Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-...Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.展开更多
Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported previously.However,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its int...Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported previously.However,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its interaction with lenalidomide treatment,are not fully understood.Methods:Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control groups.Immunohistochemical data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of DLBCL.Furthermore,in vitro and in vivo experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide treatment.Results:Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in DLBCL.Notably,31.14%and 36.0%(44/122)of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively,establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression analysis.Additionally,our studies demonstrated that the external application of the protein CCL21 promoted proliferation,migration,invasion,and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 expression.This effect was mitigated by CCR7 silencing through siRNA,application of ERK inhibitors,or lenalidomide treatment.In vivo experiments reinforced the efficacy of lenalidomide,significantly reducing tumor growth rate,tumor mass,serum total LDH levels,and expression of CCR7 and p-ERK1/2 in a SUDHL-2 xenograft model in nude mice(p<0.05).Conclusion:Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment.展开更多
BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression result...BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCF^(FBXW7),p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCF^(FBXW7),p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCF^(FBXW7)(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCF^(FBXW7) and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^(FBXW7),thereby influencing the ubiquitination and degradation of cyclin E1.展开更多
multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from e...multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from enamine ketone,aromatic ketone aldehyde hydrate,and carboxylic acid,and selectively synthesized 7-ester indoles and bis-indoles by changing the substituted enamine ketone substrate.This method had the characteristics of high regional selectivity,short reaction time,and green environmental protection.展开更多
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
Nitrogen(N)is a key component in plants and their biological macromolecules,having a profound effect on developmental stages,such as germination,vegetative growth,and flowering.However,the mechanism of nitrogen-regula...Nitrogen(N)is a key component in plants and their biological macromolecules,having a profound effect on developmental stages,such as germination,vegetative growth,and flowering.However,the mechanism of nitrogen-regulated flowering time remains unclear.In this study,CmNLP7 was isolated from the chrysanthemum cultivar‘Jinba'and was characterized.CmNLP7 is a transcription factor localized in the nucleus but has no transcriptional activity.Tissue expression pattern analysis showed that CmNLP7 was mainly transcribed in leaves and roots.Knocking down CmNLP7 through the artificial-miRNA method in chrysanthemum resulted in early flowering under optimal nitrogen(ON)and low nitrogen(LN)conditions;whereas overexpression lines showed delayed flowering under LN conditions.Transcriptome sequencing analysis showed that the nitrate transporters NRT2.5,NPF3.1,and NPF4.6;SBP-like genes SPL7 and SPL12,and flowering integration factor FT were significantly up-regulated in the knockdown lines.Based on the KEGG pathway enrichment analysis,the differentially transcribed genes were enriched in phenylpropanoid biosynthesis and starch and sucrose metabolism pathways,which indicated their alleged function in nitrogen-regulated flowering and development in chrysanthemum.Furthermore CmPP6 as a homolog of the Arabidopsis phosphatase PP6,was verified as an interacting protein of CmNLP7 by yeast two-hybrid,BiFC,pull-down and Biacore in vitro and in vivo,and the knockdown line of CmPP6(amiR-CmPP6)flowered earlier compared to that of the wild-type chrysanthemum‘Jinba'.Collectively,these results demonstrated that CmPP6 interacts with CmNLP7 to regulate chrysanthemum flowering,and CmNLP7 could regulate flowering time in response to nitrogen,which lays a foundation for the regulation of flowering and molecular breeding of chrysanthemum through changes in nutrient signaling.展开更多
Ethylene response factors(ERFs)are plant transcription agents that play a pivotal role in disease resistance through the ethylene signaling pathway.However,whether and how ERFs regulate resistance to sheath blight(ShB...Ethylene response factors(ERFs)are plant transcription agents that play a pivotal role in disease resistance through the ethylene signaling pathway.However,whether and how ERFs regulate resistance to sheath blight(ShB),caused by Rhizoctonia solani in rice,remains largely unknown.Here,we demonstrated that OsERF7 negatively regulates rice resistance to ShB by inhibiting phytoalexin biosynthesis.Overexpression of OsERF7(OsERF7OE)significantly decreased ShB resistance,whereas knockout of OsERF7(oserf7)enhanced it.Mechanistically,antioxidant enzyme activities are significantly reduced in OsERF7OE plants,but increased in oserf7 plants.Furthermore,transcriptome analysis revealed that oserf7 plants exhibited significant upregulation of pathogenesis-related(PR)and phytoalexin biosynthesis genes upon R.solani infection.Consistently,transcript levels of phytoalexin biosynthesis genes,including OsKSL7,OsKSL8,OsKOL5,and OsCPS4,were significantly elevated in oserf7 plants,but reduced in OsERF7OE plants in response to R.solani infection.Electrophoretic mobility shift assays and dual-luciferase(LUC)reporter assays further confirmed that OsERF7 directly binds to the promoters of OsKSL8,OsKOL5,and OsCPS4,thereby repressing their expression.In summary,our study revealed that OsERF7 negatively regulated rice resistance to ShB primarily by inhibiting phytoalexin biosynthesis.展开更多
