Association between hemoglobin A1c trajectory during pregnancy and adverse birth outcomes among non-gestational diabetic women.

AIMS: Previous studies have shown that higher hemoglobin A1c (HbA1c) levels within the normal range during pregnancy can increase the risk of adverse birth outcomes. However, the effects of the longitudinal HbA1c trajectory during pregnancy on adverse birth outcomes among non-gestational diabetic women are poorly characterized. We aimed to identify HbA1c trajectory during pregnancy among non-gestational diabetic women and to estimate their associations with adverse birth outcomes. METHODS: Data was extracted from the Information System of Guangdong Women and Children Hospital, China, from January 2017 to July 2022. This study involved 13,979 women who did not have gestational diabetes mellitus and underwent repeated HbA1c measurements during pregnancy. Latent mixture modeling was used to identify HbA1c trajectory groups. Logistic regression was applied to explore the associations between HbA1c trajectory groups and adverse birth outcomes, including preterm delivery, low birth weight, macrosomia, small for gestational age, and large for gestational age (LGA). RESULTS: Three HbA1c trajectory groups were identified: low-stable (range 4.0% [20 mmol/mol]-4.4% [25 mmol/mol]), moderate-stable (range 4.6% [27 mmol/mol]-5.1% [32 mmol/mol]), and elevated-increasing (range 5.0% [31 mmol/mol]-5.6% [38 mmol/mol]). Compared with the low-stable HbA1c group, the elevated-increasing group had a higher risk of preterm delivery and LGA. The adjusted OR (95% CIs) were 1.67 (1.13, 2.49) and 1.47 (1.01, 2.12) for preterm delivery and LGA, respectively. CONCLUSIONS: Among non-gestational diabetic women, the elevated-increasing HbA1c trajectory group was associated with a higher risk of preterm delivery and LGA. This finding emphasizes the importance of maintaining optimal HbA1c levels throughout pregnancy.

Polystyrene microplastics induce male reproductive toxicity in mice by activating spermatogonium mitochondrial oxidative stress and apoptosis.

Microplastics have emerged as environmental hazards in recent years. This study was intended to prove the toxic effects of microplastics on the male reproductive system and further elucidate its mechanism. C57bl/6 mice were exposed to ultrapure water or different doses (0.25, 0.5 and 1 mg/d) of 5 µm polystyrene microplastics (PS-MPs) for 4 weeks, and the GC-1 mouse spermatogonium was treated with different concentrations of PS-MPs. The results showed that sperm count and motility were decreased, and sperm deformity rate was increased after exposure to PS-MPs. The morphology of testes in PS-MPs groups exhibited pathological changes, such as abnormal development of spermatogenic tubules, and inhibited spermatogonium function. Furthermore, the fluorescence intensity of TUNEL staining and the BAX/BCL2 ratio were increased. Exposure to PS-MPs resulted in impaired mitochondrial morphology of spermatogonium, decreased activity of GSH-px and SOD, and increased the MDA level. In vitro, after treatment with PS-MPs, the cell apoptosis rate of spermatogonium was significantly increased, mitochondrial membrane potential was decreased, mitochondrial morphology was damaged, and exposure to PS-MPs increased mitochondrial reactive oxygen species, inducing an oxidative stress state in spermatogonia. In summary, PS-MPs induced a decrease in sperm quality by activating spermatogonium mitochondrial oxidative stress and apoptosis, offering novel insights into mitigating the reproductive toxicity of microplastics.

Clinically Applicable Pan-Origin Cancer Detection for Lymph Nodes via AI-Based Pathology.

Lymph node metastasis is one of the most common ways of tumour metastasis. The presence or absence of lymph node involvement influences the cancer's stage, therapy, and prognosis. The integration of artificial intelligence systems in the histopathological diagnosis of lymph nodes after surgery is urgent. Here, we propose a pan-origin lymph node cancer metastasis detection system. The system is trained by over 700 whole slide images and is composed of two deep learning models to locate the lymph nodes and detect cancers. It achieved a area under the receiver operating characteristic (ROC) curve (AUC) of 0.958, with a 95.2% sensitivity and 72.2% specificity, on 1,402 whole-slide images (WSIs) from 49 organs at the National Cancer Center, China. Moreover, we demonstrated that the system could perform robustly with 1,051 WSIs from 52 organs from another medical center, with a AUC of 0.925. Our research represents a step forward in a pan-origin lymph node metastasis detection system, providing accurate pathological guidance by reducing the probability of missed diagnosis in routine clinical practice.

