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AIM: To study the effect of zymosan, a ligand found on the surface of fungi, on gap junctional intercellular communication (GJIC) in cultured human corneal fibroblasts (HCFs). METHODS: Zymosan was added to the medium of cultured HCFs with or without the administration of mitogen-activated protein kinase (MAPK) inhibitors or the inhibitor kappa B kinase 2 (IKK2) inhibitor IV. The protein and mRNA levels of connexin 43 (Cx43) in HCFs were measured by Western blot, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The GJIC activity was tested using a dye-coupling assay. RESULTS: The reduction of Cx43 protein and mRNA levels as well as a significant decrease in GJIC activity were observed in cultured HCFs when zymosan was added into the culture medium. Compared with controls (no zymosan), the protein level of Cx43 was reduced by 45% and 54% in the presence of zymosan at 200 and 600 μg/mL, respectively (P

Abstract Background Precise visualization of meshes and their position would greatly aid in mesh shrinkage evaluation, hernia recurrence risk assessment, and the preoperative planning of salvage repair. Lightweight (LW) meshes are able to preserve abdominal wall compliance by generating less post-implantation fibrosis and rigidity. However, conventional 3D imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) cannot visualize the LW meshes. Patients sometimes have to undergo a second-look operation for visualizing the mesh implants. The goal of this work is to investigate the potential advantages of Automated 3D breast ultrasound (ABUS) pore texture analysis for implanted LW hernia mesh identification. Methods In vitro, the appearances of four different flat meshes in both ABUS and 2D hand-held ultrasound (HHUS) images were evaluated and compared. In vivo, pore texture patterns of 87 hernia regions were analyzed both in ABUS images and their corresponding HHUS images. Results In vitro studies, the imaging results of ABUS for implanted LW meshes are much more visualized and effective in comparison to HHUS. In vivo, the inter-class distance of 40 texture features was calculated. The texture features of 2D sectional plans (axial and sagittal plane) have no significant contribution to implanted LW mesh identification. Significant contribution was observed in coronal plane. However, since the mesh may have spatial variation such as shrinkage after implantation surgery, the inter-class distance of 3D coronal plane pore texture features are bigger than 2D coronal plane, so the contribution of 3D coronal plane pore texture features are more valuable than 2D coronal plane for implanted LW mesh identification. The use of 3D pore texture features significantly improved the robustness of the identification method in distinguishing between LW mesh and fascia. Conclusions An innovative new ABUS provides additional pore texture visualization, by separating the LW mesh from the fascia tissues. Therefore, ABUS has the potential to provides more accurate features to characterize pore texture patterns, and ultimately provide more accurate measures for implanted LW mesh identification.

At present, people mainly rely on traditional try-on to observe the effect of clothes, and the research on how to make clothe virtual try-on on the image of characters through the computer has gradually become a hot topic. The results of the existing methods of virtual fitting show that the details of characters are lost and the features of non-fitting areas are changed, which affect the appearance of clothes and the judgment of tryers on clothes. Aiming at the above problems, a try on method combining style transformation and local rendering was proposed. First of all, in order to ensure the accuracy of try-on, a strategy of pixel-level semantic segmentation of human image was proposed to find the location of clothing area, and at the same time provide the implementation conditions for local rendering; Second, in order to realize try-on between different clothing styles, a learnable style transformation module was constructed; Again, in order to make the clothing better fit the body shape of the tryer, a learnable clothing deformation module was proposed; Finally, in order to retain the original details of the characters and maintain the appearance of the fitting image, a local rendering strategy was proposed, which only renders the clothing area to ensure that the details of non-fitting area will not be lost. The experimental results show that the method has a significant effect in maintaining details such as characters’ arms, hands, and other aspects. In addition to fitting area, the feature information of non-fitting area is better preserved, and the image is more realistic and of fidelity after fitting. This method was applied to the try-on task for the first time, which solves the problem that try-on cannot be done correctly when the pose is complex, so that it can meet the requirements of multi-pose try-on in daily scenarios, and also provide new research ideas for virtual try-on field.

Abstract Background Viruses are the main infectious agents of acute respiratory infections in children. We aim to describe the epidemiological characteristics of viral pathogens of acute respiratory tract infections in outpatient children. Methods From April 2018 to March 2019, the results of viral detection using oral pharyngeal swabs from 103,210 children with acute respiratory tract infection in the outpatient department of the Children’s Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. Viral antigens, including adenovirus (ADV), influenza A (FLUA), influenza B (FLUB) and respiratory syncytial virus (RSV), were detected by the colloidal gold method. Results At least one virus was detected in 38,355 cases; the positivity rate was 37.2%. A total of 1910 cases of mixed infection with two or more viruses were detected, and the positivity rate of multiple infection was 1.9%. The ADV positivity rate was highest in the 3–6-year-old group (18.7%), the FLUA positivity rate was highest in the > 6-year-old group (21.6%), the FLUB positivity rate was highest in the > 6-year-old group (6.6%), and the RSV positivity rate was highest in the

Abstract Introduction Due to advancements in treatment, the survival of breast cancer (BC) patients has significantly improved. Improving the postoperative quality of life has become a widespread concern for patients and doctors. At present, the staged rehabilitation training program for postoperative BC patients has been recognized. However, there is not yet a consensus about the optimal time to initiate rehabilitation training. We designed this study to investigate the optimal intervention times for postoperative BC patients to begin different stages of rehabilitation. Design This is a randomized controlled trial. Female participants with BC who are scheduled to undergo mastectomy, including unilateral total breast or breast-conserving surgery plus axillary lymph node dissection, will be enrolled in this study. The intervention includes the following: 200 participants will be allocated using a 1:1:1:1 ratio to the A, B, C, and D groups, which have four different rehabilitation timelines for four phases of rehabilitation exercises. A therapist will evaluate the patient’s overall health and then adjust the training intensity before initiating training. The assessments include upper limb mobility, grip, limb circumference, postoperative drainage volume (PDV), and pain. The training will last for 12 weeks, and patients will undergo follow-up twice within 6 weeks after discharge. Outcomes include the following: Constant-Murley Score (CMS) is the primary parameter. European Organization Research and Treatment of Cancer Quality of Life Questionnaire-BR23 (EORTC QLQ-BR23), SF-36, range of motion (ROM), strength, grip, circumference, PDV, and pain are the secondary parameters. All enrolled subjects will be assessed at 1 day, 3 days, 1 week, and 2, 3, 6, 9, 12, and 18 weeks after the surgery. Discussion This is a randomized controlled trial to evaluate the effect of different rehabilitation training timelines to prevent shoulder dysfunction among postoperative patients with BC. If the results are confirmed, this study will establish an optimal timeline for postoperative BC rehabilitation. Trial registration ClinicalTrials.gov NCT03658265 . Registered on September 2018.

