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ABSTRACT: Bisphenol A (BPA) is widely applied in plastic products, which will produce immunotoxicity to organisms after spilling in the environment, and become a kind of endocrine disruptor. Selenium (Se) is an essential trace element and plays an important role in maintaining redox homeostasis and immune function. BPA exposure and Se deficiency often occur together in livestock and poultry farming, however, studies on the effects of joint exposure on chicken immunotoxins have not been reported. Therefore, this study established a chicken spleen and MDCC-MSB1 cell model under the combined effects of BPA exposure or/and Se deficiency. Transcriptomic analysis showed that BPA exposure and/or Se deficiency induced differential enrichment of positive regulatory pathways such as NLRP3 inflammatory complex assembly, inflammatory response and cellular oxidative stress response. In the -Se+BPA group, pathological damage was significantly increased, Se content decreased, BPA accumulation, oxidative stress and pyroptosis. Meanwhile, the roles and mechanisms of oxidative stress and pyroptosis in BPA exposure or/and Se deficiency-induced splenic tissue injury were investigated by using IF and qRT-PCR methods. The results showed that joint BPA exposure with Se deficiency resulted in more significant changes in the above outcomes than 1 of them. The oxidative stress inhibitor NAC effectually reduced Se deficiency and BPA-induced oxidative stress and pyroptosis, further suggests that oxidative stress mediated Se deficiency or/and BPA-induced pyroptosis. This study revealed that BPA exposure and Se deficiency induced spleen pyroptosis in chickens via the ROS/NLRP3 pathway. These results provide the theoretical basis for the toxicity of BPA in poultry and enrich the toxicological mechanism of combined exposure of Se deficiency and environmental toxins.

Purpose: This study aimed to investigate the prevalence of refractive error (RE) and risk factors for myopia among older adults in the Han and various minority ethnic groups across seven provinces in China. Methods: This cross-sectional study forms a part of the ophthalmic dataset of the China National Health Survey (CNHS). Face-to-face interviews and ophthalmic examinations were conducted in seven provinces located in western and northern China. The age- and sex-adjusted prevalence of RE among Han and seven other ethnic groups aged 50–80 years were compared. A mixed-effects model was used to identify the risk factors associated with RE. Results: A total of 12,902 participants, including 8800 Han and 4102 from ethnic minorities, were included in the study. The age- and sex-adjusted prevalence of myopia, high myopia, hyperopia, and astigmatism ranged from 15.3 % (Manchu) to 22.9 % (Han), 0.2 % (Yugur) to 2.8 % (Han), 21.6 % (Tibetan) to 48.9 % (Uyghur), and 38.7 % (Yi) to 57.5 % (Manchu) across different ethnicities, respectively. Compared to the Han population, the Mongolian (odds ratios (OR) 0.62, 95 % confidence interval (CI) 0.46–0.84, p = 0.002), Tibetan (OR 0.66, 95 % CI 0.52–0.85, p = 0.001), Uyghur (OR 0.63, 95 % CI 0.49–0.80, p 18.5 kg/m2 (all p 24 kg/m2 (p = 0.038 in the >24.0 ≤ 27.0 kg/m2 group or p = 0.041 in the >27.0 kg/m2 group) were less likely to have high myopia. Factors associated with a higher prevalence of hyperopia included older age (all p

DNA methylation can deactivate tumor suppressor genes thus causing cancers. Two DNA methylation inhibitors have been approved by the Food and Drug Administration (FDA) and have entered clinical use. However, these inhibitors are nucleoside analogues that can be incorporated into DNA or RNA and induce significant side effects. DNMT1 and DNMT3 are key enzymes involved in DNA methylation. In the acute myeloid leukemia model, a non-nucleoside DNMT1-specific inhibitor has shown lower toxicity and improved pharmacokinetics compared to traditional nucleoside drugs. DNMT3 is also implicated in certain specific cancers. Thus, developing non-nucleoside inhibitors for DNMT1 or DNMT3 can help in understanding their roles in carcinogenesis and provide targeted treatment options in certain cancers. Although no non-nucleoside inhibitors have yet entered clinical trials, in this review, we focus on DNMT1 or DNMT3 selective inhibitors. For DNMT1 selective inhibitors, we have compiled information on the repurposed drugs, derivative compounds and selective inhibitors identified through virtual screening. Additionally, we have outlined potential targets for DNMT1, including protein-protein complex, RNA mimics and aptamers. Compared to DNMT1, research on DNMT3-specific inhibitors has been less extensive. In this context, our exploration has identified a limited number of molecular inhibitors, and we have proposed specific long non-coding RNAs (lncRNAs) as potential contributors to the selective inhibition of DNMT3. This collective effort aims to offer valuable insights into the development of non-nucleoside inhibitors that selectively target DNMT1 or DNMT3.

Microsatellite DNA (SSR) is extensively used as molecular markers in diverse fields, including molecular ecology, conservation biology, and molecular breeding. Nevertheless, the efficient and easy acquisition of high-quality SSR molecular markers for economically cultured marine animals remains a challenge. Holothuria leucospilota is an economically and ecologically important tropical sea cucumber. Recently, artificial breeding and cultivation of this species have been reported. However, there is still a lack of highly polymorphic SSR molecular markers for geographical population differentiation and genetic breeding. This study aims to develop and utilize SSR markers from genomic data to assess the genetic variation and population structure of H. leucospilota in the South China Sea. A comprehensive pipeline was created, integrating microsatellite discovery, primer design, and assessment into a single platform. Through this, 15 highly polymorphic microsatellite loci were identified and validated. The results revealed high genetic diversity and low genetic differentiation among H. leucospilota populations. Larval dispersal and ocean currents in the South China Sea were identified as the primary factors influencing genetic connectivity between populations. In addition, the artificial culture and releasing of H. leucospilota have influenced the genetic structure of their wild populations in the South China Sea. This study provides a pipeline for identifying SSR markers within genome data, and applies it to assess the genetic diversity and structure of H. leucospilota. The outcomes of this research are expected to be beneficial and applicable to the future aquaculture of tropical sea cucumbers.

Additively manufactured (AM) components—either made by laser-powder bed fusion or wire and arc additive manufacturing—typically contain process-related defects on and near surfaces that can be removed by machining. Various studies have shown that post-treatment, such as machining significantly improves the fatigue strength of AM parts. To this day, however, hardly any studies have investigated the fatigue strength of post-treated additively manufactured components with notches. In this study, fatigue tests were performed on plain and notched specimens to determine and compare the crack initiation and crack propagation behavior due to different manufacturing-related effects. Tests were performed on specimens produced by the two aforementioned AM processes and compared to specimens taken from wrought sheets. The fatigue strength of AM materials is influenced by microstructure, defects, residual stress, and notches. PBF-LB/M specimens exhibit the highest fatigue strength in plain, notch-free conditions, attributed to differences in microstructure and static strength affecting fatigue crack initiation. Notched specimens show larger differences among materials, with PBF-LB/M having shorter fatigue crack propagation life related to line-type defect clusters, while the plain PBF-LB/M specimens are less affected as their fatigue strength is primarily determined by fatigue crack initiation.

