Engineering Strategies for Suppressing the Shuttle Effect in Lithium–Sulfur Batteries

Lithium–sulfur(Li–S)batteries are supposed to be one of the most potential next-generation batteries owing to their high theoretical capacity and low cost.Nevertheless,the shuttle effect of firm multi-step two-electron reaction between sulfur and lithium in liquid electrolyte makes the capacity much smaller than the theoretical value.Many methods were proposed for inhibiting the shuttle effect of polysulfide,improving corresponding redox kinetics and enhancing the integral performance of Li–S batteries.Here,we will comprehensively and systematically summarize the strategies for inhibiting the shuttle effect from all components of Li–S batteries.First,the electrochemical principles/mechanism and origin of the shuttle effect are described in detail.Moreover,the efficient strategies,including boosting the sulfur conversion rate of sulfur,confining sulfur or lithium polysulfides(LPS)within cathode host,confining LPS in the shield layer,and preventing LPS from contacting the anode,will be discussed to suppress the shuttle effect.Then,recent advances in inhibition of shuttle effect in cathode,electrolyte,separator,and anode with the aforementioned strategies have been summarized to direct the further design of efficient materials for Li–S batteries.Finally,we present prospects for inhibition of the LPS shuttle and potential development directions in Li–S batteries.

Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways

Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.

A new interacting capillary bundle model on the multiphase flow in micropores of tight rocks

Surfactants are widely used in the fracturing fluid to enhance the imbibition and thus the oil recovery rate. However, current numerical models cannot capture the physics behind capillary imbibition during the wettability alteration by surfactants. Although the interacting capillary bundle(ICB) model shows potential in characterizing imbibition rates in different pores during wettability alteration, the existing ICB models neglect the influence of wettability and viscosity ratio on the imbibition behavior, making it difficult to accurately describe the oil-water imbibition behavior within the porous media. In this work,a new ICB mathematical model is established by introducing pressure balance without assuming the position of the leading front to comprehensively describe the imbibition behavior in a porous medium under different conditions, including gas-liquid spontaneous imbibition and oil-water imbibition.When the pore size distribution of a tight rock is known, this new model can predict the changes of water saturation during the displacement process in the tight rock, and also determine the imbibition rate in pores of different sizes. The water saturation profiles obtained from the new model are validated against the waterflooding simulation results from the CMG, while the imbibition rates calculated by the model are validated against the experimental observations of gas-liquid spontaneous imbibition. The good match above indicates the newly proposed model can show the water saturation profile at a macroscopic scale while capture the underlying physics of the multiphase flow in a porous medium at a microscopic scale. Simulation results obtained from this model indicate that both wettability and viscosity ratio can affect the sequence of fluid imbibition into pores of different sizes during the multiphase flow, where less-viscous wetting fluid is preferentially imbibed into larger pores while more-viscous wetting fluid tends to be imbibed into smaller pores. Furthermore, this model provides an avenue to calculate the imbibition rate in pores of different sizes during wettability alteration and capture the non-Darcy effect in micro-and nano-scale pores.

Magmatic-tectonic response of the South China Craton to the Paleo-Pacific subduction during the Triassic:a new viewpoint based on Well NK-1