Abstract Objective PCOS is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities. At present, PCOS has been confirmed to have a certain genetic background. Compared with healthy women, the vast majority of PCOS patients have hyperandrogenemia, and this excessive androgen exposure during pregnancy may affect the development of female fetuses. The aim of the current study was to investigate the effect of adiponectin intervention during early pregnancy of obese mice with PCOS on the metabolic phenotype of adult female offspring. Methods After the PCOS model was established, C57BL/6J mice were divided into maternal-control, maternal-PCOS, and maternal-PCOS + APN groups. DHEA-induced PCOS mice were supplemented with adiponectin (10 mg/kg/day) in the early pregnancy in order to eliminate adverse hormone exposure and then traced for endocrine indicators in their adult female offspring, which were observed for metabolism syndrome or endocrine disturbance and exhibited the main effects of APN. To further explore the underlying mechanism, the relative expressions of phosphorylated AMPK, PI3K, and Akt were detected in the ovaries of offspring mice. Results The serum testosterone level of the maternal-PCOS + APN group in early pregnancy was significantly lower than that of the maternal-PCOS group (p

Background: Only a small proportion of patients with compensated advanced chronic liver disease (cACLD) had varices needing treatment (VNT) after recommended esophagogastroduodenoscopy (EGD) screening. We aimed to create a non-invasive nomogram based on routine tests to detect VNT in cACLD patients. Methods: The training cohort included 162 cACLD patients undergoing EGD in a university hospital, between January 2014 and September 2019. A nomogram was developed based on the independent predictors of VNT, selected using a multivariate logistic regression analysis. Thirty-three patients from eight university hospitals were prospectively enrolled as validation cohort between December 2018 and December 2019. Results: The prevalence of VNT was 32.7% (53/162) and 39.4% (13/33) in training and validation cohorts, respectively. The univariate analysis identified six risk factors for VNT. On the multivariate analysis, four of them, i.e., gallbladder wall thickness (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 0.98-1.56), spleen diameter (OR: 1.02; 95% CI: 1.00-1.04), platelet count (OR: 0.98; 95% CI: 0.97-0.99), and international normalized ratio (OR: 0.58; 95% CI: 0.06-5.84) were independently associated with VNT. Thus, a nomogram based on the four above - mentioned variables was developed, and showed a favorable performance for detecting VNT, with an area under receiver operating characteristic curve of 0.848 (95% CI: 0.769-0.927) in training cohort. By applying a cut-off value of 105 in validation cohort, 31.0% of EGD were safely spared with 3.4% of missed VNT. Conclusion: A nomogram based on routine clinical parameters was developed for detecting VNT and avoiding unnecessary EGD in cACLD patients.

Sorbicillinoids are a class of hexaketide metabolites produced by Ustilaginoidea virens (teleomorph: Villosiclava virens), an important fungal pathogen that causes a devastating rice disease. In this study, we investigated the effects of environmental factors, including carbon and nitrogen sources, ambient pH and light exposure, on mycelial growth, sporulation, as well as the accumulation of sorbicillinoids, and the expression of related genes involved in sorbicillinoid biosynthesis. It was found that the environmental factors had great influences on mycelial growth and sporulation of U. virens. Fructose and glucose, complex nitrogen sources, acidic conditions and light exposure were favorable for sorbicillinoid production. The relative transcript levels of sorbicillinoid biosynthesis genes were up-regulated when U. virens was separately treated with those environmental factors that favored sorbicillinoid production, indicating that sorbicillinoid biosynthesis was mainly regulated at the transcriptional level by different environmental factors. Two pathway-specific transcription factor genes, UvSorR1 and UvSorR2, were found to participate in the regulation of sorbicillinoid biosynthesis. These results will provide useful information to better understand the regulation mechanisms of sorbicillinoid biosynthesis, and be conducive to develop effective means for controlling sorbicillinoid production in U. virens.

Radiotherapy (RT) is one of the most effective cancer treatments. However, successful radiation protection for normal tissue is a clinical challenge. Our previous study observed that MitoQ, a mitochondria-targeted antioxidant, was adsorbed to the inner mitochondrial membrane and remained the cationic moiety in the intermembrane space. The positive charges in MitoQ restrained the activity of respiratory chain complexes and decreased proton production. Therefore, a pseudo-mitochondrial membrane potential (PMMP) was developed via maintenance of exogenous positive charges. This study identified that PMMP constructed by MitoQ could effectively inhibit mitochondrial respiration within normal cells, disrupt energy metabolism, and activate adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling to induce autophagy. As such, it could not lead to starvation-induced autophagy among tumor cells due to the different energy phenotypes between normal and tumor cells (normal cells depend on mitochondrial respiration for energy supply, while tumor cells rely on aerobic glycolysis). Therefore, we successfully protected the normal cells from radiation-induced damage without affecting the tumor-killing efficacy of radiation by utilizing selective autophagy. MitoQ-constructed PMMP provides a new therapeutic strategy for specific radiation protection.

Genomic analysis has demonstrated that many fungi possess essential gene clusters for the production of previously unobserved secondary metabolites; however, these genes are normally reduced or silenced under most conditions. These cryptic biosynthetic gene clusters have become treasures of new bioactive secondary metabolites. The induction of these biosynthetic gene clusters under stress or special conditions can improve the titers of known compounds or the production of novel compounds. Among the inducing strategies, chemical-epigenetic regulation is considered a powerful approach, and it uses small-molecule epigenetic modifiers, which mainly act as the inhibitors of DNA methyltransferase, histone deacetylase, and histone acetyltransferase, to promote changes in the structure of DNA, histones, and proteasomes and to further activate cryptic biosynthetic gene clusters for the production of a wide variety of bioactive secondary metabolites. These epigenetic modifiers mainly include 5-azacytidine, suberoylanilide hydroxamic acid, suberoyl bishydroxamic acid, sodium butyrate, and nicotinamide. This review gives an overview on the method of chemical epigenetic modifiers to trigger silent or low-expressed biosynthetic pathways to yield bioactive natural products through external cues of fungi, mainly based on the research progress in the period from 2007 to 2022. The production of about 540 fungal secondary metabolites was found to be induced or enhanced by chemical epigenetic modifiers. Some of them exhibited significant biological activities such as cytotoxic, antimicrobial, anti-inflammatory, and antioxidant activity.

Background: The overconsumption of a high-fat diet (HFD) has been repeatedly blamed as being a possible contributor to the global prevalence of emotional problems in modern society. Our group recently demonstrated the deleterious effect of a chronic HFD throughout adulthood on both emotional behavior and neuroplasticity markers in mice. As a heightened preference for palatable HFDs from the time of the juvenile period (when the brain is particularly vulnerable to environmental insults) is universal among populations around the world, a comparison of the consequences of chronic HFDs starting from juveniles or adults will assist in obtaining better knowledge of the impact that chronic HFDs have on mental health, thus potentially leading to the discovery of more effective strategies for reducing the incidence of psychiatric disorders. Methods: In the present study, male C57BL/6J mice with an initial age of 4 weeks (IA-4 W) or 8 weeks (IA-8 W) were separately assigned to two subgroups and fed either a control diet (CD, 10 kJ% from fat) or HFD (60 kJ% from fat) for 9 months followed by an analysis focused on metabolic, emotional behavioral, and neuroplastic profiles. Results: The results illustrated that, in addition to abnormal glucolipid metabolism and insulin sensitivity, mice on a chronic HFD exhibited increased levels of anxiety and depression-like behaviors and aberrant hippocampal neuroplasticity. When compared with IA-8 W mice, several changes indicating systemic metabolic disturbance and neurobehavioral disorder after chronic HFD consumption were aggravated in IA-4 W mice, accompanied by exaggerated impairments in hippocampal insulin sensitivity and neurogenesis. Conclusions: These results not only provide in vivo evidence that the juvenile stage is a critical period of vulnerability to detrimental effects of HFD consumption on metabolic and neuronal function but also suggest dampened hippocampal insulin signaling as a potential link between prolonged HFD consumption and negative neurobehavioral outcomes. Considering the substantial burden posed by psychiatric disorders and the high prevalence of HFD among youth, these observations are meaningful for raising awareness of the harmful effects of excessive dietary fat intake and developing strategy for preventing mental disorders.

