Effects of neuraxial anesthesia in sitting and lateral positions on maternal hemodynamics in cesarean section: A systematic review and meta-analysis.

STUDY OBJECTIVE: During cesarean section, hypotension is a frequent side effect of spinal anesthesia. As a sitting or lateral position is required for spinal anesthesia performance, which of these two positions is more likely to cause intraoperative nausea, vomiting, and hypotension is still unknown. This meta-analysis compared the effects of these two positions on maternal hemodynamics and intraoperative nausea and vomiting. DESIGN: Systematic review and meta-analysis. SETTING: Operating room. PATIENTS: This study included 803 patients from 12 randomized controlled trials (RCTs). INTERVENTIONS: Neuraxial anesthesia in sitting position vs. lateral position. MEASUREMENTS: We chose RCTs comparing the effects of spinal anesthesia in the sitting and lateral positions on maternal hemodynamics by thoroughly searching PubMed, Embase, the Cochrane Library, and the Web of Science for articles published from database inception until October 31, 2022. The Cochrane Handbook was used to assess the methodological quality of each RCT; the results were analyzed using RevMan 5.4 software; and the Egger test was used to assess publication bias. MAIN RESULTS: 12 randomised controlled trials with 803 participants were ultimately included in the final analysis. No significant differences were observed between the two positions in terms of the incidence of hypotension(RR, 0.82; 95% CI, 0.58-1.16; P = 0.26; I2 = 66%), lowest systolic blood pressure(MD, -0.81; 95% CI, -7.38-5.75; P = 0.81; I2 = 86%), the dose of ephedrine(MD, -1.19; 95% CI, -4.91-2.52; P = 0.53; I2 = 83%), and number of parturients requiring ephedrine(RR, 0.97; 95% CI, 0.64-1.46; P = 0.88; I2 = 74%). For the incidence of intraoperative nausea and vomiting, there was no statistical difference between the two positions. CONCLUSION: Parturients undergoing elective cesarean section under spinal anesthesia in the sitting or lateral position experienced similar incidence of hypotension, and there were no significant differences between these two positions in terms of the amount of ephedrine administered or the number of patients needing ephedrine. In both positions, the frequency of nausea and vomiting was comparable. The ideal position for anesthesia can be chosen based on the preferences and individual circumstances of the parturient and anesthesiologist.

Association between exposure to ambient air pollution, meteorological factors and atopic dermatitis consultations in Singapore-a stratified nationwide time-series analysis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting approximately 20% of children globally. While studies have been conducted elsewhere, air pollution and weather variability is not well studied in the tropics. This time-series study examines the association between air pollution and meteorological factors with the incidence of outpatient visits for AD obtained from the National Skin Centre (NSC) in Singapore. The total number of 1,440,844 consultation visits from the NSC from 2009 to 2019 was analysed. Using the distributed lag non-linear model and assuming a negative binomial distribution, the short-term temporal association between outpatient visits for AD and air quality and meteorological variability on a weekly time-scale were examined, while adjusting for long-term trends, seasonality and autocorrelation. The analysis was also stratified by gender and age to assess potential effect modification. The risk of AD consultation visits was 14% lower (RR10th percentile: 0.86, 95% CI 0.78-0.96) at the 10th percentile (11.9 µg/m3) of PM2.5 and 10% higher (RR90th percentile: 1.10, 95% CI 1.01-1.19) at the 90th percentile (24.4 µg/m3) compared to the median value (16.1 µg/m3). Similar results were observed for PM10 with lower risk at the 10th percentile and higher risk at the 90th percentile (RR10th percentile: 0.86, 95% CI 0.78-0.95, RR90th percentile: 1.10, 95% CI 1.01-1.19). For rainfall for values above the median, the risk of consultation visits was higher up to 7.4 mm in the PM2.5 model (RR74th percentile: 1.07, 95% CI 1.00-1.14) and up to 9 mm in the PM10 model (RR80th percentile: 1.12, 95% CI 1.00-1.25). This study found a close association between outpatient visits for AD with ambient particulate matter concentrations and rainfall. Seasonal variations in particulate matter and rainfall may be used to alert healthcare providers on the anticipated rise in AD cases and to time preventive measures to reduce the associated health burden.