Oxidative stress-induced neurotoxicity of quantum dots and influencing factors.

Quantum dots (QDs) have significant potential for treating and diagnosing CNS diseases. Meanwhile, the neurotoxicity of QDs has garnered attention. In this review, we focus on elucidating the mechanisms and consequences of CNS oxidative stress induced by QDs. First, we discussed the pathway of QDs transit into the brain. We then elucidate the relationship between QDs and oxidative stress from in vivo and in vitro studies. Furthermore, the main reasons and adverse outcomes of QDs leading to oxidative stress are discussed. In addition, the primary factors that may affect the neurotoxicity of QDs are analyzed. Finally, we propose potential strategies for mitigating QDs neurotoxicity and outline future perspectives for their development.

First-principles studies on the electronic and contact properties of monolayer Ga2STe-metal contacts.

Monolayer (ML) Janus III-VI compounds have attracted the use of multiple competitive platforms for future-generation functional electronics, including non-volatile memories, field effect transistors, and sensors. In this work, the electronic and interfacial properties of ML Ga2STe-metal (Au, Ag, Cu, and Al) contacts are systematically investigated using first-principles calculations combined with the non-equilibrium Green's function method. The ML Ga2STe-Au/Ag/Al contacts exhibit weak electronic orbital hybridization at the interface, while the ML Ga2STe-Cu contact exhibits strong electronic orbital hybridization. The Te surface is more conducive to electron injection than the S surface in ML Ga2STe-metal contact. Quantum transport calculations revealed that when the Te side of the ML Ga2STe is in contact with Au, Ag and Cu electrodes, p-type Schottky contacts are formed. When in contact with the Al electrode, an n-type Schottky contact is formed with an electron SBH of 0.079 eV. When the S side of ML Ga2STe is in contact with Au and Al electrodes, p-type Schottky contacts are formed, and when it is in contact with Ag and Cu electrodes, n-type Schottky contacts are formed. Our study will guide the selection of appropriate metal electrodes for constructing ML Ga2STe devices.

Tumour-derived exosome SNHG17 induced by oestrogen contributes to ovarian cancer progression via the CCL13-CCR2-M2 macrophage axis.

Oestrogen is known to be strongly associated with ovarian cancer. There was much work to show the importance of lncRNA SNHG17 in ovarian cancer. However, no study has revealed the molecular regulatory mechanism and functional effects between oestrogen and SNHG17 in the development and metastasis of ovarian cancer. In this study, we found that SNHG17 expression was significantly increased in ovarian cancer and positively correlated with oestrogen treatment. Oestrogen could promote M2 macrophage polarization as well as ovarian cancer cells SKOV3 and ES2 cell exosomal SNHG17 expression. When exposure to oestrogen, exosomal SNHG17 promoted ovarian cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro, and tumour growth and lung metastasis in vivo by accelerating M2-like phenotype of macrophages. Mechanically, exosomal SNHG17 could facilitate the release of CCL13 from M2 macrophage via the PI3K-Akt signalling pathway. Moreover, CCL13-CCR2 axis was identified to be involved in ovarian cancer tumour behaviours driven by oestrogen. There results demonstrate a novel mechanism that exosomal SNHG17 exerts an oncogenic effect on ovarian cancer via the CCL13-CCR2-M2 macrophage axis upon oestrogen treatment, of which SNHG17 may be a potential biomarker and therapeutic target for ovarian cancer responded to oestrogen.

Oxymatrine alleviates high-fat diet/streptozotocin-induced non-alcoholic fatty liver disease in C57BL/6 J mice by modulating oxidative stress, inflammation and fibrosis.