The Nansha Block(NB)is one of the blocks separated from the southern margin of the South China Craton(SCC)by the western Pacific subduction,which contains rich information of geodynamic and tectonic transformation.To reveal the essence of western Paleo-Pacific subduction during the Triassic period,Well NK-1 in this block was selected for petrographic study,and published research data from other cooperative teams were compared.A double-cycle pattern of basic to neutral magmatic volcanism was established,and 36 lithological rhythmic layers and representative cryptoexplosive breccia facies and welded tuff bands were identified.Combined with a reanalysis of published geochronological data,geochemical elements,and isotope geochemistry,we found that the rock assemblages could be divided into an intermediate-acid dacite(DA)series(SiO_(2)>65%)and basaltic(BA)series(Co<40μg/g),which was formed during the early Late Triassic((218.6±3.2)–(217.9±3.5)Ma).BA exhibits obvious calc-alkaline island-arc magmatic properties:(^(87)Sr/^(86)Sr)_i ratio ranging 0.70377–0.71118(average:0.70645),^(147)Sm/^(144)Nd ratio ranging 0.119–0.193(average:0.168),and chondrite-normalized rare earth element(REE)curves being flat,while DA exhibits remarkable characteristics of subducted island-arc andesitic magma:(^(87)Sr/^(86)Sr)_i ratio(0.70939–0.71129;average:0.71035),εNd(t)value(-6.2–-4.8;average:-5.6)andε_(Hf)(t)value(-2.9–-1.7,average:-2.2)show obvious crust-mantle mixing characteristics.BA and DA reveal typical characteristics of island-arc magma systems and typeⅡenriched mantle(EM-Ⅱ)magma.BA magma was likely resulted from the process whereby the continental crust frontal accretionary wedge was driven by the Paleo-Pacific slab subduction into the deep and began to melt,resulting in a large amount of melt(fluid)joined the asthenosphere on the side of the continental margin.In contrast,DA magma was likely resulted from the process whereby the plate front was forced to bend with increasing subduction distance,which triggered the upwelling of the asthenosphere near the continent and subsequently led to the partial melting of the lithospheric mantle and lower crust due to continuous underplating.The lithospheric thinning environment in the study area at the end of Triassic created suitable conditions for the separation between the NB and SCC,which provided an opportunity for the formation of the early intracontinental rift during the later expansion of the South China Sea(SCS).

Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

Flavonoid extracts from chrysanthemum with appropriate anthocyanins turn blue when exposed to iron ions

Although some species that accumulate only cyanidin(Cy)in nature can produce blue flowers through iron ions,there has been no evidence of blue chrysanthemums being generated in this manner.This study revealed that flavonoid extracts from the ray florets of the chrysanthemum cultivar‘Wandai Fengguang’turned blue when exposed to Fe^(3+).Samples that could turn blue were labeled as CB(Cy-determined blue flowers),while samples that did not turn blue were labeled as CN(Cy-determined non-blue flowers).After a series of experiments,a stable screening system was established using flavonoid extracts containing NaAc buffer at pH 5.5 and a total anthocyanin concentration(TAC)of 30 μmol·L^(-1),and the addition of Fe^(3+)from 0 to 0.25 μmol·L^(-1)allowed for the selection of five CB samples from 39 chrysanthemum cultivars.All five CB samples exhibited flower color phenotypes that belonged to Cluster-I with redness(a*)values ranging from 29.03 to 45.99,yellowness(b*)values from-11.31 to 3.77,and brightness(L*)values from 29.07 to 45.99.Additionally,the ratio of TAC to total luteolin concentration(TLC)was found to be a critical factor for distinguishing between CB and CN samples.To realize the desired blue hue in the flavonoid extracts with the participation of Fe^(3+),a TAC to TLC ratio of 2.25 and above is required.Moreover,the protoplasts and ray florets of CB samples that turned blue with the involvement of Fe^(2+)showed great potential for cultivating blue chrysanthemums through ferric-anthocyanin chelate.Overall,this study reveals that blue flowers can be cultivated through the increase in the iron ion concentration,combined with the accumulation of Cy.

Progress of Lyman-alpha-based beam emission spectroscopy(Ly BES)diagnostic on the HL-2A tokamak

An edge Lyman-alpha-based beam emission spectroscopy(LyBES)diagnostic,using a heating NBI(neutral beam injection)system,is currently under development on the HL-2A tokamak.The 20-channel edge LyBES,which is intended to measure the density fluctuation in plasma edge(from R=1960 mm to R=2026 mm)with an improved spatial resolution of 3.3 mm,is a complement to the existing conventional beam emission spectroscopy(BES)diagnostic.In this article,we introduce the progress of LyBES diagnostic,including the collection optics,the monochromator,and the detector system.The reflectance of the collection mirrors is measured to be~82%at 122 nm,and the aberration geometrical radius of the collection optics is tested to be~150μm in the aimed area.The linear dispersion of the LyBES monochromator is designed to be~0.09 nm mm^(-1).The bandwidth of the detector system with the 5×10^(7)V A^(-1)preamplifier gain is measured to be~280 kHz,and the peak-to-peak noise of the detector system is tested to be~16 mV.The finalized design,components development and testing of the LyBES diagnostic have been completed at present,and an overall performance of the LyBES diagnostic is to be confirmed in the next HL-2A campaign.