Astragalus extract Astragalus polysaccharide(APS),a natural extract,has been demonstrated to exert inhibitory effects on the development of various tumors by modulating microRNA(miRNA).However,the precise regulatory m...Astragalus extract Astragalus polysaccharide(APS),a natural extract,has been demonstrated to exert inhibitory effects on the development of various tumors by modulating microRNA(miRNA).However,the precise regulatory mechanism of miRNA-223(miR-223)in brain glioma cells remains unclear.This study aimed to investigate the inhibitory effect of Astragalus extract APS on brain glioma cells through the miR-223/FBXW7 signaling pathway and its potential mechanism.Using the TargetScan tool,we predicted the binding between miR-223 and FBXW7 and confirmed this binding relationship through dual luciferase assay.We compared the expression of miR-223 and FBXW7 in glioma and adjacent tissues and followed up the prognosis.U87 cells were subjected to APS treatment or were transfected with small interfering RNA(siRNA)of miR-223 mimics to examine the effects of these treatments on cell proliferation,apoptosis,and FBXW7 expression.Our results demonstrated that miR-223 directly bound to FBXW7,as confirmed by dual luciferase assay.Moreover,the mRNA expression of miR-223 in glioma tissues was higher than that in paracancerous tissues,while the mRNA and protein levels of FBXW7 in glioma tissues were lower than those in paracancerous tissues.In addition,we observed a negative correlation between the expression of miR-223 and FBXW7(P<0.05).APS significantly inhibited the proliferation and invasion of U87 cells,suppressed the expression of miR-223,and promoted the expression of FBXW7(P<0.05).Transfection of miR-223 mimic into cells reversed the inhibition of miR-223 and the increase of FBXW7 induced by APS(P<0.05).Therefore,our findings suggested that APS might inhibit the proliferation and invasion of the glioma cell line U87 through the miR-223/FBXW7 signaling pathway.展开更多
Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions...Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 mg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.展开更多
Lacustrine shale oil reservoirs of the Upper Triassic Chang 7 Member in the Ordos Basin have demonstrated significant potential for hydrocarbon resources.Natural fractures play a crucial role in hydrocarbon enrichment...Lacustrine shale oil reservoirs of the Upper Triassic Chang 7 Member in the Ordos Basin have demonstrated significant potential for hydrocarbon resources.Natural fractures play a crucial role in hydrocarbon enrichment and production.Outcrops,cores,borehole image logs,thin sections,and FE-SEM images were used to investigate the types and characteristics of natural fractures in the Chang 7 Member.The factors controlling fracture development and the mechanisms of bedding-parallel fracture formation were revealed by integrating TOC analysis,XRD analysis,and rock pyrolysis.Results show that natural fractures in the study area include high-angle tectonic fractures and nearly horizontal bedding-parallel fractures.Brittle minerals and bed thickness control the occurrence and attributes of tectonic fractures.High TOC content and thermal maturity positively affect the development of bedding-parallel fractures,formed through the conversion of organic matter to hydrocarbons or the smectite-to-illite transformation.Additionally,the dominant orientations of tectonic fractures intersect the present-day maximum horizontal principal stress at a small angle,resulting in large apertures and good effectiveness.Bedding-parallel fractures contribute to enhance porosity and provide favorable pathways for lateral hydrocarbon migration.Collectively,this study could provide valuable insights for finding promising exploration areas in lacustrine shale oil reservoirs in the Ordos Basin and worldwide.展开更多
Bees play a crucial role in the global food chain,pollinating over 75% of food and producing valuable products such as bee pollen,propolis,and royal jelly.However,theAsian hornet poses a serious threat to bee populati...Bees play a crucial role in the global food chain,pollinating over 75% of food and producing valuable products such as bee pollen,propolis,and royal jelly.However,theAsian hornet poses a serious threat to bee populations by preying on them and disrupting agricultural ecosystems.To address this issue,this study developed a modified YOLOv7tiny(You Only Look Once)model for efficient hornet detection.The model incorporated space-to-depth(SPD)and squeeze-and-excitation(SE)attention mechanisms and involved detailed annotation of the hornet’s head and full body,significantly enhancing the detection of small objects.The Taguchi method was also used to optimize the training parameters,resulting in optimal performance.Data for this study were collected from the Roboflow platformusing a 640×640 resolution dataset.The YOLOv7tinymodel was trained on this dataset.After optimizing the training parameters using the Taguchi method,significant improvements were observed in accuracy,precision,recall,F1 score,andmean average precision(mAP)for hornet detection.Without the hornet head label,incorporating the SPD attentionmechanism resulted in a peakmAP of 98.7%,representing an 8.58%increase over the original YOLOv7tiny.By including the hornet head label and applying the SPD attention mechanism and Soft-CIOU loss function,themAP was further enhanced to 97.3%,a 7.04% increase over the original YOLOv7tiny.Furthermore,the Soft-CIOU Loss function contributed to additional performance enhancements during the validation phase.展开更多
The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of mol...The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of molecular vips.However,its moderate water solubility limits broader application.Here we report the synthesis of three CB[7]derivatives M1-M3 by modifying an average of 4.2,5.5,and 5.9 sulfonatopropoxy groups onto their"equator"carbons.Compared to CB[7],their water-solubility increased by at least 26.6-,23.6-,and 19.2-fold,respectively,while the maximum tolerated doses(MTD)of M1 and M2 improved by 2.5-and 2.3-fold.Phase solubility diagram studies demonstrate that M1 and M2 significantly enhance the water-solubility of eighteen poorly soluble drugs.In vivo experiments in rat complete Freund's arthritis reveal that M1 not only improves the anti-inflammatory efficacy of indomethacin by up to 52%,but also substantially reduces its side effect of gastric ulcer.展开更多
BACKGROUND:While theα7 nicotinic acetylcholine receptor(α7 nAChR)is implicated in sepsis-associated encephalopathy(SAE),its pathophysiological contributions require further investigation.METHODS:SAE was induced in m...BACKGROUND:While theα7 nicotinic acetylcholine receptor(α7 nAChR)is implicated in sepsis-associated encephalopathy(SAE),its pathophysiological contributions require further investigation.METHODS:SAE was induced in mice via cecal ligation and puncture(CLP),and microglia were treated with lipopolysaccharide(LPS).PHA-543613(anα7 nAChR agonist)was used to activateα7 nAChR.To study the role ofα7 nAChR in mitophagy and pyroptosis,caspase-1-deficient mice and PTEN-induced kinase 1(PINK1)small interfering RNA(siRNA)were used.Cognitive function,cerebral oxygen extraction ratio(CERO2),and brain tissue oxygen pressure(PbtO2)were measured.Blood-brain barrier(BBB)integrity was evaluated via Evan’s blue staining.Mitophagy,pyroptosis,and cytokine levels were analyzed via Western blotting and immunofl uorescence.RESULTS:CLP or LPS treatment signifi cantly down-regulatedα7 nAChR protein expression in microglia.The administration of PHA-543613 to activateα7 nAChR not only restored its expression post-sepsis,but also notably decreased BBB permeability and mitigated cognitive deficits.Bothα7 nAChR activation and caspase-1 knockout effectively suppressed microglial pyroptosis.The activation ofα7 nAChR also promoted mitophagy in microglia.This led to an amelioration of brain tissue hypoxia,as shown by elevated PbtO2 and reduced CERO2 levels.The suppression of microglial pyroptosis byα7 nAChR was counteracted when mitophagy was inhibited through the siRNA-mediated silencing of PINK1.CONCLUSION:The activation ofα7 nAChR reduces pyroptosis by enhancing microglial mitophagy,thereby mitigating SAE.展开更多
