Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,wi...Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
With the growth of global protein demand and the development of plant-based foods,pea protein,as a low-allergenic,nutritionally balanced and environmentally friendly plant protein,has shown great potential in replacin...With the growth of global protein demand and the development of plant-based foods,pea protein,as a low-allergenic,nutritionally balanced and environmentally friendly plant protein,has shown great potential in replacing animal protein.Pea protein is mainly composed of globulin and albumin,with a protein content of 20%to 30%,and has a balanced amino acid composition,as well as being rich in minerals and dietary fiber.It also possesses good foaming,gelling,emulsifying and antioxidant functional properties.However,pea protein also has inherent defects that limit its application in the food industry.This article systematically reviews the extraction techniques,functional properties,modification methods and application fields of pea protein,and focuses on evaluating the effects of different extraction and modification strategies on protein yield and functional properties.Research shows that ultrasonic-assisted alkaline extraction can reduce solvent usage by 55%,shorten extraction time by 50%,and increase extraction rate by 12.51%;under optimized conditions,ultrafiltration membrane technology can achieve a protein purity of 91%.In terms of modification,ultrasonic treatment increases foaming capacity by 37.4%,and phenolic cross-linking increases gel strength from 3.0 kPa to 48 kPa.This article provides data support and theoretical reference for the efficient extraction and functional optimization of pea protein,and has promoting significance for its wide application in plant-based foods.展开更多
The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR...The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.展开更多
α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively dete...α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.展开更多
Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Directional three-dimensional carbon-based foams are emerging as highly attractive candidates for promising electromagnetic wave absorbing materials(EWAMs)thanks to their unique architecture,but their construction usu...Directional three-dimensional carbon-based foams are emerging as highly attractive candidates for promising electromagnetic wave absorbing materials(EWAMs)thanks to their unique architecture,but their construction usually involves complex procedures and extremely depends on unidirectional freezing technique.Herein,we propose a groundbreaking approach that leverages the assemblies of salting-out protein induced by ammonium metatungstate(AM)as the precursor,and then acquire directional three-dimensional carbon-based foams through simple pyrolysis.The electrostatic interaction between AM and protein ensures well dispersion of WC_(1−x)nanoparticles on carbon frameworks.The content of WC_(1−x)nanoparticles can be rationally regulated by AM dosage,and it also affects the electromagnetic(EM)properties of final carbon-based foams.The optimized foam exhibits exceptional EM absorption performance,achieving a remarkable minimum reflection loss of−72.0 dB and an effective absorption bandwidth of 6.3 GHz when EM wave propagates parallel to the directional pores.Such performance benefits from the synergistic effects of macroporous architecture and compositional design.Although there is a directional dependence of EM absorption,radar stealth simulation demonstrates that these foams can still promise considerable reduction in radar cross section with the change of incident angle.Moreover,COMSOL simulation further identifies their good performance in preventing EM interference among different electronic components.展开更多
BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth fac...BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.展开更多
The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell d...The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.展开更多
Chronic low-grade inflammation is a major contributor to both the onset and advancement of type 2 diabetes mellitus(T2DM),and its associated microvascular complications,including diabetic nephropathy,retinopathy,and p...Chronic low-grade inflammation is a major contributor to both the onset and advancement of type 2 diabetes mellitus(T2DM),and its associated microvascular complications,including diabetic nephropathy,retinopathy,and peripheral neuropathy.This review aims to overview the roles of high sensitivity C-reactive protein(hs-CRP),C-reactive protein(CRP),CRP-to-lymphocyte count ratio(CLR),and the CRP-to-albumin ratio(CAR)as biomarkers for assessing systemic inflammation and predicting the development and severity of diabetic chronic microvascular complications.Elevated levels of CRP and hs-CRP