Ethanol extract of cassia seed alleviates metabolic dysfunction-associated steatotic liver disease by acting on multiple lipid metabolism-related pathways

Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD is an important risk factor for cardiovascular and cerebrovascular diseases,including coronary heart disease,stroke,and tumors,with no specific therapeutic drugs currently available.The ethanol extract of cassia seed(CSEE)has shown promise in lowering blood lipids and improving hepatic steatosis,but its mechanism in treating MASLD remains underexplored.This study aims to investigate the therapeutic effects and mechanisms of CSEE.Methods:MASLD models were established in male Wistar rats and golden hamsters using a high fat diet(HFD).CSEE(10,50,250 mg/kg)was administered via gavage for six weeks.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),as well as liver TC and TG,were measured using biochemical kits.Histopathological changes in the liver were evaluated using Oil Red O staining,Hematoxylin-eosin(H&E)staining,and transmission electron microscopy(TEM).HepG2 cell viability was assessed using the cell counting kit-8(CCK8)and Calcein-AM/PI staining.Network pharmacology was used to analyze drug-disease targets,and western blotting was used to confirm these predictions.Results:CSEE treatment significantly reduced serum levels of TC,TG,LDL-C,ALT,and AST,and improved liver weight,liver index,and hepatic lipid deposition in rats and golden hamsters.In addition,CSEE alleviated free fatty acid(FFA)-induced lipid deposition in HepG2 cells.Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK,p-ACC,PPARα,CPT1A,PI3K P110 and p-AKT,while decreasing the protein levels of SREBP1,FASN,C/EBPα,and PPARγ,thus improving hepatic lipid metabolism and reducing lipid deposition.The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro.Conclusion:CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK,PPARα,and PI3K/AKT signaling pathways.

Underlying mechanisms and clinical potential of circRNAs in glioblastoma

Glioblastoma(GBM)is the most malignant form of glioma and is difficult to diagnose,leading to high mortality rates.Circular RNAs(circRNAs)are noncoding RNAs with a covalently closed loop structure.CircRNAs are involved in various pathological processes and have been revealed to be important regulators of GBM pathogenesis.CircRNAs exert their biological effects by 4 different mechanisms:serving as sponges of microRNAs(miRNAs),serving as sponges of RNA binding proteins(RBPs),modulating parental gene transcription,and encoding functional proteins.Among the 4 mechanisms,sponging miRNAs is predominant.Their good stability,broad distribution and high specificity make circRNAs promising biomarkers for GBM diagnosis.In this paper,we summarized the current understanding of the characteristics and action mechanisms of circRNAs,illustrated the underlying regulatory mechanisms of circRNAs in GBM progression and explored the possible diagnostic role of circRNAs in GBM.

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies

The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chloride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl^(-)extrusion,and sodium potassium chloride cotransporters(N[K]CCs,NKCC1,NKCC2,and NCC)-mediated Cl^(-)loading.The CCCs play vital roles in cell volume regulation and ion homeostasis.Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues.In recent years,there have been considerable advances in our understanding of CCCs'control mechanisms in cell volume regulations,with many techniques developed in studying the functions and activities of CCCs.Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs.These techniques include the ammonium pulse technique,radioactive or nonradioactive rubidium ion uptakeassay,and thallium ion-uptake assay.CCCs'activity can also be indirectly observed by measuring gaminobutyric acid(GABA)activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes,radiotracer^(36)Cl^(-),and fluorescent dyes.Other techniques include directly looking at kinase regulatory sites phosphorylation,flame photometry,22Nat uptake assay,structural biology,molecular modeling,and high-throughput drug screening.This review summarizes the role of CCCs in genetic disorders and cell volume regulation,current methods applied in studying CCCs biology,and compounds developed that directly or indirectly target the CCCs for disease treatments.

