Astrocytes integrate time and space

Astrocytes read and react to synaptic transmission through tripartite synapses,where the binding of neurotransmitters onto astrocytic receptors triggers an increase in intracellular calcium.Recent investigations have revealed that astrocytes exhibit two distinct states of intracellular calcium activity:(1)graded subcellular localized clusters with independently active microdomains,likely influenced by nearby synaptic events,and(2)whole-cell astrocyte calcium surges,believed to result from the coordinated activation of multiple synapses.Notably,astrocyte calcium responses are not solely graded;instead,a spatial threshold of intracellular calcium activity can be overcome to elicit an astrocyte calcium surge.Together these calcium responses,in turn,initiate downstream signaling pathways capable of modifying synaptic communication and overall network activity.In summary,astrocytes can function as integrators of local synaptic events,actively contributing to information processing within the brain.

Danggui Shaoyao powder improves hepatic lipid metabolism in atherosclerosis mice via PPARγ-LXRα-ABCA1 pathway regulation

Objective:To observe the effects of Danggui Shaoyao powder(DSP)on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor(PPARγ)-liver X receptor(LXRα)-adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)pathway regulation.Methods: Eight C57BL/6J male mice were selected as the control group,and 24 ApoE^(−/−)male mice were randomly divided into the atherosclerosis model(AS)group,atorvastatin calcium(AC)group,and DSP group(n=8 each group).To establish an AS model,ApoE^(−/−)mice were fed a high-fat diet for 16 weeks.Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining.Triglyceride(TG),cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were determined in the livers using a single-reagent GPO-PAP method.Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver.Results: After 16 weeks of a high-fat diet,ApoE^(−/−)mice showed more Oil Red O staining in the aorta and liver compared to the CONT group.Compared to the AS group,the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees.Furthermore,DSP significantly reduced the hepatic lipid area in ApoE^(−/−)mice(P<.001)and decreased the levels of TG,TC,and LDL-C in liver(P<.001,P=.027,P<.001,respectively).DSP also significantly increased the levels of PPARγ,LXRα,ABCA1,and ABCG1 mRNA expression,as well as the PPARγ,LXRα,ABCA1,and ABCG1 protein expression in liver.Conclusion: DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.

Ultrafine ordered L1_(2)-Pt-Co-Mn ternary intermetallic nanoparticles as high-performance oxygen-reduction electrocatalysts for practical fuel cells

The long-range periodically ordered atomic structures in intermetallic nanoparticles(INPs)can significantly enhance both the electrocatalytic activity and electrochemical stability toward the oxygen reduction reaction(ORR)compared to the disordered atomic structures in ordinary solid-solution alloy NPs.Accordingly,through a facile and scalable synthetic method,a series of carbon-supported ultrafine Pt_3Co_(x)Mn_(1-x)ternary INPs are prepared in this work,which possess the"skin-like"ultrathin Pt shells,the ordered L1_(2) atomic structure,and the high-even dispersion on supports(L1_(2)-Pt_3Co_(x)Mn_(1-x)/~SPt INPs/C).Electrochemical results present that the composition-optimized L1_(2)-Pt_3Co_(0.7)Mn_(0.3)/~SPt INPs/C exhibits the highest electrocata lytic activity among the series,which are also much better than those of the pristine ultrafine Pt/C.Besides,it also has a greatly enhanced electrochemical stability.In addition,the effects of annealing temperature and time are further investigated.More importantly,such superior ORR electrocatalytic performance of L1_(2)-Pt_3Co_(0.7)Mn_(0.3)/~SPt INPs/C are also well demonstrated in practical fuel cells.Physicochemical characterization analyses further reveal the major origins of the greatly enhanced ORR electrocata lytic performance:the Pt-Co-Mn alloy-induced geometric and ligand effects as well as the extremely high L1_(2) atomic-ordering degree.This work not only successfully develops a highly active and stable ordered ternary intermetallic ORR electrocatalyst,but also elucidates the corresponding"structure-function"relationship,which can be further applied in designing other intermetallic(electro)catalysts.

Imprinting at the KBTBD6 locus involves species-specific m ternal methylation and monoallelic expression in livestock animals

Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting.Results Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter Cp G island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter Cp G islands were methylated in oocytes and/or allelically methyl-ated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these Cp G islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting.Conclusions In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.