Non-alcoholic fatty liver disease (NAFLD) represents a complex complication of type 2 diabetes mellitus (T2DM). Oxymatrine (OMT) is an alkaloid extracted from Sophora flavescens with broad pharmacological effects. However, there is currently a lack of research on OMT in the field of NAFLD. The present study aimed to explore the effects and underlying mechanisms of oxymatrine in treating T2DM with NAFLD. The T2DM mice model was induced by high-fat diet (HFD) combined with streptozotocin (STZ) injection in male C57BL/6 J mice. Animals were randomly divided into four groups (n = 8): Control group, DC group, OMT-L group (45 mg/kg i.g.), and OMT-H group (90 mg/kg, i.g.). The drug was administered once a day for 8 weeks. In addition, HepG2 hepatocytes were incubated with palmitic acid (PA) to establish a fatty liver cell model. Treated with OMT, the body weight and fasting blood glucose (FBG) of DC mice were reduced and the liver organ coefficient was significantly optimized. Meanwhile, OMT markedly enhanced the activities of key antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and also reduced malondialdehyde (MDA) levels. These biochemical alterations were accompanied by noticeable improvements in liver histopathology. Furthermore, OMT down-regulated the expression of NOD-like receptor protein 3 (NLRP3), interleukin-1ß (IL-1ß), transforming growth factor-ß1 (TGF-ß1) and collagen I significantly, highlighting its potential in modulating inflammatory and fibrotic pathways. In conclusion, OMT improved liver impairment effectively in diabetic mice by suppressing oxidative stress, inflammation and fibrosis. These results suggest that OMT may represent a novel therapy for NAFLD with diabetes.

Symptom and comorbidity burden in hypertensive patients with obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is an important but frequently overlooked risk factor for hypertension (HTN). The prevalence of hypertension is high in patients with OSA, but the differences in clinical symptoms and comorbidities between patients with OSA with hypertension and those with normal blood pressure have not been fully defined. Methods: This study retrospectively analyzed OSA patients diagnosed for the first time in Lihuili Hospital Affiliated to Ningbo University from 2016 to 2020. Patients were divided into an OSA group with hypertension and an OSA group without hypertension. The sociodemographic information, clinical symptoms, comorbidities, and polysomnography results of the two groups were compared. The independent risk factors associated with hypertension in patients with OSA were explored. Results: A total of 1108 patients with OSA initially diagnosed were included in the study, including 387 with hypertension and 721 without. Compared with OSA patients without hypertension, OSA patients with hypertension were older; had a higher body mass index (BMI) and Epworth sleepiness score (ESS); a higher incidence of nocturia; and a higher proportion of diabetes mellitus, coronary heart disease, and cerebrovascular disease. Multivariate analysis showed age (odds ratio [OR]:1.06, 95% confidence interval [CI]:1.04-1.08), BMI (OR:1.17, 95% CI:1.11-1.23), ESS score (OR:0.97, 95%CI: 0.94-1.00) and nocturia symptoms (OR:1.64, 95% CI:1.19-2.27) was independently associated with hypertension in OSA patients, and comorbid diabetes (OR: 3.86, 95% CI: 2.31-6.45), coronary heart disease (OR: 1.90, 95% CI:1.15-3.16), and ischemic stroke (OR: 3.69,95% CI:1.31-10.40) was independently associated with hypertension in OSA patients. Conclusion: Compared to OSA patients with normal blood pressure, OSA patients with hypertension had more significant daytime sleepiness, more frequent nocturnal urination, and a higher risk of diabetes, coronary heart disease, and cerebrovascular disease.

Changes in serum inflammatory factors after hip arthroplasty and analysis of risk factors for prosthesis loosening.

OBJECTIVE: To explore the relationship of serum levels of IL-1ß, IL-6, and TNF-α with prosthesis loosening after hip arthroplasty, and to establish a predictive model for prosthesis loosening. METHODS: We retrospectively analyzed the data of 501 patients who underwent hip arthroplasty in Xi'an International Medical Center Hospital from January 2020 to August 2022. Based on radiological diagnosis, the patients were divided into a prosthesis loosening group and a non-loosening group. Clinical data including postoperative serum levels of inflammatory cytokines were collected. Univariant analysis, Lasso regression, decision tree, and random forest models were used to screen feature variables. Based on the screening results, a nomogram model for predicting the risk of prosthesis loosening was established and then validated using ROC curve, and calibration curve, and other methods. RESULTS: There were 50 cases in the loosening group and 451 cases in the non-loosening group. Postoperative levels of IL-1ß, IL-6, and TNF-α were found to be significantly higher in the loosening group (P<0.0001). Univariant analysis showed that osteoporosis and postoperative infection were risk factors for prosthesis loosening (P<0.001). The machine learning algorithm identified osteoporosis, postoperative infection, IL-1ß, IL-6, and TNF-α as 5 relevant variables. The predictive model based on these 5 variables exhibited an area under the ROC curve of 0.763. The calibration curve and DCA curve verified the accuracy and practicality of the model. CONCLUSION: Serum levels of IL-1ß, IL-6, and TNF-α were significantly elevated in patients with postoperative prosthesis loosening. Osteoporosis, postoperative infection, and inflammatory cytokines are independent risk factors for prosthesis loosening. The predictive model we established through machine learning can effectively determine the risk of prosthesis loosening. Monitoring inflammatory cytokines and postoperative infections, combined with prevention of osteoporosis, can help reduce the risk of prosthesis loosening.