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is an important manifestation and mechanism of pulmonary vascular remodeling. Resolvin D1 (RvD1) is an endogenous lipid mediator promoting the resolution of inflammation. However, the role of RvD1 on EndMT in PH remains unknown. Here, we aimed to investigate the effect and mechanisms of RvD1 on the treatment of PH. We showed that RvD1 and its receptor FPR2 expression were markedly decreased in PH patients and both chronic hypoxia-induced PH (CH-PH) and sugen 5416/hypoxia-induced PH (SuHx-PH) mice models. RvD1 treatment decreased right ventricular systolic pressure (RVSP) and alleviated right ventricular function, and reduced pulmonary vascular remodeling and collagen deposition in the perivascular of both two PH mice models. Then, RvD1 inhibited EndMT in both the lungs of PH mice models and primary cultured human umbilical vein endothelial cells (HUVECs) treated with TGF-β and IL-1β. Moreover, RvD1 inhibited EndMT by downregulating Smad2/3 phosphorylation in vivo and in vitro via FPR2. In conclusion, our date suggest that RvD1/FPR2 axis prevent experimental PH by inhibiting endothelial-mensenchymal-transition and may be a therapeutic target for PH.

Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019. The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status. Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvesting, the timely application of nitrogen fertilizer is fundamental, coupled with moderate field drying for root-vigor preservation and tiller promotion before and after the mechanical harvesting of the main crop.

This article uses minimum quantity lubrication technology to replace traditional machining. A mixed nanofluid cutting fluid MNFCF was prepared using base oil, LINN4444 ionic liquid, and nanoparticles as raw materials, and its tribological and drilling properties were studied. In the tribological performance test, the friction coefficient of the mixed nanofluid MNFCF is only 0.13. Compared with the control, the wear amount of MNFCF has decreased by about 75%, indicating that MNFCF has good anti friction and wear performance. Similarly, in the drilling performance test, the drilling test temperature of MNFCF cutting fluid decreased by 36.5% compared to the same. After drilling and testing, there was almost no BUE, BUL, or wear on the surface of the tool, with only a small amount of adhesive observed. The results indicate that MNFCF has good potential in drilling Inconel 690 high-temperature alloy.

This study investigated the production performance, carcass characteristics, and meat quality attributes of broilers fed with different doses of Monascus-fermented Moringa oleifera leaves. A total of 400 one-day-old unsexed Greenleg partridge broilers were randomly divided into 4 dietary which were fed a basal diet supplemented with 0, 5% Monascus-fermented Moringa oleifera leaves, 10% Monascus-fermented Moringa oleifera leaves, and 10% Moringa oleifera leaves, respectively. Each group had 5 replicates of twenty birds each. The whole trial lasted for 63 d. The results indicated that a high dose of Moringa oleifera leaves supplement in broiler diet reduced the production performance, carcass characteristics, and meat quality attributes (P < 0.05). While the addition of the same dose of Monascus-fermented Moringa oleifera leaves reversed this adverse effect, and the 5% Monascus-fermented Moringa oleifer leaves supplement was found to be more effective (P < 0.05). In addition, Monascus-fermented Moringa oleifera leaves improved the concentration of amino acids and polyunsaturated fatty acids in the meat, which could be beneficial for human health. We conclude that, a 5% Monascus-fermented Moringa oleifera leaves supplement in the diet is beneficial in terms of improved growth performance and the functional attributes of meat than sole Moringa oleifera leaves supplement.

ABSTRACT: The present study aimed to investigate the effects of dietary fermented blueberry pomace (FBP) supplementation on production performance, egg quality and nutritional value, plasma biochemical parameters, follicle number, reproductive hormones, lipid metabolism, and antioxidant capacity of laying hens during the late laying period. A total of 320 (345-d-old) Yukou Jingfen No. 8 laying hens were randomly divided into 4 groups, with eight replicates per group and 10 hens per replicate. The birds were fed a basal diet (control group) and a basal diet supplemented with 0.25, 0.5, and 1.0% FBP. The trial lasted 56 d. The results showed that FBP (0.25−1.0%) supplementation increased the egg albumen height and Haugh unit compared with the control group on d 14, while 0.5 to 1.0% FBP increased the eggshell thickness compared with the 0.25% FBP group on d 28 of the trial (P < 0.05). The methionine content in egg white was higher (P < 0.05) in the 1.0% FBP group compared with the 0.25% FBP group. The CAT activity in the ovary was increased (P < 0.05) in the FBP groups compared with the control group, while plasma GSH-PX activity was higher (P < 0.05) in the 1.0% FBP group compared with the 0.25% FBP and 0.5% FBP groups. Dietary FBP supplementation up-regulated (P < 0.05) gene expressions related to lipid metabolism in the liver (ACC, FAS, SCD1, and SREBP1) and yolk precursor synthesis (ESR2 and VTG II). Moreover, CYP11A1 expression in the ovary was up-regulated (P < 0.05) in the FBP groups compared with the control group, as well as in the 0.25% FBP group compared with the 1.0% FBP group. In summary, dietary FBP supplementation improved egg quality and nutritional value, ovarian antioxidant capacity, and yolk precursor synthesis, while 1.0% FBP had better effects than 0.25 and 0.5% doses.

Summary: Endothelial cell (EC) damage or dysfunction serves as the initial event in the pathogenesis of various cardiovascular diseases. Progenitor cells have been postulated to be able to differentiate into ECs, facilitate endothelial regeneration, and alleviate vascular pathological remodeling. However, the precise cellular origins and underlying mechanisms remain elusive. Through single-cell RNA sequencing (scRNA-seq), we identified an increasing population of progenitors expressing stem cell antigen 1 (Sca1) during vascular remodeling in mice. Using both mouse femoral artery injury and vein graft models, we determined that Sca1+ cells differentiate into ECs, restored endothelium in arterial and venous remodeling processes. Notably, we have observed that the differentiation of Sca1+ cells into ECs is negatively regulated by the microRNA-145-5p (miR-145-5p)-Erythroblast transformation-specific-related gene (ERG) pathway. Inhibiting miR-145-5p promoted Sca1+ cell differentiation and reduced neointimal formation after vascular injury. Finally, a similar downregulation of miR-145-5p in human arteriovenous fistula was observed comparing to healthy veins.

Objective: There has been some evidence that dietary fiber may be associated with diabetic nephropathy (DN), but the relationship is still unclear. The purpose of this study was to examine the association between dietary fiber intake and DN. Methods: This cross-sectional study used National Health and Nutrition Examination Survey (NHANES) data collected between 2007 and 2020. Weighted multivariate logistic regression was used to examine the relation between dietary fiber intake and DN. In addition, fitted smoothed curves were used to explore potential non-linear relationships. If non-linearity was observed, inflection points were further calculated by a recursive algorithm. Results: The study finally included 5964 subjects ≥20 years of age. The mean age was 60.8 ± 13.4 years with males (52.4 %), and non-Hispanic Whites (62.4 %), and the weighted prevalence of DN was 36.7 %. Dietary fiber was negatively associated with the risk of DN after controlling for all confounding variables (OR = 0.89, 95%CI: 0.80, 0.99). Smoothed curve fit plots of the dose relationship showed that dietary fiber intake was linearly related to DN, whereas males (inflection point of 8.0 g/d) and non-Hispanic Blacks (inflection point of 14.9 g/d) followed a non-linear inverted U-shaped curve relationship. In United States adults aged 20 and older, dietary fiber intake may be associated with a reduced risk of DN. Conclusion: Appropriate increases in dietary fiber intake may offer potential benefits for DN. In conclusion, it appears that increasing dietary fiber intake may be one of the most effective strategies for the prevention and management of DN.