Given its excellent biological properties and the matching of its elastic modulus with that of human bone tissue,medical polyetheretherketone(PEEK)is considered a desirable candidate for bone-implant materials.However...Given its excellent biological properties and the matching of its elastic modulus with that of human bone tissue,medical polyetheretherketone(PEEK)is considered a desirable candidate for bone-implant materials.However,its poor osseointegrative and antibacterial properties greatly limit its clinical application.To address these concerns,a functional PEEK implant is needed.Herein,a novel photo-responsive multifunctional PEEK-based implant material(sPEEK/BP/E7)with both effective osteogenesis and good disinfection properties was constructed via the self-assembly of black phosphorus(BP)nanosheets,mussel-inspired polydopamine(PDA),and bioactive short peptide E7 on sulfonated PEEK(sPEEK).The versatile micro-/nano-structured PEEK surface provides superior hydrophilicity,a favorable osteogenic microenvironment,and excellent photothermal effects under near-infrared(NIR)irradiation.The in vitro results showed that sPEEK/BP/E7 displays enhanced cytocompatibility and osteogenicity in terms of cell adhesion,proliferation,alkaline phosphatase(ALP)activity,matrix mineralization,and osteogenesis-related gene expression,superior to those of the sPEEK and sPEEK/BP samples.In addition to osteogenesis,the multifunctional coating exhibited strong antibacterial activity against both Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli).Furthermore,it was confirmed in a rat femoral infection model that sPEEK/BP/E7 effectively resisted infection caused by S.aureus under NIR light irradiation and promoted osseointegration in vivo.Thus,this work presents a facile strategy to realize improvement of the“functional integration”of new polymer bone–implant materials and provide new ideas for their clinical application.展开更多
Hair follicle stem cell(HFSC),capable of self-renewal and differentiation in hair follicle,represents an emerging stem cell model for regenerative medicine.The interaction between HFSC and dermal papilla cell(DPC)gove...Hair follicle stem cell(HFSC),capable of self-renewal and differentiation in hair follicle,represents an emerging stem cell model for regenerative medicine.The interaction between HFSC and dermal papilla cell(DPC)governs hair follicle development.FGF7 functions as a paracrine protein regulating epithelial proliferation,differentiation and migration.The single-cell transcriptome profling and immunofuorescence analysis demonstrated that FGF7 localizes at DPC,while FGF7 receptor(FGFR2)expresses in both DPC and HFSC.Through co-culture experiments of HFSC and DPC,the results indicated that FGF7 secreted from DPC promotes the proliferation of DPC and HFSC via Wnt signaling pathway and induces HFSC differentiation.Furthermore,CUT&Tag assay revealed genomic colocalization between FGF7 and pluripotency-related genes and GSK3β.Electrophoretic mobility shift assay(EMSA)demonstrated that FGF7 interacts with the promoter region of CISH and PRKX.This research provides valuable insights into the molecular mechanisms underlying the hair cycle.Understanding the interaction between HFSC and DPC,as well as the role of FGF7,may advance regenerative medicine and hair loss treatment.展开更多
BACKGROUND Hepatic ischaemia-reperfusion injury(HIRI)is an unavoidable process in liver transplantation,where apoptosis plays a critical role.Human umbilical cord mesenchymal stem cell-derived exosomes(hucMSC-exos),wh...BACKGROUND Hepatic ischaemia-reperfusion injury(HIRI)is an unavoidable process in liver transplantation,where apoptosis plays a critical role.Human umbilical cord mesenchymal stem cell-derived exosomes(hucMSC-exos),which constitute a cellfree therapeutic approach,have garnered extensive attention in alleviating HIRI.However,the potential of hucMSC-exos in mitigating apoptosis and their underlying mechanisms remain largely unknown.AIM To investigate the effects of hucMSC-exos on apoptosis after HIRI and explore the underlying mechanisms.METHODS The therapeutic effects of hucMSC-exos on HIRI and hypoxia/reoxygenation injury in L02 cells were investigated.RNA sequencing was used to detect differentially expressed genes in L02 cells after hucMSC-exo treatment,and the expression of apoptosis markers in L02 cells was analyzed.MicroRNA(miRNA)sequencing was performed to analyse the miRNA expression profiles of hucMSCexos and L02 cells after hucMSC-exo treatment.Through a miRNA-mRNA integrated analysis,candidate miRNAs and their regulated target genes were identified.We subsequently studied the roles of these candidate miRNAs in mouse HIRI and L02 cell hypoxia/reoxygenation injury.RESULTSFluorescence confocal microscopy revealed that hucMSC-exos effectively homed to the liver and were taken up byhepatocytes, likely due to the presence of anti-very late antigen-4 and anti-lymphocyte function-associated antigen-1 on the surface of hucMSC-exos. HucMSC-exos alleviate hepatocyte damage by inhibiting apoptosis. Specifically,let-7i-5p within hucMSC-exos inhibited the expression of the factor-related apoptosis ligand protein in L02 cells,leading to the upregulation of B-cell lymphoma-2 and the downregulation of B-cell lymphoma-2-associated Xprotein and cysteinyl aspartate specific proteinase-3, thereby inhibiting L02 cell apoptosis and enhancing cellproliferation activity. The overexpression of let-7i-5p effectively enhanced the antiapoptotic effects of hucMSC-exosboth in vitro and in vivo.CONCLUSIONOur findings indicate that hucMSC-exos alleviate HIRI by inhibiting apoptosis. We demonstrated that hucMSCexostarget apoptosis in L02 cells and mediate the let-7i-5p/factor-related apoptosis ligand pathway, therebyameliorating HIRI. This study provides new insights into the role of hucMSC-exos in hepatocyte apoptosis andhighlights the potential of hucMSC-exos as a therapeutic strategy for HIRI.展开更多
CaBaCo_(4)O_(7)has been widely studied because of its distinctive structure and magnetic properties.This study examined the influence of different cooling atmospheres on the structure,magnetic properties,and dielectri...CaBaCo_(4)O_(7)has been widely studied because of its distinctive structure and magnetic properties.This study examined the influence of different cooling atmospheres on the structure,magnetic properties,and dielectric behavior of CaBaCo_(4)O_(7).Samples were cooled under different atmospheric conditions to assess these influences.Our findings indicate that reduced oxygen content leads to increased lattice distortion.Since oxygen atoms play a crucial role in mediating magnetic exchange,oxygen deficiency disrupts long-range magnetic order and promotes short-range antiferromagnetic interactions.Additionally,the cooling atmosphere significantly impacts grain size,thereby affecting the dielectric constant and dielectric loss.In the argon-cooled CaBaCo_(4)O_(7)(Ar)sample,oxygen deficiency reduced dielectric permittivity and increased dielectric loss.展开更多
