Amphiregulin improves ventricular remodeling after myocardial infarction by modulating autophagy and apoptosis.

Myocardial infarction (MI) is defined as sudden ischemic death of myocardial tissue. Amphiregulin (Areg) regulates cell survival and is crucial for the healing of tissues after damage. However, the functions and mechanisms of Areg after MI remain unclear. Here, we aimed to investigate Areg's impact on myocardial remodeling. Mice model of MI was constructed and Areg-/- mice were used. Expression of Areg was analyzed using western blotting, RT-qPCR, flow cytometry, and immunofluorescence staining. Echocardiographic analysis, Masson's trichrome, and triphenyltetrazolium chloride staining were used to assess cardiac function and structure. RNA sequencing was used for unbiased analysis. Apoptosis and autophagy were determined by western blotting, TUNEL staining, electron microscopy, and mRFP-GFP-LC3 lentivirus. Lysosomal acidity was determined by Lysotracker staining. Areg was elevated in the infarct border zone after MI. It was mostly secreted by macrophages. Areg deficiency aggravated adverse ventricular remodeling, as reflected by worsening cardiac function, a lower survival rate, increased scar size, and interstitial fibrosis. RNA sequencing analyses showed that Areg related to the epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR) signaling pathways, V-ATPase and lysosome pathways. Mechanistically, Areg exerts beneficial effects via increasing lysosomal acidity to promote autophagosome clearance, and activating the EGFR/PI3K/Akt/mTOR signaling pathway, subsequently inhibiting excessive autophagosome formation and apoptosis in cardiomyocytes. This study provides a novel evidence for the role of Areg in inhibiting ventricular remodeling after MI by regulating autophagy and apoptosis and identifies Areg as a potential therapeutic target in ventricular remodeling after MI.

MDA-GCNFTG: identifying miRNA-disease associations based on graph convolutional networks via graph sampling through the feature and topology graph.

Accurate identification of the miRNA-disease associations (MDAs) helps to understand the etiology and mechanisms of various diseases. However, the experimental methods are costly and time-consuming. Thus, it is urgent to develop computational methods towards the prediction of MDAs. Based on the graph theory, the MDA prediction is regarded as a node classification task in the present study. To solve this task, we propose a novel method MDA-GCNFTG, which predicts MDAs based on Graph Convolutional Networks (GCNs) via graph sampling through the Feature and Topology Graph to improve the training efficiency and accuracy. This method models both the potential connections of feature space and the structural relationships of MDA data. The nodes of the graphs are represented by the disease semantic similarity, miRNA functional similarity and Gaussian interaction profile kernel similarity. Moreover, we considered six tasks simultaneously on the MDA prediction problem at the first time, which ensure that under both balanced and unbalanced sample distribution, MDA-GCNFTG can predict not only new MDAs but also new diseases without known related miRNAs and new miRNAs without known related diseases. The results of 5-fold cross-validation show that the MDA-GCNFTG method has achieved satisfactory performance on all six tasks and is significantly superior to the classic machine learning methods and the state-of-the-art MDA prediction methods. Moreover, the effectiveness of GCNs via the graph sampling strategy and the feature and topology graph in MDA-GCNFTG has also been demonstrated. More importantly, case studies for two diseases and three miRNAs are conducted and achieved satisfactory performance.

Study of Nonlinear Excitation Circuits for Fluxgate Magnetometer.

This paper presents the common methods and corresponding drawbacks concerning nonlinear analysis of fluxgate excitation circuits and emphasizes the importance of nonlinear analysis for these circuits. With regard to the nonlinearity of the excitation circuit, this paper proposes the use of the core-measured hysteresis curve for mathematical analysis and the use of a nonlinear model that considers the coupling effect of the core and winding and influence of the historical magnetic field on the core for simulation analysis. The feasibility of mathematical calculations and simulation for the nonlinear study of fluxgate excitation circuit is verified via experiments. The results demonstrate that, in this regard, the simulation is four times better than a mathematical calculation. The simulation and experimental results of the excitation current and voltage waveforms under different excitation circuit parameters and structures are essentially consistent, with a difference in current of no more than 1 mA, thereby verifying the effectiveness of the nonlinear excitation analysis method.

PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study.

BACKGROUND: Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia. METHODS: In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule). RESULTS: A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase. CONCLUSION: Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov , number NCT03944109.

Mapping Local Climate Zones in the Urban Environment: The Optimal Combination of Data Source and Classifier.

The novel concept of local climate zones (LCZs) provides a consistent classification framework for studies of the urban thermal environment. However, the development of urban climate science is severely hampered by the lack of high-resolution data to map LCZs. Using Gaofen-6 and Sentinel-1/2 as data sources, this study designed four schemes using convolutional neural network (CNN) and random forest (RF) classifiers, respectively, to demonstrate the potential of high-resolution images in LCZ mapping and evaluate the optimal combination of different data sources and classifiers. The results showed that the combination of GF-6 and CNN (S3) was considered the best LCZ classification scheme for urban areas, with OA and kappa coefficients of 85.9% and 0.842, respectively. The accuracy of urban building categories is above 80%, and the F1 score for each category is the highest, except for LCZ1 and LCZ5, where there is a small amount of confusion. The Sentinel-1/2-based RF classifier (S2) was second only to S3 and superior to the combination of GF-6 and random forest (S1), with OA and kappa coefficients of 64.4% and 0.612, respectively. The Sentinel-1/2 and CNN (S4) combination has the worst classification result, with an OA of only 39.9%. The LCZ classification map based on S3 shows that the urban building categories in Xi'an are mainly distributed within the second ring, while heavy industrial buildings have started to appear in the third ring. The urban periphery is mainly vegetated and bare land. In conclusion, CNN has the best application effect in the LCZ mapping task of high-resolution remote sensing images. In contrast, the random forest algorithm has better robustness in the band-abundant Sentinel data.

Mediating Effects of Maternal Blood Triglycerides on the Relationship between Prepregnancy Body Mass Index and Fetal Macrosomia.

OBJECTIVE: To examine whether the association of prepregnancy body mass index (BMI) with fetal macrosomia is mediated through maternal circulating lipid concentrations during pregnancy. STUDY DESIGN: In this prospective cohort, 3011 eligible pregnant women were enrolled. Information on demographic characteristics were collected using questionnaires, and anthropometrics and laboratory tests were performed at 24 weeks of gestation and before delivery. Macrosomia was defined as birth weight ≥4000 g. Logistic regression and multivariable linear regression, adjusted for age, fetal sex, education, gestational weight gain, fasting blood glucose, gestational diabetes, gestational hypertension, gestational age at delivery, delivery mode, and parity, were used to assess the mediation path between prepregnancy BMI, maternal serum lipids, and fetal macrosomia. RESULTS: A total of 2454 participants with completed records were included in the final analyses. Among the maternal circulating lipid biomarkers, only triglyceride was significantly associated with both prepregnancy BMI and fetal macrosomia risk, adjusting for potential confounders. Mediation analyses demonstrated that the direct effect of prepregnancy BMI on fetal macrosomia was 0.0085 (95% CI, 0.0003-0.018; P < .05), the indirect effect mediated through maternal serum triglycerides was 0.0016 (95% CI, 0.0007-0.0029; P < .001), and the estimated proportion of mediated effect was 15.7% (P < .05). CONCLUSIONS: Maternal circulating triglycerides mediate the association of prepregnancy BMI with the risk of fetal macrosomia.

Polymorphisms of IL-23R predict survival of gastric cancer patients in a Chinese population.