[Analysis of Spatio-temporal Distribution Characteristics and Influencing Factors of PM2.5 Concentration in Urban Agglomerations on the Northern Slope of Tianshan Mountains].

Analysis of the spatial and temporal distribution characteristics and influencing factors of PM2.5 concentrations for the urban agglomeration on the northern slope of Tianshan Mountain is of positive significance for regional economic construction and environmental protection. The spatial and temporal distributions of PM2.5 concentrations in the Tianshan North Slope urban agglomeration from March to November 2015 to 2021 were obtained through the inversion of the MCD19A2 aerosol product combined with meteorological factors using a geographically weighted regression (GWR) model, followed by the analysis of change trends and influencing factors. The results were as follows:① the high PM2.5 concentrations in the study area were mainly distributed in the oasis city cluster between the northern foot of Tianshan Mountain and the Gurbantunggut Desert, showing the spatial distribution characteristics of being "low around and high in the middle" and "low in the west and high in the east." The annual average value of ρ(PM2.5) in the study area was 16.98 µg·m-3, with high values mainly concentrated in the urban part of Urumqi and decreasing towards Changji and Fukang. The monthly average ρ(PM2.5) distribution pattern was consistent with the annual average, but there were seasonal differences as follows:autumn (20.32 µg·m-3) > spring (18.25 µg·m-3) > summer (12.47 µg·m-3). The accumulation phenomenon was more pronounced in spring and winter. ② The study area's annual average PM2.5 concentration showed a decreasing trend from 2015 to 2021, and the average value from March to October also showed a decreasing trend, with only a slight increase in November. From the analysis of the spatial distribution of PM2.5 concentration trends, the decrease was concentrated in the urban parts of major cities, especially in the urban part of Urumqi and its surrounding areas, where the decrease was the largest and the change was the most drastic. ③ Temperature and air pressure were positively correlated with PM2.5 concentrations, whereas relative humidity, wind speed, atmospheric boundary layer height, and precipitation were negatively correlated with PM2.5 concentrations. The degree of influence of each factor was ranked from high to low as follows:atmospheric boundary layer height > relative humidity > air pressure > air temperature > wind speed > precipitation.

A hollow Ag/AgCl nanoelectrode for single-cell chloride detection.

This work reports the construction of a miniaturized Ag/AgCl nanoelectrode on a nanopipette, which is capable of dual-functions of single-cell drug infusion and chloride detection and is envisioned to promote the study of chloride-correlated therapeutic effects.

Genome-Wide Network Analysis of Above- and Below-Ground Co-growth in Populus euphratica.

Tree growth is the consequence of developmental interactions between above- and below-ground compartments. However, a comprehensive view of the genetic architecture of growth as a cohesive whole is poorly understood. We propose a systems biology approach for mapping growth trajectories in genome-wide association studies viewing growth as a complex (phenotypic) system in which above- and below-ground components (or traits) interact with each other to mediate systems behavior. We further assume that trait-trait interactions are controlled by a genetic system composed of many different interactive genes and integrate the Lotka-Volterra predator-prey model to dissect phenotypic and genetic systems into pleiotropic and epistatic interaction components by which the detailed genetic mechanism of above- and below-ground co-growth can be charted. We apply the approach to analyze linkage mapping data of Populus euphratica, which is the only tree species that can grow in the desert, and characterize several loci that govern how above- and below-ground growth is cooperated or competed over development. We reconstruct multilayer and multiplex genetic interactome networks for the developmental trajectories of each trait and their developmental covariation. Many significant loci and epistatic effects detected can be annotated to candidate genes for growth and developmental processes. The results from our model may potentially be useful for marker-assisted selection and genetic editing in applied tree breeding programs. The model provides a general tool to characterize a complete picture of pleiotropic and epistatic genetic architecture in growth traits in forest trees and any other organisms.