Cell division regulators play a vital role in neural progenitor cell (NPC) proliferation and differentiation. Cell division cycle 25C (CDC25C) is a member of the CDC25 family of phosphatases which positively regulate cell division by activating cyclin-dependent protein kinases (CDKs). However, mice with the Cdc25c gene knocked out were shown to be viable and lacked the apparent phenotype due to genetic compensation by Cdc25a and/or Cdc25b. Here, we investigate the function of Cdc25c in developing rat brains by knocking down Cdc25c in NPCs using in utero electroporation. Our results indicate that Cdc25c plays an essential role in maintaining the proliferative state of NPCs during cortical development. The knockdown of Cdc25c causes early cell cycle exit and the premature differentiation of NPCs. Our study uncovers a novel role of CDC25C in NPC division and cell fate determination. In addition, our study presents a functional approach to studying the role of genes, which elicit genetic compensation with knockout, in cortical neurogenesis by knocking down in vivo.

Climate change is a global scientific problem, and its impact on the spatiotemporal variations of precipitation has been a crucial research topic. Although previous studies have used different methods to evaluate the precipitation characteristics of the Huaihe River Basin, the time series were short and the few stations could not fully and accurately represent the precipitation characteristics. In this study, daily temperature and precipitation data were collected from 233 meteorological stations in the Huaihe River Basin from 1960–2020. The Mann–Kendall test was used to analyze the trend and significance of interannual and interseasonal scale changes in temperature and precipitation in the Basin, respectively. The correlation between temperature and precipitation was analyzed using the Pearson correlation coefficient method. The spatial distribution of the significance of temperature and precipitation changes and the spatial distribution of the correlation between temperature and precipitation in the basin were plotted. The temperature in the basin tended to increase on interannual and interseasonal scales, with more noticeable changes in spring and winter. Precipitation showed an overall decreasing trend but an increasing trend in localized areas in the south. A decreasing trend in the interseasonal variation scale was observed in spring, an increasing trend in winter, a decreasing trend in the northeastern region in summer, an increasing trend in the southwestern region, and an increasing trend in the northern and southern parts in autumn were observed. The correlation between average temperature and precipitation on interannual and interseasonal scales was analyzed using Pearson’s correlation coefficient method, and the annual average temperature and annual average precipitation in the Huaihe River basin were found to be negatively correlated, except for sporadic areas that showed extremely weakly positive correlations or no correlations.

Abstract Background Increases in the levels of serum C-reactive protein (CRP) and creatinine (Cr) and decreases in those of albumin (Alb) are commonly observed in acute pancreatitis (AP). We aimed to evaluate the efficacy of the Cr/Alb and CRP/Alb ratios in the prediction of surgical treatment effect in AP patients. Methods This study retrospectively analyzed clinical data obtained from 140 AP patients who underwent debridement from January 2008 to November 2018 in Shanghai Ruijin Hospital. The Cr/Alb and CRP/Alb ratios at admission and before surgery were assessed in the analysis of clinical statistics, prediction of prognoses, and logistic regression analysis. Results The admission Cr/Alb had the best predictive value of the four ratios. This value was significantly higher in patients with re-operation and those who died (P

After the Fukushima accident, the risk of hydrogen shall be considered by most countries in nuclear power plants. China national nuclear safety Administration has required that nuclear power plants shall install the hydrogen monitoring measurement equipment for severe accident in containment. There were some equipment used for hydrogen monitoring at severe accident, but some equipment cannot solve the leakage problem, some equipment cannot measure the hypoxic environment, and some have slower response time or long startup time. In this study, we developed a based on Pd–Ag​ alloy hydrogen monitoring equipment, Pd–Ag alloy is selected as hydrogen sensitive material, alumina ceramic is used as substrate, and Pd–Ag alloy film hydrogen core measurement component is prepared by magnetron sputtering technology. Heating​ treatment in sensor is adopted to maintain the environment in which the sensor is located at a constant 198°C environment, and protective and filtering measures are taken to ensure that hydrogen detection is not affected by aerosol and water vapor. Then, study the characterization of hydrogen monitoring equipment. Testing results indicated that the hydrogen measuring component (Pd–Ag) working at a constant temperature does not affect the measurement results and this equipment has the constant line relationship between hydrogen concentration and resistant. The response time of hydrogen decrease is longer than that of hydrogen increase, but it is within 50 s. It also has the high accuracy keeping within 1 vol% at normal anoxic environment and harsh environment. If it is applied to severe accidents in NPPs, it is necessary to study the performance under irradiation conditions in the future.

Systemic sclerosis (SSc) is a chronic, multisystem orphan disease with a highly variable clinical course, high mortality rate, and a poorly understood complex pathogenesis. We have identified an important role for a subpopulation of monocytes and macrophages characterized by surface expression of the scavenger receptor macrophage receptor with collagenous structure (MARCO) in chronic inflammation and fibrosis in SSc and in preclinical disease models. We show that MARCO+ monocytes and macrophages accumulate in lesional skin and lung in topographic proximity to activated myofibroblasts in patients with SSc and in the bleomycin-induced mouse model of SSc. Short-term treatment of mice with a potentially novel nanoparticle, poly(lactic-co-glycolic) acid (PLG), which is composed of a carboxylated, FDA-approved, biodegradable polymer and modulates activation and trafficking of MARCO+ inflammatory monocytes, markedly attenuated bleomycin-induced skin and lung inflammation and fibrosis. Mechanistically, in isolated cells in culture, PLG nanoparticles inhibited TGF-dependent fibrotic responses in vitro. Thus, MARCO+ monocytes are potent effector cells of skin and lung fibrosis and can be therapeutically targeted in SSc using PLG nanoparticles.

In sheep meat production, the rib eye area is an important index to evaluate carcass traits. However, conventional breeding programs have led to slow genetic progression in rib eye muscle area. Operationalizing molecular marker assisted breeding is an optimized breeding method that might improve this situation. Therefore, the present study used whole genome sequencing data to excavate candidate genes associated with the rib eye muscle. Male Hu lambs (n = 776) with pedigrees and 274 lambs with no pedigree were included. The genetic parameters of the rib eye area were estimated using a mixed linear mixed model. The rib eye area showed medium heritability (0.32 ± 0.13). Whole-genome sequencing of 40 large rib eye sheep [17.97 ± 1.14, (cm2)] and 40 small rib eye sheep [7.89 ± 0.79, (cm2)] was performed. Case-control genome-wide association studies and the fixation index identified candidate rib eye-associated genes. Seven single nucleotide polymorphisms (SNPs) in six genes (ALS2, ST6GAL2, LOC105611989, PLXNA4, DPP6, and COL12A1) were identified as candidates. The study population was expanded to 1050 lambs to perform KASPar genotyping on five SNPs, which demonstrated that SNPs in LOC105611989, DPP6, and COL12A1 correlated significantly with the rib eye area, which could be used as genetic markers for molecular breeding of the rib eye area. The results provided genetic parameters estimated on the rib eye area and information for breeding based on carcass traits in Hu sheep.

To the best of our knowledge, no comprehensive estimates of the descriptive epidemiology of and trends in hypertensive heart disease (HHD) in China have been reported. In this study, the temporal trends in the prevalence of HHD in China from 1990 to 2019 were estimated using an age–period–cohort model. Data related to HHD burden were collected from the Global Burden of Disease Study 2019. From 1990 to 2019, HHD prevalence in China showed decreasing trends in both sexes combined (average annual percentage change [AAPC]: −0.2%, 95% confidence interval (CI: −0.3% to −0.2%) and in males (AAPC: −0.5%, 95% CI: −0.5% to −0.4%), but significant increases in the age groups of 15–19, 20–24, …, and 60–64 years. The age effect analysis showed an increase in HHD prevalence from 50 to 94 years in both males and females, the period effect analysis showed a slight increase in HHD prevalence from 2009 to 2019 in females, and the cohort effect analysis showed a consistent decline in HHD prevalence from earlier to later birth cohorts in both males and females.