IKIP downregulates THBS1/FAK signaling to suppress migration and invasion by glioblastoma cells

Background:Inhibitor of NF-κB kinase-interacting protein(IKIP)is known to promote proliferation of glioblastoma(GBM)cells,but how it affects migration and invasion by those cells is unclear.Methods:We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases.We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays,and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved.Results:Based on data from our clinical samples and from public databases,IKIP was overexpressed in GBM tumors,and its expression level correlated inversely with survival.IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays,whereas IKIP knockdown exerted the opposite effects.IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue.The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling.Conclusions:IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.

Physics-data coupling-driven method to predict the penetration depth into concrete targets

The projectile penetration process into concrete target is a nonlinear complex problem.With the increase ofexperiment data,the data-driven paradigm has exhibited a new feasible method to solve such complex prob-lem.However,due to poor quality of experimental data,the traditional machine learning(ML)methods,whichare driven only by experimental data,have poor generalization capabilities and limited prediction accuracy.Therefore,this study intends to exhibit a ML method fusing the prior knowledge with experiment data.The newML method can constrain the fitting to experimental data,improve the generalization ability and the predic-tion accuracy.Experimental results show that integrating domain prior knowledge can effectively improve theperformance of the prediction model for penetration depth into concrete targets.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer

BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery,guide perioperative treatment strategies for gastric cancer patients,and prevent serious complications.METHODS In total,998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model,and 398 patients were included in the validation group.The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected.Three machine learning methods,lasso regression,random forest,and artificial neural networks,were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy,and their prediction efficacy and accuracy were evaluated.RESULTS The constructed complication model,particularly the random forest model,could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy.It exhibited stable performance in external validation and is worthy of further promotion in more centers.CONCLUSION Using the risk factors identified in multicenter datasets,highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established.We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture

The autonomic nervous system plays a crucial role in regulating bone metabolism,with sympathetic activation stimulating bone resorption and inhibiting bone formation.We found that fractures lead to increased sympathetic tone,enhanced osteoclast resorption,decreased osteoblast formation,and thus hastened systemic bone loss in ovariectomized(OVX)mice.However,the combined administration of parathyroid hormone(PTH)and theβ-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice.The effect of this treatment is superior to that of treatment with PTH or propranolol alone.In vitro,the sympathetic neurotransmitter norepinephrine(NE)suppressed PTH-induced osteoblast differentiation and mineralization,which was rescued by propranolol.Moreover,NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation,whereas these effects were reversed by propranolol.Furthermore,PTH increased the expression of the circadian clock gene Bmal1,which was inhibited by NE-βAR signaling.Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTHstimulated osteoblast differentiation.Taken together,these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

Optical design of a novel near-infrared phase contrast imaging(NI-PCI)diagnostic on the HL-2A tokamak

The optical design of near-infrared phase contrast imaging(NI-PCI)diagnosis on HL-2A is introduced in this paper.This scheme benefits from the great progress of near-infrared laser technology and is a broadening of traditional phase contrast technology.This diagnostic can work as a keen tool to measure plasma wavenumber spectra by inferring string-integrated plasma density fluctuations.Design of both the front optical path which is the path before the laser transmitting into the tokamak plasma and the rear optics which is the path after the laser passing through the plasma is detailed.The 1550 nm laser is chosen as the probe beam and highprecision optical components are designed to fit the laser beam,in which a phase plate with a 194-nm-deep silver groove is the key.Compared with the conventional 10.6μm laser-based PCI system on HL-2A,NI-PCI significantly overcomes the unwanted phase scintillation effect and promotes the measurement capability of high-wavenumber turbulence with an increased maximal measurable wavenumber from 15 cm^(-1)to 32.6 cm^(-1).

Development of a novel staging classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction after neoadjuvant chemotherapy

BACKGROUND Stage classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction(AEG)treated with neoadjuvant chemotherapy(NAC)has not been established.AIM To investigate the optimal stage classification for Siewert Ⅱ AEG with NAC.METHODS A nomogram was established based on Cox regression model that analyzed variables associated with overall survival(OS)and disease-specific survival(DSS).The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test,Akaike information criterion,Harrell concordance index,time-receiver operating characteristic curve,and decision curve analysis.RESULTS Data from 725 patients with Siewert type Ⅱ AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate analyses revealed that sex,marital status,race,ypT stage,and ypN stage were independent prognostic factors of OS,whereas sex,race,ypT stage,and ypN stage were independent prognostic factors for DSS.These factors were incorporated into the OS and DSS nomograms.Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer.Finally,a user-friendly web application was developed for clinical use.CONCLUSION The nomogram established specifically for patients with Siewert type Ⅱ AEG receiving NAC demonstrated good prognostic performance.Validation using external data is warranted before its widespread clinical application.