5-hydroxytryptamine(5-HT)is a biological monoamine neurotransmitter in the central nervous system and gonads of crustaceans to induce gonadal maturation.To better understand the effects of 5-HT and its receptors on re...5-hydroxytryptamine(5-HT)is a biological monoamine neurotransmitter in the central nervous system and gonads of crustaceans to induce gonadal maturation.To better understand the effects of 5-HT and its receptors on reproductive development in Artemia,a 5-HT type 7 receptor gene(5-HT_(7Ar))was identified in parthenogenetic Artemia and characterized.Sequence analysis revealed that the open reading frame of 5-HT_(7Ar) encodes a 414-aa protein.5-HT_(7Ar) showed higher expression in both brain and ovary at early embryo stage,5-HT_(7Ar) could be detected during ovarian development and the highest expression was observed at early embryo stage.Silencing of the 5-HT_(7Ar) in Artemia at early embryo stage decreased significantly the expression level of 5-HT_(7Ar) gene and protein at late oocyte,early embryo,and late embryo stage.Moreover,silencing of the 5-HT_(7Ar) resulted in a decreased fecundity,which corresponds to abnormal oocytes during the embryo development.Artemia tended to produce nauplii after the silencing of 5-HT_(7Ar),indicating that 5-HT_(7Ar) may also involve in the determination of its reproduction mode.The findings of this study provide an insight into the regulation of reproductive development in Artemia and the function of 5-HT_(7Ar).展开更多
Selective separation of amino acids and proteins is crucial in various areas of research,including proteomics,protein structure and function studies,protein purification and drug development,and biosensing and biodete...Selective separation of amino acids and proteins is crucial in various areas of research,including proteomics,protein structure and function studies,protein purification and drug development,and biosensing and biodetection.A nanocomposite film is formed by combining layer-by-layer self-assembled gold nanospheres(Au NPs)driven by cucurbit[7]uril(CB[7])and polymethyl methacrylate(PMMA)film.Due to the host-vip interactions,the selective transmission of l-tryptophan in the nanocomposite film is confirmed by the current-voltage measurements using a picoammeter.Furthermore,by adjusting the particle size of Au NPs to increase channel size,lysozyme containing multiple tryptophan residues can selectively pass through the nanocomposite film,indicating the high versatility and adaptability of the nanocomposite film.This study will provide a new direction for the selective separation of amino acids and proteins.展开更多
BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche ...BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche drive the continuous self-renewal of intestinal epithelium,preserving its barrier functions.Paneth cells secrete antimicrobial peptide and signaling molecules within the intestine crypt,thereby playing a crucial role in intestinal immune defense and providing ISCs functional support.However,the regulatory function of Paneth cells under pathological conditions,such as RV infection,remains unclear.AIM To determine the impact of RV infection on Paneth cells and how Paneth cells regulate ISCs during intestinal injury repair.METHODS We constructed a reference genome for the RV enteric cytopathogenic human orphan virus strain and reanalyzed published single-cell RNA sequencing data to investigate Paneth cell responses to RV-induced intestinal injury.We derived Paneth-ISC communication networks using CellChat,tracked ISC differentiation with pseudotime analysis,and validated our findings in leucine-rich repeat-containing G protein-coupled receptor 5-enhanced green fluorescent protein-internal ribosomal entry site-Cre recombinase estrogen receptor variant 2 mice and organoids via immunofluorescence,flow cytometry,and reverse transcription quantitative polymerase chain reaction.RESULTS We found that RV directly infects Paneth cells,leading to a reduction in mature Paneth cells and an increase in kallikrein 1-high immature Paneth cells.Paneth-ISC communication was significantly enhanced.In particular,the bone morphogenic protein 7(BMP7)-activin A receptor type 2B/BMP receptor type 1A-Smad pathway was upregulated post-infection,suggesting that Paneth cells suppress excessive ISC proliferation.Functional validation confirmed activation of this pathway.CONCLUSION Paneth cells regulate ISC proliferation during RV infection by activating BMP7 signaling,limiting excessive stem cell expansion and preserving crypt homeostasis for effective epithelial repair.展开更多
基金funded by the Natural Science Foundation of Guangdong Province(grant number 2022A1515012315)Guangdong Medical Science and Technology Research Fund Project(grant number A2023185)+2 种基金the Discipline Construction Project of Guangdong Medical University(grant number 4SG22005G)the 2023 Provincial Basic and Applied Basic Research Fund Enterprise Joint Fund Project(grant number 2023A1515220149)Southern Medical University Shunde Hospital 2023 Research Initiation Programme Project(SRSP2023016).
文摘Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.
基金supported by the Key Research and Development Program of Science and Technology Department of Guizhou Province(No.20204Y147).
文摘Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported previously.However,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its interaction with lenalidomide treatment,are not fully understood.Methods:Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control groups.Immunohistochemical data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of DLBCL.Furthermore,in vitro and in vivo experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide treatment.Results:Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in DLBCL.Notably,31.14%and 36.0%(44/122)of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively,establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression analysis.Additionally,our studies demonstrated that the external application of the protein CCL21 promoted proliferation,migration,invasion,and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 expression.This effect was mitigated by CCR7 silencing through siRNA,application of ERK inhibitors,or lenalidomide treatment.In vivo experiments reinforced the efficacy of lenalidomide,significantly reducing tumor growth rate,tumor mass,serum total LDH levels,and expression of CCR7 and p-ERK1/2 in a SUDHL-2 xenograft model in nude mice(p<0.05).Conclusion:Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment.