Aldo-keto reductases:Role in cancer development and theranostics

Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various cancers.AKRs are aberrantly expressed in a wide range of malignant tumors.Dysregulated expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to chemoresistance.AKRs have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and progression.Inhibition of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for cancer.Several classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical trials.Many AKR inhibitors from natural sources also exhibit anticancer effects.Small molecule inhibitors targeting specific AKR isoforms have shown promise in preclinical studies.These inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to chemotherapy.In this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug resistance.Finally,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized.

Adaptive State-Dependent Diffusion for Derivative-Free Optimization

This paper develops and analyzes a stochastic derivative-free optimization strategy.A key feature is the state-dependent adaptive variance.We prove global convergence in probability with algebraic rate and give the quantitative results in numerical examples.A striking fact is that convergence is achieved without explicit information of the gradient and even without comparing different objective function values as in established methods such as the simplex method and simulated annealing.It can otherwise be compared to annealing with state-dependent temperature.

Physical and psychological symptoms and survey importance in celiac disease

Celiac disease is an autoimmune condition that affects approximately 1%of the worldwide community.Originally thought to be confined mostly to the small intestine,resulting in villous atrophy and nutrient malabsorption,it has more recently been implicated in systemic manifestations as well,particularly when undiagnosed or left untreated.Herein,the physical and psychological symptoms of celiac disease are described and explored.An emphasis is placed on efforts to query prospective and confirmed celiac disease patients via the use of surveys.Suggestions are made regarding the development of efficacious surveys for the purpose of screening for celiac disease in undiagnosed persons,and monitoring efficacy of the gluten-free diet in persons diagnosed with celiac disease.There are broad categories of physical and psychological symptoms associated with celiac disease.There is also an essential interaction between such physical and the psychological symptoms.It is important to capture the association between symptoms,via queries directed toward suspected and confirmed persons with celiac disease.The use of anonymous online surveys can be helpful to determine the qualities and characteristics which may be associated with this condition.It is suggested that personal surveys should be given a greater role in screening and to lessen the time for diagnosis.Querying the subject directly via a survey can provide clues as to the types of symptoms being experienced by those with celiac disease currently,as well as to determine the salient aspects of the symptomatology,which will be useful for rapid screening and monitoring in future work.

Procyanidin C1 Modulates the Microbiome to Increase FOXO1 Signaling and Valeric Acid Levels to Protect the Mucosal Barrier in Inflammatory Bowel Disease

Inflammatory bowel disease(IBD)refers to a pair of prevalent conditions(Crohn’s disease and ulcerative colitis)distinguished by persistent inflammation of the large intestine.Procyanidin C1(PCC1)is a natu-rally occurring substance derived from grape seeds that has demonstrated notable anti-inflammatory properties.This study examines the potential utility of PCC1 as a treatment for IBD and subsequently examines the host-cell-and microbiome-related mechanisms underlying the detected therapeutic bene-fits.Working with a classic dextran sodium sulfate(DSS)-induced mouse IBD model,we show that PCC1 protects the mucosal barrier and thereby confers strong protective effects against IBD.PCC1 pretreatment resulted in anti-inflammatory effects and protection against multiple pathological phenotypes in the IBD model mice,including reduced weight loss,lower disease activity index(DAI)totals,and enhanced colon size,as well as obviously beneficial effects on the mucosal barrier(e.g.,barrier thickness and activity of mucus-degrading enzymes).We also analyzed the autophagy marker microtubule-associated protein1 light chain 3(LC3)and found that the level of LC3 was significantly elevated in the intestinal epithelial cell samples of the PCC1-pretreatment group as compared with the non-model mice samples.PCC1 altered the fecal microbiome composition,which included elevating the abundance of Akkermansia muci-niphila and Christensenella minuta.Fecal microbiome transplant(FMT)experiments showed that deliver-ing a microbiome from PCC1-treated animals into PCC1-naïve animals conferred protection.Metabolic profiling revealed that both the PCC1-pretreatment and PCC1 FMT groups had elevated levels of the microbiota-derived metabolite valeric acid,and supplementation with this short-chain fatty acid(SCFA)also conferred strong protection against IBD.Finally,inhibitor experiments confirmed that the beneficial effects of valeric acid on the mucus layer are mediated by FOXO1 signaling in the goblet cells of the intestinal epithelium.Beyond showing that PCC1 confers anti-inflammatory effects and protection against IBD by altering the microbiome,our study demonstrates proof of principle for multiple straight-forward interventions(PCC1,FMT,and valeric acid supplementation)for ameliorating mucosal barrier damage to treat IBD.