Microbial Fertilizer: A Sustainable Strategy for Medicinal Plants Production

Medicinal plants have aroused considerable interest as an alternative to chemical drugs due to the beneficial effects of their active secondary metabolites.However,the extensive use of chemical fertilizers and pesticides in pursuit of yield has caused serious pollution to the environment,which is not conducive to sustainable devel-opment in thefield of medicinal plants.Microbial fertilizers are a type of“green fertilizer”containing specific microorganisms that can improve the soil microbial structure,enhance plant resistance to biological and abiotic stresses,and increase the yield of medicinal plants.The root exudates of medicinal plants attract different micro-organisms to the rhizosphere,which then migrate further to the plant tissues.These microbes can increase the levels of soil nutrients,and improve the physical and chemical properties of soil through nitrogenfixation,and phosphorus and potassium solubilization.In addition,soil microbes can promote the synthesis of hormones that increase plant growth and the accumulation of active compounds,eventually improving the quality of med-icinal plants.In 2022,the total value of the global microbial fertilizer market was$4.6 billion and is estimated to reach$10.36 billion by 2030.In this review,we have summarized the types of microbial fertilizers,the coloniza-tion and migration of microorganisms to plant tissues,and the beneficial effects of microbial fertilizers.In addi-tion,the prospects of developing microbial fertilizers and their application for medicinal plants have also been discussed.It aims to provide a reference for the rational application of microbial fertilizers in thefield of med-icinal plants and the green and sustainable development of medicinal plant resources.

3M syndrome patient with a novel mutation:A case rep

BACKGROUND A rare autosomal recessive genetic disorder,3M syndrome,is characterized by severe intrauterine and postnatal growth retardation.Children with 3M syndrome typically exhibit short stature,facial deformities,long tubular bones,and high vertebral bodies but generally lack mental abnormalities or other organ damage.Pathogenic genes associated with 3M syndrome include CUL7,OBSL1 and CCDC8.The clinical and molecular characteristics of patient with 3M syn-drome are unique and serve as important diagnostic indicators.CASE SUMMARY In this case,the patient displayed square shoulders,scoliosis,long slender tubular bones,and normal neurological development.Notably,the patient did not exhibit the typical dysmorphic facial features,relative macrocephaly,or growth retardation commonly observed in individuals with 3M syndrome.Whole exon sequencing revealed a novel heterozygous c.56681+1G>C(Splice-3)variant and a previously reported nonsense heterozygous c.3341G>A(p.Trp1114Ter)variant of OBSL1.Therefore,it is important to note that the clinical features of 3M syndrome may not always be observable,and genetic confirmation is often required.Additionally,the identification of the c.5683+1G>C variant in OBSL1 is notewor-thy because it has not been previously reported in public databases.CONCLUSION Our study identified a new variant(c.5683+1G>C)of OBSL1 that contributes to expanding the molecular profile of 3M syndrome.

Acute upper gastrointestinal bleeding due to portal hypertension in a patient with primary myelofibrosis:A case report

BACKGROUND Acute upper gastrointestinal bleeding is a common medical emergency that has a 10%hospital mortality rate.According to the etiology,this disease can be divided into acute varicose veins and nonvaricose veins.Bleeding from esophageal varices is a life-threatening complication of portal hypertension.Portal hypertension is a clinical syndrome defined as a portal venous pressure that exceeds 10 mmHg.Cirrhosis is the most common cause of portal hypertension,and thrombosis of the portal system not associated with liver cirrhosis is the second most common cause of portal hypertension in the Western world.Primary myeloproliferative disorders are the main cause of portal venous thrombosis,and somatic mutations in the Janus kinase 2 gene(JAK2 V617F)can be found in approximately 90% of polycythemia vera,50% of essential thrombocyrosis and 50% of primary myelofibrosis.CASE SUMMARY We present a rare case of primary myelofibrosis with gastrointestinal bleeding as the primary manifestation that presented as portal-superior-splenic mesenteric vein thrombosis.Peripheral blood tests revealed the presence of the JAK2 V617F mutation.Bone marrow biopsy ultimately confirmed the diagnosis of myelofibrosis(MF-2 grade).CONCLUSION In patients with acute esophageal variceal bleeding due to portal hypertension and vein thrombosis without cirrhosis,the possibility of myeloproliferative neoplasms should be considered,and the JAK2 mutation test should be performed.