In aged animals, the physiological functions of the gastrointestinal tract (GIT) are reduced. Dietary intervention is necessary to re-activate GIT functions. The objective of this study was to investigate the impacts of dietary combination of quercetin (Q) and vitamin E (VE) on the intestinal structure and barrier integrity in aged breeder chickens. A sum of 400 (65-wks-old) Tianfu breeder hens were randomly allotted into four (4) groups with four (4) replicates, and fed with basal diet; basal diet supplemented with 0.4g/kg of Q; basal diet supplemented with 0.2g/kg of VE; and basal diet supplemented with the combination of Q (0.4 g/kg) and VE (0.2 g/kg) for 14 weeks. At the end of the 14th week, serum and gut segments were collected from eight hens per group for analyses. The results showed that Q+VE exerted synergistic effects on intestinal morphology by promoting villi height and crypt depth (P < 0.05), as well as mitigated the intestinal inflammatory damage of the aged hens, but decreased the concentration of serum D-lactate and diamine oxidase; and increased the levels of secretory immunoglobulin A (sIgA) and Mucin-2 mRNA (P < 0.05). Furthermore, the mRNA expression of intestinal tight junction proteins including occludin, ZO1, and claudin-1 was increased by Q+VE (P < 0.05). Moreover, Q+VE decreased the mRNA expression of the pro-inflammatory genes (TNF-α, IL-6, and IL-1β), and increased the expression of anti-inflammatory genes (IL-10 and IL-4) (P < 0.05). These results were consistent with the mRNA expression of Bax and Bcl-2. In addition, Q+VE protected the small intestinal tract from oxidative damage by increasing the levels of superoxide dismutase, total antioxidant capacity, glutathione peroxidase, catalase (P < 0.05), and the mRNA expression of SOD1 and GPx-2. However, Q+VE decreased malondialdehyde levels in the intestine compared to the control (P < 0.05). These results indicated that dietary Q+VE improved intestinal function in aged breeder hens, by protecting the intestinal structure and integrity. Therefore, Q+VE could act as an anti-aging agent to elevate the physiological functions of the small intestine in chickens.

The operational uncertainty of the power system is significantly increased by the high penetration of renewable energy and diversification of load behavior, which have aroused the novel research on stochastic steady-state security assessment (SSSA) urgently when the operational condition gets worse and contingency happens more frequently. First of all, a novel contingency analysis model has been proposed based on chance constrained optimal power flow (CCOPF) in this work, which is able to give a comprehensive consideration on conventional generator outage, uncertainty of system operation and load shedding of interruptible loads (ILs). Moreover, the proposed model is very practical and can be solved much efficiently by an iteration method so that the purpose of secure system operation after contingency can be better realized. Second, to further enhance the steady-state security of the system, a novel pricing method for ILs has been developed here. In addition, a composite contingency ranking index has been also established to reflect the severity of generator outage more accurately. Finally, extensive study results based on a modified IEEE-39 test system have demonstrated the validity of the proposed model, which can hold a good balance amongst security, economy, controllability, and maneuverability.

Helium is a strategic resource with many scientific, technical and industrial applications. However, despite its importance and scarcity, there is a lack of understanding on its origin, migration and accumulation processes. In view of this, the distribution patterns and enrichment mechanisms of helium are studied based on systematic analysis of the genetic types of helium in petroliferous basins in China. The helium in the petroliferous basins in China is mainly radiogenic, which involves the decay of U and Th. As expected, we found that, in one gas field, the helium content in natural gas increases with the age of reservoir rock, and in the same layer of the same structure within one reservoir, the helium content in natural gas in high altitude part of the structure is higher than that in the lower part. Enrichment of helium is closely related to old deep groundwater. The helium produced by radioactive decay in old strata is dissolved in water and transported and enriched through water migration. Due to large uplift of the structure during the Himalayan period, the helium dissolved in water was exsolved and accumulated with natural gas in the trap above the water. And thus, the helium-rich natural gas reservoirs formed. So, the helium contents in natural gas fields increase gradually along the flow direction of groundwater. The area with large range of uplift often shows higher helium content. This study not only provides a basis for the study of helium enrichment research, but also provides a new idea for industrial helium resource exploration.

Background and ObjectivesCraniocervical artery dissection (CAD) is the most common cause of ischemic stroke in young adults. The etiologies of CAD can be classified into three types, such as spontaneous (sCAD), minor traumatic (mtCAD), and genetic origin. Recent studies indicated that clinical presentations and imaging features could guide management and inform prognosis. This retrospective analysis sought to compare the clinical and imaging features of sCAD vs. mtCAD in providing evidence-based advice on medical treatment, functional rehabilitation, secondary stroke prevention, and prognosis, ultimately formulating clinical guidelines in managing CAD.MethodsIn total, 148 patients with CAD were identified from the medical records database and subdivided into sCAD and mtCAD based on the clinical presentations and imaging features. A retrospective comparative analysis was performed according to their clinical presentations and imaging features.ResultsPatients with mtCAD are significantly younger than sCAD with 120 cases of sCAD average aged 43.61 ± 12.75, while 28 cases of mtCAD average aged 35.68 ± 14.54. Patients with mtCAD had more cases of neck pain compared to sCAD. Patients with mtCAD had more cases of CAD at extracranial locations compared to sCAD. Patients with mtCAD had more cases of multiple site dissection compared to sCAD. Double lumen and intramural haematoma are the most common imaging findings with mtCAD patients having statistical significantly more cases of intramural haematoma and long tapering stenosis.ConclusionPatients with mtCAD were presented at a much younger age with symptoms of neck pain compared to sCAD. Patients with mtCAD predominantly presented at extracranial sites with more prominent features of multiple site dissection, intramural haematoma, and long tapering stenosis. These clinical and imaging features can translate into clinical practice guidelines for patients with CAD to improve the optimal functional outcome and reduce both morbidity and mortality.

Endophytic fungi of medicinal plants are abundant, and their metabolites often have antioxidant, antibacterial, and antitumor effects and can produce secondary metabolites identical or similar to those of their hosts, which can mitigate the problem of insufficient supply of medicinal plants. In this study, we screened endophytic fungi for strains that produce the same diterpene lactones as Andrographis paniculata based on their biological activity. Firstly, the dominant group of endophytic fungi of Andrographis paniculata was screened and pathogenicity was studied using Koch’s rule. Secondly, DPPH, ABTS, OH, PTIO radical scavenging, and FRAP assays were used to detect the antioxidant activity of the extracellular extracts of the strains, and total phenol and total flavonoid contents of the strains with high antioxidant capacity were determined. S. aureus, B. subtilis, E. coli, and P. aeruginosa were used to determine the antibacterial activity of the mycelial extracts of the strains. Finally, the secondary metabolites of the mycelial extracts of the strains were examined by high-performance liquid chromatography. The results showed that 32 strains of Andrographis paniculata were relatively isolated > 70% and non-pathogenic. Extracellular extracts of strains AP-1 and AP-4 showed vigorous antioxidant activity, and AP-4, AP-12, AP-47, and AP-48 showed antibacterial activity against four strains of bacteria. The HPLC results indicated that the mycelial extracts of AP-4 and AP-12 contained diterpene lactones. The two endophytic fungi were recognized as Colletotrichum sp. The study successfully obtained diterpene lactones from the endophytic fungus of Andrographis paniculata and confirmed the feasibility of using endophytic fungal strains to produce active substances consistent with the host. It was also useful for exploring endophytic fungi and medicinal plants. The relationship provides theoretical guidance.