Background: Recent genetic evidence supports that circulating biochemical and metabolic traits (BMTs) play a causal role in Alzheimer's disease (AD), which might be mediated by changes in brain structure. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between blood BMTs, brain image-derived phenotypes (IDPs) and AD. Methods: Utilizing the genetic variants associated with 760 blood BMTs and 172 brain IDPs as the exposure and the latest AD summary statistics as the outcome, we analyzed the causal relationship between blood BMTs and brain IDPs and AD by using a two-sample Mendelian randomization (MR) method. Additionally, we used two-step/mediation MR to study the mediating effect of brain IDPs between blood BMTs and AD. Results: Twenty-five traits for genetic evidence supporting a causal association with AD were identified, including 12 blood BMTs and 13 brain IDPs. For BMTs, glutamine consistently reduced the risk of AD in 3 datasets. For IDPs, specific alterations of cortical thickness (atrophy in frontal pole and insular lobe, and incrassation in superior parietal lobe) and subcortical volume (atrophy in hippocampus and its subgroups, left accumbens and left choroid plexus, and expansion in cerebral white matter) are vulnerable to AD. In the two-step/mediation MR analysis, superior parietal lobe, right hippocampal fissure and left accumbens were identified to play a potential mediating role among three blood BMTs and AD. Conclusions: The results obtained in our study suggest that 12 circulating BMTs and 13 brain IDPs play a causal role in AD. Importantly, a subset of BMTs exhibit shared genetic architecture and potentially causal relationships with brain structure, which may contribute to the alteration of brain IDPs in AD.

In myocardial ischemia/reperfusion injury (MIRI), moderate mitophagy is a protective or adaptive mechanism because of clearing defective mitochondria accumulates during MIRI. However, excessive mitophagy lead to an increase in defective mitochondria and ultimately exacerbate MIRI by causing overproduction or uncontrolled production of mitochondria. Phosphatase and tensin homolog (PTEN)-induced kinase 1 (Pink1), Parkin, FUN14 domain containing 1 (FUNDC1) and B-cell leukemia/lymphoma 2 (BCL-2)/adenovirus E1B19KD interaction protein 3 (BNIP3) are the main mechanistic regulators of mitophagy in MIRI. Pink1 and Parkin are mitochondrial surface proteins involved in the ubiquitin-dependent pathway, while BNIP3 and FUNDC1 are mitochondrial receptor proteins involved in the non-ubiquitin-dependent pathway, which play a crucial role in maintaining mitochondrial homeostasis and mitochondrial quality. These proteins can induce moderate mitophagy or inhibit excessive mitophagy to protect against MIRI but may also trigger excessive mitophagy or insufficient mitophagy, thereby worsening the condition. Understanding the actions of these mitophagy mechanistic proteins may provide valuable insights into the pathological mechanisms underlying MIRI development. Based on the above background, this article reviews the mechanism of mitophagy involved in MIRI through Pink1/Parkin pathway and the receptor mediated pathway led by FUNDC1 and BNIP3, as well as the related drug treatment, aim to provide effective strategies for the prevention and treatment of MIRI.

Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.

Objectives: The Albumin-Bilirubin (ALBI) score has been widely used to assess the prognosis in patients with cirrhosis and hepatocellular carcinoma. This study aimed to analyze the relationship between ALBI score and all-cause mortality in patients with hepatitis B virus (HBV) infection in general. Methods: Patients aged ≥ 18 years with previous or current HBV infection from the National Health and Nutrition Examination Survey (NHANES) in the United States between 1999 and 2018 were enrolled in this retrospective cohort study. Weight univariate and multivariate Cox regression models were used to assess the relationship between ALBI score and all-cause mortality. The area under the receiver operating characteristic curve (AUC) was utilized to assess the predictive effect of ALBI score for all-cause mortality. Results: A total of 3,666 patients were included, of whom 925 (23.53 %) patients died. Compared with ALBI score ≤ -2.6, HBV-infected patients with ALBI score > -2.6 [hazard ratio (HR) = 1.75; 95 % confidence interval (CI): 1.43–2.14] were corrected with a higher all-cause mortality risk after adjusting for confounders. Stratified analyses showed that higher ALBI score was related to a higher risk of all-cause mortality in different patients with HBV infection (All P

Rice ratooning is a resource-saving and environment-friendly cropping system. It is therefore critical to accelerating the development of ratoon rice production, which has become an important guarantee to stabilize the rice planting area, improve the self-sufficiency rate of rice, and increase farmers' income in Fujian Province. This paper summarized the general rice production trend, the research progress of mechanically harvested ratoon rice technology in variety selection (breeding), fertilizer and water management, and stubble height management. Rice cultivars such as Yongyou 1540, Yongyou 4949, Longliangyouhuazhan, and Y-liangyou 900 were used in farmers' fields in major ratoon rice growing counties such as Pucheng, Jianyang, and Fuqing. The demonstration fields with the application of the ‘3–2–1’ mechanized rice ratooning technology achieved an annual yield of more than 15.00 ​t ​ha−1 for seven consecutive years. In 2021 and 2022, the yield of ratoon crop by the application of the ‘3–2–1’ mechanized rice ratooning technology reached 9.29 and 9.48 ​t ​ha−1, respectively. In this review, the challenges for the sustainable development of mechanized ratoon rice production were also discussed, and the countermeasures and policy interventions for promoting sound ratoon rice system in Fujian were further proposed.

Background: Although the neural mechanisms of the theory of mind (ToM) in children with autism spectrum disorder (ASD) through fMRI using the social animation task have been investigated, little is known in adults with ASD. Therefore, the present study aimed to explore the neural substrates of ToM in adults with ASD. Moreover, we aimed to elucidate the relationship between brain activation and behavior of social interaction in adults with ASD. Methods: Twenty-four healthy controls and 24 adults with the clinical diagnosis of ASD were recruited. Participants were asked to complete the social animation task in functional magnetic resonance imaging. The imaging analyses of within (whole brain analysis) and between (5 regions of interest) group comparisons were conducted to explore the process of ToM. The correlation analyses were further conducted to explore the relationship between neural activations associated with ToM and social interaction abilities assessed by ADI-R. Results: The ASD group showed greater activation in the left precuneus and right superior temporal gyrus (STG) than the control group. For correlation analyses, greater right STG activation was positively correlated with autistic symptoms assessed by the ADI-R in the ASD group. Conclusion: ASD adults might spend a lot of effort on identification processing, thereby influencing social communication skills. Also, the neural deficits of ToM in ASD adults might be associated with their social interaction difficulties.

Numerous smokers attempt to quit smoking, but most cessation efforts prove unsuccessful. Scarce evidence exists regarding predictors of long-term relapse in China. This study aims to evaluate the probability of relapse and examine factors may contribute to relapse among Chinese adults. A dynamic cohort of 6,036 observations on 2,378 adult quitters was constructed from the China Family Panel Studies in 2010, 2012, 2014, 2016 and 2018. The life table method was employed to calculate the probability of relapse for long-term smoking abstinence. Multivariate complementary log-log survival models were developed to examine the predictors of smoking relapse. We found that the probability of relapse decreased as the duration of abstinence increased, with rates of 49.07 %, 20.05 %, 10.29 %, and 6.63 % at 2, 4, 6, and 8 years of abstinence, respectively. The cumulative probability of relapse within 8 years was 65.89 %. Age ≥65 years, higher educational attainment, respiratory disease, and a satisfying lifestyle were associated with a reduced likelihood of relapse. Conversely, higher occupational prestige, alcohol drinking, cohabitant smoking, and greater future confidence were associated with an increased risk of relapse. These findings demonstrated that the probability of relapse decreased progressively over time, with most relapses occurring in the initial two years following quit attempts. Predictors of Chinese quitters’ relapse behavior in our study were similar to those in previous studies. Drinking and cohabitant smoking were identified as strong predictors of relapse in this population.