have been consistently associated with increased risk of these complications,reflecting ongoing inflammatory processes that contribute to endothelial dysfunction and tissue damage.Furthermore,CAR and CLR,which combine CRP with albumin and lymphocyte counts respectively,offer a more nuanced understanding of the inflammatory and immune response in T2DM patients.While individual studies have demonstrated the clinical relevance of these biomarkers in predicting disease onset and progression,further investigation is needed to establish their utility in clinical practice.This review highlights the potential of these biomarkers for enhancing early detection,risk stratification,and personalized management of diabetic patients,ultimately aiming to improve outcomes and reduce the burden of diabetic chronic microvascular complications.展开更多
Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes pathology.This condition could be protected by the upregulation of t...Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes pathology.This condition could be protected by the upregulation of the gene encoding polycytosine RNA-binding protein 1(PCBP1).Additionally,Ma et al used a lentivirus infection system to express PCBP1.As the authors’method of administration can be improved in terms of stability and cost,we propose delivering PCBP1 to treat type 2 diabetic osteoporosis by encapsulating it in protein nanoparticles.First,PCBP1 is small and druggable.Second,intravenous injection can help deliver PCBP1 across the mucosa while avoiding acid and enzyme-catalyzed degradation.Furthermore,incorporating PCBP1 into nanoparticles prevents its interaction with water or oxygen and protects PCBP1’s structure and activity.Notably,the safety of the protein materials and the industrialization techniques for large-scale production of protein nanoparticles must be comprehensively investigated before clinical application.展开更多
Trail, a tumor necrosis factor-related apoptosis-inducing ligand, is a novel potent endogenous activator of the cell death pathway through the activation of cell surface death receptors Trail-R1 and Trail-R2. Its role...Trail, a tumor necrosis factor-related apoptosis-inducing ligand, is a novel potent endogenous activator of the cell death pathway through the activation of cell surface death receptors Trail-R1 and Trail-R2. Its role, like FasL in activation-induced cell death (AICD), has been demonstrated in immune system. However the mechanism of Trail induced apoptosis remains unclear. In this report, the recombinant Trail protein was expressed and purified. The apoptosis-inducing activity and the regulation mechanism of recombinant Trail on Jurkat T cells were explored in vitro. Trypan blue exclusion assay demonstrated that the recombinant Trail protein actively killed Jurkat T cells in a dose-dependent manner. Trail-induced apoptosis in Jurkat T cells were remarkably reduced by Bcl-2 over expression in Bcl-2 gene transfected cells. Treatment with PMA (phorbol 12-myristate 13-acetate), a PKC activator, suppressed Trail-induced apoptosis in Jurkat T cells. The inhibition of apoptosis by PMA was abolished by pretreatment with Bis, a PKC inhibitor. Taken together, it was suggested that Bcl-2 over-expression and PMA activated PKC actively down-regulated the Trail-mediated apoptosis in Jurkat T cell.展开更多
The events of cell death and the expression of nuclear matrix protein (NMP) have been investigated in a promyelocytic leukemic cell line HL-60 induced with etoposide. By means of TUNEL assay, the nuclei displayed a ch...The events of cell death and the expression of nuclear matrix protein (NMP) have been investigated in a promyelocytic leukemic cell line HL-60 induced with etoposide. By means of TUNEL assay, the nuclei displayed a characteristic morphology change, and the amount of apoptotic cells increased early and reached maximun about 39% after treatment with etoposide for 2 h. Nucleosomal DNA fragmentation was observed after treatment for 4 h. The morphological change of HL-60 cells, thus, occurred earlier than the appearance of DNA ladder. Total nuclear matrix proteins were analyzed by 2-dimensional gel electrophoresis. Differential expression of 59 nuclear matrix proteins was found in 4 h etoposide treated cells. Western blotting was then performed on three nuclear matrix acssociated proteins, PML, HSC70 and NuMA. The expression of the suppressor PML protein and heat shock protein HSC70 were significantly upregulated after etoposide treatment, while NuMA, a nuclear mitotic apparatus protein, was down regulated. These results demonstrate that significant biochemical alterations in nuclear matrix proteins take place during the apoptotic process.展开更多
