial roles in cancer development and progression. Several experiments have explored the association between VPS4 and different types of cancer, including gastrointestinal and reproductive system tumors, providing insight into the underlying mechanisms. Understanding the structure and function of VPS4 series proteins is critical in assessing their potential role in cancer. The evidence supporting the involvement of VPS4 series proteins in cancer provides a promising avenue for future research and therapeutic development. However, further researches are necessary to fully understand the mechanisms underlying the relationship between VPS4 series proteins and cancer and to develop effective strategies for targeting these proteins in cancer therapy. This article aims to review the structures and functions of VPS4 series proteins and the previous experiments to analyze the relationship between VPS4 series proteins and cancer.

ObjectiveThe aims of this study were to estimate the rates of regular exercise and its trends among the adult population in Jiangsu, from 2010 to 2018, China, and to assess associations with sociodemographic factors.MethodsChronic disease and risk factor surveillance data from adults aged ≥18 years were gathered in Jiangsu Province from 2010 to 2018. Rates of regular exercise were calculated after post-stratification weighting, and time trends were compared among participants with different characteristics, including gender, age, urban–rural region, educational level, occupation, annual household income, body mass index (BMI), baseline self-reported chronic diseases, smoking status, alcohol consumption, and region. Multivariable logistic regression analyses were performed to assess the associations of sociodemographic characteristics with regular exercise.ResultsA total of 33,448 participants aged 54.05 ± 14.62 years and 55.4% female (8,374 in 2010, 8,302 in 2013, 8,372 in 2015, and 8,400 in 2018) were included in this study. The weighted rate of regular exercise was 12.28% (95% confidence interval [CI]: 9.11–15.45%) in 2010 and 21.47% (95% CI, 17.26–25.69%) in 2018, showing an overall increasing trend (P for trend = 0.009). Nevertheless, stratification analysis showed that the regular exercise rate decreased from 33.79% in 2010 to 29.78% in 2018 among retired adults. Significant associations were observed between regular exercise and age >45 years (45–

We have generated an iPSCs line (CTGUi001-A) from dermal fibroblasts of a 16-year-old male Fabry disease patient with a novel GLA gene mutation (c.156C > A) using Sendai virus encoding the four Yamanaka factors OCT4, SOX2, KLF4, and c-MYC. The CTGUi001-A iPSC line displayed typical embryonic stem cell-like morphology, carried the GLA gene mutation, expressed several pluripotent stem cell makers, retained normal karyotype (46, XY) and was capable of forming teratomas containing three germ layers.

We optimized and fabricated an ultra-bend-resistant 4-core simplex cable (SXC) employing 4-core multicore fiber (MCF) suitable for short-reach dense spatial division multiplexing (DSDM) optical transmission in the O-band. The characteristics of transmission loss, macro-bending and cross-talk (XT) between adjacent cores after cabling were firstly clarified. By introducing the trapezoid index and optimizing the cabling process, the maximum values of added XT of 1.17 dB/km due to 10 loops with a bending radius of 6 mm imposed over the 4-core SXC and a macro-bending loss of 0.37 dB/10 turns were, respectively, achieved.P Then, the optical transmission with low bit error rate (BER) was presented using a 100GBASE-LR4 transceiver over the 1.2 km long 4-core SXC. The excellent bending resistance of the 4-core SXC may pave the way for a reduction in space pressure and increase in access density on short-reach optical interconnect (OI) based on DSDM.

Structural basis of V-ATPase regulation by endogenous proteins is unclear. Here, the authors find mEAK7 as an endogenous V-ATPase modulator and determine its structure with V-ATPase, suggesting the potential role of mEAK7 in V-ATPase regulation.

The activation of Sphingosine-1-phosphate receptor 1 (S1PR1) by S1P promotes lymphocyte egress from lymphoid organs, a process critical for immune surveillance and T cell effector activity. Multiple drugs that inhibit S1PR1 function are in use clinically for the treatment of autoimmune diseases. Cluster of Differentiation 69 (CD69) is an endogenous negative regulator of lymphocyte egress that interacts with S1PR1 in cis to facilitate internalization and degradation of the receptor. The mechanism by which CD69 causes S1PR1 internalization has been unclear. Moreover, although there are numerous class A GPCR structures determined with different small molecule agonists bound, it remains unknown whether a transmembrane protein per se can act as a class A GPCR agonist. Here, we present the cryo-EM structure of CD69-bound S1PR1 coupled to the heterotrimeric Gi complex. The transmembrane helix (TM) of one protomer of CD69 homodimer contacts the S1PR1-TM4. This interaction allosterically induces the movement of S1PR1-TMs 5–6, directly activating the receptor to engage the heterotrimeric Gi. Mutations in key residues at the interface affect the interactions between CD69 and S1PR1, as well as reduce the receptor internalization. Thus, our structural findings along with functional analyses demonstrate that CD69 acts in cis as a protein agonist of S1PR1, thereby promoting Gi-dependent S1PR1 internalization, loss of S1P gradient sensing, and inhibition of lymphocyte egress.

BackgroundSerum creatinine is associated with cardiovascular risk and cardiovascular events, however, the relationship between serum creatinine levels and cardiovascular risk is not well established in hypertensive population in Jiangsu Province. We aimed to evaluate the association of serum creatinine levels with traditional cardiovascular risk factors and 10-year cardiovascular risk in a Chinese hypertensive population.MethodsParticipants were patients with hypertension registered and enrolled in health service centers in 5 counties or districts from January 2019 to May 2020 in Jiangsu Province of China followed strict inclusion and exclusion criteria, demographics as well as clinical indicators and disease history and lifestyle were collected. Participants were divided into four groups according to quartiles of serum creatinine levels, then the China-PAR model was used to calculate 10-year cardiovascular risk for each individual.ResultsA total of 9978 participants were enrolled in this study, 4173(41.82%) were males. The blood pressure level and prevalence of dyslipidemia, elderly, current smokers and drinking as well as obesity were higher in the Q4 group than the Q1 group (all P < 0.05). Multivariable logistic regression showed that serum creatinine in the Q4 group compared with that in the Q1 group was positively associated with overweight and obesity (OR=1.432, 95% CI 1.237-1.658, P