Overexpression of GPX2 gene regulates the development of porcine preadipocytes and skeletal muscle cells through MAPK signaling pathway.

Glutathione peroxidase 2 (GPX2) is a selenium-dependent enzyme and protects cells against oxidative damage. Recently, GPX2 has been identified as a candidate gene for backfat and feed efficiency in pigs. However, it is unclear whether GPX2 regulates the development of porcine preadipocytes and skeletal muscle cells. In this study, adenoviral gene transfer was used to overexpress GPX2. Our findings suggest that overexpression of GPX2 gene inhibited proliferation of porcine preadipocytes. And the process is accompanied by the reduction of the p-p38. GPX2 inhibited adipogenic differentiation and promoted lipid degradation, while ERK1/2 was reduced and p-p38 was increased. Proliferation of porcine skeletal muscle cells was induced after GPX2 overexpression, was accompanied by activation in JNK, ERK1/2, and p-p38. Overexpression methods confirmed that GPX2 has a promoting function in myoblastic differentiation. ERK1/2 pathway was activated and p38 was suppressed during the process. This study lays a foundation for the functional study of GPX2 and provides theoretical support for promoting subcutaneous fat reduction and muscle growth.

The burden and predictors of 30-day unplanned readmission in patients with acute liver failure: a national representative database study.

BACKGROUND: Liver diseases were significant source of early readmission burden. This study aimed to evaluate the 30-day unplanned readmission rates, causes of readmissions, readmission costs, and predictors of readmission in patients with acute liver failure (ALF). METHODS: Patients admitted for ALF from 2019 National Readmission Database were enrolled. Weighted multivariable logistic regression models were applied and based on Directed Acyclic Graphs. Incidence, causes, cost, and predictors of 30-day unplanned readmissions were identified. RESULTS: A total of 3,281 patients with ALF were enrolled, of whom 600 (18.3%) were readmitted within 30 days. The mean time from discharge to early readmission was 12.6 days. The average hospital cost and charge of readmission were $19,629 and $86,228, respectively. The readmissions were mainly due to liver-related events (26.6%), followed by infection (20.9%). The predictive factors independently associated with readmissions were age, male sex (OR 1.227, 95% CI 1.023-1.472; P = 0.028), renal failure (OR 1.401, 95% CI 1.139-1.723; P = 0.001), diabetes with chronic complications (OR 1.327, 95% CI 1.053-1.672; P = 0.017), complicated hypertension (OR 1.436, 95% CI 1.111-1.857; P = 0.006), peritoneal drainage (OR 1.600, 95% CI 1.092-2.345; P = 0.016), etc. CONCLUSIONS: Patients with ALF are at relatively high risk of early readmission, which imposes a heavy medical and economic burden on society. We need to increase the emphasis placed on early readmission of patients with ALF and establish clinical strategies for their management.

Prevalence of metabolic syndrome among patients with hepatocellular carcinoma of different etiologies: a retrospective study.

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

Prediction of mechanical ventilation in Guillain-Barré syndrome at admission: Construction of a nomogram and comparison with the EGRIS model.

Background: Respiratory failure requiring mechanical ventilation (MV) is a common and severe complication of Guillain-Barré syndrome (GBS) with a reported incidence ranging from 20 % to 30 %. Thus, we aim to develop a nomogram to evaluate the risk of MV in patients with GBS at admission and tailor individualized care and treatment. Methods: A total of 633 patients with GBS (434 in the training set, and 199 in the validation set) admitted to the First Hospital of Jilin University, Changchun, China from January 2010 to January 2021 were retrospectively enrolled. Subjects (n = 71) from the same institution from January 2021 to May 2022 were prospectively collected and allocated to the testing set. Multivariable logistic regression analysis was applied to build a predictive model incorporating the optimal features selected in the least absolute shrinkage and selection operator (LASSO) in the training set. The predictive model was validated using internal bootstrap resampling, an external validation set, and a prospective testing set, and the model's performance was assessed by using the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Finally, we established a multivariable logistic model by using variables of the Erasmus GBS Respiratory Insufficiency Score (EGRIS) and did the same analysis to compare the performance of our predictive model with the EGRIS model. Results: Variables in the final model selected by LASSO included time from onset to admission, facial and/or bulbar weakness, Medical Research Council sum score at admission, neutrophil-to-lymphocyte ratio, and platelet-lymphocyte ratio. The model presented as a nomogram displaying favorable discriminative ability with a C-index of 0.914 in the training set, 0.903 in the internal validation set, 0.953 in the external validation set, and 0.929 in the testing set. The model was well-calibrated and clinically useful as assessed by the calibration curve and DCA. As compared with the EGRIS model, our predictive model displayed satisfactory performance. Conclusions: We constructed a nomogram for early prediction of the risk of MV in patients with GBS. This model had satisfactory performance and appeared more efficient than the EGRIS model in Chinese patients with GBS.