Incorporating contextual evidence to improve implicit discourse relation recognition in Chinese

The discourse analysis task,which focuses on understanding the semantics of long text spans,has received increasing attention in recent years.As a critical component of discourse analysis,discourse relation recognition aims to identify the rhetorical relations between adjacent discourse units(e.g.,clauses,sentences,and sentence groups),called arguments,in a document.Previous works focused on capturing the semantic interactions between arguments to recognize their discourse relations,ignoring important textual information in the surrounding contexts.However,in many cases,more than capturing semantic interactions from the texts of the two arguments are needed to identify their rhetorical relations,requiring mining more contextual clues.In this paper,we propose a method to convert the RST-style discourse trees in the training set into dependency-based trees and train a contextual evidence selector on these transformed structures.In this way,the selector can learn the ability to automatically pick critical textual information from the context(i.e.,as evidence)for arguments to assist in discriminating their relations.Then we encode the arguments concatenated with corresponding evidence to obtain the enhanced argument representations.Finally,we combine original and enhanced argument representations to recognize their relations.In addition,we introduce auxiliary tasks to guide the training of the evidence selector to strengthen its selection ability.The experimental results on the Chinese CDTB dataset show that our method outperforms several state-of-the-art baselines in both micro and macro F1 scores.

基于绿色化学的有机化学实验室废弃物的原点处理

有机化学实验是培养学生掌握实验基本技能和技术、提高动手能力的必修课。有机化学实验产生的废液成分复杂,尽管目前广大师生的环保意识比较强,实验室废液能够做到分类收集并交由有资质的公司进行处理,但是完全依赖环保公司的处理成本比较高。因此我们尝试对有机化学实验室产生的废液进行实验室原点处理,真正做到谁污染、谁治理,有效降低废液的处理成本,并实现有机试剂的循环使用。

基于租户的访问控制模型T-ARBAC

SaaS服务模式极大地降低了企业成本、提高了企业效率,同时也提高了企业的管理水平及加快了其创新步伐。但由于租户数据存储于服务提供商数据存储平台,如何保障租户的数据安全是一个无法回避的问题,并且平台用户数量巨大,如何有效地对用户进行管理也是一个值得探索的问题。本文结合基于角色的访问控制模型,设计出一个支持多租户、方便租户权限控制与管理的SaaS平台访问控制模型T-ARBAC (Tenant-Admin- istrative Role Based Access Control),满足了租户访问控制策略多样性与安全、独立访问共存数据的要求。

Superior adsorption performance of graphitic carbon nitride nanosheets for both cationic and anionic heavy metals from wastewater

Water pollution caused by highly toxic Cd(II), Pb(II), and Cr(VI) is a serious problem. In the present work,a green and low-cost adsorbent of g-C_3N_4 nanosheets was developed with superior capacity for both cationic and anionic heavy metals. The adsorbent was easily fabricated through one-step calcination of guanidine hydrochloride with thickness less than 1.6 nm and specific surface area of 111.2 m^2·g^(-1). Kinetic and isotherm studies suggest that the adsorption is an endothermic chemisorption process, occurring on the energetically heterogeneous surface based on a hybrid mechanism of multilayer and monolayer adsorption. The tri-s-triazine units and surface N-containing groups of g-C_3N_4 nanosheets are proposed to be responsible for the adsorption process.Further study on pH demonstrates that electrostatic interaction plays an important role. The maximum adsorption capacity of Cd(II), Pb(II), and Cr(VI) on g-C_3N_4 nanosheets is 123.205 mg·g^(-1), 136.571 mg·g^(-1),and 684.451 mg·g^(-1), respectively. The better adsorption performance of the adsorbent than that of the recently reported nanomaterials and low-cost adsorbents proves its great application potential in the removal of heavy metal contaminants from wastewater. The present paper developed a promising adsorbent which will certainly find applications in wastewater treatment and also provides guiding significance in designing adsorption processes.

Plexiform Angiomyxoid Myofibroblastic Tumor of the Stomach

Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a recently described gastric tumor with a peculiar plexiform pattern, bland spindle cells and a myxoid stroma rich in arborizing blood vessels. PAMT of the stomach is a very rare tumor without distinctive clinical manifestations. In this study, we report a new case of PAMT which is the first Chinese case in English literature. A 47-year-old Chinese woman was admitted with a 6-month history of intermittent epigastric discomfort, and abdominal pain for 2 months. Gastroscopy showed an elevated mass in the anterior wall of the gastric antrum. Endoscopic ultrasound revealed a focal hypoechoic lesion protruding into the lumen. A laparoscopic distal gastrectomy was performed, and the patient made an uneventful recovery and remains well 1.5 years later. A diagnosis of PAMT was made by histopathology and immunochemistry.