Corn straw biochar was used as a carrier to immobilize white rot fungi and the removal performance of immobilized pellets for acid red G (ARG) dye was studied. The results showed that the removal rate of ARG could reach 96.17% under the best preparation conditions of immobilized pellets (3% sodium alginate concentration, 0.7% corn straw biochar, 5% white rot fungus mycelium suspension, 4% CaCl2, and 36 h immobilization time). The orthogonal test results showed that the best combination was the immobilized pellets dosage of 200/100 mL, pH of 4.5, rotation speed of 150 r/min, and initial concentration of 20 mg/L dye at 30 °C. The degradation pathway of ARG by immobilized microspheres was studied by ultraviolet-visible spectrometer, Fourier transform infrared spectroscopy, and liquid chromatography-mass spectrometry. The results showed that ARG was degraded into aniline and 5-(acetamino)-4-hydroxy-3-amino-2,7-naphthalene disulfonic acid. Aniline was further deaminated to form benzene, and benzene was ring opened to form other organic compounds; 5-(acetylamino)-4-hydroxy-3-amino-2,7-naphthalene disulfonic acid was dehydroxylated to form 5-(acetylamino)-3-amino-2,7-naphthalene disulfonic acid. This study shows that the prepared biochar immobilized pellets can be used as an efficient water treatment material to remove ARG dye from wastewater. HIGHLIGHTS The use of biochar as a fungal fixation material not only saved energy, provided an effective solution for the disposal of agricultural waste and conformed to China's concept of waste treatment, but also provided a theoretical research basis for biochar as a fungal fixation material.; The combination of biochar and other materials provided a theoretical basis for the compound fixation fungus treatment dye wastewater.;

Abstract Previous studies reported on the association between physical activity (PA) and cardiovascular diseases (CVDS) among the Western population. However, evidence on the association between different patterns of PA and the risk of CVDS among Chinese population are limited. This study aims to evaluate the association of different PA types and the risk of CVDS in a Chinese adult population. A total of 3568 community residents were recruited from Jiangsu Province of China using a stratified multistage cluster sampling method. The latent class analysis method was employed to identify the types of PA, and the Framingham risk score (FRS) was used to estimate the risk of CVDS within 10 years. Three types of PA were identified: CLASS1 represented participants with high occupational PA and low sedentary PA (32.1% of male, 26.5% of female), ClASS2 represented those engaging in low occupational PA and high leisure-time PA (27.0% of male, 14.2% of female), and CLASS3 represented low leisure-time and high sedentary PA (40.9% of male, 59.3% of female). The average of FRS in males was higher than that in females across PA types. CLASS1 (OR = 0.694, 95%CI 0.553–0.869) and CLASS2 (OR = 0.748, 95%CI 0.573–0.976) were both found to be protective against CVDS in males; however, such associations were not statistically significant among females. Therefore, higher occupational or leisure-time PA appear to be associated with decreased risk of CVDS, while more sedentary behaviors may increase the risk of CVDS, particularly for male Chinese adults.

Abstract Background Glioma is a common malignant brain tumor. The purpose of this study was to investigate the role of the transcription factor SPI1 in glioma. Methods SPI1 expression in glioma was identified using qRT-PCR and Western blotting. Cell proliferation was assessed using the CCK8 assay. Transwell and wound healing assays were utilized to evaluate cell migration. Additionally, cell cycle and apoptosis were detected using flow cytometry. Results We observed that the expression level of SPI1 was up-regulated in glioma tissues, compared to normal tissues. Furthermore, we found that SPI1 is able to promote proliferation and migration of glioma cells in vitro. Flow cytometry results demonstrate that, compared to si-NC cells, si-SPI1 cells stagnated in the G1 phase, and down-regulation of SPI1 expression is able to increase rates of apoptosis. Double luciferase activity and chromatin immunoprecipitation assay results indicated that SPI1 can bind to the promoter sites and promote the proliferation and migration of glioma cells by regulating the expression of oncogenic PAICS. Conclusions Our results suggest that SPI1 can promote proliferation and migration of glioma. Furthermore, SPI1 can be utilized as a potential diagnostic marker and therapeutic target for glioma.

Objective: This study aims to establish an indirect competitive enzyme-linked immunosorbent assay for the detection of amanitin (AMA) in mushroom. Methods: In this study, the hapten was obtained by introducing 6-aminocaproic acid into the carboxyl position of the α-amanotropin molecule through EDC/NHS, and further coupled with different carrier proteins to prepare immunogens and coating antigen. Afterwards, Balb/c mice were immunized with the immunogen to prepare monoclonal antibodies. Based on the obtained antibody, an indirect competitive ELISA method for the detection of amanitin in mushroom was established by optimizing the working concentrations of coating antigen and antibody, coating conditions, blocking conditions, working concentrations of enzyme labeled secondary antibody and incubation time. Finally, the sensitivity, recovery rate, intra batch and inter batch variation of the established method were evaluated. Results: The molecular weight of the synthesized hapten in this study was 1033.12, and the coupling ratio of the immunogen identified by MALDI-TOF was about 10.03. Based on hybridoma technology, the IC50 of the mouse monoclonal antibody 13H4 was 1.91 μg/L. Based on the obtained monoclonal antibody, the detection limit of the established ic-ELISA method for amanitin in mushroom was 0.88 μg/kg, the recovery rate was 85.66%~113.05%, the intra-assay coefficient of variation was 5.35%~9.54%, and the inter-assay coefficient of variation was less than 15%. Conclusion: The ic-ELISA method established in this study had high accuracy, precision, sensitivity, and stable performance. It provided a simple, reliable and rapid detection method for the analysis of the toxicogen of sudden mushroom poisoning.

Abstract Background Decreased physical activity had been reported to be a common causal and modifiable risk factor for major vascular events. However, the relationship of physical activity and sedentary leisure time with carotid atherosclerosis in population with high risk for cardiovascular diseases (CVDs) is still inconclusive. We aimed to evaluate the association of physical activity and sedentary leisure time with the risk of carotid atherosclerosis, and investigate any possible effect modifiers in population with high risk for CVDs. Methods The study population was drawn from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project-Jiangsu project, which is a population-based screening project that included permanent residents aged 35-75 years from 6 surveillance cities in Jiangsu Province. Linear regression models were used to evaluate the association of physical activity and sedentary leisure time with carotid intima-media thickness (CIMT). The risks of abnormal carotid artery and carotid plaque (CP) were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. Results Overall, a total of 10,920 participants were enrolled in the final analysis. There was a significant inverse association of physical activity level with CIMT (per SD increase: β=-0.0103; 95%CI: -0.0154, -0.0053). The risk of abnormal carotid artery and CP decreased significantly with the increase of physical activity level (per SD increase: OR=0.908, 95%CI: 0.869-0.948; OR=0.900, 95%CI: 0.857-0.945, respectively). When physical activity level was categorized as quartiles, a significantly lower risk of abnormal carotid artery and CP was found in quartiles 2-4 with quartile 1 as reference (P

Abstract The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

A 240 $\times$ 160 single-photon avalanche diode (SPAD) sensor integrated with a 3D-stacked 65nm/65nm CMOS technology is reported for direct time-of-flight (dToF) 3D imaging in mobile devices. The top tier is occupied by backside illuminated SPADs with 16 $\mu {\mathrm{ m}}$ pitch and 49.7% fill-factor. The SPADS consists of multiple 16 $\times$ 16 SPADs top groups, in which each of 8 $\times$ 8 SPADs sub-group shares a 10-bit, 97.65ps and 100ns range time-to-digital converter (TDC) in a quad-partition rolling shutter mode. During the exposure of each rolling stage, partial histogramming readout (PHR) approach is implemented to compress photon events to in-pixel histograms. Since the fine histograms is incomplete, for the first time we propose histogram distortion correction (HDC) algorithm to solve the linearity discontinuity at the coarse bin edges. With this algorithm, depth measurement up to 9.5m achieves an accuracy of 1cm and precision of 9mm in office lighting condition. Outdoor measurement with 10 klux sunlight achieves a maximum distance detection of 4m at 20 fps, using a VCSEL laser with the average power of 90 mW and peak power of 15 W.