基金Supported by Innovative Practice Platform for Undergraduate Students,School of Public Health Xiamen University,No.2021001.
文摘BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCF^(FBXW7),p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCF^(FBXW7),p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCF^(FBXW7)(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCF^(FBXW7) and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^(FBXW7),thereby influencing the ubiquitination and degradation of cyclin E1.
文摘multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from enamine ketone,aromatic ketone aldehyde hydrate,and carboxylic acid,and selectively synthesized 7-ester indoles and bis-indoles by changing the substituted enamine ketone substrate.This method had the characteristics of high regional selectivity,short reaction time,and green environmental protection.
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
基金supported by grants from the National Natural Science Foundation of China(Grant No.31930100)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Nitrogen(N)is a key component in plants and their biological macromolecules,having a profound effect on developmental stages,such as germination,vegetative growth,and flowering.However,the mechanism of nitrogen-regulated flowering time remains unclear.In this study,CmNLP7 was isolated from the chrysanthemum cultivar‘Jinba'and was characterized.CmNLP7 is a transcription factor localized in the nucleus but has no transcriptional activity.Tissue expression pattern analysis showed that CmNLP7 was mainly transcribed in leaves and roots.Knocking down CmNLP7 through the artificial-miRNA method in chrysanthemum resulted in early flowering under optimal nitrogen(ON)and low nitrogen(LN)conditions;whereas overexpression lines showed delayed flowering under LN conditions.Transcriptome sequencing analysis showed that the nitrate transporters NRT2.5,NPF3.1,and NPF4.6;SBP-like genes SPL7 and SPL12,and flowering integration factor FT were significantly up-regulated in the knockdown lines.Based on the KEGG pathway enrichment analysis,the differentially transcribed genes were enriched in phenylpropanoid biosynthesis and starch and sucrose metabolism pathways,which indicated their alleged function in nitrogen-regulated flowering and development in chrysanthemum.Furthermore CmPP6 as a homolog of the Arabidopsis phosphatase PP6,was verified as an interacting protein of CmNLP7 by yeast two-hybrid,BiFC,pull-down and Biacore in vitro and in vivo,and the knockdown line of CmPP6(amiR-CmPP6)flowered earlier compared to that of the wild-type chrysanthemum‘Jinba'.Collectively,these results demonstrated that CmPP6 interacts with CmNLP7 to regulate chrysanthemum flowering,and CmNLP7 could regulate flowering time in response to nitrogen,which lays a foundation for the regulation of flowering and molecular breeding of chrysanthemum through changes in nutrient signaling.
基金supported by the National Natural Science Foundation of China(Grant Nos.32200430 and 32272110)Jiangsu Province Higher Vocational College Teacher Professional Leader High-End Training Program,China(Grant No.2023GRFX083)+2 种基金China Postdoctoral Science Foundation(Grant No.2022M712700)Jiangsu Funding Program for Excellent Postdoctoral Talent,China(Grant No.2022ZB628)a Project Funded by Priority Academic Program Development of Jiangsu Higher Education Institutions,China.
文摘Ethylene response factors(ERFs)are plant transcription agents that play a pivotal role in disease resistance through the ethylene signaling pathway.However,whether and how ERFs regulate resistance to sheath blight(ShB),caused by Rhizoctonia solani in rice,remains largely unknown.Here,we demonstrated that OsERF7 negatively regulates rice resistance to ShB by inhibiting phytoalexin biosynthesis.Overexpression of OsERF7(OsERF7OE)significantly decreased ShB resistance,whereas knockout of OsERF7(oserf7)enhanced it.Mechanistically,antioxidant enzyme activities are significantly reduced in OsERF7OE plants,but increased in oserf7 plants.Furthermore,transcriptome analysis revealed that oserf7 plants exhibited significant upregulation of pathogenesis-related(PR)and phytoalexin biosynthesis genes upon R.solani infection.Consistently,transcript levels of phytoalexin biosynthesis genes,including OsKSL7,OsKSL8,OsKOL5,and OsCPS4,were significantly elevated in oserf7 plants,but reduced in OsERF7OE plants in response to R.solani infection.Electrophoretic mobility shift assays and dual-luciferase(LUC)reporter assays further confirmed that OsERF7 directly binds to the promoters of OsKSL8,OsKOL5,and OsCPS4,thereby repressing their expression.In summary,our study revealed that OsERF7 negatively regulated rice resistance to ShB primarily by inhibiting phytoalexin biosynthesis.
基金National Key Research and Development Project(Grant No.2016YFC1101503)。
文摘Astragalus extract Astragalus polysaccharide(APS),a natural extract,has been demonstrated to exert inhibitory effects on the development of various tumors by modulating microRNA(miRNA).However,the precise regulatory mechanism of miRNA-223(miR-223)in brain glioma cells remains unclear.This study aimed to investigate the inhibitory effect of Astragalus extract APS on brain glioma cells through the miR-223/FBXW7 signaling pathway and its potential mechanism.Using the TargetScan tool,we predicted the binding between miR-223 and FBXW7 and confirmed this binding relationship through dual luciferase assay.We compared the expression of miR-223 and FBXW7 in glioma and adjacent tissues and followed up the prognosis.U87 cells were subjected to APS treatment or were transfected with small interfering RNA(siRNA)of miR-223 mimics to examine the effects of these treatments on cell proliferation,apoptosis,and FBXW7 expression.Our results demonstrated that miR-223 directly bound to FBXW7,as confirmed by dual luciferase assay.Moreover,the mRNA expression of miR-223 in glioma tissues was higher than that in paracancerous tissues,while the mRNA and protein levels of FBXW7 in glioma tissues were lower than those in paracancerous tissues.In addition,we observed a negative correlation between the expression of miR-223 and FBXW7(P<0.05).APS significantly inhibited the proliferation and invasion of U87 cells,suppressed the expression of miR-223,and promoted the expression of FBXW7(P<0.05).Transfection of miR-223 mimic into cells reversed the inhibition of miR-223 and the increase of FBXW7 induced by APS(P<0.05).Therefore,our findings suggested that APS might inhibit the proliferation and invasion of the glioma cell line U87 through the miR-223/FBXW7 signaling pathway.