IL-17/IL-23 pathway has been hypothesized to play a role in occurrence and progression of gastric cancer. To investigate the susceptibility and prognostic value of polymorphisms in genes in the IL-17/IL-23 pathway to gastric cancer, we performed a case-control study combined a retrospective study in a Chinese population. The Sequenom's MassARRAY® genotyping platform was used to genotype the polymorphisms, and infection of Helicobacter pylori (H. pylori) was determined by using a commercial H. pylori immunogold testing kit. The results showed that IL-17A rs3748067 T allele carriers have a higher gastric cancer risk than non-carriers in the subgroup of individuals with age >64 years old (CT/TT vs. CC: adjusted OR = 1.55, 95% CI = 1.04-2.29). The result of prognosis shown that IL-23R rs1884444 GG and rs6682925 CC genotype were associated with unfavorable survival (rs1884444 GG vs. GT/TT: adjusted HR = 1.40, 95%CI:1.02-1.93; rs6682925 CC vs. CT/TT: HR = 1.43, 95%CI:1.06-1.92), respectively. The stratified analysis revealed that the significant association of rs1884444 was maintained in the subgroup of older than 64 years old, and that rs6682925 was associated with unfavorable survival in the subgroup of female and patients received chemotherapy. In short, we concluded two polymorphisms (rs1884444 and rs6682925) in IL-23R were associated with prognosis of gastric cancer patients.

Genome sequencing of rice subspecies and genetic analysis of recombinant lines reveals regional yield- and quality-associated loci.

BACKGROUND: Two of the most widely cultivated rice strains are Oryza sativa indica and O. sativa japonica, and understanding the genetic basis of their agronomic traits is of importance for crop production. These two species are highly distinct in terms of geographical distribution and morphological traits. However, the relationship among genetic background, ecological conditions, and agronomic traits is unclear. RESULTS: In this study, we performed the de novo assembly of a high-quality genome of SN265, a cultivar that is extensively cultivated as a backbone japonica parent in northern China, using single-molecule sequencing. Recombinant inbred lines (RILs) derived from a cross between SN265 and R99 (indica) were re-sequenced and cultivated in three distinct ecological conditions. We identify 79 QTLs related to 15 agronomic traits. We found that several genes underwent functional alterations when the ecological conditions were changed, and some alleles exhibited contracted responses to different genetic backgrounds. We validated the involvement of one candidate gene, DEP1, in determining panicle length, using CRISPR/Cas9 gene editing. CONCLUSIONS: This study provides information on the suitable environmental conditions, and genetic background, for functional genes in rice breeding. Moreover, the public availability of the reference genome of northern japonica SN265 provides a valuable resource for plant biologists and the genetic improvement of crops.

Polymorphisms of TGFBR1, TLR4 are associated with prognosis of gastric cancer in a Chinese population.

BACKGROUND: Helicobacter pylori (H. pylori)-induced gastric cancer is an intricate progression of immune response against H. pylori infection. IL-16, TGF-ß1 and TLR4 pathways were the mediators involved in the immune response. We hypothesized that genetic variations in genes of these pathways have potential susceptibility to gastric cancer risk, and predict clinical outcomes of patients. METHODS: To investigate the susceptibility and prognostic value of genetic variations of IL-16, TGFBR1 and TLR4 pathways to gastric cancer, we performed a case-control study combined a retrospective study in a Chinese population. Genotyping for all polymorphisms was based on the Sequenom's MassARRAY platform, and H. pylori infection was determined by using an immunogold testing kit. RESULTS: We found rs10512263 CC genotype was found to be a decreased risk of gastric cancer (CC vs. TT: adjusted OR = 0.54, 95% CI 0.31-0.97); however, rs334348 GG genotype was associated with increased risk of gastric cancer (GG vs. AA: adjusted OR = 1.51, 95% CI 1.05-2.18). We found that carriers harboring rs1927911 A allele (GA/AA) or rs10512263 C allele (CT/CC) have unfavorable survival time than none carriers (rs1927911: GA/AA vs. GG: adjusted HR = 1.27, 95% CI 1.00-1.63; rs10512263: CT/CC vs. TT: adjusted HR = 1.29, 95% CI 1.02-1.63) and that individuals harboring both two minor alleles (rs1927911 GA/AA and rs10512263 CT/CC) suffered a significant unfavorable survival (adjusted HR = 1.64, 95% CI 1.17-2.31). CONCLUSION: In short, we concluded that two polymorphisms (rs334348, rs10512263) in TGFBR1 were associated with risk of gastric cancer, and that TLR4 rs1927911 and TGFBR1 rs10512263 were associated with clinical outcomes of gastric cancer patients.