Abstract Background Sleep characteristics associated with dementia are poorly defined and whether their associations vary by demographics and APOE genotype among older adults are unclear. Methods This population-based cross-sectional study included 4742 participants (age ≥ 65 years, 57.1% women) living in rural China. Sleep parameters were measured using the self-rated questionnaires of the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, and the National Institute on Aging-Alzheimer’s Association criteria for Alzheimer’s disease (AD). Data were analysed using multiple logistic and general linear regression models. Results Dementia was diagnosed in 173 participants (115 with AD). Multivariable-adjusted odds ratio (OR) of dementia was 1.71 (95%CI, 1.07-2.72) for sleep duration ≤4 h/night (vs. > 6-8 h/night), 0.76 (0.49-1.18) for > 4-6 h/night, 1.63 (1.05-2.55) for > 8 h/night, 1.11 (1.03-1.20) for lower sleep efficiency (per 10% decrease), and 1.85 (1.19-2.89) for excessive daytime sleepiness. Very short sleep duration (≤4 h/night), lower sleep efficiency, and excessive daytime sleepiness were significantly associated with being diagnosed with AD (multivariable-adjusted OR range = 1.12-2.07; p

Abstract Excessive discharge of phosphorus into the water bodies is the key factor to cause eutrophication. The fruit and vegetable wastewater contains large amounts of phosphorus, and it may be directly discharged into water bodies, which has a great burden on the municipal sewage pipe network. Therefore, coagulation was used to remove phosphorus, recovered the phosphorus from the wastewater into the precipitate, and then the precipitate was pyrolyzed as an efficient adsorbent for phosphate removal. By comparing the adsorption effects of adsorbents (XT-300, XT-400, and XT-500) with pyrolysis temperatures of 300 °C, 400 °C, and 500 °C on phosphate in actual phosphorus-containing wastewater and simulated phosphorus-containing wastewater at different adsorbent dosage (4 g/L, 7 g/L, and 10 g/L), it was found that XT-300 had the best performance of adsorption, and the adsorption of phosphate was endothermic and obeyed the Langmuir isotherms and Elovich kinetics. The influence of pH, coexisting anions, and the structure of XT-300 revealed that the removal of phosphate was associated with electrostatic attraction, pore filling, but could not be determined whether it was related to surface precipitation. This study provides a way and method for the recovery and utilization of phosphorus in fruit and vegetable wastewater and proves that the synthetic adsorbent was an efficient phosphorus adsorbent. In the long term, we can try to use the adsorbent after phosphorus adsorption to promote plant growth in agricultural systems.

This study selected five points in the middle and upper mainstream of the Three Gorges Reservoir area. Starting from May 2016, the greenhouse gases CO2 and CH4 from the water–air formation at the sampling points have been monitored month by month for 10 months. Using the headspace balance method and the thin boundary layer model estimation method, we obtained the CO2 and CH4 partial pressure ranges and the water–air formation diffusion flux at the mainstream point. It is found that the CH4 partial pressure of water body is significantly positively correlated with water temperature, and significantly negatively correlated with DO; the CH2 partial pressure of water body is positively correlated with water temperature, but negatively correlated with conductivity, DO, pH and wind speed. The diffusion fluxes of CH4 and CO2 at the water–air formation are positively correlated with CH4 partial pressure and water temperature, and negatively correlated with ph, DO and conductivity. It is also found that the reservoir has a certain mitigation effect on the release of CO2 from the river water body, and the CH4 diffusion flux at the water–air formation is roughly equivalent. HIGHLIGHTS This study adopts the headspace balance technology to establish a water body carbon source greenhouse gas monitoring method suitable for reservoirs in the upper reaches of the Yangtze River.; This study monitors and analyzes the greenhouse gas concentrations of carbon sources in water bodies at typical points of upstream reservoirs in different seasons and different operating conditions.;

Introduction: Heart failure is a rapidly growing public health problem and has become a major cause of hospitalization in middle-aged and older adults. Biomarkers are clinically important in managing heart failure and have attracted more attention from researchers in recent years. This study aimed to evaluate the global research of heart failure biomarkers by bibliometrics and to identify the hot spots and perspectives for further advancement. Methods: Selection of relevant documents was from the Web of Science Core Collection. Microsoft Excel, VOSviewer, SciMA, and CiteSpace software were used for bibliometric analysis. Results: As of October 29, 2021, 5,978 documents for heart failure biomarkers have been identified from 1989 to 2021. European Journal of Heart Failure and Circulation respectively ranked first in terms of the number of publications and the number of co-citations. A total of 5,698 institutions from 90 countries participated in these publications, with the USA leading with 2,045 documents. The most productive institution was Harvard University. Januzzi, J.L. and Maisel, A.S. were the most productive and most cited authors respectively. Natriuretic peptide, copeptin, valsartan, ferric carboxymaltose, empagliflozin, preserved ejection fraction, myocardial fibrosis, and heart transplantation were hot themes. Conclusions: Extensive national and inter-institutional collaboration should be enhanced to bridge the gap between developed and less developed countries in heart failure biomarkers research. The research in this field seems to have reached a relatively mature stage, with a decrease in research fervor in recent years. The study of the natriuretic peptide family still has high centrality, with advances in the study of expression products and inflammatory markers. Cardiac fibrosis, cardiac remodeling, and therapies regarding heart failure have become hot spots.