Study region: Haihe River Basin (HRB) in North China Plain. Study focus: Changes in streamflow due to climate change and human activities are highly uncertain. An improved Soil and Water Assessment Tool (SWAT) model equipped with a dynamic CO2 input method was used to quantify the environmental change impacts on streamflow in the HRB. Streamflow changes were analyzed based on 22 bias-corrected CMIP6 GCMs under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 during two 30-year periods of the middle (2041–2070) and end (2071–2100) of the 21st century relative to the historical period (1971–2000). New hydrological insights for the region: Long-term simulations of annual streamflow in the HRB demonstrated substantial discrepancies between the dynamic and constant CO2 input methods under the SSP1-2.6 and SSP5-8.5 scenarios, which highlighted the importance of using the dynamic CO2 input method for streamflow simulations. Spatio-temporal analysis using the improved SWAT model revealed that streamflow generally increased under four emission scenarios compared to the historical period. In the HRB, annual streamflow in the downstream plains was higher than in the upstream mountains, and this was more evident under the highest emission scenario of SSP5-8.5. Monthly streamflow showed considerable intra-annual variability that was generally greater from July to November. The strongest increment in streamflow was projected in the SSP3-7.0 and SSP5-8.5 scenarios, indicating that flood risk would possibly increase in the late 21st century.

Introduction: Cervical insufficiency is an increased risk of midterm miscarriage and early preterm birth which increase the risk of fetal loss. This study aimed to construct a nomogram for patients with cervical insufficiency after cervical cerclage, which may assist clinicians to have individualized treatment for patients with cervical insufficiency. Methods: A study was done retrospectively from January 2013 through July 2022 in our hospital. The primary outcomes were delivered at more than 28, 30, 32, or 34 gestational weeks. Kaplan-Meier curves were applied to analyze 17 variables. All patients were randomly split (147:64) into development and validation cohorts. Based on the multivariate Cox regression analysis, a nomogram was constructed through the 'rms' package in R. Results: A total of 211 patients with cervical insufficiency were enrolled: 121 had history-indicated cerclage; 58 had ultrasound-indicated cerclage and 32 had emergency cerclage. Times of gestations, times of miscarriages, IVF, abdominal pain, diagnostic classification, preoperative and postoperative management were demonstrated to impact overall extended days when delivering at more than 28 gestational weeks was set as the primary outcome. Except for preoperative and postoperative management, the above other five variables impacted the primary outcomes of delivering at more than 30, 32, or 34 gestational weeks. Postoperative tocolytics had an impact on the prognosis of patients who delivered at more than 30 gestational weeks. In development cohort data, a nomogram was established to predict overall extended days of patients with cervical cerclage. In present study, C-index was 0.662 in the development cohort and 0.687 in the validation cohort respectively, suggesting that the model presented some satisfied prediction. Moreover, the clinical decision curves for patients with delivering at more than 28, 30, 32 or 34 weeks set as primary outcomes also displayed that this nomogram demonstrated good clinical predictive usefulness. Conclusions: The nomogram developed in this study may be a valuable tool assisting clinicians to evaluate outcomes of patients with cervical insufficiency after cervical cerclage, which helps them develop individualized management for the patients.

Purpose: Cardiac radioablation is an emerging therapy for recurrent ventricular tachycardia. Electrophysiology (EP) data, including electroanatomic maps (EAM) and electrocardiographic imaging (ECGI), provide crucial information for defining the arrhythmogenic target volume. The absence of standardized workflows and software tools to integrate the EP maps into a radiation planning system limits their use. This study developed a comprehensive software tool to enable efficient utilization of the mapping for cardiac radioablation treatment planning. Methods and Materials: The tool, HeaRTmap, is a Python-scripted plug-in module on the open-source 3D Slicer software platform. HeaRTmap is able to import EAM and ECGI data and visualize the maps in 3D Slicer. The EAM is translated into a 3D space by registration with cardiac magnetic resonance images (MRI) or computed tomography (CT). After the scar area is outlined on the mapping surface, the tool extracts and extends the annotated patch into a closed surface and converts it into a structure set associated with the anatomic images. The tool then exports the structure set and the images as The Digital Imaging and Communications in Medicine Standard in Radiotherapy for a radiation treatment planning system to import. Overlapping the scar structure on simulation CT, a transmural target volume is delineated for treatment planning. Results: The tool has been used to transfer Ensite NavX EAM data into the Varian Eclipse treatment planning system in radioablation on 2 patients with ventricular tachycardia. The ECGI data from CardioInsight was retrospectively evaluated using the tool to derive the target volume for a patient with left ventricular assist device, showing volumetric matching with the clinically used target with a Dice coefficient of 0.71. Conclusions: HeaRTmap smoothly fuses EP information from different mapping systems with simulation CT for accurate definition of radiation target volume. The efficient integration of EP data into treatment planning potentially facilitates the study and adoption of the technique.

Objective: This study aims at investigating the potential targets and functional mechanisms of Scutellariae Radix-Coptidis Rhizoma (QLYD) against atherosclerosis (AS) through network pharmacology, molecular docking, bioinformatic analysis and experimental validation. Methods: The compositions of QLYD were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature, where the main active components of QLYD and corresponding targets were identified. The potential therapeutic targets of AS were excavated using the OMIM database, DrugBank database, DisGeNET database, CTD database and GEO datasets. The protein-protein interaction (PPI) network of common targets was constructed and visualized by Cytoscape 3.7.2 software. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to analyze the function of core targets in the PPI network. Molecular docking was carried out using AutoDockTools, AutoDock Vina, and PyMOL software to verify the correlation between the main components of QLYD and the core targets. Mouse AS model was established and the results of network pharmacology were verified by in vivo experiments. Results: Totally 49 active components and 225 corresponding targets of QLYD were obtained, where 68 common targets were identified by intersecting with AS-related targets. Five hub genes including IL6, VEGFA, AKT1, TNF, and IL1B were screened from the PPI network. GO functional analysis reported that these targets had associations mainly with cellular response to oxidative stress, regulation of inflammatory response, epithelial cell apoptotic process, and blood coagulation. KEGG pathway analysis demonstrated that these targets were correlated to AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, and NF-kappa B signaling pathway. Results of molecular docking indicated good binding affinity of QLYD to FOS, AKT1, and TNF. Animal experiments showed that QLYD could inhibit inflammation, improve blood lipid levels and reduce plaque area in AS mice to prevent and treat AS. Conclusion: QLYD may exert anti-inflammatory and anti-oxidative stress effects through multi-component, multi-target and multi-pathway to treat AS.