Different relationship between ANGPTL3 and HDL components in female non-diabetic subjects and type-2 diabetic patients.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is a major lipoprotein regulator and shows positive correlation with high-density lipoprotein-cholesterol (HDL-c) in population studies and ANGPTL3 mutated subjects. However, no study has looked its correlation with HDL components nor with HDL function in patients with type 2 diabetes mellitus (T2DM). METHODS: We studied 298 non-diabetic subjects and 300 T2DM patients who were randomly recruited in the tertiary referral centre. Plasma levels of ANGPTL3 were quantified by ELISA. Plasma samples were fractionated to obtain HDLs. HDL components including apolipoprotein A-I (apoA-I), triglyceride, serum amyloid A (SAA), phospholipid and Sphingosine-1-phosphate were measured. HDLs were isolated from female controls and T2DM patients by ultracentrifugation to assess cholesterol efflux against HDLs. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, body mass index and lipid lowering drugs were performed in male or female non-diabetic participants or diabetic patients, respectively. RESULTS: We demonstrated that plasma level of ANGPTL3 was lower in female T2DM patients than female controls although no difference of ANGPTL3 levels was detected between male controls and T2DM patients. After adjusting for confounding factors, one SD increase of ANGPTL3 (164.6 ng/ml) associated with increase of 2.57 mg/dL cholesterol and 1.14 µg/mL apoA-I but decrease of 47.07 µg/L of SAA in HDL particles of non-diabetic females (p < 0.05 for cholesterol and SAA; p < 0.0001 for apoA-I). By contrast, 1-SD increase of ANGPTL3 (159.9 ng/ml) associated with increase of 1.69 mg/dl cholesterol and 1.25 µg/mL apoA-I but decrease of 11.70 µg/L of SAA in HDL particles of female diabetic patients (p < 0.05 for cholesterol; p < 0.0001 for apoA-I; p = 0.676 for SAA). Moreover, one SD increase of ANGPTL3 associated with increase of 2.11 % cholesterol efflux against HDLs in non-diabetic females (p = 0.071) but decrease of 1.46 % in female T2DM patients (p = 0.13) after adjusting for confounding factors. CONCLUSIONS: ANGPTL3 is specifically correlated with HDL-c, apoA-I, SAA and HDL function in female non-diabetic participants. The decrease of ANGPTL3 level in female T2DM patients might contribute to its weak association to HDL components and function. ANGPTL3 could be considered as a novel therapeutic target for HDL metabolism for treating diabetes.

Hematopoietic stem/progenitor cells directly contribute to arteriosclerotic progression via integrin ß2.

Recent studies described the association between hematopoietic stem/progenitor cell (HSPC) expansion in the bone marrow (BM), leukocytosis in the peripheral blood, and accelerated atherosclerosis. We hypothesized that circulating HSPC may home to inflamed vessels, where they might contribute to inflammation and neointima formation. We demonstrated that Lin(-) Sca-1(+) cKit(+) (LSK cells) in BM and peripheral blood of LDLr(-/-) mice on high fat diet expressed significantly more integrin ß2 , which was responsible for LSK cell adhesion and migration toward ICAM-1 in vitro, and homing to injured arteries in vivo, all of which were blocked with an anti-CD18 blocking antibody. When homed LSK cells were isolated from ligated artery and injected to irradiated recipients, they resulted in BM reconstitution. Injection of CD18(+/+) LSK cells to immunodeficient Balb/C Rag2(-) É£C(-/-) recipients resulted in more severe inflammation and reinforced neointima formation in the ligated carotid artery, compared to mice injected with PBS and CD18(-/-) LSK cells. Hypercholesterolemia stimulated ERK phosphorylation (pERK) in LSK cells of LDLr(-/-) mice in vivo. Blockade of pERK reduced ARF1 expression, leading to decreased integrin ß2 function on HSPC. In addition, integrin ß2 function could be regulated via ERK-independent LRP1 pathway. Integrin ß2 expression on HSPC is regulated by hypercholesterolemia, specifically LDL, in pERK-dependent and -independent manners, leading to increased homing and localization of HSPC to injured arteries, which is highly correlated with arteriosclerosis.