Type 2 diabetes mellitus (T2DM) has caused a huge clinical and economic burden worldwide. The management strategy of T2DM has been mentioned in many guidelines. However, controversy still exists in the recommendation of anti-hyperglycemic agents. To this end, this protocol has been written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will make an overview of systematic reviews based-on network meta-analysis firstly that report on safety and efficacy of different category of anti-hyperglycemic agents for T2DM patients. We will identify network meta-analysis by applying a robust and standardized search strategy within Embase, PubMed, Web of Science, and Cochrane Database of Systematic Reviews. Hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) will be defined as the primary outcomes. We will assess the methodological quality of included reviews by applying the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR-2) tool, and quality of evidence for all outcomes will be judged by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). This will provide an accessible narrative synthesis to clinicians, patients, policy makers, and developers of clinical guidelines based on published high-quality network meta-analysis. We will submit our results for peer-review publication and presentation at domestic and international conferences. We will also disseminate our results through established clinical networks and consumer networks, using pamphlet where appropriate. Ethics approval is not required for this overview as we will analysis published network meta-analysis only. Trial registration number: INPLASY202070118.

Background: The potential effectiveness of traditional Chinese medicine (TCM) against “epidemic diseases” has highlighted the knowledge gaps associated with TCM in COVID-19 management. This study aimed to map the matrix for rigorously assessing, organizing, and presenting evidence relevant to TCM in COVID-19 management.Methods: In this study, we used the methodology of evidence mapping (EM). Nine electronic databases, the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal, ClinicalTrials.gov, gray literature, reference lists of articles, and relevant Chinese conference proceedings, were searched for articles published until 23 March 2022. The EndNote X9, Rayyan, EPPI, and R software were used for data entry and management.Results: In all, 126 studies, including 76 randomized controlled trials (RCTs) and 50 systematic reviews (SRs), met our inclusion criteria. Of these, only nine studies (7.14%) were designated as high quality: four RCTs were assessed as “low risk of bias” and five SRs as “high quality.” Based on the research objectives of these studies, the included studies were classified into treatment (53 RCTs and 50 SRs, 81.75%), rehabilitation (20 RCTs, 15.87%), and prevention (3 RCTs, 2.38%) groups. A total of 76 RCTs included 59 intervention categories and 57 efficacy outcomes. All relevant trials consistently demonstrated that TCM significantly improved 22 outcomes (i.e., consistent positive outcomes) without significantly affecting four (i.e., consistent negative outcomes). Further, 50 SRs included nine intervention categories and 27 efficacy outcomes, two of which reported consistent positive outcomes and two reported consistent negative outcomes. Moreover, 45 RCTs and 38 SRs investigated adverse events; 39 RCTs and 30 SRs showed no serious adverse events or significant differences between groups.Conclusion: This study provides evidence matrix mapping of TCM against COVID-19, demonstrating the potential efficacy and safety of TCM in the treatment and prevention of COVID-19 and rehabilitation of COVID-19 patients, and also addresses evidence gaps. Given the limited number and poor quality of available studies and potential concerns regarding the applicability of the current clinical evaluation standards to TCM, the effect of specific interventions on individual outcomes needs further evaluation.

ObjectiveTo investigate the diagnostic value of diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) whole-lesion histogram parameters in differentiating benign and malignant solitary pulmonary lesions (SPLs).Materials and MethodsPatients with SPLs detected by chest CT examination and with further routine MRI, DKI and IVIM-DWI functional sequence scanning data were recruited. According to the pathological results, SPLs were divided into a benign group and a malignant group. Independent samples t tests (normal distribution) or Mann‒Whitney U tests (nonnormal distribution) were used to compare the differences in DKI (Dk, K), IVIM (D, D*, f) and ADC whole-lesion histogram parameters between the benign and malignant SPL groups. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of the histogram parameters and determine the optimal threshold. The area under the curve (AUC) of each histogram parameter was compared by the DeLong method. Spearman rank correlation was used to analyze the correlation between histogram parameters and malignant SPLs.ResultsMost of the histogram parameters for diffusion-related values (Dk, D, ADC) of malignant SPLs were significantly lower than those of benign SPLs, while most of the histogram parameters for the K value of malignant SPLs were significantly higher than those of benign SPLs. DKI (Dk, K), IVIM (D) and ADC were effective in differentiating benign and malignant SPLs and combined with multiple parameters of the whole-lesion histogram for the D value, had the highest diagnostic efficiency, with an AUC of 0.967, a sensitivity of 90.00% and a specificity of 94.03%. Most of the histogram parameters for the Dk, D and ADC values were negatively correlated with malignant SPLs, while most of the histogram parameters for the K value were positively correlated with malignant SPLs.ConclusionsDKI (Dk, K) and IVIM (D) whole-lesion histogram parameters can noninvasively distinguish benign and malignant SPLs, and the diagnostic performance is better than that of DWI. Moreover, they can provide additional information on SPL microstructure, which has important significance for guiding clinical individualized precision diagnosis and treatment and has potential clinical application value.

In recent years, scientists have paid special attention to the greenhouse gas emissions of the Three Gorges Reservoir. This study took Fuling to Wanzhou, located at the middle section of the Three Gorges Reservoir, as the research locations. From August 2017 to August 2018, the partial pressure of carbon dioxide (CO2) and methane (CH4) and the flux of CO2 and CH4 at the water–gas interface were studied. Spearman's correlation between the partial pressure and discharge flux of CO2 and CH4 in water and environmental variables was analyzed. The research results showed that the variation of partial pressure and flux was consistent. At different sample locations, there was no statistical difference in CO2 and CH4 fluxes, but under different operating periods, the CO2 and CH4 fluxes were significantly different. The highest values happened during the drainage period as well as the low-water period, respectively. Total organic carbon and total nitrogen were significantly positively correlated, and dissolved oxygen was extremely negatively correlated. The high value of CH4 flux in the middle of the reservoir area was related to the spatial distribution of the sediment and the amount of sediment deposition. HIGHLIGHTS This paper focuses on the greenhouse gas change in the middle section of the Three Gorges Reservoir area, which has received relatively little attention at present.; The research time span of this paper is long, and the analysis of greenhouse gas (GHG) is comprehensive.;

Abstract Lung function impairment and hypertension, especially hypertension, are risk factors of major adverse cardiovascular events (MACEs). However, the relationships among lung function impairment, hypertension, and MACEs have not been well‐reported. We aimed to investigate the association between lung function and hypertension and MACEs. We studied 6769 people who were a representative sample of the general population in Jiangsu Province using the multi‐stage stratified cluster sampling method. The average age was 51.54 years. Cox proportional hazards models were used to analyze the relationships between the blood pressure status and various types of lung function impairment related to MACEs. Over a follow‐up of 10 years, 236 MACEs occurred. After adjusting for age, sex, BMI, smoking, drinking, education, physical activity, diabetes mellitus, dyslipidemia, creatine and use of antihypertensive drugs, hypertension [hazard ratio (HR) = 2.154, 95% confidence intervals (CI): 1.565–2.966], and restrictive lung function impairment (RLFI) (HR = 1.398, 95% CI: 1.021–1.879) were independently associated with MACEs. Individuals with hypertension and RFLI had the highest risk for MACEs (HR = 2.930, 95% CI: 1.734–4.953) and stroke (HR = 3.296, 95% CI: 1.862–5.832). Moreover, when combined with hypertension, obstructive lung function impairment (OLFI) (HR = 2.376, 95% CI: 1.391–4.056) and mixed lung function impairment (MLFI) (HR = 2.423, 95% CI: 1.203–4.882) were associated with MACEs. There is a synergistic effect of lung function impairment (especially RLFI) and hypertension on MACEs. Therefore, more attention should be paid to the incidence of MACEs in individuals with impaired lung function, especially those who have hypertension.