Domain Switching Characteristics in Ga-Doped HfO2 Ferroelectric Thin Films with Low Coercive Field.

The gallium-doped hafnium oxide (Ga-HfO2) films with different Ga doping concentrations were prepared by adjusting the HfO2/Ga2O3 atomic layer deposition cycle ratio for high-speed and low-voltage operation in HfO2-based ferroelectric memory. The Ga-HfO2 ferroelectric films reveal a finely modulated coercive field (Ec) from 1.1 (HfO2/Ga2O3 = 32:1) to an exceptionally low 0.6 MV/cm (HfO2/Ga2O3 = 11:1). This modulation arises from the competition between domain nucleation and propagation speed during polarization switching, influenced by the intrinsic domain density and phase dispersion in the film with specific Ga doping concentrations. Higher Ec samples exhibit a nucleation-dominant switching mechanism, while lower Ec samples undergo a transition from a nucleation-dominant to a propagation-dominant reversal mechanism as the electric field increases. This work introduces Ga as a viable dopant for low Ec and offers insights into material design strategies for HfO2-based ferroelectric memory applications.

Exposure to high concentrations of triphenyl phosphate altered functional performance, liver metabolism and intestinal bacterial composition of aquatic turtles.

Organophosphorus flame retardants, such as triphenyl phosphate (TPhP), exist ubiquitously in various environments owing to their widespread usage. Potential toxic effects of residual flame retardants on cultured non-fish species are not concerned commonly. TPhP-induced physiological and biochemical effects in an aquatic turtle were evaluated here by systematically investigating the changes in growth and locomotor performance, hepatic antioxidant ability and metabolite, and intestinal microbiota composition of turtle hatchlings after exposure to different TPhP concentrations. Reduced locomotor ability and antioxidant activity were only observed in the highest concentration group. Several metabolic perturbations that involved in amino acid, energy and nucleotide metabolism, in exposed turtles were revealed by metabolite profiles. No significant among-group difference in intestinal bacterial diversity was observed, but the composition was changed markedly in exposed turtles. Increased relative abundances of some bacterial genera (e.g., Staphylococcus, Vogesella and Lawsonella) probably indicated adverse outcomes of TPhP exposure. Despite having only limited impacts of exposure at environmentally relevant levels, our results revealed potential ecotoxicological risks of residual TPhP for aquatic turtles considering TPhP-induced metabolic perturbations and intestinal bacterial changes.

Comparison of drug-eluting bead with conventional transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: A randomized clinical trial.

BACKGROUND: Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear. OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT. METHODS: The study was conducted in a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio to the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not limited. RESULTS: Between September 2018, and July 2020, 163 patients were randomized to undergo DEB-TACE (n=82) or cTACE (n=81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78 y), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0 to 10.0) versus 4.0 months (95% CI, 3.0 to 5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42 to 0.95; P=0.027). The DEB-TACE group showed a higher response rate (51[66.2%] vs. 36 [46.8%]; P=0.0015) and a longer median OS (12.0 months [95% CI, 9.0 to 16.0] vs. 8.0 months [95% CI, 7.0 to 11.0], P=0.039) than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combined with surgery were independently correlated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AEs. CONCLUSION: DEB-TACE is superior to cTACE in treating HCC patients with PVTT due to the improved PFS and OS with an acceptable safety profile and may become a promising treatment strategy for HCC patients with PVTT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018035.

Alkenyl oxindole is a novel PROTAC moiety that recruits the CRL4DCAF11 E3 ubiquitin ligase complex for targeted protein degradation.