PML nuclear bodies:new players in familial amyotrophic lateral sclerosis-frontotemporal dementia?

Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al.,2013).The major pathological hallmark of ALS and FTD are the depletion from the nucleus of the RNA-binding proteins TAR DNA‐binding protein 43(TDP-43)and FUsed in Sarcoma(FUS)and their abnormal accumulation in ubiquitin-positive cytoplasmic inclusions(Ling et al.,2013).

Decadal Forecasts of Large Earthquakes along the Northern San Andreas Fault System, California: Increased Activity on Regional Creeping Faults Prior to Major and Great Events

The three largest earthquakes in northern California since 1849 were preceded by increased decadal activity for moderate-size shocks along surrounding nearby faults. Increased seismicity, double-difference precise locations of earthquakes since 1968, geodetic data and fault offsets for the 1906 great shock are used to re-examine the timing and locations of possible future large earthquakes. The physical mechanisms of regional faults like the Calaveras, Hayward and Sargent, which exhibit creep, differ from those of the northern San Andreas, which is currently locked and is not creeping. Much decadal forerunning activity occurred on creeping faults. Moderate-size earthquakes along those faults became more frequent as stresses in the region increased in the latter part of the cycle of stress restoration for major and great earthquakes along the San Andreas. They may be useful for decadal forecasts. Yearly to decadal forecasts, however, are based on only a few major to great events. Activity along closer faults like that in the two years prior to the 1989 Loma Prieta shock needs to be examined for possible yearly forerunning changes to large plate boundary earthquakes. Geodetic observations are needed to focus on identifying creeping faults close to the San Andreas. The distribution of moderate-size earthquakes increased significantly since 1990 along the Hayward fault but not adjacent to the San Andreas fault to the south of San Francisco compared to what took place in the decades prior to the three major historic earthquakes in the region. It is now clear from a re-examination of the 1989 mainshock that the increased level of moderate-size shocks in the one to two preceding decades occurred on nearby East Bay faults. Double-difference locations of small earthquakes provide structural information about faults in the region, especially their depths. The northern San Andreas fault is divided into several strongly coupled segments based on differences in seismicity.

Community-Based Hepatitis B Campaign in Asian Americans

Chronic hepatitis B (CHB) disproportionately affects minority groups in the US, particularly Asian Americans, with numerous factors contributing to this disparity. Of the 2.4 million people living with chronic HBV in the US, 60% are Asian American. Many are unaware of their status and lack access to proper clinical care, with less than ten percent receiving necessary antiviral treatment. Barriers to screening and care include lack of disease awareness, language and cultural barriers, and financial constraints. Additionally, healthcare providers and systems in the US often overlook the importance of CHB, leading to inadequate care. In response, the Center for Viral Hepatitis (CVH) has implemented a community-based outreach program over the past sixteen years, employing a multifaceted approach involving all sectors of society and various organizations to combat health disparities in CHB. This grassroots campaign has proven highly effective, leveraging CVH’s leadership in spearheading numerous collaborative activities with community members, healthcare professionals, and policymakers. We have summarized the key points of CVH's efforts and their significance in combating CHB-related health disparities. The CHB Screening and Awareness Campaign, tailored to the Asian American community, serves as a successful model for increasing CHB screening, linkage-to-care, and addressing socio-cultural barriers and health literacy. Insights from these outreach programs have guided the development of culturally relevant resources and education initiatives. These findings suggest that such community-driven approaches are essential for addressing health disparities. The strategies and outcomes of CVH’s efforts can inform future health initiatives for other minority communities in the US and globally.

Modifiers of the Effects of Vitamin D Supplementation on Cardiometabolic Risk Factors:A Systematic Review and Meta-Analysis