To improve the biogas potential in anaerobic digestion of cattle manure in cold regions, we investigated, in this study, the potential of the anaerobic digestion of cattle manure through sequencing batch anaerobic digestion experiments at sub-mesophilic temperatures (15°C, 20°C, 25°C, and 37°C) for 50 days. Specifically, the changes in the biogas yield, pH, sCOD concentration, enzyme activity, and microbial community structure were examined. The maximum daily yield of biogas was 19.18 mL·gVS−1, which was recorded on day 6 at 37°C, and the final biogas accumulation yield at this temperature was 403.64 mL·gTS−1. The concentration of sCOD gradually increased as enzyme activity increased. The maximum activities of cellulase, hemicellulase, protease, and amylase were recorded in the 37°C experimental group. The decrease in temperature severely limited the activity of different types of enzymes, resulting in a decrease in the activity of microorganisms, which greatly influenced the methanogenic reaction. The dominant bacteria at the phylum level were Bacteroidetes and Proteobacteria, and the dominant methanogen at the genus level was Methanosaeta.

Abstract Background Fractional vegetation cover (FVC) is an important basic parameter for the quantitative monitoring of the alpine grassland ecosystem on the Qinghai-Tibetan Plateau. Based on unmanned aerial vehicle (UAV) acquisition of measured data and matching it with satellite remote sensing images at the pixel scale, the proper selection of driving data and inversion algorithms can be determined and is crucial for generating high-precision alpine grassland FVC products. Methods This study presents estimations of alpine grassland FVC using optimized algorithms and multi-dimensional features. The multi-dimensional feature set (using original spectral bands, 22 vegetation indices, and topographical factors) was constructed from many sources of information, then the optimal feature subset was determined based on different feature selection algorithms as the driving data for optimized machine learning algorithms. Finally, the inversion accuracy, sensitivity to sample size, and computational efficiency of the four machine learning algorithms were evaluated. Results (1) The random forest (RF) algorithm (R2: 0.861, RMSE: 9.5%) performed the best for FVC inversion among the four machine learning algorithms driven by the four typical vegetation indices. (2) Compared with the four typical vegetation indices, using multi-dimensional feature sets as driving data obviously improved the FVC inversion accuracy of the four machine learning algorithms (R2 of the RF algorithm increased to 0.890). (3) Among the three variable selection algorithms (Boruta, sequential forward selection [SFS], and permutation importance-recursive feature elimination [PI-RFE]), the constructed PI-RFE feature selection algorithm had the best dimensionality reduction effect on the multi-dimensional feature set. (4) The hyper-parameter optimization of the machine learning algorithms and feature selection of the multi-dimensional feature set further improved FVC inversion accuracy (R2: 0.917 and RMSE: 7.9% in the optimized RF algorithm). Conclusion This study provides a highly precise, optimized algorithm with an optimal multi-dimensional feature set for FVC inversion, which is vital for the quantitative monitoring of the ecological environment of alpine grassland.

We demonstrate subwavelength resolution, full-field, and lensless terahertz ptychography via longitudinal shifts of the sample. An extended illumination is adopted to realize full-field recording. Compared to a typical scheme, this implementation requires fewer diffraction patterns, which improves the imaging throughput. To suppress the incoherent infrared background, an optical chopper is introduced and a preprocessing algorithm based on digital phase-locked is proposed. By combining the ideas of multi-plane phase retrieval and ptychographic reconstruction, a reconstruction algorithm is proposed to simultaneously retrieve the object and the probe. Due to the lensless single-beam mode and full-field illumination, the sample is placed as close to the detector as possible, and the aperture of the whole sensor is utilized to achieve the highest numerical aperture. Note that the proposed approach could be applied to other wavebands as well. We apply this method to a biological material, a polymer sample, and a resolution target. The uneven illumination, as well as the diffraction effects associated with detector edges, is separated from the object reconstruction. The secondary veins of the dragonfly forewing, as small as ∼20 µm, are observed, and the lateral resolution achieves 88 µm (0.74λ).

Traditional Chinese Medicine (TCM) provides unique therapeutic effects for many diseases with identified efficacy during long practice. Astragalus Membranaceus (AM) is the Chinese herbal applied for kidney injury in the clinic, but it remains challenging to further enhance the efficacy. Cycloastragenol (CAG) is the ingredient isolated from AM with poor water solubility, which has shown a renoprotective effect. Herein we designed and synthesized the corresponding solid-phase module of CAG, from which CAG as a pharmaceutical element was incorporated into oligonucleotides (ON) as an ON-CAG conjugate in a programmable way by a DNA synthesizer. Cell viability study demonstrated that ON-CAG conjugate remains similar renoprotective effect as that of CAG, which efficiently recovers the activity of HK-2 cells pretreated with cisplatin. Similarly, in the renal cells treated with the conjugate, the biomarkers of kidney injury such as KIM-1 and IL-18 are downregulated, and cytokines are reduced as treated with anti-inflammatory agents. Overall, we have managed to incorporate a hydrophobic ingredient of TCM into ON and demonstrate the oligonucleotide synthesis technology as a unique approach for the mechanism study of TCM, which may facilitate the discovery of new therapeutics based on TCM.

Summary: Hippocampal theta and gamma rhythms are hypothesized to play a role in the physiology of higher cognition. Prior research has reported that an offset in theta cycles between the entorhinal cortex, CA3, and CA1 regions promotes independence of population activity across the hippocampus. In line with this idea, it has recently been observed that CA1 pyramidal cells can establish and maintain coordinated place cell activity intrinsically, with minimal reliance on afferent input. Counter to these observations is the contemporary hypothesis that CA1 neuron activity is driven by a gamma oscillation arising from the medial entorhinal cortex (MEC) that relays information by providing precisely timed synchrony between MEC and CA1. Reinvestigating this in rats during appetitive track running, we found that theta is the dominant frequency of cross-frequency coupling between the MEC and hippocampus, with hippocampal gamma largely independent of entorhinal gamma.