Computational dissection of genetic variation modulating the response of multiple photosynthetic phenotypes to the light environment.

BACKGROUND: The expression of biological traits is modulated by genetics as well as the environment, and the level of influence exerted by the latter may vary across characteristics. Photosynthetic traits in plants are complex quantitative traits that are regulated by both endogenous genetic factors and external environmental factors such as light intensity and CO2 concentration. The specific processes impacted occur dynamically and continuously as the growth of plants changes. Although studies have been conducted to explore the genetic regulatory mechanisms of individual photosynthetic traits or to evaluate the effects of certain environmental variables on photosynthetic traits, the systematic impact of environmental variables on the dynamic process of integrated plant growth and development has not been fully elucidated. RESULTS: In this paper, we proposed a research framework to investigate the genetic mechanism of high-dimensional complex photosynthetic traits in response to the light environment at the genome level. We established a set of high-dimensional equations incorporating environmental regulators to integrate functional mapping and dynamic screening of gene‒environment complex systems to elucidate the process and pattern of intrinsic genetic regulatory mechanisms of three types of photosynthetic phenotypes of Populus simonii that varied with light intensity. Furthermore, a network structure was established to elucidate the crosstalk among significant QTLs that regulate photosynthetic phenotypic systems. Additionally, the detection of key QTLs governing the response of multiple phenotypes to the light environment, coupled with the intrinsic differences in genotype expression, provides valuable insights into the regulatory mechanisms that drive the transition of photosynthetic activity and photoprotection in the face of varying light intensity gradients. CONCLUSIONS: This paper offers a comprehensive approach to unraveling the genetic architecture of multidimensional variations in photosynthetic phenotypes, considering the combined impact of integrated environmental factors from multiple perspectives.

The Global Leadership Initiative on Malnutrition criteria for diagnosis of malnutrition and outcomes prediction in emergency abdominal surgery.

OBJECTIVES: Malnutrition has adverse postoperative outcomes, especially in emergency surgery. Among the numerous tools for nutritional assessment, this study aims to investigate malnutrition diagnosed by Global Leadership Initiative on Malnutrition criteria and the Global Leadership Initiative on Malnutrition predictive value for outcomes after emergency abdominal surgery. METHODS: This was a prospective observational study. Among the 468 patients undergoing emergency abdominal surgery admitted to a department of emergency surgery from June 2020 to December 2021, 53 patients were not eligible for enrollment, and 19 patients had missing data. Thus, the final number of participants was 396. Muscle mass was evaluated by skeletal muscle index at the third lumbar vertebra on computed tomography scans, and the lower quartile was defined as the threshold of muscle mass reduction. The associations of Global Leadership Initiative on Malnutrition, Global Leadership Initiative on Malnutrition (muscle mass reduction excluded), and skeletal muscle index with in-hospital mortality, postoperative complications, and postoperative stay were evaluated using χ2. In addition, confounding factors were screened, regression models were established, and the Global Leadership Initiative on Malnutrition predictive value was analyzed for clinical outcome. Ethical approval was obtained from the appropriate department. RESULTS: Malnutrition was observed in 19.9% of the total 396 patients based on the Global Leadership Initiative on Malnutrition and in 12.4% on the Global Leadership Initiative on Malnutrition (muscle mass reduction excluded). Sarcopenia by skeletal muscle index was found in 24.7% of patients. Univariate analysis indicated that in-hospital mortality, postoperative complications, infective complication rate, and postoperative hospital stay were significantly higher in malnourished and sarcopenic patients. Multivariate analysis found that malnutrition diagnosed by the Global Leadership Initiative on Malnutrition was predictive for complications, infective complications, and postoperative stay (total postoperative complications: odds ratio = 3.620; 95% CI, 1.635-8.015; P = 0.002; infective complications: odds ratio = 3.127; 95% CI, 1.194-8.192; P = 0.020; and postoperative stay: regression coefficient = 2.622; P = 0.022). The Global Leadership Initiative on Malnutrition (muscle mass reduction excluded) identified postoperative complications and postoperative stay (total postoperative complications: odds ratio = 3.364; 95% CI, 1.247-9.075; P = 0.017 and postoperative stay: regression coefficient = 3.547; P = 0.009). Sarcopenia by skeletal muscle index was a risk factor for postoperative complications (odds ratio = 3.366; 95% CI, 1.587-7.140; P = 0.002). CONCLUSION: The Global Leadership Initiative on Malnutrition and Global Leadership Initiative on Malnutritison (muscle mass reduction excluded) had predictive value for adverse clinical outcomes due to malnutrition in patients undergoing emergency abdominal surgery.