The inconsistent findings concerning the effects of vitamin D supplementation on cardiometabolic risk factors and the large heterogeneity in the published literature call for further research to identify sources of heterogeneity and potential effect modifiers.We performed a meta-analysis of randomized controlled trials(RCTs)published until March 2024 that reported estimates for the effects of vitamin D supplementation on cardiometabolic factors and relevant baseline covariates of RCT participants.A total of 17656 participants from 99 RCTs were analyzed,and weighted mean differences(95%confidence intervals(CI))for the intervention status were derived using random-effects modeling.Overall,compared with the placebo,vitamin D supplementation(median dose:3320 international unit(IU)·day^(-1);range 40-120000 IU·day^(-1))had favorable effects on systolic blood pressure(SBP;-2.04(95%CI,-3.50,-0.59)mmHg;1 mmHg=0.133 kPa),diastolic blood pressure(DBP;-3.00(95%CI,-3.61,-2.39)mmHg),total cholesterol(TC;-0.12(95%CI,-0.21,-0.03)mmol·L^(-1)),fasting blood glucose(FBG;-0.13(95%CI,-0.20,-0.05)mmol·L^(-1)),hemoglobin A1C(A1C;-0.09%(95%CI,-0.13%,-0.05%)),and fasting blood insulin(FBI:-7.61(95%CI,-11.93,-3.30)pmol·L^(-1)).The benefits of vitamin D were most evident in trials performed in non-Westerners,participants with baseline 25-hydroxyvitamin D(25[OH]D)lower than 15.0 ng·mL^(-1),non-obese(body mass index(BMI)<30 kg·m^(-2)),and older(age-50 years).The findings of this study underscore the need for personalized vitamin D intervention strategies that comprehensively account for individual patient characteristics(such as ethnocultural background,age,BMI,and circulating 25[OH]D level),intervention dosage,and intervention duration to optimize cardiometabolic health outcomes.

Prevalence of malignant neoplasms in celiac disease patients-a nationwide United States population-based study

BACKGROUND Celiac disease(CeD)is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals.Recent research has unveiled a heightened risk of developing specific malignant neoplasms(MN)and various malignancies,including gastrointestinal,lymphomas,skin,and others,in individuals with CeD.AIM To investigate the prevalence of MN in hospitalized CeD patients in the United States.METHODS Using data from the National Inpatient Sample spanning two decades,from January 2000 to December 2019,we identified 529842 CeD patients,of which 78128(14.75%)had MN.Propensity score matching,based on age,sex,race,and calendar year,was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio.RESULTS Positive associations were observed for several malignancies,including small intestine,lymphoma,nonmelanoma skin,liver,melanoma skin,pancreas myelodysplastic syndrome,biliary,stomach,and other neuroendocrine tumors(excluding small and large intestine malignant carcinoid),leukemia,uterus,and testis.Conversely,CeD patients exhibited a reduced risk of respiratory and secondary malignancies.Moreover,certain malignancies showed null associations with CeD,including head and neck,nervous system,esophagus,colorectal,anus,breast,malignant carcinoids,bone and connective tissues,myeloma,cervix,and ovary cancers.CONCLUSION Our study is unique in highlighting the detailed results of positive,negative,or null associations between different hematologic and solid malignancies and CeD.Furthermore,it offers insights into evolving trends in CeD hospital outcomes,shedding light on advancements in its management over the past two decades.These findings contribute valuable information to the understanding of CeD’s impact on health and healthcare utilization.

Trans-Frame Aortic Regurgitation of New-Generation Aortic Bioprosthesis

A widely used aortic valve bioprosthesis is susceptible to regurgitation between the sewing ring and the frame of the valve due to its relatively thin fabric coverage. In some cases this leak has been shown to resolve with administration of protamine, however, tension on this area from annular sutures placed in an asymmetric bicuspid valve annulus may exacerbate the defect.

A State-Migration Particle Swarm Optimizer for Adaptive Latent Factor Analysis of High-Dimensional and Incomplete Data

High-dimensional and incomplete(HDI) matrices are primarily generated in all kinds of big-data-related practical applications. A latent factor analysis(LFA) model is capable of conducting efficient representation learning to an HDI matrix,whose hyper-parameter adaptation can be implemented through a particle swarm optimizer(PSO) to meet scalable requirements.However, conventional PSO is limited by its premature issues,which leads to the accuracy loss of a resultant LFA model. To address this thorny issue, this study merges the information of each particle's state migration into its evolution process following the principle of a generalized momentum method for improving its search ability, thereby building a state-migration particle swarm optimizer(SPSO), whose theoretical convergence is rigorously proved in this study. It is then incorporated into an LFA model for implementing efficient hyper-parameter adaptation without accuracy loss. Experiments on six HDI matrices indicate that an SPSO-incorporated LFA model outperforms state-of-the-art LFA models in terms of prediction accuracy for missing data of an HDI matrix with competitive computational efficiency.Hence, SPSO's use ensures efficient and reliable hyper-parameter adaptation in an LFA model, thus ensuring practicality and accurate representation learning for HDI matrices.