With ambitious carbon peak and carbon neutral targets, China has to realize it relies heavily on significant reductions in energy-related carbon emissions. Therefore, as the largest contributing region, resource-based cities (RBCs) must achieve an energy transition. Unfortunately, these cities are facing serious environmental problems. The aim of this study is to analyze the development history and problems of RBCs by using the example of the Northeast region. The results show the reasons blocking the green development of these cities include management policies and life cycles. This implies the management of RBCs needs to develop toward a win-win situation of industrial transformation and ecological protection. Finally, some policy recommendations are proposed to achieve emission reduction and sustainable development.

Fractional vegetation coverage (FVC) is an important indicator of ecosystem change. At present, FVC products are mainly concentrated at low and medium spatial resolution and lack high temporal and spatial resolution, which brings certain challenges to the fine monitoring of ecological environments. In this study, we evaluated the accuracy of four remote sensing inversion models for FVC based on high-spatial-resolution Sentinel-2 imagery and unmanned aerial vehicle (UAV) field-measured FVC data in 2019. Then the inversion models were optimized by constructing a multidimensional feature dataset. Finally, the Source Region of the Yellow River (SRYR) FVC product was created using the best inversion model, and the spatial-temporal variation characteristics of the FVC in the region were analyzed. The study’s findings revealed that: (1) The accuracies of the four FVC inversion models were as follows: the Gradient Boosting Decision Tree (GBDT) model (R2 = 0.967, RMSE = 0.045) > Random Forest (RF) model (R2 = 0.962, RMSE = 0.049) > Support Vector Machine (SVM) model (R2 = 0.925, RMSE = 0.072) > Pixel Dichotomy (PD) model (R2 = 0.869, RMSE = 0.097). (2) Constructing a multidimensional feature dataset to optimize the driving data can improve the accuracy of the inversion model. NDVI and elevation are important factors affecting the accuracy of machine learning inversion algorithms, and the visible blue band is the most important feature factor of the GBDT model. (3) The FVC in the SRYR gradually increased from west to east and from north to south. The change trajectories of grassland FVC from 2017 to 2022 were not significant. The areas that tend to improve were mainly distributed in the southeast (1.31%), while the areas that tend to degrade were mainly distributed in the central and northwest (1.89%). This study provides a high-spatial-resolution FVC inversion optimization scheme, which is of great significance for the fine monitoring of alpine grassland ecological environments.

The high-temperature heat pump, as a low-carbonization technology, has broad application prospects in replacing boiler heating, reducing carbon dioxide emissions, and improving the energy utilization efficiency. In this paper, the working fluid, cycle process, key equipment (compressor), and application scenarios of high-temperature heat pumps are introduced in detail. Firstly, the research direction of the working fluid is introduced and the existing working fluid substitution is analyzed and summarized. Then, the characteristics of different heat pump cycles such as compression, absorption, and hybrid heat pumps are introduced. In the aspect of key equipment, the application range and research status of different types of compressors are emphatically introduced. Finally, the application scenario of high-temperature heat pumps is prospected. In addition to the application of industrial heating, it is often used for heat storage to improve the regulatory characteristics of the system. The new heat pump electricity storage system has great application potential in the field of renewable energy consumption. Based on the above analysis of high-temperature heat pumps, four development prospects are put forward: low-Global-Warming-Potential (GWP) working fluid; cycles of temperature lift greater than 80 °C; a compressor with better high-temperature performance; and circulation characteristics of heat pump electricity storage.

Starch nanoparticles (SNPs) are generally defined as starch grains smaller than 600–1000 nm produced from a series of physical, chemical, or biologically modified starches. Many studies have reported the preparation and modification of SNPs, which are mostly based on the traditional “top-down” strategy. The preparation process generally has problems with process complexity, long reaction periods, low yield, high energy consumption, poor repeatability, etc. A “bottom-up” strategy, such as an anti-solvent method, is proven to be suitable for the preparation of SNPs, and they are synthesized with small particle size, good repeatability, a low requirement on equipment, simple operation, and great development potential. The surface of raw starch contains a large amount of hydroxyl and has a high degree of hydrophilicity, while SNP is a potential emulsifier for food and non-food applications.

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody ID50 titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the BIBP inactivated COVID-19 vaccine (BBIBP-CorV). Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

Most patients with neovascular age-related macular degeneration (nvAMD), the leading cause of severe vision loss in elderly US citizens, respond inadequately to current therapies targeting a single angiogenic mediator, vascular endothelial growth factor (VEGF). Here, we report that aqueous fluid levels of a second vasoactive mediator, angiopoietin-like 4 (ANGPTL4), can help predict the response of patients with nvAMD to anti-VEGF therapies. ANGPTL4 expression was higher in patients who required monthly treatment with anti-VEGF therapies compared with patients who could be effectively treated with less-frequent injections. We further demonstrate that ANGPTL4 acts synergistically with VEGF to promote the growth and leakage of choroidal neovascular (CNV) lesions in mice. Targeting ANGPTL4 expression was as effective as targeting VEGF expression for treating CNV in mice, while simultaneously targeting both was more effective than targeting either factor alone. To help translate these findings to patients, we used a soluble receptor that binds to both VEGF and ANGPTL4 and effectively inhibited the development of CNV lesions in mice. Our findings provide an assay that can help predict the response of patients with nvAMD to anti-VEGF monotherapy and suggest that therapies targeting both ANGPTL4 and VEGF will be a more effective approach for the treatment of this blinding disease.

An arbitrary multi-way radial power divider/combiner with high-power capacity based on the coaxial waveguide TE01-mode is presented in this paper. The study of the TE01-mode in the coaxial waveguide shows the radial power divider can operate in the base mode with a large diameter, which can allow arbitrary multi-way waveguides to be radially distributed along the circumference of the coaxial waveguide. An equivalent circuit model of the arbitrary multi-way radial power divider is used to analyze its design procedure including the matching section, which can improve the transmission coefficient and isolation between output ports. To verify these, a 4-way and a 20-way radial power divider/combiner with a matching section are designed; the simulation results show that the power capability is >43 kW within 0.5 dB insertion loss for the four-way radial power divider. The average value of isolation between adjacent ports has improved by 11.1 dB after using the periodic matching structure as well as 2.78 dB between opposite ports in the frequency range of 34.08–36.32 GHz. The insertion loss of the 20-way radial power divider is less than 1 dB in the frequency range of 33.4–37.6 GHz, while the return loss is greater than 25 dB.