Hemodynamics study of a multilayer stent for the treatment of aneurysms.

BACKGROUND: The changes of hemodynamics caused by the implantation of multilayer stent (MS) have significant effects for aneurysm sac. METHODS: Comparisons of 3D numerical models with/without a MS in an abdominal aortic aneurysm with a 90° branch vessel were numerically studied from the viewpoint of hemodynamics. RESULTS: The results showed that: (1) The flow fields and Wall Shear Stress (WSS) are changed dramatically after MS implantation. The velocity of the blood flow in aneurysm sac decreases significantly and the regions of low-WSS increase. These help thrombus formation; (2) The pressure in aneurysm slightly decreases and keeps close to the normal level of blood pressure, however the risk of aneurysm enlargement or even rupture still exists; (3) The flux and the velocity in branch artery are reduced by about half after MS implantation. Due to the implantation of MS, the changes in the flow field causes the decrease of pressure/WSS in aneurysm sac and the blood flow in branch vessel. CONCLUSIONS: The implantation of MS into abdominal artery results in more low-WSS regions inside aneurysm which induces thrombus formation. The pressure is reduced slightly means the risk of aneurysm rupture exists.

Effects of Different Limb Remote Ischaemic Preconditioning on Ischaemia Reperfusion Injury in an Acute Left Anterior Descending Artery Occlusion Rat Model.

BACKGROUND: The aim is to compare effects of three different protocols of limb remote ischaemic preconditioning (LRIP) on ischaemia reperfusion injury in an acute left anterior descending artery (LAD) occlusion model rat. METHODS: Forty adult male Wistar rats were randomly assigned into four groups: group A, control; group B, LRIP in bilateral upper-limb (BUL) IP; group C, LRIP in bilateral lower-limb (BLL) IP; group D, LRIP in bilateral upper and lower limbs (ULL) IP. The 60min ligation and 180min reperfusion in LAD were applied to all rats. Limb remote ischaemic preconditioning was performed using 5min occlusion and 15min reperfusion (six cycles). Heart rate, blood pressure and electrogastrography (EGG) were recorded. Creatine kinase isoenzyme (CK-MB) level and infarct size were measured. RESULTS: Limb remote ischaemic preconditioning did not significantly affect heart rate, systolic blood pressure and arrhythmia score. However, LRIP significantly increased DBP value and decreased CK-MB levels and infarct size in group B, C, and D. Moreover, LRIP in ULL had a significantly better effect on reducing infarct size than LRIP in BUL and BLL. CONCLUSIONS: Limb remote ischaemic preconditioning at limbs could significantly reduce reperfusion injury in the heart. Moreover, LRIP in ULL indicated a better effect in reducing infarct size than LRIP in BUL and BLL.

Encapsulating stable perovskite catalysts in hollow nanoreactors for enhanced pollutants degradation.

Creating a microenvironment for enhanced peroxymonosulfate (PMS) activation is vital in advanced oxidation processes. The objective of this study was to fabricate nanoshells composed of titanium dioxide embedded with cobalt titanate nanoparticles of perovskite to act as nanoreactors for effectively initiating PMS and degrading contaminants. The unique porous structure and confined space of the nanoreactor facilitated reactant absorption and mass transfer to the active sites, resulting in exceptional catalytic performance for pollutant elimination. Experimental findings revealed close to 100% decomposition efficiency of 4-chlorophenol (4-CP) within an hour utilizing the nanoreactors over a wide pH range. The TiO2/CoTiO3 hollow nanoshells catalysts also displayed adaptability in disintegrating organic dyes and antibiotics. The radicals SO4•-, •OH, and non-radicals 1O2 were determined to be accountable for eliminating pollutants, as supported by trapping experiments and electron paramagnetic resonance spectra. The catalyst was confirmed as an electron donor and PMS as an electron acceptor through electrochemical tests and density functional theory calculations. This study underscores the potential of incorporating stable perovskite catalysts in hollow nanoreactors to enhance wastewater treatment.