Alkenyl oxindoles have been characterized as autophagosome-tethering compounds (ATTECs), which can target mutant huntingtin protein (mHTT) for lysosomal degradation. In order to expand the application of alkenyl oxindoles for targeted protein degradation, we designed and synthesized a series of heterobifunctional compounds by conjugating different alkenyl oxindoles with bromodomain-containing protein 4 (BRD4) inhibitor JQ1. Through structure-activity relationship study, we successfully developed JQ1-alkenyl oxindole conjugates that potently degrade BRD4. Unexpectedly, we found that these molecules degrade BRD4 through the ubiquitin-proteasome system, rather than the autophagy-lysosomal pathway. Using pooled CRISPR interference (CRISPRi) screening, we revealed that JQ1-alkenyl oxindole conjugates recruit the E3 ubiquitin ligase complex CRL4DCAF11 for substrate degradation. Furthermore, we validated the most potent heterobifunctional molecule HL435 as a promising drug-like lead compound to exert antitumor activity both in vitro and in a mouse xenograft tumor model. Our research provides new employable proteolysis targeting chimera (PROTAC) moieties for targeted protein degradation, providing new possibilities for drug discovery.

[Impurity profile analysis of amphotericin B using on-line two-dimensional high performance liquid chromatography-quadrupole time-of-flight mass spectrometry].

Amphotericin B (AmB) is a polyene-macrolide antimicrobial drug with a broad antibacterial spectrum and remarkable efficacy against deep fungal infections. It binds to ergosterol on the fungal cell membrane and alters its permeability, thereby destroying the membrane. AmB is a multicomponent antimicrobial medication that contains a wide range of impurities, rendering quality analysis extremely difficult. In the current Chinese Pharmacopoeia (Edition 2020) and European Pharmacopoeia (EP10.3), high performance liquid chromatography (HPLC) is applied to examine related substances in AmB. However, this technique presents a number of issues. For instance, the mobile phases used in the HPLC method described in both references contain nonvolatile inorganic salts, which cannot be coupled with a mass spectrometry (MS) detector. In addition, because the mobile phases used have a low pH, the component/impurities of AmB drug can easily be degraded or interconverted during the analytical process, leading to reduced analytical accuracy. Therefore, the accuracy and sensitivity of this method must be improved. In this study, a method based on on-line two-dimensional high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (2D HPLC-Q TOF/MS) was developed to analyze the impurity profile of AmB in accordance with the Chinese Pharmacopoeia (Edition 2020) and European Pharmacopoeia (EP10.3). The method combines on-line dilution and a multiple-capture HPLC system to achieve the efficient separation of AmB component/impurities. It also resolves the issue of poor solvent compatibility in 2D HPLC, increases the analytical flux, enhances the automation capability, reduces the mutual conversion of AmB and its impurities during the analytical process, and increases the detection sensitivity of the method. MS was also used to determine the structural inference of unstable components and impurities. An XBridge Shield C18 column (250 mm×4.6 mm, 3 µm) was used for first-dimensional-liquid chromatography with gradient elution using methanol-acetonitrile-4.2 g/L citric acid monohydrate solution (10∶30∶60, v/v/v, pH 4.7) as mobile phase A and methanol-acetonitrile-4.2 g/L citric acid monohydrate solution (12∶68∶20, v/v/v, pH 3.9) as mobile phase B. An Xtimate C8 column (10 mm×2.1 mm, 5 µm) was used as the trap column, and trapping and desalting were performed using 10 mmol/L ammonium formate aqueous solution containing 0.1% formic acid-acetonitrile (95∶5, v/v). An Xtimate C8 column (250 mm×2.1 mm, 5 µm) was used for second-dimensional-liquid chromatography with gradient elution using 10 mmol/L ammonium formate aqueous solution containing 0.1% formic acid-acetonitrile (95∶5, v/v) and 10 mmol/L ammonium formate aqueous solution containing 0.1% formic acid-acetonitrile (5∶95, v/v) as mobile phases. The data were collected in positive-ion mode. In this study, the structures of six impurities in amphotericin B were inferred, according to the fragmentation, the MS and MS2 spectra of each impurity. The developed method can be used to quickly and sensitively analyze the impurity profile of AmB. Furthermore, the research results on impurity profiles can be applied to guide improvements in AmB production.