Purpose. To investigate the relationships between visual function and the retinal and choroid microstructure in idiopathic macular hole patients after surgery. Methods. A prospective study investigated changes in the fundus structure and visual function in 16 macular hole patients before and after surgery. Patients’ best-corrected visual acuity (BCVA) and retinal sensitivity were measured by an EDTRS visual chart and microperimetry (MP1), respectively. The thickness of the retina and the blood supply to the retina and superficial choroid were detected by OCTA, and the choroidal capillary blood flow density was analysed with MATLAB. The thickness of the choroid and the aperture size of the macular hole were detected by Heidelberg OCT. Results. Compared with before surgery and one month after surgery, the BCVA (3 months: 0.47 ± 0.27, before: 1.02 ± 0.22, 1 month: 0.66 ± 0.27, and P

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been observed in several large cardiovascular outcome trials to significantly reduce the incidence of major cardiovascular event (MACE) with type 2 diabetic patients. The clinical trials of GLP-1 RAs, including lixisenatide, exenatide, liraglutide, semaglutide, albiglutide, and dulaglutide, are associated with a significantly 14% lower risk of MACE in patients with T2DM and a history of CV disease, and with a nonsignificantly 6% lower risk in patients without history of CV disease. Some of the interpretation with GLP-1 RA trials suggested the possible role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in primary prevention of cardiovascular diseases in nondiabetic individual, echoed by a recent editorial redefining the role of GLP-1 RAs being beyond glycaemic control. The narrative review provides an in-depth insight into GLP-1 RA use guideline in different countries and regions of the world and examines the safety and concern of GLP-1 RA use. The narrative review draws the comparison of GLP-1 RA use between diabetic and nondiabetic individual in terms of cardiovascular and metabolic benefits and points out the direction of future clinical trials of GLP-1 RAs in nondiabetic individuals. The focus of the review is on GLP-1 RAs’ preventive roles in nondiabetic individuals with cardiovascular disease, chronic kidney diseases, obesity, dyslipidaemia, hypertension, nonalcoholic fatty liver diseases, polycystic ovarian syndrome (PCOS), and perioperative complications of bariatric surgery, albeit in small studies and subset analysis of clinical trials of diabetic patients.

With the rise of manufacturing informatization, many transactions are conducted on the Internet, but the final form of transaction completion is the transaction of actual products, which makes the logistics industry emerge as the times require. How to achieve the optimal allocation scheme and the fastest efficiency in the supply chain has become an urgent problem to be solved. This paper considers the characteristics and advantages of 3D image processing technology, describes the characteristics of 3D image processing supply chain (SC), and analyzes the channels that 3D image technology affects SC. Combining the respective characteristics of fuzzy theory and grey theory, the two theories are combined to develop strengths and circumvent weaknesses to form grey fuzzy theory. Comprehensive evaluation of supply chain logistics capability can achieve better evaluation results. The application of grey theory in this chapter includes constructing the factor set of the evaluation index system and determining the weight matrix of the factor set with the game method. The grey fuzzy evaluation weight matrix (i.e., single index evaluation result) is determined with the grey theory, and the fuzzy comprehensive evaluation result is finally calculated. This paper studies the supply chain logistics capability evaluation and optimization system from the aspects of system analysis, system function module design, and system architecture design and analyzes the overall goal, demand, feasibility, system business process, and data flow of the system construction. At the same time, this paper designs the supply chain logistics capability evaluation and optimization system and shows some functional interfaces. It is of great significance to improve the responsiveness, total inventory level, total cost level, supply chain performance, agility, and flexibility of the supply chain in the new environment.

BackgroundCerebrospinal fluid (CSF) plays an important role in maintaining tissue homeostasis in the central nervous system. In 2012, the new CSF outflow pathway, “the glymphatic system,” was discovered. The glymphatic system mediates CSF and interstitial fluid exchange through the perivascular pathway, which eliminates harmful solutes in the brain parenchyma. In recent studies, the importance of the glymphatic system has been demonstrated in healthy and neurodegenerative disease brains. However, there is limited research on the function of the CSF in brain tumors. Intracranial hypertension caused by glioma can affect CSF drainage, which impacts the delivery of chemotherapy drugs via intrathecal injection. This study focused on changes in the glymphatic system and the role of aquaporin 4 (AQP4) in glymphatic transport in glioma.MethodsIn glioma-bearing rats, the effect of tracer infusion on the intracranial pressure (ICP) was evaluated using an ICP microsensor. In vivo magnetic resonance imaging and ex vivo bright field were used to monitor CSF tracer distribution after cisterna magna injection. AQP4 expression was quantitatively detected, and AQP4 in the astrocytes around the vessels was observed using immunofluorescence.ResultsThe ICP of the tumor group was higher than that of the control group and the infusion rate of 2 µl/min did not affect ICP. In vivo and ex vivo imaging showed that the circulation of CSF tracers was significantly impaired in the tumor. High-power confocal microscopy revealed that, in the tumor, the surrounding of AQP4 by Evans Blue was decreased. In both tumor and contralateral areas, data indicated that the number of cluster designation 34 (CD34+) alpha-smooth muscle actin (α-SMA−) veins were more than that of CD34+α-SMA+ arteries. Moreover, in the tumor area, AQP4 in the astrocytes around the vessels was decreased.ConclusionsThese findings indicate that the para-arterial influx of subarachnoid CSF is limited in glioma, especially in those with reduced levels of the fundamental protein AQP4. Our results provide evidence toward a potential new treatment method for glioma in the future.

PurposeThis study aimed to develop a radiomics signature for the preoperative prognosis prediction of isocitrate dehydrogenase (IDH)-wild-type glioblastoma (GBM) patients and to provide personalized assistance in the clinical decision-making for different patients.Materials and MethodsA total of 142 IDH-wild-type GBM patients classified using the new classification criteria of WHO 2021 from two centers were included in the study and randomly divided into a training set and a test set. Firstly, their clinical characteristics were screened using univariate Cox regression. Then, the radiomics features were extracted from the tumor and peritumoral edema areas on their contrast-enhanced T1-weighted image (CE-T1WI), T2-weighted image (T2WI), and T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) magnetic resonance imaging (MRI) images. Subsequently, inter- and intra-class correlation coefficient (ICC) analysis, Spearman’s correlation analysis, univariate Cox, and the least absolute shrinkage and selection operator (LASSO) Cox regression were used step by step for feature selection and the construction of a radiomics signature. The combined model was established by integrating the selected clinical factors. Kaplan–Meier analysis was performed for the validation of the discrimination ability of the model, and the C-index was used to evaluate consistency in the prediction. Finally, a Radiomics + Clinical nomogram was generated for personalized prognosis analysis and then validated using the calibration curve.ResultsAnalysis of the clinical characteristics resulted in the screening of four risk factors. The combination of ICC, Spearman’s correlation, and univariate and LASSO Cox resulted in the selection of eight radiomics features, which made up the radiomics signature. Both the radiomics and combined models can significantly stratify high- and low-risk patients (p < 0.001 and p < 0.05 for the training and test sets, respectively) and obtained good prediction consistency (C-index = 0.74–0.86). The calibration plots exhibited good agreement in both 1- and 2-year survival between the prediction of the model and the actual observation.ConclusionRadiomics is an independent preoperative non-invasive prognostic tool for patients who were newly classified as having IDH-wild-type GBM. The constructed nomogram, which combined radiomics features with clinical factors, can predict the overall survival (OS) of IDH-wild-type GBM patients and could be a new supplement to treatment guidelines.