Response of Extremely Small Populations to Climate Change-A Case of Trachycarpus nanus in Yunnan, China.

Climate change affects the geographical distribution of plant species. Rare Trachycarpus nanus with a narrow distribution range, high medicinal value and extremely small population is facing increasing extinction risks under global climate change. In this study, 96 recorded occurrences and 23 environmental factors are used to predict the potential suitable area of T. nanus based on the optimized MaxEnt (3.4.4) model and ArcGIS (10.7) software. The results show that when the parameters are FC = LQ and RM = 1, the MaxEnt model is optimal and AUC = 0.946. The distribution patterns were predicted in the past, present, and four future phases, i.e., 2021-2040 (2030), 2041-2060 (2050), 2061-2080 (2070), and 2081-2100 (2090). The main factors are the annual precipitation (bio12), mean temperature of the coldest quarter (bio11), temperature seasonality (bio4), precipitation of the wettest quarter (bio16), and isothermality (bio3). The potential distribution of T. nanus is primarily concentrated in central Chuxiong, encompassing a total potential suitable area of 5.65 × 104 km2. In historical periods, the total habitat area is smaller than that in the present. In the future, the potential suitable area is generally increased. The centroid analysis shows that T. nanus will move to a high-altitude area and to the southeast. But its dispersal capacity may not keep up with the climate change rate. Therefore, additional protection sites for this species should be appropriately established and the habitat connectivity should be enhanced.

Quantum dot-enabled infrared hyperspectral imaging with single-pixel detection.

Near-infrared (NIR) hyperspectral imaging is a powerful technique that enables the capture of three-dimensional (3D) spectra-spatial information within the NIR spectral range, offering a wide array of applications. However, the high cost associated with InGaAs focal plane array (FPA) has impeded the widespread adoption of NIR hyperspectral imaging. Addressing this challenge, in this study, we adopt an alternative approach-single-pixel detection for NIR hyperspectral imaging. Our investigation reveals that single-pixel detection outperforms conventional FPA, delivering a superior signal-to-noise ratio (SNR) for both spectral and imaging reconstruction. To implement this strategy, we leverage self-assembled colloidal quantum dots (CQDs) and a digital micromirror device (DMD) for NIR spectral and spatial information multiplexing, complemented by single-pixel detection for simultaneous spectral and image reconstruction. Our experimental results demonstrate successful NIR hyperspectral imaging with a detection window about 600 nm and an average spectral resolution of 8.6 nm with a pixel resolution of 128 × 128. The resulting spectral and spatial data align well with reference instruments, which validates the effectiveness of our approach. By circumventing the need for expensive and bulky FPA and wavelength selection components, our solution shows promise in advancing affordable and accessible NIR hyperspectral imaging technologies, thereby expanding the range of potential applications.

[Spatiotemporal Pattern and Influencing Factors of Thermal Environment Based on SEM Model: A Case Study in Xi'an Metropolitan Area].