A Grading System for Assessing the Status of the Sphincter of Oddi During Intraoperative Choledochoscopy: A Surgeon's Perspective.

BACKGROUND: The aim of this study was to establish a simple and practical grading system for evaluating the status of the sphincter of Oddi (SO) during intraoperative choledochoscopy. This system helps identify relevant variables that influence the status of the SO and provides recommendations for preventing stone recurrence. METHODS: Ninety-three patients were selected retrospectively from a total of 316 patients diagnosed with choledocholithiasis between July 2020 and June 2023. All patients underwent common bile duct (CBD) exploration surgery and intraoperative choledochoscopy. The status of the SO was assessed during choledochoscopy. According to the severity of the condition, the patients were categorized into 4 groups. Data from each group, grades 1, 2, 3, 4, was analyzed statistically. RESULTS: The number of patients in grade 1 was significantly lower than that of the other 3 groups. Except for grade 1, patients in grade 4 exhibited significant differences compared with the other 2 groups in terms of the diameter of the CBD, size of stones, presence of pneumobilia, and history of endoscopic retrograde cholangiopancreatography (ERCP) (P<0.05). There were no significant differences between the groups in terms of sex, age, liver function, number of stones, history of gastrectomy, cholecystectomy, or CBD exploration. CONCLUSIONS: The grading system helps us classify different sphincter functions and better understand the formation of choledocholithiasis by subdividing the status of the SO. Endoscopic sphincterotomy (EST) treatment can easily result in the loss of SO function, which increases the risk of stone recurrence.

Analysis of risk characteristics for early progression and late progression in locally advanced rectal cancer patients: a large population-based and validated study.

BACKGROUND AND OBJECTIVE: The current study aimed to explore the factors influencing early progression (EP) and late progression (LP) in locally advanced rectal cancer (LARC) patients. METHODS: The patients were classified into EP and LP groups using one year as a cutoff. The random survival forest model was utilized to calculate the probability of time-to-progression. Besides, inverse probability of treatment weighting (IPTW) analysis and the Surveillance, Epidemiology, and End Results (SEER) were conducted to validate our results. RESULTS: Our study revealed that PNI, CEA level, and pathological stage were independent prognostic factors for PFS both in EP group and LP group. For EP group patients, Group 1 had the highest probability of progression at the 9th month of follow-up, while Group 2 exhibited the highest probability at the 6th month. Group 3, on the other hand, showed two peaks of progression at the 4th and 8th months of follow-up. As for LP group patients, Groups 4, 5, and 6 all exhibited peaks of progression between the 18th and 24th months of follow-up. Furthermore, our results suggested that PNI was also an independent prognostic factor affecting OS in both EP group and LP group. Finally, the analysis of IPTW and SEER database further confirmed our findings. CONCLUSIONS: Our results indicated a significant correlation between immune and nutritional status with PFS and OS in both EP and LP groups. These insights can aid healthcare professionals in effectively identifying and evaluating patients' nutritional status, enabling them to develop tailored nutrition plans and interventions.

A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

Endothelial Reprogramming in Atherosclerosis.

Atherosclerosis (AS) is a severe vascular disease that results in millions of cases of mortality each year. The development of atherosclerosis is associated with vascular structural lesions, characterized by the accumulation of immune cells, mesenchymal cells, lipids, and an extracellular matrix at the intimal resulting in the formation of an atheromatous plaque. AS involves complex interactions among various cell types, including macrophages, endothelial cells (ECs), and smooth muscle cells (SMCs). Endothelial dysfunction plays an essential role in the initiation and progression of AS. Endothelial dysfunction can encompass a constellation of various non-adaptive dynamic alterations of biology and function, termed "endothelial reprogramming". This phenomenon involves transitioning from a quiescent, anti-inflammatory state to a pro-inflammatory and proatherogenic state and alterations in endothelial cell identity, such as endothelial to mesenchymal transition (EndMT) and endothelial-to-immune cell-like transition (EndIT). Targeting these processes to restore endothelial balance and prevent cell identity shifts, alongside modulating epigenetic factors, can attenuate atherosclerosis progression. In the present review, we discuss the role of endothelial cells in AS and summarize studies in endothelial reprogramming associated with the pathogenesis of AS.