What is the interplay of high-tech industrial agglomeration and urban innovation? How does high-tech industrial agglomeration affect urban innovation? What are the heterogeneous effects of high-tech industry agglomeration on urban innovation in different conditions? To answer these questions, this paper analyzes the interrelationship between high-tech industry agglomeration and urban innovation based on panel data of China’s Yangtze River Delta urban agglomeration from 2010 to 2019. We discuss the influence mechanism of high-tech industrial agglomeration on urban innovation by exploring the mediating effect of industrial structure optimization and the threshold effect of industrial attributes. The heterogeneous impact of high-tech industry agglomeration on urban innovation is also been further studied. We find that (1) the interaction relationship between high-tech industry agglomeration and urban innovation output is positive. (2) The advancement of industrial structure plays a positive intermediary role between high-tech industrial agglomeration and urban innovation output, while the rationalization of industrial structure shows a suppressing effect. (3) There are different threshold effects between capital intensity and technology intensity. The influence of high-tech agglomeration on urban innovation is positive only when the capital intensity exceeds 1.125. However, the influence is always positive in different levels of technology intensity, significantly. When the technology intensity is higher than 9.012E − 06, the degree and significance of this positive impact would decrease. (4) There are heterogeneous impacts of high-tech industry agglomeration on urban innovation output in the Yangtze River Delta urban agglomeration in different time stages, urban innovation development stages, and urban circles.

Abstract Background The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. Methods Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. Results Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6–81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3–36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. Conclusions Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.

Abstract Background Our objective was to investigate the efficacy of the beta-3 adrenergic receptor (β3-AR) agonist BRL37344 for the prevention of liver steatosis and inflammation associated with nonalcoholic fatty liver disease (NAFLD). Methods Four groups were established: a control group (given a standard diet), a high-fat diet (HFD) group, an HFD + β3-AR agonist (β3-AGO) group, and an HFD + β3-AR antagonist (β3-ANT) group. All rats were fed for 12 weeks. The β3-AR agonist BRL37344 and the antagonist L748337 were administered for the last 4 weeks with Alzet micro-osmotic pumps. The rat body weights (g) were measured at the end of the 4th, 8th, and 12th weeks. At the end of the 12th week, the liver weights were measured. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed with a Hitachi automatic analyzer. The lipid levels of the triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) and the concentrations of free fatty acids (FFAs) were also measured. An oil red O kit was used to detect lipid droplet accumulation in hepatocytes. Steatosis, ballooning degeneration and inflammation were histopathologically determined. The protein and mRNA expression levels of β3-AR, peroxisome proliferator-activated receptor-alpha (PPAR-α), peroxisome proliferator-activated receptor-gamma (PPAR-γ), mitochondrial carnitine palmitoyltransferase-1 (mCPT-1), and fatty acid translocase (FAT)/CD36 were measured by western blot analysis and RT-qPCR, respectively. Results After treatment with the β3-AR agonist BRL37344 for 4 weeks, the levels of ALT, AST, TGs, TC, LDL-C and FFAs were decreased in the NAFLD model group compared with the HFD group. Body and liver weights, liver index values and lipid droplet accumulation were lower in the HFD + β3-AGO group than in the HFD group. Decreased NAFLD activity scores (NASs) also showed that liver steatosis and inflammation were ameliorated after treatment with BRL37344. Moreover, the β3-AR antagonist L748337 reversed these effects. Additionally, the protein and gene expression levels of β3-AR, PPAR-α, and mCPT-1 were increased in the HFD + β3-AGO group, whereas those of PPAR-γ and FAT/CD36 were decreased. Conclusion The β3-AR agonist BRL37344 is beneficial for reducing liver fat accumulation and for ameliorating liver steatosis and inflammation in NAFLD. These effects may be associated with PPARs/mCPT-1 and FAT/CD36.

Abstract Background A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. Methods A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. Results A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57–70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5–17) days, and the duration from onset of symptoms to the study date was 31 (24–36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2–8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. Conclusions Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. Trial registration Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4

ABSTRACTCOVID-19 is caused by SARS-CoV-2 infection and was initially discovered in Wuhan. This outbreak quickly spread all over China and then to more than 20 other countries. SARS-CoV-2 fluorescent microsphere immunochromatographic test strips were prepared by the combination of time-resolved fluorescence immunoassay with a lateral flow assay. The analytical performance and clinical evaluation of this testing method was done and the clinical significance of the testing method was verified. The LLOD of SARS-CoV-2 antibody IgG and IgM was 0.121U/L and 0.366U/L. The specificity of IgM and IgG strips in healthy people and in patients with non-COVID-19 disease was 94%, 96.72% and 95.50%, 99.49%, respectively; and sensitivity of IgM and IgG strips for patients during treatment and follow-up was 63.02%, 37.61% and 87.28%, 90.17%, respectively. The SARS-CoV-2 antibody test strip can provide rapid, flexible and accurate testing, and is able to meet the clinical requirement for rapid on-site testing of virus. The ability to detect IgM and IgG provided a significant benefit for the detection and prediction of clinical course with COVID-19 patients.

With the growing concerns about energy saving and security problems in wireless sensor networks (WSNs), we investigated a joint energy saving scheduling and secure routing algorithm for critical event reporting in WSN. When a critical event has been detected, the notification must be safely sent to the sink node through the uplink transmission, and the sink node needs to broadcast the alarm messages to the whole network through the downlink transmission. In the uplink, a joint power allocation and secure routing strategy (JPASR) has been proposed to maximize the routing secure connection probability (RSCP) under the constraint of power. Meanwhile, combined with the level-by-level sleeping scheduling method, the energy-saving and secure uplink transmission can be guaranteed. In the downlink, an energy-first multi-point relays set selection mechanism (EFMSS) is designed to choose the backbone nodes to broadcast messages, and the backbone nodes are waken up by the same level-by-level sleeping scheduling method as the uplink transmission. With the two-step procedure, the critical events are appropriately dealt with and the responses are broadcast to the whole network. Extensive simulations results demonstrate that the energy saving and security performances of the proposed method are superior to the existing ones.

To address the problem that high-reliability and long-life complex products are susceptible to coupled fault mechanisms, and to address the challenge of constructing a macro fault behavior model for reliability evaluation, the reliability of a smart meter based on a Phase-Type (PH) distribution under a degradation-shock load is examined. This reliability assessment method considers the impacts of environmental stress and lightning shock on a smart meter. The performance degradation process caused by environmental stress is described by a Wiener model, which is converted into a representation of a PH distribution in a subsequent step. A lightning impulse can cause performance degradation or direct failure of a smart meter. The arrival time of the lightning, the magnitude of the lightning, and the damage caused by the lightning are analyzed separately, and then, the obtained model is expressed in the form of a PH distribution. Finally, a reliability evaluation model of a smart meter based on the PH model under a degradation-shock load is established. The accuracy of the model is verified by comparing the model results with Monte Carlo simulation results.

Human antigen R (HuR) is an RNA binding protein that promotes mRNA stability. Here the authors show that HuR represses adipogenesis in white and brown adipose tissue by stabilizing Insig1 and other targets.

Noise-induced hearing loss (NIHL) is one of the most prevalent forms of acquired hearing loss, and it is associated with aberrant microglial status and reduced hippocampal neurogenesis; however, the nature of these associations is far from being elucidated. Beyond its direct effects on the auditory system, exposure to intense noise has previously been shown to acutely activate the stress response, which has increasingly been linked to both microglial activity and adult hippocampal neurogenesis in recent years. Given the pervasiveness of noise pollution in modern society and the important implications of either microglial activity or hippocampal neurogenesis for cognitive and emotional function, this study was designed to investigate how microglial status and hippocampal neurogenesis change over time following acoustic exposure and to analyze the possible roles of the noise exposure-induced stress response and hearing loss in these changes. To accomplish this, adult male C57BL/6J mice were randomly assigned to either a control or noise exposure (NE) group. Auditory function was assessed by measuring ABR thresholds at 20 days post noise exposure. The time-course profile of serum corticosterone levels, microglial status, and hippocampal neurogenesis during the 28 days following noise exposure were quantified by ELISA or immunofluorescence staining. Our results illustrated a permanent moderate-to-severe degree of hearing loss, an early but transient increase in serum corticosterone levels, and time-dependent dynamic alterations in microglial activation status and hippocampal neurogenesis, which both present an early but transient change and a late but enduring change. These findings provide evidence that both the stress response and hearing loss contribute to the dynamic alterations of microglia and hippocampal neurogenesis following noise exposure; moreover, noise-induced permanent hearing loss rather than noise-induced transient stress is more likely to be responsible for perpetuating the neurodegenerative process associated with many neurological diseases.