模拟太阳光下驱动H_(2)O_(2)生成及含量测定的综合实验

近年来,新能源研发和太阳能储能在“双碳”背景下受到广大学生的关注。然而,在本科生教学实验中,缺乏涉及能源转换的实验,导致学生对低碳和绿色化学的理解停留在理论层面。本实验方案深入结合科学前沿的热门领域,利用模拟太阳光制备过氧化氢(H_(2)O_(2)),实现太阳能到化学能的转换和储存。整个实验过程不使用任何有毒有害试剂,充分体现绿色低碳的化学宗旨。本实验以双氰胺合成石墨相氮化碳(g-C_(3)N_(4))纳米片为例,分析聚合反应机制,充分融合了无机、物化和分析的基本操作,同时结合一些现代分析手段,进行g-C_(3)N_(4)催化H_(2)O_(2)生成和含量测定的开放性综合实验。实验中结合无机到有机材料的聚合反应,基于有氧实验环境的处理,利用紫外分光光度计测定产率,可有效提升学生的综合素质和创新能力,实现了“融时政于教学,培育全面发展的学生”的目标。

Effects of Quercetin Extracted from Flower Buds of Sophora japonica cv.jinhuai on Proliferation and Apoptosis of Human Breast Cancer MCF-7 Cells

[Objectives]To investigate the effects of quercetin extracted from flower buds of Sophora japonica cv.jinhuai on the proliferation,apoptosis and migration of human breast cancer MCF-7 cells.[Methods]MTT assay,inverted microscope observation,hoechst33342 staining,flow cytometry(FCM)and wound healing assay were adopted to investigate the proliferation,morphological changes,apoptosis level and cell migration ability of human breast cancer MCF-7 cells,respectively.[Results]The morphological changes of cells in the treatment groups included gradually decreased number,reduced volume,vague cell contour,loose intercellular connection,uneven cytoplasm distribution and increased cell debris.With the increase of drug concentration,quercetin significantly inhibited the proliferation of human breast cancer MCF-7 cells(P<0.05).The number of apoptotic bodies increased gradually.When the concentration reached 100μmol/L,a large number of nuclear fragments appeared,and the level of apoptosis was statistically different(P<0.05).The mobility and migration ability of cells showed a decreasing trend,and the differences were statistically significant(P<0.05).[Conclusions]This study can provide experimental basis for clinical application of quercetin against breast cancer.

Yinchenhao decoction attenuates obstructive jaundice-induced liver injury and hepatocyte apoptosis by suppressing protein kinase RNA-like endoplasmic reticulum kinase-induced pathway