Maize(Zea mays),which is a vital source of food,feed,and energy feedstock globally,has significant potential for higher yields.However,environmental stress conditions,including drought and salt stress,severely restric...Maize(Zea mays),which is a vital source of food,feed,and energy feedstock globally,has significant potential for higher yields.However,environmental stress conditions,including drought and salt stress,severely restrict maize plant growth and development,leading to great yield losses.Leucine-rich repeat receptor-like kinases(LRR-RLKs)function in biotic and abiotic stress responses in the model plant Arabidopsis(Arabidopsis thaliana),but their roles in abiotic stress responses in maize are not entirely understood.In this study,we determine that the LRR-RLK ZmMIK2,a homolog of the Arabidopsis LRR-RK MALE DISCOVERER 1(MDIS1)-INTERACTING RECEPTOR LIKE KINASE 2(MIK2),functions in resistance to both drought and salt stress in maize.Zmmik2 plants exhibit enhanced resistance to both stresses,whereas overexpressing ZmMIK2 confers the opposite phenotypes.Furthermore,we identify C2-DOMAIN-CONTAINING PROTEIN 1(ZmC2DP1),which interacts with the intracellular region of ZmMIK2.Notably,that region of ZmMIK2 mediates the phosphorylation of ZmC2DP1,likely by increasing its stability.Both ZmMIK2 and ZmC2DP1 are mainly expressed in roots.As with ZmMIK2,knockout of ZmC2DP1 enhances resistance to both drought and salt stress.We conclude that ZmMIK2-ZmC2DP1 acts as a negative regulatory module in maize drought-and salt-stress responses.展开更多
Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein ...Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.展开更多
Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understan...Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.展开更多
The awn can contribute to photosynthesis and carbohydrates,enhancing grain yield in wheat.We mapped QAwn.sxau-5A,a major QTL for awn development in wheat(Triticum aestivum).This QTL was delimited to a 994-kb interval ...The awn can contribute to photosynthesis and carbohydrates,enhancing grain yield in wheat.We mapped QAwn.sxau-5A,a major QTL for awn development in wheat(Triticum aestivum).This QTL was delimited to a 994-kb interval at the B1 locus on chromosome 5A,which included the candidate gene encoding a zinc finger protein(TraesCS5A01G542800)as an awn length inhibitor(ALI).The Ali-A1 allele for the awnless trait showed abundant sequence differences in the promoter regions compared to the ali-A1 allele for the long-awn trait.The results of the swap experiment on the promoters from the two ALI-A1 alleles showed that the two promoters caused a difference in the protein level,indicating the gene was regulated at the transcript level.However,the ali-A1 allele contained an SNP that caused a premature stop codon in its coding region,resulting in a truncated protein compared to the functional Ali-A1 protein.The Ali-A1 protein contained two ethylene-responsive element binding factor-associated amphiphilic repression(EAR)motifs,one at the N terminus(EAR-N)and the other at the C terminus(EAR-C),and they were involved in interactions with the wheat co-repressor protein TOPLESS(TPL1).The ali-A1 protein retained the EAR-N motif but lost the EAR-C motif,resulting in the attenuated ability to interact with TPL1.The tpl1 mutant produced a longer awn compared to the wild type.Ali-A1 repressed the transcription of two downstream genes,TaLRP-A1 and TaARF-B1,involved in endogenous auxin concentrations and auxin responses in wheat.We concluded that the awn length is regulated not only by the ALI-A1 gene at transcript levels but also by Ali-A1 and TPL1 at the protein level in wheat.展开更多
BACKGROUND Neonatal sepsis is a serious health problem,with high morbidity and mortality during the first 28 days of life.Clinical diagnosis at presentation is challenging due to the nonspecific signs and symptoms.Alt...BACKGROUND Neonatal sepsis is a serious health problem,with high morbidity and mortality during the first 28 days of life.Clinical diagnosis at presentation is challenging due to the nonspecific signs and symptoms.Although blood culture is the gold standard for diagnosis,it is not always positive.AIM To evaluate the diagnostic and prognostic utility of D-dimer and heparin-binding protein(HBP)in neonatal sepsis.METHODS This prospective case-control study included 90 neonates in two groups:A sepsis group(n=45)and a control group(n=45)without sepsis.Sepsis group was further subdivided based on blood culture results into proven sepsis(n=28 culturepositive sepsis)and suspected sepsis(n=17 culture-negative sepsis).All neonates underwent complete history taking,thorough clinical examination and investigations[complete blood count,C-reactive protein(CRP),liver and kidney function tests,plasma D-dimer and HBP].RESULTS Levels of CRP,D-dimer and HBP were significantly higher in the sepsis group compared to the controls.At a cutoff value above 517.9 ng/mL,D-dimer outperformed CRP and HBP in distinguishing sepsis group from controls with 95.6%sensitivity and 97.8%specificity.D-dimer was also a better prognostic marker than the neonatal sequential organ failure assessment(nSOFA)for predicting mortality,with 100%sensitivity and 92.5%specificity vs 80%sensitivity and 82.5%specificity.There was a significant positive correlation between CRP,D-dimer and HBP.CONCLUSION D-dimer demonstrated superior diagnostic accuracy compared to CRP and HBP in predicting sepsis,and demonstrated superior prognostic accuracy compared to nSOFA in predicting the outcome of neonatal sepsis.展开更多
