Functional CLT for sample covariance matrices

Using Bernstein polynomial approximations, we prove the central limit theorem for linear spectral statistics of sample covariance matrices, indexed by a set of functions with continuous fourth order derivatives on an open interval including $[(1-\sqrt{y})^2,(1+\sqrt{y})^2]$, the support of the Mar\u{c}enko--Pastur law. We also derive the explicit expressions for asymptotic mean and covariance functions.Comment: Published in at http://dx.doi.org/10.3150/10-BEJ250 the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

Rhodioloside inhibits apoptosis of hippocampal neurons exposed to sevoflurane via cAMP/PKA signaling pathway

Purpose: Neural injury affects patients after using inhalational anesthetics such as sevoflurane. Rhodioloside, a compound which is obtained from the Rhodiola rosea plant has been implicated to be the most commonly used psychostimulant that can improve a range of conditions. The study was aimed at finding the molecular mechanism underlying the Rhodioloside treatment of sevoflurane-injured hippocampal neurons.Methods: Main hippocampal neurons, secluded from Sprague Dawley embryonic rats were employed to create an injury model using 3 % sevoflurane. The sevoflurane-injured hippocampal neurons were treated with varying concentrations (10, 20, 40 and 80 μM/ml) of Rhodioloside to create different experimental groups: RHSD10+SEV, RHSD20+SEV, RHSD40+SEV, RHSD80+SEV, while untreated cells were considered as the Control group. Cell viability was identified using the CCK-8 assay. The CFSE assay was used to verify the promotion function of Rhodioloside on cell differentiation of neurons. FCM assay was employed to determine cell proliferation and apoptosis. Expression levels of apoptosisrelated factors, like Caspase-3, Bcl-2 and Bax were examined by RT-qPCR, while Western blot was used to measure phosphorylation of PKA.Results: Rhodioloside stimulated cell viability and prevented cell apoptosis in sevoflurane-injured hippocampal neurons in doses between 10-80 μM. The apoptosis-inhibitory effect of Rhodioloside was observed to be through cAMP/PKA pathway activation. Also, expression levels of Bcl-2, and PKA were enhanced and the level of Caspase-3 and Bax was reduced in a dose-dependent pattern. The PKA inhibitor reversed the above observation in the 40 μM Rhodioloside-treatment.Conclusion: Rhodioloside promoted cell viability and prevented apoptosis of primary hippocampal neurons injured by sevoflurane, through cAMP/PKA pathway activation. Inhibition of PKA network deteriorated the function of Rhodioloside by stimulating cell apoptosis. Our findings present a novel evidence that Rhodioloside could attenuate neurotoxicity of inhalational anesthetics. Keywords: Cell apoptosis, cAMP/PKA pathway, Hippocampal neurons, Rhodioloside, Sevofluran

Poredbeno istraživanje dviju metoda ispravljanja torzije maternice u krava tijekom teljenja.

Uterine torsion is a common form of dystocia in cattle often associatedwith an oversized fetus. Cows are considered to be more susceptible to this condition than other domestic animals. On the basis of our current clinical practices, a novel retorsion method called “Ball rolling” has been developed to correct uterine torsion. In order to evaluate the effect of this new method, a total of 263 uterine torsion cases admitted to our animal hospital in the past 5 years were investigated, of which 79 cases were treated with the conventional rolling method and 184 cases were subjected to the “Ball rolling” method. In our “Ball rolling” method, the animals were immobilized by tying their forelegs, whereas their hind legs are left loosened, and are rolled like a ball towards the torsion direction to bring the uterus back into its physiological position. Then the clinical symptoms of the animals were recorded using basic physiological indicators, such as pulse, the degree of amniotic fluid choke rate and respiratory rate, pulse, and cervical injury bleeding. On the basis of the evaluation of the outcome, the parturient cows subjected to the “Ball rolling” method recovered faster with higher fetus survival rate.Torzija maternice čest je uzrok teškog teljenja krava, nerijetko povezan s prevelikim plodom. U krava su teški porođaji češći nego u drugih domaćih životinja. Na osnovi vlastite kliničke prakse razvijena je nova metoda retorzije nazvana „valjanje poput lopte“. Radi procjene učinka te nove metode ukupno su bila analizirana 263 slučaja torzije maternice bolnički obrađena u proteklih pet godina. Od toga je 79 slučajeva bilo obrađeno uobičajenom metodom valjanja, a 184 krave bile su podvrgnute novoj metodi „valjanja poput lopte“. U toj su metodi životinje bile imobilizirane vezanjem prednjih nogu dok su stražnje bile slobodne i valjane kao lopta prema smjeru torzije kako bi se maternica dovela u fiziološki položaj. Nakon toga klinički su znakovi bili procijenjeni na osnovi fizioloških pokazatelja kao što su: bilo, stupanj gušenja u amnionskoj tekućini, frekvencija disanja i krvarenje zbog ozljeda cerviksa. Na osnovi prosudbe ishoda, krave pri teljenju podvrgnute „valjanju“ oporavile su se brže i s većom stopom preživljavanja teladi