Phellinus igniarius polysaccharides induced mitochondrial apoptosis of hepatic carcinoma by enhancing reactive oxygen species-mediated AKT/p53 signalling pathways.

Phellinus igniarius (PI) has various kinds of biological activities, such as antitumour activities, and polysaccharides are one of its main components. In this study, polysaccharides from PI (PIP) were prepared, purified, analysed for their structure and investigated for their antitumour activity and mechanism in vitro. PIP consists of 12138 kDa of carbohydrates containing 90.5 ± 1.6% neutral carbohydrates. PIP consists of glucose, galactose, mannose, xylose, D-fructose, L-guluronic acid, glucosamine hydrochloride, rhamnose, arabinose and D-mannoturonic acid. PIP can significantly inhibit HepG2 cell proliferation, induce cell apoptosis and also inhibited migration and invasion in a concentration-dependent manner. PIP increased reactive oxygen species (ROS), increased the expression of p53, and induced cytochrome c release into the cytoplasm to activate caspase-3. PIP is a promising potential candidate for the therapeutic treatment of hepatic carcinoma via the ROS-mediated mitochondrial apoptosis pathway.

Targeting Diverse Wounds and Scars: Recent Innovative Bio-design of Microneedle Patch for Comprehensive Management.

Wounds and the subsequent formation of scars constitute a unified and complex phased process. Effective treatment is crucial; however, the diverse therapeutic approaches for different wounds and scars, as well as varying treatment needs at different stages, present significant challenges in selecting appropriate interventions. Microneedle patch (MNP), as a novel minimally invasive transdermal drug delivery system, has the potential for integrated and programmed treatment of various diseases and has shown promising applications in different types of wounds and scars. In this comprehensive review, the latest applications and biotechnological innovations of MNPs in these fields are thoroughly explored, summarizing their powerful abilities to accelerate healing, inhibit scar formation, and manage related symptoms. Moreover, potential applications in various scenarios are discussed. Additionally, the side effects, manufacturing processes, and material selection to explore the clinical translational potential are investigated. This groundwork can provide a theoretical basis and serve as a catalyst for future innovations in the pursuit of favorable therapeutic options for skin tissue regeneration.

Erbin accelerates TFEB-mediated lysosome biogenesis and autophagy and alleviates sepsis-induced inflammatory responses and organ injuries.

Mounting attention has been focused on defects of the autophagy-lysosomal pathway in sepsis, however, the precise mechanisms governing the autophagy-lysosomal process in sepsis are poorly known. We have previously reported that Erbin deficiency aggravated the inflammatory response and organ injuries caused by sepsis. In the present study, we found that Erbin knockout impaired the autophagy process in both muramyl dipeptide (MDP)-induced bone marrow-derived macrophages (BMDMs) and sepsis mouse liver and lung, as detected by the accumulation of LC3-II and SQSTM1/p62, and autophagosomes. Pretreatment with autophagy inhibitor chloroquine (CQ) further aggravated inflammatory response and organ injuries in vivo and in vitro sepsis model. We also observed that the impaired lysosomal function mediated autophagic blockade, as detected by the decreased expression of ATP6V, cathepsin B (CTSB) and LAMP2 protein. Immunoprecipitation revealed that the C-terminal of Erbin (aa 391-964) interacts with the N-terminal of transcription factor EB (TFEB) (aa 1-247), and affects the stability of TFEB-14-3-3 and TFEB-PPP3CB complexes and the phosphorylation status of TFEB, thereby promote the nucleus translocation of TFEB and the TFEB target genes transcription. Thus, our study suggested that Erbin alleviated sepsis-induced inflammatory responses and organ injuries by rescuing dysfunction of the autophagy-lysosomal pathway through TFEB-14-3-3 and TFEB-PPP3CB pathway.

Exposure to organochlorine pesticides and polychlorinated biphenyls, adherence to an ideal cardiovascular health, and arterial stiffness among Chinese adults.