基金supported by grants from the National Natural Science Foundation of China(Grant NOs.:82272935,91957120 and 21974114)the Postdoctoral Fellowship Program of CPSF(Program No.:GZC20240901)+5 种基金the Xiamen Medical Industry Combined Guidance Project,China(Project No.:3502Z20244ZD2022)the Scientific Research Foundation for Advanced Talents,Xiang'an Hospital of Xiamen University,China(Grant No.:PM20180917008)the Fundamental Research Funds for the Central Universities,China(Grant No.:20720210001)Major Science and Technology Special Project of Fujian Province,China(Project No.:2022YZ036012)Joint Laboratory of School of Medicine,Xiamen University-Shanghai Jiangxia Blood Technology Co.,Ltd.,China(Grant No.:XDHT2020010C)Joint Research Center of School of Medicine,Xiamen University-Jiangsu Charity Biotech Co.,Ltd.,China(Grant No.:20233160C0002).
文摘Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 mg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
基金supported by the National Natural Science Foundation of China(42090025,42302148)State Key Laboratory of Shale Oil and Gas Enrichment Mechanisms and Effective Development(33550000-22-ZC0613-0336)CNPC Innovation Found(2023DQ02-0103)。
文摘Lacustrine shale oil reservoirs of the Upper Triassic Chang 7 Member in the Ordos Basin have demonstrated significant potential for hydrocarbon resources.Natural fractures play a crucial role in hydrocarbon enrichment and production.Outcrops,cores,borehole image logs,thin sections,and FE-SEM images were used to investigate the types and characteristics of natural fractures in the Chang 7 Member.The factors controlling fracture development and the mechanisms of bedding-parallel fracture formation were revealed by integrating TOC analysis,XRD analysis,and rock pyrolysis.Results show that natural fractures in the study area include high-angle tectonic fractures and nearly horizontal bedding-parallel fractures.Brittle minerals and bed thickness control the occurrence and attributes of tectonic fractures.High TOC content and thermal maturity positively affect the development of bedding-parallel fractures,formed through the conversion of organic matter to hydrocarbons or the smectite-to-illite transformation.Additionally,the dominant orientations of tectonic fractures intersect the present-day maximum horizontal principal stress at a small angle,resulting in large apertures and good effectiveness.Bedding-parallel fractures contribute to enhance porosity and provide favorable pathways for lateral hydrocarbon migration.Collectively,this study could provide valuable insights for finding promising exploration areas in lacustrine shale oil reservoirs in the Ordos Basin and worldwide.
文摘Bees play a crucial role in the global food chain,pollinating over 75% of food and producing valuable products such as bee pollen,propolis,and royal jelly.However,theAsian hornet poses a serious threat to bee populations by preying on them and disrupting agricultural ecosystems.To address this issue,this study developed a modified YOLOv7tiny(You Only Look Once)model for efficient hornet detection.The model incorporated space-to-depth(SPD)and squeeze-and-excitation(SE)attention mechanisms and involved detailed annotation of the hornet’s head and full body,significantly enhancing the detection of small objects.The Taguchi method was also used to optimize the training parameters,resulting in optimal performance.Data for this study were collected from the Roboflow platformusing a 640×640 resolution dataset.The YOLOv7tinymodel was trained on this dataset.After optimizing the training parameters using the Taguchi method,significant improvements were observed in accuracy,precision,recall,F1 score,andmean average precision(mAP)for hornet detection.Without the hornet head label,incorporating the SPD attentionmechanism resulted in a peakmAP of 98.7%,representing an 8.58%increase over the original YOLOv7tiny.By including the hornet head label and applying the SPD attention mechanism and Soft-CIOU loss function,themAP was further enhanced to 97.3%,a 7.04% increase over the original YOLOv7tiny.Furthermore,the Soft-CIOU Loss function contributed to additional performance enhancements during the validation phase.
基金National Natural Science Foundation of China(Nos.21921003 and 22201293)the National Key R&D Program of China(No.2023YFC3503400)for financial support。
文摘The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of molecular vips.However,its moderate water solubility limits broader application.Here we report the synthesis of three CB[7]derivatives M1-M3 by modifying an average of 4.2,5.5,and 5.9 sulfonatopropoxy groups onto their"equator"carbons.Compared to CB[7],their water-solubility increased by at least 26.6-,23.6-,and 19.2-fold,respectively,while the maximum tolerated doses(MTD)of M1 and M2 improved by 2.5-and 2.3-fold.Phase solubility diagram studies demonstrate that M1 and M2 significantly enhance the water-solubility of eighteen poorly soluble drugs.In vivo experiments in rat complete Freund's arthritis reveal that M1 not only improves the anti-inflammatory efficacy of indomethacin by up to 52%,but also substantially reduces its side effect of gastric ulcer.
基金supported by grants from the Natural Science Foundation of Hunan Province(2022JJ70037 and 2022JJ40402)the National Natural Science Foundation of China(82472220 and 82002074)+1 种基金the Natural Science Foundation of Guangdong Province(2023A1515010267,2023A1515012665 and 2024A1515010073)the China International Medical Foundation Cerebrovascular Disease Youth Innovation Fund(Z-2016-20-2201).
文摘BACKGROUND:While theα7 nicotinic acetylcholine receptor(α7 nAChR)is implicated in sepsis-associated encephalopathy(SAE),its pathophysiological contributions require further investigation.METHODS:SAE was induced in mice via cecal ligation and puncture(CLP),and microglia were treated with lipopolysaccharide(LPS).PHA-543613(anα7 nAChR agonist)was used to activateα7 nAChR.To study the role ofα7 nAChR in mitophagy and pyroptosis,caspase-1-deficient mice and PTEN-induced kinase 1(PINK1)small interfering RNA(siRNA)were used.Cognitive function,cerebral oxygen extraction ratio(CERO2),and brain tissue oxygen pressure(PbtO2)were measured.Blood-brain barrier(BBB)integrity was evaluated via Evan’s blue staining.Mitophagy,pyroptosis,and cytokine levels were analyzed via Western blotting and immunofl uorescence.RESULTS:CLP or LPS treatment signifi cantly down-regulatedα7 nAChR protein expression in microglia.The administration of PHA-543613 to activateα7 nAChR not only restored its expression post-sepsis,but also notably decreased BBB permeability and mitigated cognitive deficits.Bothα7 nAChR activation and caspase-1 knockout effectively suppressed microglial pyroptosis.The activation ofα7 nAChR also promoted mitophagy in microglia.This led to an amelioration of brain tissue hypoxia,as shown by elevated PbtO2 and reduced CERO2 levels.The suppression of microglial pyroptosis byα7 nAChR was counteracted when mitophagy was inhibited through the siRNA-mediated silencing of PINK1.CONCLUSION:The activation ofα7 nAChR reduces pyroptosis by enhancing microglial mitophagy,thereby mitigating SAE.