The urban thermal environment is an important indicator for evaluating the ecological environment of a city. It directly affects the health of residents and the sustainable development of the urban economy. However, there is currently a lack of analysis on the impact pathways of the thermal environment considering both natural and human factors. Based on the MODIS MYD11A2 land surface temperature data, meteorological data, and human activity data of Xi'an metropolitan area in 2020, ArcGIS spatial geostatistical analysis was used to study the temporal and spatial distribution pattern of the thermal environment in different seasons, and redundancy analysis was utilized to select the main factors affecting the thermal environment. Then, structural equation modeling was used to quantify the direct and indirect effects of the dominant factors on the urban thermal environment. The results showed that:① The surface temperature in the Xi'an urban area showed a spatial pattern of higher temperatures in the north and lower temperatures in the south, with a decrease in temperature from the city center to the surrounding areas. The most severe heat environment pollution occurred in the summer. ② The redundancy analysis (RDA) results indicated that the main factors that affected the thermal environment were air temperature, impermeable surfaces, vegetation, and precipitation. ③ The results of the structural equation modeling (SEM) indicated that meteorological, surface, and anthropogenic factors affected the urban thermal environment mainly through direct pathways, which were much more important than all indirect pathways. Factors such as temperature, impervious surfaces, and point of interest density had a significant positive effect on the thermal environment (0.10 and 0.33). On the other hand, factors such as water bodies, precipitation, and vegetation had a significant negative effect on the thermal environment (-0.29 and -0.25). Human activities had a greater direct impact on nocturnal surface temperatures than surface and meteorological factors. Increasing economic efficiency is beneficial for mitigating the urban heat island effect. The results of the study can provide a reference for studying local climate change in urban heat islands and for the construction of green and ecologically livable urban environments.

Cross-Sectional and Prospective Association of Serum 25-Hydroxyvitamin D with Gut Mycobiota during Pregnancy among Women with Gestational Diabetes.

SCOPE: Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits. METHODS AND RESULTS: The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels. CONCLUSION: Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health.

Current Status of Weekly Insulin Analogs and Their Pharmacokinetic/Pharmacodynamic Evaluation by the Euglycemic Clamp Technique.

Diabetes mellitus represents a significant global health threat characterized by hyperglycemia caused by inadequate insulin secretion and/or insulin resistance. Exogenous insulin supplements had been recognized as a crucial treatment for achieving successful glycemic control in patients with Type 1 and most patients with Type 2 diabetes. Over the past century, substantial progress has been made in the development of novel insulin formulations, including the super-fast-acting and long-acting basal insulin analogs, of which the latter is indispensable for the management of nocturnal fasting and intraprandial blood glucose within the normal physiological range. Recently, combining chemical and genetic engineering with drug optimization have resulted in a formidable evolution in ultra-long-acting weekly insulin. Here, the current state of once-weekly insulin analogs and the euglycemic clamp technique used in the early clinical development to elucidate the pharmacokinetics and pharmacodynamics of this type of novel weekly insulin analogs were systematically overviewed.

Changes in air pollution, land surface temperature, and urban heat islands during the COVID-19 lockdown in three Chinese urban agglomerations.

COVID-19 has notably impacted the world economy and human activities. However, the strict urban lockdown policies implemented in various countries appear to have positively affected pollution and the thermal environment. In this study, Moderate Resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) and aerosol optical depth (AOD) data were selected, combined with Sentinel-5P images and meteorological elements, to analyze the changes and associations among air pollution, LST, and urban heat islands (UHIs) in three urban agglomerations in mainland China during the COVID-19 lockdown. The results showed that during the COVID-19 lockdown period (February 2020), the levels of the AOD and atmospheric pollutants (fine particles (PM2.5), NO2, and CO) significantly decreased. Among them, PM2.5 and NO2 decreased the most in all urban agglomerations, by >14 %. Notably, the continued improvement in air pollution attributed to China's strict control policies could lead to overestimation of the enhanced air quality during the lockdown. The surface temperature in all three urban agglomerations increased by >1 °C during the lockdown, which was mainly due to climate factors, but we also showed that the lockdown constrained positive LST anomalies. The decrease in the nighttime urban heat island intensity (UHIInight) in the three urban agglomerations was greater than that in the daytime quantity by >25 %. The reduction in surface UHIs at night was mainly due to the reduced human activities and air pollutant emissions. Although strict restrictions on human activities positively affected air pollution and UHIs, these changes were quickly reverted when lockdown policies were relaxed. Moreover, small-scale lockdowns contributed little to environmental improvement. Our results have implications for assessing the environmental benefits of city-scale lockdowns.