Best management practices (BMPs) have wide application in non-point source (NPS) pollution abatement in agricultural watersheds. Multivariate analysis of BMPs reduction effects taking their randomness and correlations into account is significant to spatial optimization of BMPs configuration. However, quantifying the correlations among high-dimensional random variables of BMPs effects is challenging and remains unexplored thoroughly. This study coupled the SWAT with the Vine Copula model to conduct multivariate analysis of BMPs reduction effects considering their randomness caused by hydro-meteorological variability along with correlations among different indicators (ammonium nitrogen, NH3-N; and total phosphorus, TP) and BMPs. The coupled model was applied to evaluate the multi-indicator effect of individual BMP and combined effect of various BMPs in the upper Boyang River basin, China. Results showed that bivariate copulas and three-dimensional vine copulas can efficaciously describe the dependence of BMPs effects. Simulation results indicate 43–100% probabilities of 45% NH3-N loads reduction, while 0–79% probabilities of 45% TP loads reduction for combined BMPs scenarios. Besides, the joint probabilities of different indicators in combined BMPs scenarios are generally lower than separate probabilities with 0–21% decrease, which is similar to individual BMP. Generally, joint probabilities using copulas can provide more accurate and factual knowledge of the risk and dependability of implementation of BMPs than univariate variables. The proposed model can conduct multivariate analysis of BMPs reduction effects and has great prospect in the future risk-based decision-making of NPS pollution management.

To date, studies on apoptosis in echinoderms mainly focus on the caspase-dependent extrinsic apoptotic pathway, while knowledges regarding the intrinsic apoptotic pathway is still limited. In this study, 55 genes belong to 7 families of the intrinsic apoptotic pathway, namely, Bcl-2, caspase, AIF, Cyt c, Apaf-1, Smac, HTRA2 and Endo G, were identified by screening of the genomic database of the tropical sea cucumber Holothuria leucospilota. The Bcl-2 family showed significant gene expansion in H. leucospilota but not in other echinoderms, while the pro-apoptotic factor Endo G is generally lost in echinoderms. Transcriptomic data showed that the genes of the intrinsic apoptotic pathway were ubiquitously expressed in all tissues, and all embryonic and larval developmental stages of H. leucospilota. The gene numbers and functional domains of the caspase family and AIF family were further clarified and showed conserved with their counterparts in vertebrates. In primary coelomocytes, the transcript expression of different caspases showed different responses to pathogenic challenges of vibrio and pathogen-associated molecular patterns, and environmental challenges of heave metal and reactive oxygen species. Overall, this study indicates that the intrinsic apoptotic pathway is conserved between vertebrates and echinoderms by using the sea cucumber H. leucospilota as a model. This study may contribute in increasing the knowledge of development and innate immunity in ancestral deuterostomia species.

Hydrogen sulfide (H2S) is the most recently discovered gasotransmitter molecule that activates multiple intracellular signaling pathways and exerts concentration-dependent antitumor effect by interfering with mitochondrial respiration and inhibiting cellular ATP generation. Inspired by the fact that H2S can also serve as a promoter for intracellular Ca2+ influx, tumor-specific nanomodulators (I-CaS@PP) have been constructed by encapsulating calcium sulfide (CaS) and indocyanine green (ICG) into methoxy poly (ethylene glycol)-b-poly (lactide-co-glycolide) (PLGA-PEG). I-CaS@PP can achieve tumor-specific biodegradability with high biocompatibility and pH-responsive H2S release. The released H2S can effectively suppress the catalase (CAT) activity and synergize with released Ca2+ to facilitate abnormal Ca2+ retention in cells, thus leading to mitochondria destruction and amplification of oxidative stress. Mitochondrial dysfunction further contributes to blocking ATP synthesis and downregulating heat shock proteins (HSPs) expression, which is beneficial to overcome the heat endurance of tumor cells and strengthen ICG-induced photothermal performance. Such a H2S-boosted Ca2+-involved tumor-specific therapy exhibits highly effective tumor inhibition effect with almost complete elimination within 14-day treatment, indicating the great prospect of CaS-based nanomodulators as antitumor therapeutics.

Herbal organic compounds (HOCs) are bioactive natural products from medicinal plants and some traditional Chinese medicines (TCMs). Recently, ingestion of a few HOCs with low bioavailability has been associated with alterations in gut microbiota, but the extent of this phenomenon remains unclear. Here, we systematically screened 481 HOCs against 47 representative gut bacterial strains in vitro and found that almost one-third of the HOCs exhibited unique anticommensal activity. Quinones showed a potent anticommensal activity, while saturated fatty acids exhibited stronger inhibition of the Lactobacillus genus. Flavonoids, phenylpropanoids, terpenoids, triterpenoids, alkaloids and phenols displayed weaker anticommensal activity, but steroids, saccharides and glycosides had hardly any effect on strain growth. Notably, S-configuration HOCs demonstrated stronger anticommensal activity than R-configuration HOCs. The strict screening conditions ensured high accuracy (95%) through benchmarking validation. Additionally, the effects of HOCs on human fecal microbiota profiling were positively correlated with their anticommensal activity against bacterial strains. Molecular and chemical features such as AATS3i and XLogP3 were correlated with the anticommensal activity of the HOCs in the random forest classifier. Finally, we validated that curcumin, a polyhydric phenol with anticommensal activity, improved insulin resistance in HFD mice by modulating the composition and metabolic function of gut microbiota. Our results systematically mapped the profile of HOCs directly affecting human gut bacterial strains, offering a resource for future research on HOC-microbiota interaction, and broadening our understanding of natural product utilization through gut microbiota modulation.

Objectives: Jian-Pi-Yin decoction (JPY), a prescription derived from the traditional Chinese medicine Shen-Ling-Bai-Zhu-San, has shown good clinical efficacy in the treatment of diarrhea caused by lactose intolerance. However, the mechanism of action of JPY in the treatment of diarrhea is not fully understood. Design: In this study, a rat diarrhea model was induced by high lactose feeding combined with standing on a small platform to investigate the ameliorating effect of JPY on hyper lactose-induced diarrhea in rats and its possible mechanism. Methods: The rat model of hyper lactose diarrhea was given high, medium, and low doses of JPY and the positive control drug Smida by gavage for 1 week. At the same time, NA+-H+ exchanger 3 (NHE3) inhibitor Tenapanor was administered orally for 3 weeks. Body weight, food intake, water intake, grip strength, and severity of diarrhea symptoms were measured in rats throughout the study. The serum, colon, and jejunum tissues of the model and drug-treated rats were collected for histopathological examination and analysis of relevant indicators. Results: JPY significantly alleviated the symptoms of fatigue, diet reduction and diarrhea in the model group. Glucagon-like peptide-1 (GLP-1) and cyclic adenosine monophosphate (cAMP) expression were also down-regulated after JPY treatment. JPY can significantly promote NHE3 in intestinal tissues of rats with diarrhea, and the mechanism is related to the decrease of GLP-1, inhibition of cAMP/PKA pathway activation, an increase of ubiquitin-specific protease 7 (USP7) and USP10 expression, and decrease of NHE3 ubiquitination and phosphorylation. Conclusion: JPY can reduce the expression of GLP-1, reduce the ubiquitination and phosphorylation of NHE3, regulate the expression of NHE3, at least partly improve ion transport in the intestinal epithelium, and improve the imbalance of electrolyte absorption, thus significantly reducing the diarrhea symptoms of rats with high lactose combined with small platform standing. Innovation: In this study, we explored the mechanism of intestinal GLP-1 activation of cAMP/PKA signaling pathway from multiple dimensions, and increased its expression by reducing phosphorylation and ubiquitination of NHE3, thereby treating chronic diarrhea associated with lactose intolerance.