BACKGROUND Chronic biliary obstruction results in ischemia and hypoxia of hepatocytes,and leads to apoptosis.Apoptosis is very important in regulating the homeostasis of the hepatobiliary system.Endoplasmic reticulum(ER)stress is one of the signaling pathways that induce apoptosis.Moreover,the protein kinase RNA-like endoplasmic reticulum kinase(PERK)-induced apoptotic pathway is the main way;but its role in liver injury remains unclear.Yinchenhao decoction(YCHD)is a traditional Chinese medicine formula that alleviates liver injury and apoptosis,yet its mechanism is unknown.We undertook this study to investigate the effects of YCHD on the expression of ER stress proteins and hepatocyte apoptosis in rats with obstructive jaundice(OJ).AIM To investigate whether YCHD can attenuate OJ-induced liver injury and hepatocyte apoptosis by inhibiting the PERK-CCAAT/enhancer-binding protein homologous protein(CHOP)-growth arrest and DNA damage-inducible protein 34(GADD34)pathway and B cell lymphoma/leukemia-2 related X protein(Bax)/B cell lymphoma/leukemia-2(Bcl-2)ratio.METHODS For in vivo experiments,30 rats were divided into three groups:control group,OJ model group,and YCHD-treated group.Blood was collected to detect the indicators of liver function,and liver tissues were used for histological analysis.For in vitro experiments,30 rats were divided into three groups:G1,G2,and G3.The rats in group G1 had their bile duct exposed without ligation,the rats in group G2 underwent total bile duct ligation,and the rats in group G3 were given a gavage of YCHD.According to the serum pharmacology,serum was extracted and centrifuged from the rat blood to cultivate the BRL-3A cells.Terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling(TUNEL)assay was used to detect BRL-3A hepatocyte apoptosis.Alanine aminotransferase(ALT)and aspartate transaminase(AST)levels in the medium were detected.Western blot and quantitative real-time polymerase chain reaction(qRT-PCR)analyses were used to detect protein and gene expression levels of PERK,CHOP,GADD34,Bax,and Bcl-2 in the liver tissues and BRL-3A cells.RESULTS Biochemical assays and haematoxylin and eosin staining suggested severe liver function injury and liver tissue structure damage in the OJ model group.The TUNEL assay showed that massive BRL-3A rat hepatocyte apoptosis was induced by OJ.Elevated ALT and AST levels in the medium also demonstrated that hepatocytes could be destroyed by OJ.Western blot or qRT-PCR analyses showed that the protein and mRNA expression levels of PERK,CHOP,and GADD34 were significantly increased both in the rat liver tissue and BRL-3A rat hepatocytes by OJ.The Bax and Bcl-2 levels were increased,and the Bax/Bcl-2 ratio was also increased.When YCHD was used,the PERK,CHOP,GADD34,and Bax levels quickly decreased,while the Bcl-2 levels increased,and the Bax/Bcl-2 ratio decreased.CONCLUSION OJ-induced liver injury and hepatocyte apoptosis are associated with the activation of the PERK-CHOP-GADD34 pathway and increased Bax/Bcl-2 ratio.YCHD can attenuate these changes.

Multimodal Identification by Transcriptomics and Multiscale Bioassays of Active Components in Xuanfeibaidu Formula to Suppress Macrophage-Mediated Immune Response

Xuanfeibaidu Formula (XFBD) is a Chinese medicine used in the clinical treatment of coronavirus disease 2019 (COVID-19) patients. Although XFBD has exhibited significant therapeutic efficacy in clinical practice, its underlying pharmacological mechanism remains unclear. Here, we combine a comprehensive research approach that includes network pharmacology, transcriptomics, and bioassays in multiple model systems to investigate the pharmacological mechanism of XFBD and its bioactive substances. High-resolution mass spectrometry was combined with molecular networking to profile the major active substances in XFBD. A total of 104 compounds were identified or tentatively characterized, including flavonoids, terpenes, carboxylic acids, and other types of constituents. Based on the chemical composition of XFBD, a network pharmacology-based analysis identified inflammation-related pathways as primary targets. Thus, we examined the anti-inflammation activity of XFBD in a lipopolysaccharide-induced acute inflammation mice model. XFBD significantly alleviated pulmonary inflammation and decreased the level of serum proinflammatory cytokines. Transcriptomic profiling suggested that genes related to macrophage function were differently expressed after XFBD treatment. Consequently, the effects of XFBD on macrophage activation and mobilization were investigated in a macrophage cell line and a zebrafish wounding model. XFBD exerts strong inhibitory effects on both macrophage activation and migration. Moreover, through multimodal screening, we further identified the major components and compounds from the different herbs of XFBD that mediate its anti-inflammation function. Active components from XFBD, including Polygoni cuspidati Rhizoma, Phragmitis Rhizoma, and Citri grandis Exocarpium rubrum, were then found to strongly downregulate macrophage activation, and polydatin, isoliquiritin, and acteoside were identified as active compounds. Components of Artemisiae annuae Herba and Ephedrae Herba were found to substantially inhibit endogenous macrophage migration, while the presence of ephedrine, atractylenolide I, and kaempferol was attributed to these effects. In summary, our study explores the pharmacological mechanism and effective components of XFBD in inflammation regulation via multimodal approaches, and thereby provides a biological illustration of the clinical efficacy of XFBD.