Electrical stress and acid orange 7 synergistically clear the blockage of electron flow in the methanogenesis of low-strength wastewater.

Energy recovery from low-strength wastewater through anaerobic methanogenesis is constrained by limited substrate availability. The development of efficient methanogenic communities is critical but challenging. Here we develop a strategy to acclimate methanogenic communities using conductive carrier (CC), electrical stress (ES), and Acid Orange 7 (AO7) in a modified biofilter. The synergistic integration of CC, ES, and AO7 precipitated a remarkable 72-fold surge in methane production rate compared to the baseline. This increase was attributed to an altered methanogenic community function, independent of the continuous presence of AO7 and ES. AO7 acted as an external electron acceptor, accelerating acetogenesis from fermentation intermediates, restructuring the bacterial community, and enriching electroactive bacteria (EAB). Meanwhile, CC and ES orchestrated the assembly of the archaeal community and promoted electrotrophic methanogens, enhancing acetotrophic methanogenesis electron flow via a mechanism distinct from direct electrochemical interactions. The collective application of CC, ES, and AO7 effectively mitigated electron flow impediments in low-strength wastewater methanogenesis, achieving an additional 34% electron recovery from the substrate. This study proposes a new method of amending anaerobic digestion systems with conductive materials to advance wastewater treatment, sustainability, and energy self-sufficiency.

Effects of dietary supplementation of polysaccharide from Agaricus blazei Murr on productive performance, egg quality, blood metabolites, intestinal morphology and microbiota of Korean quail.

Objective: This study aimed to investigate the effects of dietary supplementation with Agaricus blazei polysaccharide (ABP) at varying concentrations on the performance, egg quality, blood biochemistry, intestinal morphology, and microflora of quail. Methods: The study involved a total of 2,700 Korean quails, which were randomly divided into three groups. The measured variables encompassed productive performance, egg parameters, carcass parameters, serum metabolites, immune response parameters, antioxidative properties, and gut microbiome. Results: The addition of ABP did not have a significant effect on average daily feed intake. However, it was found to increase the average daily egg weight and egg production rate, reduce the feed-egg ratio. There were no significant impacts on egg quality measures such as egg shape index, egg yolk index and color, egg yolk and protein content. However, ABP supplementation significantly increased the Hough Unit (HU) (p<0.01) and decreased the rate of unqualified eggs(p<0.01). Regarding serum parameters, the inclusion led to an increase in total protein concentration(p<0.05) and a reduction in low-density lipoprotein cholesterol (LDL-C) (p<0.05). There were no significant effects observed on immune indicators such as immune globulin A (IgA) and immune globulin M (IgM). ABP supplementation increased the levels of serum antioxidant indicators, including glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD) (p<0.05), and total antioxidant capacity colorimeter (T-AOC) (p<0.05). Furthermore, ABP supplementation significantly elevated the intramuscular fatty acid content in quail meat. Additionally, ABP supplementation demonstrated a significant improvement in the diversity of gut microbiota and induced alterations in the composition of the gut microbiota. Conclusion: The findings of this study indicate that dietary supplementation of ABP enhanced production performance and antioxidant capacity while increasing the levels of polyunsaturated fatty acids (PUFA) in quail muscle.

Collective effects of rising average temperatures and heat events on oviparous embryos.

Survival of the immobile embryo in response to rising temperature is important to determine a species' vulnerability to climate change. However, the collective effects of 2 key thermal characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population-specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species' range shifts under climate change. Embryos' tolerance of chronic heat (T-chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T-acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low-latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species' vulnerability to climate change.