PRPS2 mutations drive acute lymphoblastic leukemia relapse through influencing PRPS1/2 hexamer stability

Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia(ALL),yet the underlying mechanisms are still elusive.Here,we demonstrate that phosphoribosyl pyrophosphate synthetase 2(PRPS2)mutations drive ALL relapse through influencing PRPS1/2 hexamer stability.Ultra-deep sequencing was performed to identify PRPS2 mutations in ALL samples.The effects of PRPS2 mutations on cell survival,cell apoptosis,and drug resistance were evaluated.In vitro PRPS2 enzyme activity and ADP/GDP feedback inhibition of PRPS enzyme activity were assessed.Purine metabolites were analyzed by ultra-performance liquid-chromatography tandem mass spectrometry(UPLC–MS/MS).Integrating sequencing data with clinical information,we identified PRPS2 mutations only in relapsed childhood ALL with thiopurine therapy.Functional PRPS2 mutations mediated purine metabolism specifically on thiopurine treatment by influencing PRPS1/2 hexamer stability,leading to reduced nucleotide feedback inhibition of PRPS activity and enhanced thiopurine resistance.The 3-amino acid V103-G104-E105,the key difference between PRPS1 and PRPS2,insertion in PRPS2 caused severe steric clash to the interface of PRPS hexamer,leading to its low enzyme activity.In addition,we demonstrated that PRPS2 P173R increased thiopurine resistance in xenograft models.Our work describes a novel mechanism by which PRPS2 mutants drive childhood ALL relapse and highlights PRPS2 mutations as biomarkers for relapsed childhood ALL.

Natural overlaying behaviors push the limit of planar cyclic deformation performance in few-layer MoS_(2) nanosheets

As a typical two-dimensional(2D)transition metal dichalcogenides(TMDCs)material with nonzero band gap,MoS_(2)has a wide range of potential applications as building blocks in the field of nanoelectronics.The stability and reliability of the corresponding nanoelectronic devices depend critically on the mechanical performance and cyclic reliability of 2D MoS_(2).Although an in situ technique has been used to analyze the mechanical properties of 2D materials,the cyclic mechanical behavior,that is,fatigue,remains a major challenge in the practical application of the devices.This study was aimed at analyzing the planar cyclic performance and deformation behavior of three-layer MoS_(2)nanosheets(NSs)using an in situ transmission electron microscopy(TEM)variable-amplitude uniaxial low-frequency and cyclic loading-unloading tensile acceleration test.We also elucidated the strengthening effect of the natural overlaying affix fragments(other external NSs)or wrinkle folds(internal folds from the NS itself)on cycling performances and service life of MoS_(2)NSs by delaying the whole process of fatigue crack initiation,propagation,and fracture.The results have been confirmed by molecular dynamics(MDs)simulations.The overlaying enhancement effect effectively ensures the long-term reliability and stability of nanoelectronic devices made of few-layer 2D materials.

A literature review of perishable medical resource management

In recent decades,healthcare providers have faced mounting pressure to effectively manage highly perishable and limited medical resources.This article offers a comprehensive review of supply chain management pertaining to such resources,which include transplantable organs and healthcare products.The review encompasses 93 publications from 1990 to 2022,illustrating a discernible upward trajectory in annual publications.The surveyed literature is categorized into three levels:Strategic,tactical,and operational.Key problem attributes and methodologies are analyzed through the assessment of pertinent publications for each problem level.Furthermore,research on service innovation,decision analytics,and supply chain resilience elucidates potential areas for future research.

Multiple-quantum-well perovskite for hole-transport-layer-free light-emitting diodes

We demonstrate hole-transport-layer-free light-emitting diodes(LEDs) based on solution-processed multiple-quantum-well(MQW) perovskite. The MQW perovskite can self-assemble to a unique structure of vertically graded distribution with two-dimensional layered perovskite covered by three-dimensionallike perovskite at top, which can naturally form a barrier of electron transporting to the anode interface,thereby enhancing the charge capture efficiency. This leads to hole-transport-layer-free MQW perovskite LEDs reaching an external quantum efficiency(EQE) of 9.0% with emission peak at 528 nm, which is over6 times of LEDs based on three-dimensional perovskite with the same device structure, representing the record EQE of hole-transport-layer-free perovskite LED.