An Improved Machine Learning Model for Pure Component Property Estimation

Information on the physicochemical properties of chemical species is an important prerequisite when performing tasks such as process design and product design.However,the lack of extensive data and high experimental costs hinder the development of prediction techniques for these properties.Moreover,accuracy and predictive capabilities still limit the scope and applicability of most property estimation methods.This paper proposes a new Gaussian process-based modeling framework that aims to manage a discrete and high-dimensional input space related to molecular structure representation with the group-contribution approach.A warping function is used to map discrete input into a continuous domain in order to adjust the correlation between different compounds.Prior selection techniques,including prior elicitation and prior predictive checking,are also applied during the building procedure to provide the model with more information from previous research findings.The framework is assessed using datasets of varying sizes for 20 pure component properties.For 18 out of the 20 pure component properties,the new models are found to give improved accuracy and predictive power in comparison with other published models,with and without machine learning.

Recombinant vaccines:Current updates and future prospects

Recombinant technology-based vaccines have emerged as a highly effective way to prevent a wide range of illnesses.The technology improved vaccine manufacturing,rendering it more efficient and economical.These vaccines have multiple advantages compared to conventional vaccines.The pandemic has heightened awareness of the advantages of these vaccine technologies;trust and acceptance of these vaccines are steadily growing globally.This work offers an overview of the prospects and advantages associated with recombinant vaccines.Additionally,it discusses some of the challenges likely to arise in the future.Their ability to target diverse pathogen classes underscores their contributions to preventing previously untreatable diseases(especially vector-borne and emerging diseases)and hurdles faced throughout the vaccine development process,especially in enhancing the effectiveness of these vaccines.Moreover,their compatibility with emerging vaccination platforms of the future like virus-like particles and CRISPR/Cas9 for the production of next-generation vaccines may offer many prospects.This review also reviewed the hurdles faced throughout the vaccine development process,especially in enhancing the effectiveness of these vaccines against vector-borne diseases,emerging diseases,and untreatable diseases with high mortality rates like AIDS as well as cancer.

Left inferior phrenic arterial malformation mimicking gastric varices: A case report and review of literature

BACKGROUND Gastric submucosal arterial dilation resulting from splenic artery occlusion represents an exceedingly rare etiology of acute upper gastrointestinal bleeding(UGIB).Although endoscopy is a widely utilized diagnostic and therapeutic modality for gastrointestinal bleeding,it has limitations in detecting arterial abnormalities.CASE SUMMARY This report presents a rare case of massive UGIB in a 57-year-old male with a tortuous left inferior phrenic artery accompanied by splenic artery occlusion.“Gastric varices”was identified during the patient's endoscopy one year before hemorrhage.Despite initial hemostasis by endoscopic clipping,the patient experienced massive rebleeding after one month,requiring intervention with transcatheter arterial embolization(TAE)to achieve hemostasis.CONCLUSION This is the first case to report UGIB due to a tortuous left inferior phrenic artery.This case highlights the limitations of endoscopy in identifying arterial abnormalities and emphasizes the potential of TAE as a viable alternative for the management of arterial bleeding in the gastrointestinal tract.

Denoising Data with Random Matrix Theory

Properties from random matrix theory allow us to uncover naturally embedded signals from different data sets. While there are many parameters that can be changed, including the probability distribution of the entries, the introduction of noise, and the size of the matrix, the resulting eigenvalue and eigenvector distributions remain relatively unchanged. However, when there are certain anomalous eigenvalues and their corresponding eigenvectors that do not follow the predicted distributions, it could indicate that there’s an underlying non-random signal inside the data. As data and matrices become more important in the sciences and computing, so too will the importance of processing them with the principles of random matrix theory.

Classical Correlations vs Quantum Correlations—Similarities, Differences, Opportunities

Classical Correlations were founded in 1900 by Karl Pearson and have since been applied as a statistical tool in virtually all sciences. Quantum correlations go back to Albert Einstein et al. in 1935 and Erwin Schrödinger’s responses shortly after. In this paper, we contrast classical with quantum correlations. We find that classical correlations are weaker than quantum correlations in the CHSH framework. With respect to correlation matrices, the trace of classical correlation matrices is dissimilar to quantum density matrices. However, the off-diagonal terms have equivalent interpretations. We contrast classical dynamic (i.e., time evolving) stochastic correlation with dynamic quantum density matrices and find that the off-diagonal elements, while different in nature, have similar interpretations. So far, due to the laws of quantum physics, no classical correlations are applied to the quantum spectrum. However, conversely, quantum correlations are applied in classical environments such as quantum computing, cryptography, metrology, teleportation, medical imaging, laser technology, the quantum Internet and more.