BACKGROUND: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often dif...BACKGROUND: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often difficult to distinguish. Myxovirus resistance protein A(MxA), an essential antiviral factor induced by interferon after viral infection, holds promise for distinguishing between viral and bacterial infections. This study aimed to determine the ability of Mx A to distinguish viral from bacterial infections.METHODS: We quantified MxA in 121 infected patients via dry immunofluorescence chromatography. The Kruskal-Wallis test and receiver operating characteristic(ROC) curve analysis were used to determine the diagnostic value of Mx A, either alone or in combination with C-reactive protein(CRP) or procalcitonin(PCT), in patients with viral, bacterial, or co-infections.RESULTS: The value of MxA(ng/mL) was significantly higher in patients with viral infections than in those with bacterial and co-infections(82.3 [24.5–182.9] vs. 16.4 [10.8–26.5], P<0.0001)(82.3 [24.5–182.9] vs. 28.5 [10.2–106.8], P=0.0237). The area under the curve(AUC) of the ROC curve for distinguishing between viral and bacterial infections was 0.799(95% confidence interval [95% CI] 0.696–0.903), with a sensitivity of 68.9%(95% CI 54.3%–80.5%) and specificity of 90.0%(95% CI 74.4%–96.5%) at the threshold of 50.3 ng/mL. Combining the MxA level with the CRP or PCT level improved its ability. MxA expression was low in cytomegalovirus(15.8 [9.6–47.6] ng/mL) and Epstein-Barr virus(12.9 [8.5–21.0] ng/mL) infections.CONCLUSION: Our study showed the diagnostic efficacy of Mx A in distinguishing between viral and bacterial infections, with further enhancement when it was combined with CRP or PCT. Moreover, EpsteinBarr virus and human cytomegalovirus infections did not elicit elevated Mx A expression.展开更多
OBJECTIVE:To clarify the effect of Hamayou(Oviductus Ranae) protein hydrolysate(ORPH) on depression and its exact underlying mechanism from a new perspective. METHODS:We used the Chronic Unpredictable Mild Stress(CUMS...OBJECTIVE:To clarify the effect of Hamayou(Oviductus Ranae) protein hydrolysate(ORPH) on depression and its exact underlying mechanism from a new perspective. METHODS:We used the Chronic Unpredictable Mild Stress(CUMS) method to prepare a mouse model of depression and lipopolysaccharide(LPS) to prepare a model of BV2 cellular inflammation to investigate the antidepressant effect and mechanism of action of ORPH. Behavioral changes in mice and cerebral blood flow were detected by behavioral experiments and scatter imaging. Levels of corticosterone(CORT), proinflammatory cytokines and neurotransmitter were detected by enzyme-linked immunosorbent assay. Furthermore, hematoxylin-eosin staining, Tunel staining were used to evaluate the effect of ORPH. The distribution and expression of ionized calcium bindingadaptor molecule-1(Iba-1) in mouse hippocampal tissue and BV2 cells were detected by immunofluorescence. Mitogen-activated protein kinase(MAPK) pathway related protein expression was detected by Western blot. RESULTS:ORPH improved depression-like behavior, ameliorated brain tissue damage and apoptosis, and inhibited microglia activation in brain tissue in mice. In addition, ORPH reduced expression of B-cell lymphoma-2(Bcl-2)-associated X(Bax), cysteinyl aspartate specific proteinase 3(Caspase3), cysteinyl aspartate specific proteinase 9(Caspase9), nuclear factor-kappa B(NF-κB), phosphorylation-p38(p-p38), phosphorylation-Jun Nterminal kinase(p-JNK) proteins, and increased expression of Bcl-2, inhibitory kappa B alpha(IκB-α), phosphorylation-extracellular regulated protein kinases 1/2(p-ERK1/2) proteins. On the other hand, there were fewer Iba-1-positive cells, lower expression of NF-κB, pp38, p-JNK and p-ERK1/2 proteins, and higher expression of IκB-α proteins in BV2 cells in the ORPH group. In addition, ORPH increased 5-hydroxytryptamine, norepinephrine levels and decreased CORT, interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) levels. CONCLUSION:ORPH was able to improve depressionlike behaviors and that it took effects by promoting cerebral blood flow, inhibition of hypothalamic-pituitaryadrenal axis overactivation, improving the structural damage of hippocampal tissues, and inhibiting the inflammatory response. ORPH can reduced neuronal damage and inhibiting apoptosis by promoting the MAPK pathway.展开更多
基金financially supported by the Hainan Province Science and Technology Special Fund(Grant no:ZDYF2024XDNY187).