Investigation of lead-free BiFeO_(3)–BaTiO_(3)piezoelectric ceramics through precise composition control

BiFeO_(3)-BaTiO_(3)is a promising lead-free piezoelectric ceramic,exhibiting high Curie temperature and superior electrochemical characteristics.In this work,e_(1-x)TBiFeO_(3)-xBaTiO_(3)(BF-xBT,x=0.26,0.28,0.30,0.32,0.34,0.36)ceramics were fabricated using the conventional solid-state reaction method through precise composition control.Multiple characterization techniques,including X-ray powder diffraction(XRD),scanning electron microscope(SEM),and electrical property testing systems,were applied to systematically examine the crystallographic structure,microstructure,as well as the dielectric,ferroelectric and piezoelectric properties of the BF-xBT ceramics.The XRD results confirm that all compositions exhibit a typical perovskite structure,transitioning from a single rhombohedral phase to a rhombohedral-cubic phase mixture as the BT content increases.SEM shows apparent core-shell microstructures in the ceramics.Notably,the results demonstrated that the BF-0.30BT ceramic exhibits the maximum piezoelectric constant(d_(33))-217 pC/N,while the BF-0.34BT ceramic displays the maximum converse piezoelectric constant(d_(33)^(*))-323 pm/V,which highlights the suitability of BF-BT ceramics for high-performance piezoelectric applications.

Photoenzymatic synthesis of 1-alkenes and hydroxyl fatty acids bycascading a COF photocatalyst and P450 peroxygenases

Fuels and oleochemicals have been chemically produced fromabundant biological oils or fatty acids for more than a century,and modern biotechnology is now accelerating the advances infatty acid chemistry [1,2]. A number of enzymes responsible forthe biosynthesis of hydrocarbons from fatty acids have been discovered, providing a promising strategy for enzymatic synthesisof fatty hydrocarbons [3]. CYP152 peroxygenases have attracted agreat deal of attention due to their ability to one-step oxidativelydecarboxylate or hydroxylate fatty acids using H2O2 as sole oxidant, generating valuable a-olefins or hydroxylated fatty acids[4,5] (Fig. 1a). In addition to a-olefins as biofuels and chemicalintermediates, hydroxylated fatty acids are also an important classof compounds with various applications in food, cosmetic, pharmaceutical, and biomaterial industries [6,7] (Fig. 1b). Among them,P450BSb is considered as the most promising CYP152 peroxygenasefor practical applications due to its high stability and activity tocatalyze both b-hydroxylation (the preferred reaction) and decarboxylation (the side reaction) of fatty acids that are both mechanistically initiated by Cb-H abstraction. Of note, directed evolutioncould remodel its catalytic preference on decarboxylation orb-hydroxylation (e.g., the P450BSb-DC mutant with 67% decarboxylation selectivity) [5].

Enhanced photoresponse of Cu2O/ZnO heterojunction with piezo-modulated interface engineering

The ability to arbitrarily regulate semiconductor interfaces provides the most effective way to modulate the performance of optoelectronic devices. However, less work has been reported on piezo-modulated interface engineering in all-oxide systems. In this paper, an enhanced photoresponse of an all-oxide Cu2O/ZnO heterojunction was obtained by taking advantage of the piezotronic effect. The illumination density-dependent piezoelectric modulation ability was also comprehensively investigated. An 18.6% enhancement of photoresponse was achieved when applying a a-0.88% compressive strain. Comparative experiments confirmed that this enhancement could be interpreted in terms of the band modification induced by interfacial piezoelectric polarization. The positive piezopotential generated at the ZnO side produces an increase in space charge region in Cu2O, thus providing an extra driving force to separate the excitons more efficiently under illumination. Our research provides a promising method to boost the performance of optoelectronics without altering the interface structure and could be extended to other metal oxide devices.