Plant species diversity (PSD) is essential in evaluating the function and developing the management and conservation strategies of grassland. However, over a large region, an efficient and high precision method to monitor multiscale PSD (α-, β-, and γ-diversity) is lacking. In this study, we proposed and improved an unmanned aerial vehicle (UAV)-based PSD monitoring method (UAVB) and tested the feasibility, and meanwhile, explored the potential relationship between multiscale PSD and precipitation on the alpine grassland of the source region of the Yellow River (SRYR), China. Our findings showed that: (1) UAVB was more representative (larger monitoring areas and more species identified with higher α- and γ-diversity) than the traditional ground-based monitoring method, though a few specific species (small in size) were difficult to identify; (2) UAVB is suitable for monitoring the multiscale PSD over a large region (the SRYR in this study), and the improvement by weighing the dominance of species improved the precision of α-diversity (higher R2 and lower P values of the linear regressions); and (3) the species diversity indices (α- and β-diversity) increased first and then they tended to be stable with the increase of precipitation in SRYR. These findings conclude that UAVB is suitable for monitoring multiscale PSD of an alpine grassland community over a large region, which will be useful for revealing the relationship of diversity–function, and helpful for conservation and sustainable management of the alpine grassland.

Abstract Background The effect of high levels of physical activity and relationship between daily total physical activity and the risk of cardiovascular disease (CVD) among hypertensive people were not clear. This study aimed to explore the optimum level of physical activity for CVD prevention. Methods Data used in the present study was derived from the sub-study of China Kadoorie Biobank study (CKB) in Jiangsu province of China. The CKB was a prospective cohort study established during 2004–2008. At baseline, 53,259 participants aged 35–74 years were recruited for the CKB Jiangsu sub-study conducted in Wuzhong district of Suzhou City. Among those 53,259 participants, the 20,179 hypertensive individuals were our study population. The outcome events were cardiovascular diseases (CVDs), while the independent variable was total daily physical activity. The Cox proportional hazard models were introduced to investigate the association between total physical activity and CVDs, reporting as hazard ratios (HR) and 95% confidence intervals (CIs). Results During a 10.1-year follow-up, 2419 CVD cases were identified. After adjustment for potential confounding factors, compared with participants at the lowest level of daily total physical activity, the hazard ratios for CVDs were 0.87 (95%CI: 0.79–0.97), 0.73 (95%CI: 0.65–0.83) and 0.75 (95%CI: 0.65–0.85) for participants within 2, 3 and 4 quartiles of physical activity. Such a negative association between total physical activity and CVDs were also observed among participants by gender and age-group, but within patients with stage 1 hypertension only. Moreover, the association of physical activity with CVDs was U-shape and the lowest HR (0.63, 95%CI: 0.54–0.74) was observed at 35.4 MET-h/d of total physical activity. Conclusions Total daily physical activity was negatively associated with CVDs among hypertensive adults in China, and this association was U-shape. It has some public health implications that community-based total physical activity intervention campaigns can be of help for CVDs prevention among hypertensive people in China.

A large amount of the waste heat generated during industrial production is not used, which leads to a low energy utilization rate. The recovery of industrial waste heat using heat pumps has the advantages of low energy consumption, high efficiency, safety, and environmental protection. Industrial waste heat has a wide temperature distribution range. Traditional absorption and compression heat pumps can only work in a narrow temperature range due to the thermodynamic cycle, the thermal properties of the working medium, the temperature and pressure resistance of the compressor, and other factors; they cannot simultaneously meet the requirements of a “high heating temperature” and “wide temperature-range heat transfer”. To solve the above problems, this paper proposes a high-temperature heat pump unit based on a coupled cycle of absorption and compression, which can recover low-temperature steam and 50 °C waste heat and produce hot water at 110–130 °C. EES software is used for the mathematical modeling and simulation analysis of the heat pump unit. The results show that, when the driving steam temperature is 140 °C and the waste heat temperature is 50 °C, the heating temperature can reach 110~130 °C and the COP of the system can reach 4.22. Increasing the waste heat outlet temperature and the condensation temperature of the absorption cycle strengthens the COP of the coupled cycle; meanwhile, increasing the evaporation temperature and heating temperature of the absorption cycle reduces the COP of the coupled cycle. The results of this study significantly broaden the operating temperature range and heating temperature of electric heat pumps; our findings therefore have essential research significance for improving energy efficiency in industrial fields.

Hawthorn (Crataegus pinnatifida var. major), a cultivated fruit tree, is native and unique to China. Its fruits have high nutritional, health, and medicinal values. However, the development and ripening process of hawthorns is accompanied by dramatic changes in flavor, aroma, and bioactive phytochemicals, which are the fundamental factors that contribute to the potential health benefits and establishment of fruit quality. Therefore, an exploration of the dynamic changes in metabolites and their regulatory networks during the development of hawthorn fruits can elucidate the formation mechanisms of active substances in hawthorn fruits. In this study, we used a broad targeted metabolomics approach to identify and analyze the dynamics of metabolites in hawthorn fruits at five developmental stages. The results revealed 998 primary and secondary metabolites that were classified into 15 categories. The accumulation levels of most sugars increased during fruit development and then accelerated at the fruit ripening stage. The accumulation levels of a few organic acids (e.g., citric acid, isocitric acid, and quinic acid) continuously increased. Many organic acids exhibited significant decreasing trends. Among the 561 secondary metabolites detected, 189 were phenolic acids and 199 were flavonoids. The levels of many flavonoids were significantly reduced at later stages of fruit development; in contrast, the levels of two anthocyanins significantly increased during fruit ripening. Correlation analysis revealed that there is a certain correlation within and between primary as well as secondary metabolites during fruit development. Furthermore, the integration of metabolomic and transcriptomic data in this study revealed that changes in the expression of some differentially expressed genes (DEGs) were associated with the accumulation of metabolites such as sugars, organic acids, and flavonoids, e.g., the upregulated expression levels of CS (citrate synthase) genes were consistent with the continued accumulation of citric acid. Overall, this study demonstrates the metabolic changes that occur during the development of hawthorn fruit, explores the molecular mechanisms that underlie metabolite changes during fruit development, and lays a strong theoretical foundation for the improvement of hawthorn fruit quality and the development of functional components.

Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NH4HCO3; abc) and chemotherapeutic agent doxorubicin (DOX) were loaded into the pores of mesoporous silica. Indocyanine green (ICG) as a photothermal and photodynamic agent was loaded onto the polydopamine (PDA) layer surface. The synthesized nanoparticles displayed a narrow polydispersity (PDI) and small particle size as characterized through dynamic light scattering-autosizer analysis. The nanoparticles also showed high targeting efficacy through RGD modification as indicated by cellular uptake and animal studies. DOX release analysis confirmed that the nanoparticles were pH-dependent and that NH4HCO3 accelerated drug release. At the same time, the nanoparticles had obvious photothermal and photodynamic effects performed by ICG which restrained tumor growth remarkably. In summary, the multifunctional nanoparticles presented a promising system for combination therapy.