Endosulfan is an organochlorine pesticide, which poses a potential danger to human health and safety. It is known that dysfunction of glomerular mesangial cells causes glomerular sclerosis, associated with chronic kidney diseases. In the present study, we investigated the effects of endosulfan on cell proliferation and extracellular matrix accumulation (ECM) in human renal mesangial cells (HRMCs). Cells were treated with endosulfan, endosulfan (10 μM) plus specific inhibitor of TGF-β signaling (LY2109761) or antioxidant (NAC). The results showed that endosulfan significantly promoted cell proliferation, accompanied with the decrease of p27 mRNA expression and the increase in the mRNA expression levels of p21 and inflammatory factors IL-6/IL-8. qRT-PCR results showed that matrix metalloproteinase-2 (MMP2) and tissue metalloproteinase-3 (TIMP3) were down-regulated whereas laminin was up-regulated when exposure to endosulfan. Western blot results showed that p-Smad2/3 was up-regulated, while Smad7 was down-regulated when exposure to endosulfan, which were reversed in the presence of LY2109761. Endosulfan significantly decreased the activity of SOD and increased the MDA level and CAT activity, which were reversed in the presence of NAC. These findings suggest that endosulfan can cause excessive proliferation and massive accumulation of ECM through TGF-β/Smad signaling pathway, and also induced oxidative stress and inflammation in HRMCs.

Objective: The age-related changes in the resting-state networks (RSNs) exhibited temporally specific patterns in humans, and humans and rhesus monkeys have similar RSNs. We hypothesized that the RSNs in rhesus monkeys experienced similar developmental patterns as humans. Methods: We acquired resting-state fMRI data from 62 rhesus monkeys, which were divided into childhood, adolescence, and early adulthood groups. Group independent component analysis (ICA) was used to identify monkey RSNs. We detected the between-group differences in the RSNs and static, dynamic, and effective functional network connections (FNCs) using one-way variance analysis (ANOVA) and post-hoc analysis. Results: Eight rhesus RSNs were identified, including cerebellum (CN), left and right lateral visual (LVN and RVN), posterior default mode (pDMN), visuospatial (VSN), frontal (FN), salience (SN), and sensorimotor networks (SMN). In internal connections, the CN, SN, FN, and SMN mainly matured in early adulthood. The static FNCs associated with FN, SN, pDMN primarily experienced fast descending slow ascending type (U-shaped) developmental patterns for maturation, and the dynamic FNCs related to pDMN (RVN, CN, and SMN) and SMN (CN) were mature in early adulthood. The effective FNC results showed that the pDMN and VSN (stimulated), SN (inhibited), and FN (first inhibited then stimulated) chiefly matured in early adulthood. Conclusion: We identified eight monkey RSNs, which exhibited similar development patterns as humans. All the RSNs and FNCs in monkeys were not widely changed but fine-tuned. Our study clarified that the progressive synchronization, exploration, and regulation of cognitive RSNs within the pDMN, FN, SN, and VSN denoted potential maturation of the RSNs throughout development. We confirmed the development patterns of RSNs and FNCs would support the use of monkeys as a best animal model for human brain function.

Purpose Urine can sensitively reflect early pathophysiological changes in the body. The purpose of this study was to explore the changes of urine proteome in rats with regular swimming exercise. Methods In this study, experimental rats were subjected to daily moderate-intensity swimming exercise for 7 weeks. Urine samples were collected at weeks 2, 5, and 7 and were analyzed by using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Results Unsupervised clustering analysis of all urinary proteins identified at week 2 showed that the swimming group was distinctively different from the control group. Compared to the control group, a total of 112, 61 and 44 differential proteins were identified in the swimming group at weeks 2, 5 and 7, respectively. Randomized grouping statistical analysis showed that more than 85% of the differential proteins identified in this study were caused by swimming exercise rather than random allocation. According to the Human Protein Atlas, the differential proteins that have human orthologs were strongly expressed in the liver, kidney and intestine. Functional annotation analysis revealed that these differential proteins were involved in glucose metabolism and immunity-related pathways. Conclusion Our results revealed that the urinary proteome could reflect significant changes after regular swimming exercise. These findings may provide an approach to monitor the effects of exercise of the body.

The mall heterodimer partner (SHP) plays an important regulatory role in mammal inflammation. The main objective of this study was to investigate the response of SHP to inflammatory stimulation and its underlying mechanism. The shp gene from large yellow croakers, was cloned, and this gene is mainly expressed in the liver and intestine. Lipopolysaccharide (LPS) stimulation induced the mRNA expression and protein level of SHP in macrophages of large yellow croakers. Overexpression of SHP significantly decreased mRNA expression of tnfα, il-1β, il-6 and cox2 induced by LPS treatment in macrophages. LPS stimulation increased the phosphorylation level of Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) in macrophages. AMPK inhibitor treatment significantly decreased the expression of SHP induced by LPS while AMPK activator significantly increased the expression of SHP. The nuclear factor-erythroid 2-related factor 2 (NRF2) increased the promoter activity of SHP in large yellow croakers and the level of nuclear NRF2 was increased by LPS stimulation and AMPK activation. NRF2 inhibitor treatment significantly decreased mRNA expression of shp induced by LPS and AMPK activator. In conclusion, LPS can induce SHP expression by activating the AMPK-NRF2 pathway while SHP could negatively regulate LPS-induced inflammation in large yellow croakers. This study may be benefit to the development of immunology of marine fish and provide new ideas for inflammation-related diseases.

Background: Sepsis is a dysregulated host response to pathogens. Delay in sepsis diagnosis has become a primary cause of patient death. This study determines some factors to prevent septic shock in its early stage, contributing to the early treatment of sepsis. Methods: The sequencing data (RNA- and miRNA-sequencing) of patients with septic shock were obtained from the NCBI GEO database. After re-annotation, we obtained lncRNAs, miRNA, and mRNA information. Then, we evaluated the immune characteristics of the sample based on the ssGSEA algorithm. We used the WGCNA algorithm to obtain genes significantly related to immunity and screen for important related factors by constructing a ceRNA regulatory network. Result: After re-annotation, we obtained 1708 lncRNAs, 129 miRNAs, and 17 326 mRNAs. Also, through the ssGSEA algorithm, we obtained 5 important immune cells. Finally, we constructed a ceRNA regulation network associated with SS pathways. Conclusion: We identified 5 immune cells with significant changes in the early stage of septic shock. We also constructed a ceRNA network, which will help us explore the pathogenesis of septic shock.

Most fermented foods need a natural aging process to enrich desired flavours. This process is normally the bottleneck for cost-effective production. Therefore, it is desirable to accelerate the process and obtain products with the same flavour profile. Here, we used physical interventions (ultrasonic field, alternating magnetic field, or combination of both) to assist the aging process with naturally brewed vinegar as a case example. Flavour profiles of different physical-assisted aging process were compared with that of the naturally aged vinegar by using gas-chromatography mass-spectrometry (GC–MS) and electronic nose. Principal component analysis (PCA) and Pearson correlation analyses show that ultrasonic and alternating magnetic fields treatment could accelerate the aging process of vinegar. The highest accelerating aging effect was combination of ultrasonic and magnetic field followed by individual ultrasonic or magnetic field and natural process (combination of ultrasonic and magnetic field > ultrasonic or magnetic field individual > natural process). These results suggest that physical field intervention could potentially be used for acceleration of aging of fermented products without affecting flavour quality.