Iodine has been successed in combating bacteria over a century, but its toxic effects on human skin tissues and cells have been overlooked. In this work, a cow dung biochar-based polyvinyl alcohol/polyvinylpyrrolidone hydrogel (BCPP) was designed to in situ produce iodine on-demand and regulate its release via the light triggering strategy for the infected wound therapy. Benefiting from the reactive oxygen species (ROS) generation and the photothermal conversion properties of cow dung biochar (BC), the as-prepared hydrogel in situ transformed iodide into active iodine under the visible (Vis) light irradiation and regulated the release of active iodine under the near-infrared (NIR) light irradiation. The active iodine combined with photodynamic and photothermal effects of BCPP endowed hydrogel excellent antibacterial effects on ampicillin-resistant Escherichia coli (AREC) and methicillin-resistant Staphylococcus aureus (MRSA) while showing low toxicity to the mammalian cells. The in vivo wound therapy test results demonstrated that this hydrogel resisted MRSA infection, accelerated the healing process, and promoted epithelial regeneration.

The change of in situ viscosity in micro-scale of tight oil reservoir has great influence on the seepage process. Due to the imperfection of in situ viscosity model and measuring method, the prediction of development effect and scientific guidance is affected. Here, an in situ viscosity model of seepage fluid in tight reservoirs is established, and the main influencing factors are studied. The in situ viscosity changes linearly with the bulk viscosity; When the average pore radius less than 500 nm, the in situ viscosity increased sharply. The approximate properties of boundary fluid and heavy oil are verified by experiments, and a method for measuring boundary fluid viscosity based on nuclear magnetic resonance (NMR) is found. According to the viscosity property of boundary fluid, the experiment is designed to verify the measurement method of boundary fluid viscosity by NMR.

Objectives: This study aimed to investigate the application status of preventive measures for feeding intolerance in patients with severe traumatic brain injury (STBI) in China and analysis the differences and their causes. Methods: A cross-sectional survey was conducted. From December 2019 to January 2020, ICU nurses and physicians of 89 hospitals in China were surveyed by using a questionnaire on preventive strategies for feeding intolerance in patients with STBI. The questionnaire included two parts: the general information of participants (10 items) and application of preventive measures for feeding intolerance in STBI patients (18 items). Results: Totally 996 nurses and physicians completed the questionnaire. Among various methods, gastrointestinal symptoms(85.0%) and injury severity (71.4%) were mostly used to assess gastrointestinal functions and risk of feeding intolerance among STBI patients, respectively. Initiating enteral nutrition (EN) within 24–48 h (61.5%), nasogastric tubes (91.2%), 30°–45° of head-of-bed elevation (89.5%), continuous feeding by pump (72.9%), EN solution temperature of 38–40 °C (65.5%),

Objective: To alleviate radiation-induced lung injury and prevent the related pneumonitis and pulmonary fibrosis by inhaled amifostine (AMI). Methods: 15 ​Gy 60Co γ-ray irradiation was performed on the thoracic area of rats once to establish the radiation injury model. AMI was intraperitoneally (i.p.) injected or intratracheally (i.t.) administered to the rats 30 ​min pre-irradiation. The protective effects of the two AMI administration manners were compared in the aspects of hematopoietic system, lung edema, and histopathological examination, and the mechanisms were explored. Results: Compared to i.p. AMI, i.t. AMI remarkably alleviated radiation-induced lung injury and prevented consequent pneumonitis or pulmonary fibrosis. Specifically, i.t. AMI notably protected white blood cells and platelets, reduced the lung wet/dry weight ratio, and decreased collagen volume fractions compared to the model group (P ​ ​0.05). The high therapeutic efficiency of i.t. AMI was related to its high antioxidation and anti-inflammation effects with downregulation of pro-inflammatory cytokines, the enhanced superoxide dismutase activity, the low levels of malondialdehyde and total proteins. Conclusion: Inhaled AMI is a promising medicine for preventing radiation-induced lung injury, including pneumonitis and pulmonary fibrosis.

Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ-ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy 60Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.

Air pollution remains a risk factor for the global burden of disease. Middle-aged and older people are more susceptible to air pollution because of their declining physical function and are more likely to develop diseases from long-term air pollution exposure. Studies of the effects of air pollution on cognitive function in middle-aged and older adults have been inconsistent. More representative and definitive evidence is needed. This study analysed data from the Chinese Family Panel Study, an ongoing nationwide prospective cohort study, collected in waves 2014, 2016 and 2018. Rigorously tested instrument was selected for analysis and participants’ PM2.5 and instrument exposures were assessed using high-precision satellite data. The causal relationship between long-term exposure to air pollution and poor cognitive function in middle-aged and older adults was investigated using the Correlated Random Effects Control Function (CRE-CF) method within a quasi-experimental framework. This study included a total of 7042 participants aged 45 years or older. A comparison of CRE-CF with other models (OLS model, ordered probit model, and ordered probit-CRE model) demonstrated the necessity of using CRE-CF given the endogeneity of air pollution. The credibility and validity of the instrumental variable were verified. In the CRE-CF model, long-term exposure to PM2.5 was found to accelerate cognitive decline in middle-aged and older adults (coefficients of −0.159, −0.336 and −0.244 for the total cognitive, verbal and mathematical scores, respectively). Taken together, these results suggest that chronic exposure to ambient air pollution is associated with cognitive decline in middle-aged and older adults, which highlights the need for appropriate protective policies.

Objective: Obesity and related diseases are becoming a growing risk for public health around the world due to the westernized lifestyle. Sema7A, an axonal guidance molecule, has been known to play a role in neurite growth, bone formation, and immune regulation. Whether Sema7A participates in obesity and metabolic diseases is unknown. As several SNPs in SEMA7A and its receptors were found to correlate with BMI and metabolic parameters in the human population, we investigated the potential role of Sema7A in obesity and hepatic steatosis. Methods: GWAS and GEPIA database was used to analyze SNPs in SEMA7A and the correlation of Sema7A expression with lipid metabolism related genes. Sema7A−/− mice and recombinant Sema7A (rSema7A) were used to study the role of Sema7A in HFD-induced obesity and hepatic steatosis. Adipose tissue-derived mesenchymal stem cells (ADSCs) were used to examine the role of Sema7A in adipogenesis, lipogenesis and downstream signaling. Results: Deletion of Sema7A aggravated HFD-induced obesity. Sema7A deletion enhanced adipogenesis in both subcutaneous and visceral ADSCs, while the addition of rSema7A inhibited adipogenesis of ADSCs and lipogenesis of differentiated mature adipocytes. Sema7A inhibits adipo/lipogenesis potentially through its receptor integrin β1 and downstream FAK signaling. Importantly, administration of rSema7A had protective effects against diet-induced obesity in mice. In addition, deletion of Sema7A led to increased hepatic steatosis and insulin resistance in mice. Conclusions: Our findings reveal a novel inhibitory role of Sema7A in obesity and hepatic steatosis, providing a potential new therapeutic target for obesity and metabolic diseases.