基金support by the Fundamental Research Funds for the Central Universities(YG2024QNB16)the National Natural Science Foundation of China(82270953 and 82201115)+3 种基金Shanghai Rising-Star Program(21QA1405400)the Natural Science Foundation of Shanghai(22ZR1436400)the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZLCX20212400)the Opening Research fund from Shanghai Key Laboratory of Stomatology,Shanghai Ninth People’s Hospital,College of Stomatology,Shanghai Jiao Tong University School of Medicine(2022SKLS-KFKT008).
文摘Given its excellent biological properties and the matching of its elastic modulus with that of human bone tissue,medical polyetheretherketone(PEEK)is considered a desirable candidate for bone-implant materials.However,its poor osseointegrative and antibacterial properties greatly limit its clinical application.To address these concerns,a functional PEEK implant is needed.Herein,a novel photo-responsive multifunctional PEEK-based implant material(sPEEK/BP/E7)with both effective osteogenesis and good disinfection properties was constructed via the self-assembly of black phosphorus(BP)nanosheets,mussel-inspired polydopamine(PDA),and bioactive short peptide E7 on sulfonated PEEK(sPEEK).The versatile micro-/nano-structured PEEK surface provides superior hydrophilicity,a favorable osteogenic microenvironment,and excellent photothermal effects under near-infrared(NIR)irradiation.The in vitro results showed that sPEEK/BP/E7 displays enhanced cytocompatibility and osteogenicity in terms of cell adhesion,proliferation,alkaline phosphatase(ALP)activity,matrix mineralization,and osteogenesis-related gene expression,superior to those of the sPEEK and sPEEK/BP samples.In addition to osteogenesis,the multifunctional coating exhibited strong antibacterial activity against both Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli).Furthermore,it was confirmed in a rat femoral infection model that sPEEK/BP/E7 effectively resisted infection caused by S.aureus under NIR light irradiation and promoted osseointegration in vivo.Thus,this work presents a facile strategy to realize improvement of the“functional integration”of new polymer bone–implant materials and provide new ideas for their clinical application.
基金supported by the National Key Research And Development Program of China(2022YFD1300204)。
文摘Hair follicle stem cell(HFSC),capable of self-renewal and differentiation in hair follicle,represents an emerging stem cell model for regenerative medicine.The interaction between HFSC and dermal papilla cell(DPC)governs hair follicle development.FGF7 functions as a paracrine protein regulating epithelial proliferation,differentiation and migration.The single-cell transcriptome profling and immunofuorescence analysis demonstrated that FGF7 localizes at DPC,while FGF7 receptor(FGFR2)expresses in both DPC and HFSC.Through co-culture experiments of HFSC and DPC,the results indicated that FGF7 secreted from DPC promotes the proliferation of DPC and HFSC via Wnt signaling pathway and induces HFSC differentiation.Furthermore,CUT&Tag assay revealed genomic colocalization between FGF7 and pluripotency-related genes and GSK3β.Electrophoretic mobility shift assay(EMSA)demonstrated that FGF7 interacts with the promoter region of CISH and PRKX.This research provides valuable insights into the molecular mechanisms underlying the hair cycle.Understanding the interaction between HFSC and DPC,as well as the role of FGF7,may advance regenerative medicine and hair loss treatment.
基金Supported by Natural Science Foundation Project of Yunnan Province,No.202302AA310025 and No.202449CE340016Health Research Project of Yunnan Province,No.300068.
文摘BACKGROUND Hepatic ischaemia-reperfusion injury(HIRI)is an unavoidable process in liver transplantation,where apoptosis plays a critical role.Human umbilical cord mesenchymal stem cell-derived exosomes(hucMSC-exos),which constitute a cellfree therapeutic approach,have garnered extensive attention in alleviating HIRI.However,the potential of hucMSC-exos in mitigating apoptosis and their underlying mechanisms remain largely unknown.AIM To investigate the effects of hucMSC-exos on apoptosis after HIRI and explore the underlying mechanisms.METHODS The therapeutic effects of hucMSC-exos on HIRI and hypoxia/reoxygenation injury in L02 cells were investigated.RNA sequencing was used to detect differentially expressed genes in L02 cells after hucMSC-exo treatment,and the expression of apoptosis markers in L02 cells was analyzed.MicroRNA(miRNA)sequencing was performed to analyse the miRNA expression profiles of hucMSCexos and L02 cells after hucMSC-exo treatment.Through a miRNA-mRNA integrated analysis,candidate miRNAs and their regulated target genes were identified.We subsequently studied the roles of these candidate miRNAs in mouse HIRI and L02 cell hypoxia/reoxygenation injury.RESULTSFluorescence confocal microscopy revealed that hucMSC-exos effectively homed to the liver and were taken up byhepatocytes, likely due to the presence of anti-very late antigen-4 and anti-lymphocyte function-associated antigen-1 on the surface of hucMSC-exos. HucMSC-exos alleviate hepatocyte damage by inhibiting apoptosis. Specifically,let-7i-5p within hucMSC-exos inhibited the expression of the factor-related apoptosis ligand protein in L02 cells,leading to the upregulation of B-cell lymphoma-2 and the downregulation of B-cell lymphoma-2-associated Xprotein and cysteinyl aspartate specific proteinase-3, thereby inhibiting L02 cell apoptosis and enhancing cellproliferation activity. The overexpression of let-7i-5p effectively enhanced the antiapoptotic effects of hucMSC-exosboth in vitro and in vivo.CONCLUSIONOur findings indicate that hucMSC-exos alleviate HIRI by inhibiting apoptosis. We demonstrated that hucMSCexostarget apoptosis in L02 cells and mediate the let-7i-5p/factor-related apoptosis ligand pathway, therebyameliorating HIRI. This study provides new insights into the role of hucMSC-exos in hepatocyte apoptosis andhighlights the potential of hucMSC-exos as a therapeutic strategy for HIRI.