EvEval: A Comprehensive Evaluation of Event Semantics for Large Language Models

Events serve as fundamental units of occurrence within various contexts. The processing of event semantics in textual information forms the basis of numerous natural language processing (NLP) applications. Recent studies have begun leveraging large language models (LLMs) to address event semantic processing. However, the extent that LLMs can effectively tackle these challenges remains uncertain. Furthermore, the lack of a comprehensive evaluation framework for event semantic processing poses a significant challenge in evaluating these capabilities. In this paper, we propose an overarching framework for event semantic processing, encompassing understanding, reasoning, and prediction, along with their fine-grained aspects. To comprehensively evaluate the event semantic processing abilities of models, we introduce a novel benchmark called EVEVAL. We collect 8 datasets that cover all aspects of event semantic processing. Extensive experiments are conducted on EVEVAL, leading to several noteworthy findings based on the obtained results

Global trends and hotspots of gastrointestinal microbiome and toxicity based on bibliometrics

BackgroundToxicity concerns persist in the fields of public health, environmental science, and pharmacology. The intricate and vital role of the gastrointestinal microbiome in influencing toxicity and overall human health has gained increasing recognition in recent years. This study presents a comprehensive bibliometric analysis to evaluate the global scientific output, emerging trends, and research focal points in the area of gastrointestinal microbiome and toxicity.MethodsThe Web of Science Core Collection database was retrieved for publications on the gastrointestinal microbiome and toxicity from 1980 to 2022. Our analysis included scholarly research papers written in English and excluded duplicate publications. We used Biblioshiny and R to summarize the count and citation metrics of included articles, and visualized research trends and keywords. CiteSpace was used to identify reference literature, keywords, and citation bursts. VOSviewer was used to visualize the network of related countries, institutions, authors, co-cited authors, and keywords.ResultsA total of 2,140 articles were included, allowing us to identify significant countries, institutions, authors, and research focal points. Our results indicate a growing trend in the field, with China and the United States leading the research. The most productive journal in this area is Science of the Total Environment. Key findings revealed that research hotspots have shifted from drugs to environmental pollutants, emphasizing microplastics. Important mechanisms studied include oxidative stress, metabolism, inflammation, and apoptosis, with target organs being the gastrointestinal tract, liver, and brain. Furthermore, we highlight the rising significance of the gut-brain axis and the usage of zebrafish as a model organism.ConclusionDespite certain limitations, such as focusing solely on English-language publications and excluding unpublished literature, our findings provide valuable insights into the current state of research on toxicity and the gastrointestinal microbiome. In the future, modifications to the gastrointestinal microbiome could offer new directions for treating and mitigating toxicity. These discoveries provide a comprehensive perspective on the broader scope of this research field

Astrocytic p75NTR expression provoked by ischemic stroke exacerbates the blood-brain barrier disruption

The disruption of the blood–brain barrier (BBB) plays a critical role in the pathology of ischemic stroke. p75 neurotrophin receptor (p75NTR) contributes to the disruption of the blood-retinal barrier in retinal ischemia. However, whether p75NTR influences the BBB permeability after acute cerebral ischemia remains unknown. The present study investigated the role and underlying mechanism of p75NTR on BBB integrity in an ischemic stroke mouse model, middle cerebral artery occlusion (MCAO). After 24 h of MCAO, astrocytes and endothelial cells in the infarct-affected brain area up-regulated p75NTR. Genetic p75NTR knockdown (p75NTR+/ ) or pharmacological inhibition of p75NTR using LM11A-31, a selective inhibitor of p75NTR, both attenuated brain damage and BBB leakage in MCAO mice. Astrocyte-specific conditional knockdown of p75NTR mediated with an adeno-associated virus significantly ameliorated BBB disruption and brain tissue damage, as well as the neurological functions after stroke. Further molecular biological examinations indicated that astrocytic p75NTR activated NF-κB and HIF-1α signals, which upregulated the expression of MMP-9 and vascular endothelial growth factor (VEGF), subsequently leading to tight junction degradation after ischemia. As a result, increased leukocyte infiltration and microglia activation exacerbated brain injury after stroke. Overall, our results provide novel insight into the role of astrocytic p75NTR in BBB disruption after acute cerebral ischemia. The p75NTR may therefore be a potential therapeutic target for the treatment of ischemic stroke