This study aimed to assess the relationships between exposure to individual organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and their mixture and arterial stiffness and explore whether adherence to an ideal cardiovascular health (CVH) could mitigate these associations. The cross-sectional study enrolled 1437 Chinese adults between March and May 2019 in Wuhan, China. OCPs and PCBs concentrations were measured using solid phase extraction coupled with gas chromatography-tandem mass spectrometry. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). CVH was determined by three behavioral and four biological metrics and categorized as ideal, intermediate, and poor CVH. We applied generalized linear model and weighted quantile sum (WQS) regression to evaluate the associations of exposure to individual OCPs or PCBs and their mixture with baPWV, respectively. We found that participants with detectable levels of heptachlor epoxide, PCB-153, and PCB-180 had higher baPWV (ß: 34.25, 95% CI 14.28-54.22; ß: 27.64, 95% CI 7.90-47.38; and ß: 30.51, 95% CI 10.68-50.35) than those with undetectable levels. In WQS regression, the mixture of OCPs and PCBs was related to a higher baPWV (ß: 24.93, 95% CI 2.70-47.15). Compared with participants with ideal CVH and undetectable OCPs or PCBs levels, those with poor CVH and detectable OCPs or PCBs levels had the highest increase in baPWV (heptachlor epoxide: ß: 147.94, 95% CI 112.52-183.55; PCB-153: ß: 150.22, 95% CI 115.40-185.04; PCB-180: ß: 147.02, 95% CI 111.66-182.38). Our findings suggested that individual OCPs, PCBs, and their mixture exposure were positively associated with arterial stiffness, and adherence to an ideal CVH may mitigate the adverse effect.

Alternative splicing of histone demethylase Kdm6bb mediates temperature-induced sex reversal in the Nile tilapia.

Sex determination in many fish species is remarkably plastic and temperature sensitive. Nile tilapia display a genetic sex-determination system (XX/XY). However, high-temperature treatment during critical thermosensitive periods can induce XX females into XXm pseudo-males, and this phenomenon is termed temperature-induced sex reversal (TISR). To investigate the molecular mechanism of TISR in Nile tilapia, we performed Iso-seq analysis and found a dramatic effect of high temperature on gene alternative splicing (AS). Kdm6bb histone demethylase showed a novel AS at intron 5 that generates Kdm6bb_tv1 transcripts without intron 5 and Kdm6bb_tv2 with intron 5. Kdm6bb_tv1 encodes a full-length protein while Kdm6bb_tv2 encodes a truncated protein. Expression analysis revealed that intron 5 splicing of Kdm6bb is male and gonad biased at larval stage, and only gonad biased at adult stage. High-temperature treatment induced intron 5 splicing in the gonads of XX and XY fish, resulting in increased Kdm6bb_tv1 expression. To directly test the role of Kdm6bb_tv1 in Nile tilapia TISR, we knocked out expression of Kdm6bb_tv1. However, Kdm6bb_tv1-/- homozygous mutants showed embryonic lethality. Overexpression of Kdm6bb_tv1, but not Kdm6bb_tv2, induced sex reversal of XX females into pseudo-males. Overexpression of Kdm6bb_tv1, as with high-temperature treatment, modified the promotor region of Gsdf and Dmrt1 by demethylating the trimethylated lysine 27 of histone 3 (H3K27me3), thereby increasing expression. Collectively, these studies demonstrate that AS of Kdm6bb intron 5 increases the expression of Kdm6bb_tv1, which acts as a direct link between high temperature and activation of Gsdf and Dmrt1 expression, leading to male sex determination.

Interfacial electronic states and self-formed asymmetric Schottky contacts in polar α-In2Se3/Au contacts.

In recent years, the two-dimensional (2D) semiconductor α-In2Se3 has great potential for applications in the fields of electronics and optoelectronics due to its spontaneous iron electrolysis properties. Through ab initio electronic structure calculations and quantum transport simulations, the interface properties and transport properties of α-In2Se3/Au contacts with different polarization directions are studied, and a two-dimensional α-In2Se3 asymmetric metal contact design is proposed. When α-In2Se3 is polarized upward, it forms an n-type Schottky contact with Au. While when α-In2Se3 is polarized downward, it forms a p-type Schottky contact with Au. More importantly, significant rectification effect is found in the asymmetric Au/α-In2Se3/Au field-effect transistor. The carrier transports under positive and negative bias voltages are found to be dominated by thermionic excitation and tunneling, respectively. These findings provide guidance for the further design of 2D α-In2Se3-based transistors.