基金Project supported by the Key Research Project of Colleges and Universities of Henan Province(Grant No.23A140017)the Research Project of Department of Science and Technology of Henan Province(Grant No.242102231072)+1 种基金the National Natural Sciences Foundation of China(Grant No.52402336)the special fund of the Ningbo Institute of Materials Technology and Engineering,Chinese Academy of Sciences“New magnetic materials and structural devices for 5G communication”(Grant No.E41602QB01).
文摘CaBaCo_(4)O_(7)has been widely studied because of its distinctive structure and magnetic properties.This study examined the influence of different cooling atmospheres on the structure,magnetic properties,and dielectric behavior of CaBaCo_(4)O_(7).Samples were cooled under different atmospheric conditions to assess these influences.Our findings indicate that reduced oxygen content leads to increased lattice distortion.Since oxygen atoms play a crucial role in mediating magnetic exchange,oxygen deficiency disrupts long-range magnetic order and promotes short-range antiferromagnetic interactions.Additionally,the cooling atmosphere significantly impacts grain size,thereby affecting the dielectric constant and dielectric loss.In the argon-cooled CaBaCo_(4)O_(7)(Ar)sample,oxygen deficiency reduced dielectric permittivity and increased dielectric loss.
基金Supported by the Tianjin Key Laboratory of Marine Resources and Chemistry(Tianjin University of Science&Technology),Tianjin,China(No.202302)the National Natural Science Foundation of China(No.32460154)the China Postdoctoral Science Foundation(No.2023MD734227)。
文摘5-hydroxytryptamine(5-HT)is a biological monoamine neurotransmitter in the central nervous system and gonads of crustaceans to induce gonadal maturation.To better understand the effects of 5-HT and its receptors on reproductive development in Artemia,a 5-HT type 7 receptor gene(5-HT_(7Ar))was identified in parthenogenetic Artemia and characterized.Sequence analysis revealed that the open reading frame of 5-HT_(7Ar) encodes a 414-aa protein.5-HT_(7Ar) showed higher expression in both brain and ovary at early embryo stage,5-HT_(7Ar) could be detected during ovarian development and the highest expression was observed at early embryo stage.Silencing of the 5-HT_(7Ar) in Artemia at early embryo stage decreased significantly the expression level of 5-HT_(7Ar) gene and protein at late oocyte,early embryo,and late embryo stage.Moreover,silencing of the 5-HT_(7Ar) resulted in a decreased fecundity,which corresponds to abnormal oocytes during the embryo development.Artemia tended to produce nauplii after the silencing of 5-HT_(7Ar),indicating that 5-HT_(7Ar) may also involve in the determination of its reproduction mode.The findings of this study provide an insight into the regulation of reproductive development in Artemia and the function of 5-HT_(7Ar).
基金financially supported by National Natural Science Foundation of China(Nos.22371086,22071074,21772055)the National Key Research and Development Program(No.2021YFA0716702)+3 种基金the 111 Project(No.B17019)the China Postdoctoral Science Foundation(No.2020 M672388)Self-determined research funds of CCNU from the colleges’basic research and operation of MOE,National Natural Science Foundation of China(No.22006055)the State Key Laboratory of Environmental Chemistry and Ecotoxicology,RCEES,CAS(No.KF2017-4)。
文摘Selective separation of amino acids and proteins is crucial in various areas of research,including proteomics,protein structure and function studies,protein purification and drug development,and biosensing and biodetection.A nanocomposite film is formed by combining layer-by-layer self-assembled gold nanospheres(Au NPs)driven by cucurbit[7]uril(CB[7])and polymethyl methacrylate(PMMA)film.Due to the host-vip interactions,the selective transmission of l-tryptophan in the nanocomposite film is confirmed by the current-voltage measurements using a picoammeter.Furthermore,by adjusting the particle size of Au NPs to increase channel size,lysozyme containing multiple tryptophan residues can selectively pass through the nanocomposite film,indicating the high versatility and adaptability of the nanocomposite film.This study will provide a new direction for the selective separation of amino acids and proteins.
文摘BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche drive the continuous self-renewal of intestinal epithelium,preserving its barrier functions.Paneth cells secrete antimicrobial peptide and signaling molecules within the intestine crypt,thereby playing a crucial role in intestinal immune defense and providing ISCs functional support.However,the regulatory function of Paneth cells under pathological conditions,such as RV infection,remains unclear.AIM To determine the impact of RV infection on Paneth cells and how Paneth cells regulate ISCs during intestinal injury repair.METHODS We constructed a reference genome for the RV enteric cytopathogenic human orphan virus strain and reanalyzed published single-cell RNA sequencing data to investigate Paneth cell responses to RV-induced intestinal injury.We derived Paneth-ISC communication networks using CellChat,tracked ISC differentiation with pseudotime analysis,and validated our findings in leucine-rich repeat-containing G protein-coupled receptor 5-enhanced green fluorescent protein-internal ribosomal entry site-Cre recombinase estrogen receptor variant 2 mice and organoids via immunofluorescence,flow cytometry,and reverse transcription quantitative polymerase chain reaction.RESULTS We found that RV directly infects Paneth cells,leading to a reduction in mature Paneth cells and an increase in kallikrein 1-high immature Paneth cells.Paneth-ISC communication was significantly enhanced.In particular,the bone morphogenic protein 7(BMP7)-activin A receptor type 2B/BMP receptor type 1A-Smad pathway was upregulated post-infection,suggesting that Paneth cells suppress excessive ISC proliferation.Functional validation confirmed activation of this pathway.CONCLUSION Paneth cells regulate ISC proliferation during RV infection by activating BMP7 signaling,limiting excessive stem cell expansion and preserving crypt homeostasis for effective epithelial repair.