TiF1-Gamma Plays an Essential Role in Murine Hematopoiesis and Regulates Transcriptional Elongation of Erythroid Genes

Transcriptional regulators play critical roles in the regulation of cell fate during hematopoiesis. Previous studies in zebrafish have identified an essential role for the transcriptional intermediary factor TIF1γ in erythropoiesis by regulating the transcription elongation of erythroid genes. To study if TIF1γ plays a similar role in murine erythropoiesis and to assess its function in other blood lineages, we generated mouse models with hematopoietic deletion of TIF1γ. Our results showed a block in erythroid maturation in the bone marrow following tif1γ deletion that was compensated with enhanced spleen erythropoiesis. Further analyses revealed a defect in transcription elongation of erythroid genes in the bone marrow. In addition, loss of TIF1γ resulted in defects in other blood compartments, including a profound loss of B cells, a dramatic expansion of granulocytes and decreased HSC function. TIF1γ exerts its functions in a cell-autonomous manner as revealed by competitive transplantation experiments. Our study therefore demonstrates that TIF1γ plays essential roles in multiple murine blood lineages and that its function in transcription elongation is evolutionally conserved.Stem Cell and Regenerative Biolog

A New Screening Evaluation Method for Carbon Dioxide Miscible Flooding Candidate Reservoirs

Prior to the implementation of CO2 injection EOR projects, the screening evaluation of candidate reservoirs will promote the economic benefits of CO2 injection. Currently, a uniform screening method for CO2 miscible flooding does not exist. Based on more than 112 successfully implemented CO2 miscible flooding reservoirs, which was referred in 2010 Worldwide EOR Survey, and CO2 miscible flooding mechanisms, this paper picks out 12 reservoir and fluid parameters affecting CO2 miscible flooding results as comprehensive evaluation parameters for screening candidate reservoirs. According to investigations on a large number of domestic and international CO2 miscible flooding projects, the quantitative methods are determined by theoretical analyses, field experience, and probability statistics. By means of calculating the combinational weights by improved analytical hierarchy process (AHP) and entropy method and combining the advantages of technique for order preference by similarity to ideal solution (TOPSIS) with gray relational analysis to construct a new similarity nearness degree, the weighted GC-TOPSIS model is established for screening candidate reservoirs. This screening method was employed for the assessment of five classical candidate reservoirs proposed for CO2 miscible flooding. The results show that this new method can correctly evaluate and compare the potential of CO2 miscible flooding.</span

Electroacupuncture Improves Neurobehavioral Function Through Targeting of SOX2-Mediated Axonal Regeneration by MicroRNA-132 After Ischemic Stroke

Our previous studies have shown that electroacupuncture (EA) enhances neurobehavioral functional recovery after ischemic stroke, however, the underlying regulatory mechanisms remain unclear. MicroRNAs (miRNAs) are abundant in the brain and are involved in post-transcriptional gene regulation. During cerebral ischemia reperfusion, miRNAs perform numerous biological functions in the central nervous system related to regeneration and repair of damaged nerves. Our previous studies also have shown that the expression of miRNA-132 (miR-132) is obviously down-regulated after stroke by middle cerebral artery occlusion (MCAO), which can be up-regulated by EA. This study aimed to identify whether up-regulation of miR-132 by EA improved the damaged nerves after stroke and to screen the potential target of miR-132. The results showed that EA up-regulated miR-132 thus suppressing SOX2 expression in vivo after MCAO, which obviously ameliorated neurobehavioral functional recovery. Moreover, our results also suggested that up-regulated miR-132 suppressed SOX2 in primary neurons after oxygen-glucose deprivation (OGD), which promoted neurite outgrowth. In conclusion, EA enhances neurobehavioral functional recovery against ischemic stroke through targeting of SOX2-mediated axonal regeneration by miR-132