Land subsidence is considered a threat to developing cities and is triggered by several natural (geological and seismic) and human (mining, groundwater withdrawal, oil and gas extraction, constructions) factors. This research has gathered datasets consisting of 80 Sentinel-1A ascending and descending SLC images from July 2017 to July 2019. This dataset, concerning InSAR and PS-InSAR, is processed with SARPROZ software to determine the land subsidence in Gwadar City, Balochistan, Pakistan. Later, the maps were created with ArcGIS 10.8. Due to InSAR’s limitations in measuring millimeter-scale surface deformation, Multi-Temporal InSAR techniques, like PS-InSAR, are introduced to provide better accuracy, consistency, and fewer errors of deformation analysis. This remote-based SAR technique is helpful in the Gwadar area; for researchers, city mobility is constrained and has become more restricted post-Covid-19. This technique requires multiple images acquired of the same place at different times for estimating surface deformation per year, along with surface uplifting and subsidence. The InSAR results showed maximum deformation in the Koh-i-Mehdi Mountain from 2017 to 2019. The PS-InSAR results showed subsidence up to −92 mm/year in ascending track and −66 mm/year in descending track in the area of Koh-i-Mehdi Mountain, and up to −48 mm/year in ascending track and −32 mm/year in descending track in the area of the deep seaport. From our experimental results, a high subsidence rate has been found in the newly evolving Gwadar City. This city is very beneficial to the country’s economic development because of its deep-sea port, developed by the China-Pakistan Economic Corridor (CPEC). The research is associated with a detailed analysis of Gwadar City, identifying the areas with significant subsidence, and enlisting the possible causes that are needed to be resolved before further developments. Our findings are helpful to urban development and disaster monitoring as the city is being promoted as the next significant deep seaport with the start of CPEC.

A high sensitivity temperature sensor based on polymer and liquid modified anti-resonant reflection principle is proposed. The sensor is made of a section of liquid-filled and UV-curable adhesive coated silica capillary, sandwiched between single mode fibers. The guiding mechanism of the waveguide is affected by both the liquid inside the hollow core, and the adhesive outside the silica cladding. The location of the resonant dips are influenced by the refractive index (RI) of the liquid, while the fringe visibility (resonant strength) is tuned by the both the liquid and the adhesive. By carefully selecting the refractive index value of the infiltrated liquid, and controlling the curing time of the adhesive, sharp resonant dips can be obtained. The sensor exhibits very high temperature sensitivity against temperature. A high sensitivity of 3.369 nm/°C is achieved with an infiltration index of 1.39, in the temperature range from 25 °C to 60 °C. The detection limit of the proposed sensors are 0.04 °C. Moreover, the temperature sensitivity of the sensor is found to be decreasing with the order of resonance. The sensor is easy to fabricate and cost effective, and is applicable in both dry and wet environments, which can find wide applications in biochemical and pharmaceutical industry.

High- and low-latitude climatic processes in the North Pacific Ocean are important components of the global climate system. For example, the interplay among North Pacific atmospheric circulation, ocean circulation, and biological productivity affects atmospheric carbon dioxide levels and marine oxygen concentrations. Here we review recent research on the North Pacific paleoclimatic and paleoceanographic evolution during the late Quaternary and its response to external forcings such as orbital insolation, ice-sheet extent, and greenhouse gas concentrations. First, we summarize the principles and application of relative paleointensity as a critical chronological tool in North Pacific paleoclimate research. Second, we illustrate the latest discoveries on the interaction between North Pacific Intermediate Water formation and high-to-low latitude teleconnection processes. Third, recent progress in linking dust fluxes and marine productivity and their global significance for the carbon cycle are presented. Finally, several key scientific problems are highlighted for future research on ocean-atmosphere-climate interactions in the North Pacific, pointing to the importance of combining paleo-records and modeling simulations. Overall, this review also aims to provide a broad insight into possible future changes of ocean-atmosphere circulation in the North Pacific region under a rapidly warming climate.

Cancer remains one of the leading causes of death globally and metastasis always leads to treatment failure. Here, we develop a versatile hydrogel loading photothermal agents, chemotherapeutics, and immune-adjuvants to eradicate orthotopic tumors and inhibit metastasis by combinational therapy. Hydrogel networks were synthesized via the thiol-Michael addition of polydopamine (PDA) with thiolated hyaluronic acid. PDA acted as a cross-linking agent and endowed the hydrogel with excellent photothermal property. Meanwhile, a chemotherapeutic agent, doxorubicin (DOX), was loaded in the hydrogel via π‒π stacking with PDA and an immune-adjuvant, CpG-ODN, was loaded via electrostatic interaction. The release of DOX from the hydrogel was initially slow but accelerated due to near infrared light irradiation. The hydrogels showed remarkably synergistic effect against 4T1 cancer cells and stimulated plenty of cytokines secreting from RAW264.7 cells. Moreover, the hydrogels eradicated orthotopic murine breast cancer xenografts and strongly inhibited metastasis after intratumoral injection and light irradiation. The high anticancer efficiency of this chemo-photothermal immunotherapy resulted from the strong synergistic effect of the versatile hydrogels, including the evoked host immune response. The combinational strategy of chemo-photothermal immunotherapy is promising for highly effective treatment of breast cancer.

Class B G protein-coupled receptors (GPCRs) are important targets in the treatment of metabolic syndrome and diabetes. Although multiple structures of class B GPCRs–G protein complexes have been elucidated, the detailed activation mechanism of the receptors remains unclear. Here, we combine Gaussian accelerated molecular dynamics simulations and Markov state models (MSM) to investigate the activation mechanism of a canonical class B GPCR, human glucagon receptor–GCGR, including the negative allosteric modulator-bound inactive state, the agonist glucagon-bound active state, and both glucagon- and Gs-bound fully active state. The free-energy landscapes of GCGR show the conformational ensemble consisting of three activation-associated states: inactive, active, and fully active. The structural analysis indicates the high dynamics of GCGR upon glucagon binding with both active and inactive conformations in the ensemble. Significantly, the H8 and TM6 exhibits distinct features from the inactive to the active states. The additional simulations demonstrate the role of H8 in the recruitment of Gs. Gs binding presents a crucial function of stabilizing the glucagon binding site and MSM highlights the absolute requirement of Gs to help the GCGR reach the fully active state. Together, our results reveal the detailed activation mechanism of GCGR from the view of conformational dynamics.

As a key regulator for the renin-angiotensin system, a class A G protein-coupled receptor (GPCR), AngII type 2 receptor (AT2R), plays a pivotal role in the homeostasis of the cardiovascular system. Compared with other GPCRs, AT2R has a unique antagonist-bound conformation and its mechanism is still an enigma. Here, we applied combined dynamic and evolutional approaches to investigate the conformational space and intrinsic properties of AT2R. With molecular dynamic simulations, Markov State Models, and statistics coupled analysis, we captured the conformational landscape of AT2R and identified its uniquity from both dynamical and evolutional viewpoints. A cryptic pocket was also discovered in the intermediate state during conformation transitions. These findings offer a deeper understanding of the AT2R mechanism at an atomic level and provide hints for the design of novel AT2R modulators.

A rhombic metallocycle [CoII6Cl6(L)2(HL)2]·5.5DMF·3.5H2O (1) (H2L = tris(2-naphthimidazolylmethyl) amine) composed of two CoIICl(HL) moieties and two CoIICl(L) moieties alternately bridged by two μ3-CoII ions has been synthesized under solvothermal condition. Each metallocycle associate with its six neighbors through intermolecular π···π interactions between naphthimidazolylmethyl arms forming a supramolecular framework with a pcu network. Magnetic measurements on the metallocycle reveal dominant antiferromagnetic couplings between CoII centers.