Background: Whether digoxin is associated with increased mortality in atrial fibrillation (AF) remains controversial. We aimed to assess the risk of mortality and clinical effects of digoxin use in patients with AF.Methods: PubMed, Embase, and the Cochrane library were systematically searched to identify eligible studies comparing all-cause mortality of patients with AF taking digoxin with those not taking digoxin, and the length of follow-up was at least 6 months. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted and pooled.Results: A total of 29 studies with 621,478 patients were included. Digoxin use was associated with an increased risk of all-cause mortality in all patients with AF (HR 1.17, 95% CI 1.13–1.22, P < 0.001), especially in patients without HF (HR 1.28, 95% CI 1.11–1.47, P < 0.001). There was no significant association between digoxin and mortality in patients with AF and HF (HR 1.06, 95% CI 0.99–1.14, P = 0.110). In all patients with AF, regardless of concomitant HF, digoxin use was associated with an increased risk of sudden cardiac death (SCD) (HR 1.40, 95% CI 1.23–1.60, P < 0.001) and cardiovascular (CV) mortality (HR 1.27, 95% CI 1.08–1.50, P < 0.001), and digoxin use had no significant association with all-cause hospitalization (HR 1.13, 95% CI 0.92–1.39, P = 0.230).Conclusion: We conclude that digoxin use is associated with an increased risk of all-cause mortality, CV mortality, and SCD, and it does not reduce readmission for AF, regardless of concomitant HF. Digoxin may have a neutral effect on all-cause mortality in patients with AF with concomitant HF.Systematic Review Registration:https://www.crd.york.ac.ukPROSPERO.

Cow manure derived biochar (CMBC) can serve as a promising functional material, and CMBC can be regarded as an ecofriendly approach compared to conventional ones. CM bioadsorbent can be employed for heavy metal immobilization (such as for lead) as well as an amendment to increase soil fertility (e.g., phosphorus). Few studies have examined the surface interactions between pollutants and bioadsorbents when inherent nutrient release is present. In this work, CMBC was prepared and applied for Pb(II) removal, and the vital roles of released phosphorus from CMBC were comprehensively disclosed. Furthermore, CMBC could immobilize part of the Pb(II) in soil and promote plant growth. CM400 was an effective adsorbent whose calculated Qe reached 691.34 mg·g−1, and it rapidly adsorbed 98.36 mg·g−1 of Pb(II) within 1 min. The adsorption mechanisms of Pb(II) by CMBC include ion exchange, physical adsorption, electrostatic attraction, chemical precipitation, surface complexation, and cation–π bond interaction. Based on the residual phosphorus content and adsorption effect, complexation rather than the chemical precipitation had a greater contribution toward adsorption. Besides, as the concentration of Pb(II) increased, the main adsorption mechanisms likely transformed from chemical precipitation to ion exchange and complexation. CMBC not only had a good effect on Pb(II) removal in the solution, but also immobilized the Pb(II) in soil to restrain plant uptake as well as promote plant growth. The main novelty of this work is providing more insights to the cow manure bio adsorbent on Pb immobilization and phosphorus release. This study is expected to serve as a basis and reference for analyzing the release effects of inherent nutrients and the interfacial behaviors with heavy metals when using CMBC and other nutrient–rich carbon–based fertilizers for pollution control.

Due to the heavy computation load of closed-loop simulations, optimal control of greenhouse climate is usually simulated in an open-loop form to produce control strategies and profit indicators. Open-loop simulations assume the model, measurements, and predictions to be perfect, resulting in too-idealistic indicators. The method of two-time-scale decomposition reduces the computation load, thus facilitating the online implementation of optimal control algorithms. However, the computation time of nonlinear dynamic programming is seldom considered in closed-loop simulations. This paper develops a two-time-scale decomposed closed-loop optimal control algorithm that involves the computation time. The obtained simulation results are closer to reality since it considers the time delay in the implementation. With this algorithm, optimal control of Venlo greenhouse lettuce cultivation is investigated in Lhasa. Results show that compared with open-loop simulations, the corrections in yield and profit indicators can be up to 2.38 kg m−2 and 11.01 CNY m−2, respectively, through closed-loop simulations without considering the computation time. When involving the time delay caused by the computation time, further corrections in yield and profit indicators can be up to 0.1 kg m−2 and 0.87 CNY m−2, respectively. These conservative indicators help investors make wiser decisions before cultivation. Moreover, control inputs and greenhouse climate states are within their bounds most of the time during closed-loop simulations. This verifies that the developed algorithm can be implemented in real time.

Flocking for fixed-Wing Unmanned Aerial Vehicles (UAVs) is an extremely complex challenge due to fixed-wing UAV’s control problem and the system’s coordinate difficulty. Recently, flocking approaches based on reinforcement learning have attracted attention. However, current methods also require that each UAV makes the decision decentralized, which increases the cost and computation of the whole UAV system. This paper researches a low-cost UAV formation system consisting of one leader (equipped with the intelligence chip) with five followers (without the intelligence chip), and proposes a centralized collision-free formation-keeping method. The communication in the whole process is considered and the protocol is designed by minimizing the communication cost. In addition, an analysis of the Proximal Policy Optimization (PPO) algorithm is provided; the paper derives the estimation error bound, and reveals the relationship between the bound and exploration. To encourage the agent to balance their exploration and estimation error bound, a version of PPO named PPO-Exploration (PPO-Exp) is proposed. It can adjust the clip constraint parameter and make the exploration mechanism more flexible. The results of the experiments show that PPO-Exp performs better than the current algorithms in these tasks.

Clinical and animal studies suggest that paternal exposure to adverse environments (bad living habits and chronic stress, etc.) has profound impacts on offspring development; however, the mechanism of paternal disease has not been clarified. In this study, a meta-analysis was first performed to suggest that paternal exposure to nicotine, ethanol, or caffeine is a high-risk factor for adverse pregnancy outcomes. Next, we created a rat model of paternal nicotine/ethanol/caffeine mixed exposure (PME), whereby male Wistar rats were exposed to nicotine (0.1 mg/kg/d), ethanol (0.5 g/kg/d), and caffeine (7.5 mg/kg/d) for 8 weeks continuously, then mated with normal female rats to obtain a fetus (n = 12 for control group, n = 10 for PME group). Then, we analyzed the changes in paternal hypothalamic–pituitary–adrenal (HPA) axis activity, testicular function, pregnancy outcomes, fetal serum metabolic indicators, and multiple organ functions to explore the mechanism from the perspective of chronic stress. Our results demonstrated that PME led to enhanced paternal HPA axis activity, decreased sperm quality, and adverse pregnancy outcomes (stillbirth and absorption, decreased fetal weight and body length, and intrauterine growth retardation), abnormal fetal serum metabolic indicators (corticosterone, glucolipid metabolism, and sex hormones), and fetal multi-organ dysfunction (including hippocampus, adrenal, liver, ossification, and gonads). Furthermore, correlation analysis showed that the increased paternal corticosterone level was closely related to decreased sperm quality, adverse pregnancy outcomes, and abnormal offspring multi-organ function development. Among them, the decreased activity of the glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis may be the main mechanism of offspring development and multi-organ dysfunction caused by PME. This study explored the impact of common paternal lifestyle in daily life on offspring development, and proposed the GC-IGF1 programming mechanisms of paternal chronic stress-induced offspring dysplasia, which provides a novel insight for exploring the important role of paternal chronic stress in offspring development and guiding a healthy lifestyle for men.