In this study, we report high-performance amorphous Ga2O3 metal-oxide (AMO) thin film transistor (TFT) using an low-temperature solution-process coupling with In alloy engineering. In doping can lower the activation temperature of gallium oxide and increase the oxygen vacancy concentration to further activate the device. The optical bandgap of IGO film can be changed from 5.3 to 4.25 eV with the In doping concentration ( $\text{C}_{\mathrm{ In}}$ ) increasing from 0 % to 50 %. All TFTs with IGO channels exhibit n-type transistor characteristics and the evolution of their key electrical parameters with the In-dopant is well elucidated by the structural and morphological characterization. With the increase of $\text{C}_{\mathrm{ In}}$ , the performance of the device becomes better. Finally, a saturation field-effect mobility of 3.63 cm2V−1s−1, a current on/off ratio of 106, and a threshold voltage of 2.5 V are achieved by the In0.5Ga0.5O ( $\text{C}_{\mathrm{ In}}= 50$ %) based device. The In0.5Ga0.5O TFT also demonstrates good bias stress stability. Under the action of 20 V and −20 V gate bias for 3000 s, the ${\Delta }\text{V}_{\mathrm{ TH}}$ is +2.27 V and −1.95 V, respectively.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to disperse globally with worrisome speed, identifying amino acid variations in the virus could help to understand the characteristics of it. Here, we studied 489 SARS-CoV-2 genomes obtained from 32 countries from the Nextstrain database and performed phylogenetic tree analysis by clade, country, and genotype of the surface spike glycoprotein (S protein) at site 614. We found that virus strains from mainland China were mostly distributed in Clade B and Clade undefined in the phylogenetic tree, with very few found in Clade A. In contrast, Clades A2 (one case) and A2a (112 cases) predominantly contained strains from European regions. Moreover, Clades A2 and A2a differed significantly from those of mainland China in age of infected population (P = 0.0071, mean age 40.24 to 46.66), although such differences did not exist between the US and mainland China. Further analysis demonstrated that the variation of the S protein at site 614 (QHD43416.1: p.614D>G) was a characteristic of stains in Clades A2 and A2a. Importantly, this variation was predicted to have neutral or benign effects on the function of the S protein. In addition, global quality estimates and 3D protein structures tended to be different between the two S proteins. In summary, we identified different genomic epidemiology among SARS-CoV-2 strains in different clades, especially in an amino acid variation of the S protein at 614, revealing potential viral genome divergence in SARS-CoV-2 strains.

Abstract The objective of this study was to investigate the expression and clinical role of ATP-binding cassette transporter 13 (ABCA13) gene previously shown to be associated with schizophrenia (SZ) through Genome-wide association studies studies. Thirty-two first-episode drug-naive SZ patients and forty-eight age and gender-matched healthy controls were enrolled in this study. We measured ABCA13 mRNA expression levels using quantitative real-time PCR at baseline and 12 weeks after antipsychotic therapy. Moreover, clinical symptoms were measured by the Positive and Negative Syndrome Scale (PANSS) at baseline and 12-week follow-up. We found that ABCA13 mRNA levels were significantly lower in SZ patients compared with healthy controls at baseline. SZ patients’ symptoms were decreased, but ABCA13 mRNA levels were increased after 12 weeks antipsychotic therapy. In addition, there was a significant difference in ABCA13 mRNA levels among SZ patients at baseline and 12-week follow-up. The ABCA13 mRNA levels were not associated with age, BMI, years of education. Of the clinical symptoms measured, the ABCA13 mRNA levels were negatively associated with the PANSS scores at baseline and 12-week follow-up. The results indicated that the ABCA13 mRNA expression level is of interest, and upon further studies, it could be used as a biomarker for SZ treatment outcome.

Reactive oxygen species (ROS) produced in the ischemic myocardium can induce cardiomyocyte injury and death, resulting in cardiac remodeling. Ferroptosis, known as a newly type of cell death caused by iron-dependent oxidative stress, which is an essential death mechanism in cardiomyocytes. However, it is unclear whether oxidative stress products can further induce ferroptosis and aggravate cardiomyocyte injury. Geniposide (GEN), a major active component of Gardenia jasminoides J. Ellis, possesses the natural antioxidant activity and cardioprotective effect. Herein, we evaluated the role of ferroptosis in myocardial oxidative injury and the protective effect of GEN on myocardial ferroptosis. We first detected iron overload, massive ROS, and lipid peroxidation in ferric ammonium citrate (FAC)-treated cardiomyocytes, which were typical characteristics of ferroptosis. The iron overload-induced oxidative stress and ferroptosis aggravated cardiomyocyte injury, which were significantly alleviated by GEN treatment. Similar phenotypic changes of ferroptosis were consistently discovered in hydrogen peroxide (H2O2)-induced cells, which were reversed by GEN treatment as well. Interestingly, the RNA-binding protein Grsf1, which directly upregulated Gpx4 at the translational level, was activated by GEN following myocardial oxidative injury. The specific knockdown of Grsf1 increased their sensitivity to ferroptosis and weakened the cardioprotective effect of GEN in H2O2-treated cardiomyocytes. Moreover, GEN treatment reduced iron overload and lipid peroxidation in myocardial infarction (MI) rats, thereby fighting against the cardiac ischemic injury. Collectively, our study revealed the pathogenesis of oxidative stress and ferroptosis associated with myocardial ischemia, and indicated the antioxidant and anti-ferroptosis effects of GEN on preventing myocardial injury by activating the Grsf1/GPx4 axis, serving as a potential therapeutic target.

Tumor-infiltrating immune cells are associated with prognosis and immunotherapy targets in colorectal cancer (CRC). The recently developed CIBERSORT method allows immune cell analysis by deconvolution of high-throughput data onto gene expression. In this study, we analyzed the relative proportions of immune cells in GEO (94 samples) and TCGA (522 samples) CRC data based on the CIBERSORT method. A total of 22 types of tumor-infiltrating immune cells were evaluated. Combined with GEO and TCGA data, it was found that naive B cells, M2 macrophages, and resting mast cells were highly expressed in normal tissues, while M0 macrophages, M1 macrophages, activated mast cells, and neutrophils were highly expressed in tumors. Moreover, we constructed a prognostic model by infiltrating immune cells that showed high specificity and sensitivity in both the training (AUC of 5-year survival = 0.699) and validation (AUC of 5-year survival = 0.844) sets. This provides another basis for clinical prognosis. The results of multiple immunofluorescence detection showed that there were differences in the results of bioinformatics analysis. Neutrophils were highly expressed in normal tissues, and M2 macrophages were highly expressed in tumor tissues. Collectively, our data suggested that infiltrating immune cells in CRC may be an important determinant of prognosis and immunotherapy.