Efectos colectivos del aumento de las temperaturas promedio y los eventos de calor en embriones ovíparos Resumen La supervivencia de los embriones inmóviles en respuesta al incremento de temperatura es importante para determinar la vulnerabilidad de las especies al cambio climático. Sin embargo, los efectos colectivos de dos características térmicas claves asociadas con el cambio climático (i. e., aumento de temperatura promedio y eventos de calor agudo) sobre la supervivencia embrionaria permanecen en gran parte inexplorados. Utilizamos mediciones empíricas y modelos de nicho para investigar cómo el estrés térmico crónico y agudo influye de forma independiente y colectiva en la supervivencia embrionaria de los lagartos en todas las latitudes. Recolectamos y criamos lagartos de cinco latitudes e incubamos sus huevos en un rango de temperaturas para cuantificar las respuestas específicas de la población al estrés por calor crónico y agudo. Posteriormente, mediante un modelo de desarrollo embrionario parametrizado con mediciones de tolerancia embrionaria al calor, identificamos un impacto colectivo de las tolerancias embrionarias al calor agudo y crónico en la supervivencia embrionaria. También incorporamos la tolerancia embrionaria crónica y aguda al calor en modelos de distribución de especies híbridas para determinar los cambios de distribución de las especies bajo el cambio climático. La tolerancia embrionaria al calor crónico (T­crónico) permaneció constante, mientras que la tolerancia al calor agudo (T­agudo) fue mayor en latitudes altas que en latitudes bajas. La tolerancia al calor agudo ejerció una influencia más pronunciada que la tolerancia al calor crónico. En los modelos de distribución de especies, el cambio climático provocó la pérdida de hábitat más significativa para cada población y especie en su distribución de latitudes bajas. En consecuencia, el hábitat para poblaciones en todas las latitudes se desplazará a latitudes altas. Nuestro estudio también resalta la importancia de considerar la supervivencia embrionaria bajo estrés térmico crónico y agudo para predecir la vulnerabilidad de las especies al cambio climático.

Two heat shock cognate 70 genes involved in spermatogenesis regulate the male fertility of Zeugodacus cucurbitae, as potential targets for pest control.

The melon fly Zeugodacus cucurbitae Coquillett (Diptera: Tephritidae) is an agricultural quarantine pest threatening fruit and vegetable production. Heat shock cognate 70 (Hsc70), which is a homolog of the heat shock protein 70 (Hsp70), was first discovered in mice testes and plays an important role in spermatogenesis. In this study, we identified and cloned five Hsc70 genes from melon fly, namely ZcHsc70_1/2/3/4/5. Phylogenetic analysis showed that these proteins are closely related to Hsc70s from other Diptera insects. Spatiotemporal expression analysis showed that ZcHsc70_1 and ZcHsc70_2 are highly expressed in Z. cucurbitae testes. Fluorescence in situ hybridization further demonstrated that ZcHsc70_1 and ZcHsc70_2 are expressed in the transformation and maturation regions of testes, respectively. Moreover, RNA interference-based suppression of ZcHsc70_1 or ZcHsc70_2 resulted in a significant decrease of 74.61% and 63.28% in egg hatchability, respectively. Suppression of ZcHsc70_1 expression delayed the transformation of sperm cells to mature sperms. Meanwhile, suppression of ZcHsc70_2 expression decreased both sperm cells and mature sperms by inhibiting the meiosis of spermatocytes. Our findings show that ZcHsc70_1/2 regulates spermatogenesis and further affects the male fertility in the melon fly, showing potential as targets for pest control in sterile insect technique by genetic manipulation of males.

Minor envelope proteins from GP2a to GP4 contribute to the spread pattern and yield of type 2 PRRSV in MARC-145 cells.

In China, porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are widely used. These vaccines, which contain inactivated and live attenuated vaccines (LAVs), are produced by MARC-145 cells derived from the monkey kidney cell line. However, some PRRSV strains in MARC-145 cells have a low yield. Here, we used two type 2 PRRSV strains (CH-1R and HuN4) to identify the genes responsible for virus yield in MARC-145 cells. Our findings indicate that the two viruses have different spread patterns, which ultimately determine their yield. By replacing the viral envelope genes with a reverse genetics system, we discovered that the minor envelope proteins, from GP2a to GP4, play a crucial role in determining the spread pattern and yield of type 2 PRRSV in MARC-145 cells. The cell-free transmission pattern of type 2 PRRSV appears to be more efficient than the cell-to-cell transmission pattern. Overall, these findings suggest that GP2a to GP4 contributes to the spread pattern and yield of type 2 PRRSV.