In the present paper, resonance characteristics of the vapor bubble oscillating in an acoustic field are investigated analytically. The analytical solution of the non-dimensional perturbation of the instantaneous bubble radius during the transient process in the initial oscillation stage is explicitly obtained and physically analyzed at the resonance situation based on the Laplace transform method. And the typical oscillation behaviors obtained from the analytical solution are thoroughly exhibited and analyzed in the time and frequency domains. In addition, the corresponding oscillation behaviors at the non-resonance situation are also investigated for the purpose of comparisons. Through our investigation, several essential conclusions can be drawn as follows: (1) The analytical solution of the non-dimensional perturbation of the instantaneous bubble radius can be divided into four terms according to the physical meaning. Among them, it is the term related to the acoustic field that causes the progressively violent bubble oscillation. (2) The vapor bubble with a smaller equilibrium radius could respond faster and more significantly to the acoustic field during the oscillation. (3) The bubble oscillation characteristics always exhibit significant differences at the resonance and non-resonance situations in both the time and frequency domains, even if the difference between the natural frequency of the oscillating vapor bubble and the angular frequency of the acoustic field is greatly small.

The MnFe2O4/g-C3N4/diatomite composites (Mn/G/D) were prepared via a facile precipitation-calcination method in this study. The Mn/G/D possessed higher specific surface area, lower electron-hole pairs’ recombination rate, as well as wider and stronger visible light absorption capacity. Since the synergistic effect between g-C3N4 and MnFe2O4, the photogenerated electron could transfer from g-C3N4 to MnFe2O4, which could promote the migration of electrons as well as enhance the photocatalytic activity and peroxymonosulfate (PMS) activation efficiency. Mn/G/D-5% composite displayed the excellent degradation performance of bisphenol A (BPA) with the removal efficiency of 99.9% under PMS/Vis system, which was approximately 2.47 and 63.8 times as high as that of the Mn/G/D-5%/PMS and Mn/G/D-5%/Vis system, respectively. Moreover, negative electricity derived from diatomite surface also promoted the photogenerated carriers’ migration, and the degradation rate constant was around 2.4 times higher than that of MnFe2O4/g-C3N4 (Mn/G). In addition, quenching experiments showed that both radical pathway (h+, ·OH, ·O2− and SO4·−) and non-radical pathway (1O2) were responsible for the degradation of BPA.

Agricultural land use changes are essential in addressing global urbanization demands. The improper management of agricultural land may lead to the alteration of the microbial ecosystem, which ultimately affects soil quality. Here, we assessed how soil microbial diversity, communities, and physicochemical properties in three layers of soil; upper (0–15 cm), middle (15–30 cm), and lower (30–45 cm), responded to a long-term land use change from paddy land (PL) to dry land of different chronosequences; PD3 (3 years), PD5 (5 years), and PD10 (10 years). We found PL conversion into dry lands increased soil pH, soil 3 phase R-value, bulk density (BD), organic matter (OM), total phosphorus (TP), total nitrogen (TN), and decreased electrical conductivity (EC), water holding capacity (WHC), and moisture content (MC) in all three layers. The land use change from PL to dry lands initially (PD3) decreased (11–25 %) bacterial diversity, while it significantly increased in PD5 (0.1–16 %), and PD10 (1–14 %) in all three layers. Unlike bacterial diversity, fungal diversity was high in PD5 in the upper layer, while the middle and lower layer was the least affected. We also found the conversion of PL to dry land altered relative abundance (RA) of bacteria on the upper layer, while RA of fungi was reshaped in all three layers. The Pearson’s correlation coefficient showed that MC, OM, pH, R-value, TN, TP, and WHC were important physicochemical factors, which significantly (P

Gastric mucosal injury is the initial stage of the occurrence and development of gastric diseases. Oxidative stress and ferroptosis caused by the imbalance of redox and iron dynamics in gastric mucosal epithelial cells are present throughout the occurrence and development of gastric mucosal injury. Therefore, the inhibition of oxidative stress and ferroptosis is a potential target for the treatment of the gastric mucosal injury. Xiaojianzhong decoction (XJZ), which consists of six Chinese herbal medicines and extracts, is used for the treatment of diseases related to gastrointestinal mucosal injury; however, its specific mechanism of action has yet to be clarified. In this study, we clarified the protective effect of XJZ on gastric mucosa and revealed its underlying mechanism. We established a gastric mucosal injury model using aspirin and administered XJZ. Furthermore, we systematically evaluated the mucosal injury and examined the expression of genes related to oxidative stress, ferroptosis, and inflammation. The study found that XJZ significantly counteracted aspirin-induced gastric mucosal injury and inhibited oxidative stress and ferroptosis in mice. Upon examining SQSTM1/p62(p62)/Kelch-like ECH-associated protein 1 (Keap1)/Nuclear Factor erythroid 2-Related Factor 2 (Nrf2), a well-known signaling pathway involved in the regulation of oxidative stress and ferroptosis, we found that its activation was significantly inhibited by aspirin treatment and that this signaling pathway was activated after XJZ intervention. Our study suggests that XJZ may inhibit aspirin induced oxidative stress and ferroptosis via the p62/Keap1/Nrf2 signaling pathway, thereby attenuating gastric mucosal injury.

Summary: Strong cellular immunity contributes to the control of HIV infection. Here, we describe a step-by-step protocol to assess the simian immunodeficiency virus (SIV)-specific CD8+ T cell responses by quantifying the degranulation, cytokine and chemokine production from SHIVSF162P3-infected rhesus macaques with an HIV fusion-inhibitory lipopeptide (LP-98) monotherapy. We also present the steps for adoptive transfer of an anti-CD8 antibody into a stable virologic control (SVC) group of LP-98-treated monkeys, confirming a direct role of CD8+ T cells in SVC macaques.For complete details on the use and execution of this protocol, please refer to Xue et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In mammals, leptin is an endocrine hormone involved in the regulation of feeding and energy metabolism, and glucocorticoids were previously reported to induce leptin gene expression. However, the link between glucocorticoids and leptin in fish has not been investigated. Goldfish are tetraploid teleosts because of genomic replication events (FSGD or 3-R), and some specific genes have quadrupled. In this study, two goldfish leptin-B genes, namely, leptin-BI (GenBank: ON468243) and leptin-BII (GenBank: ON468244), were cloned. The cDNA sequences of leptin-AI (GenBank: FJ534535.1) and leptin-AII (GenBank: FJ854572.1) have been reported by our team previously. Goldfish leptin-AI, -AII, -BI and -BII genes are located on chromosomes 43, 18, 29 and 4, respectively. In goldfish, leptin-B proteins shared approximately 30 % amino acid identities with leptin-A proteins and only 20 % with human leptin; however, either goldfish leptin-A or leptin-B showed high amino acid homology between themselves, 79.29 % and 82.74 %, respectively. The four leptin genes in goldfish are all highly conserved in three-dimensional (3-D) protein structures and gene structures. A tissue expression study showed that both the A and B forms of goldfish leptins are predominantly in the brain and liver. The effects of glucocorticoids on four leptin transcripts expression in goldfish were investigated by in vivo intraperitoneal injection and in vitro cell incubation approaches. The results showed that cortisol inhibited hepatic leptin-A transcript expression in a dose-dependent manner, while cortisol stimulated hepatic leptin-B mRNA expression, and RU486 (glucocorticoid receptor inhibitor) abolished cortisol’s effect on hepatic leptin-A and leptin-B mRNA expression. These results reflected the differential regulation of leptin-A and leptin-B by glucocorticoids in goldfish, which implied that leptin-A and leptin-B may mediate different functions in goldfish.