文摘Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
文摘With the growth of global protein demand and the development of plant-based foods,pea protein,as a low-allergenic,nutritionally balanced and environmentally friendly plant protein,has shown great potential in replacing animal protein.Pea protein is mainly composed of globulin and albumin,with a protein content of 20%to 30%,and has a balanced amino acid composition,as well as being rich in minerals and dietary fiber.It also possesses good foaming,gelling,emulsifying and antioxidant functional properties.However,pea protein also has inherent defects that limit its application in the food industry.This article systematically reviews the extraction techniques,functional properties,modification methods and application fields of pea protein,and focuses on evaluating the effects of different extraction and modification strategies on protein yield and functional properties.Research shows that ultrasonic-assisted alkaline extraction can reduce solvent usage by 55%,shorten extraction time by 50%,and increase extraction rate by 12.51%;under optimized conditions,ultrafiltration membrane technology can achieve a protein purity of 91%.In terms of modification,ultrasonic treatment increases foaming capacity by 37.4%,and phenolic cross-linking increases gel strength from 3.0 kPa to 48 kPa.This article provides data support and theoretical reference for the efficient extraction and functional optimization of pea protein,and has promoting significance for its wide application in plant-based foods.
基金the National Natural Science Foundation of China(82573571)the Shanghai 2025 Basic Research Plan Natural Science Foundation(25ZR1401393)the First Batch of Open Topics of the Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices(2025QN13)。
文摘The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.
基金supported by the Natural Science Foundation of Guangxi Zhuang Automomous Region,Nos.2019GXNSFDA245015(to MC),2022GXNSFBA035654(to HL)the National Natural Science Foundation of China,Nos.82360241(to MC),82304876(to HL)+1 种基金Scientific Research and Technology Development Project of Guilin City,Nos.20220139-3(to MC),20210218-5(to HL)Guangxi Medical and Health Key Discipline Construction Project(to QL)。
文摘α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
基金financially supported by the National Natural Science Foundation of China(Nos.22475057 and No.52373262).
文摘Directional three-dimensional carbon-based foams are emerging as highly attractive candidates for promising electromagnetic wave absorbing materials(EWAMs)thanks to their unique architecture,but their construction usually involves complex procedures and extremely depends on unidirectional freezing technique.Herein,we propose a groundbreaking approach that leverages the assemblies of salting-out protein induced by ammonium metatungstate(AM)as the precursor,and then acquire directional three-dimensional carbon-based foams through simple pyrolysis.The electrostatic interaction between AM and protein ensures well dispersion of WC_(1−x)nanoparticles on carbon frameworks.The content of WC_(1−x)nanoparticles can be rationally regulated by AM dosage,and it also affects the electromagnetic(EM)properties of final carbon-based foams.The optimized foam exhibits exceptional EM absorption performance,achieving a remarkable minimum reflection loss of−72.0 dB and an effective absorption bandwidth of 6.3 GHz when EM wave propagates parallel to the directional pores.Such performance benefits from the synergistic effects of macroporous architecture and compositional design.Although there is a directional dependence of EM absorption,radar stealth simulation demonstrates that these foams can still promise considerable reduction in radar cross section with the change of incident angle.Moreover,COMSOL simulation further identifies their good performance in preventing EM interference among different electronic components.
文摘BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.
基金supported by the National Institutes of Health(Grants P30 CA036727 and R01 CA258621)and funding from the University of Nebraska Medical Center Graduate Studies Assistantship.
文摘The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.
文摘Chronic low-grade inflammation is a major contributor to both the onset and advancement of type 2 diabetes mellitus(T2DM),and its associated microvascular complications,including diabetic nephropathy,retinopathy,and peripheral neuropathy.This review aims to overview the roles of high sensitivity C-reactive protein(hs-CRP),C-reactive protein(CRP),CRP-to-lymphocyte count ratio(CLR),and the CRP-to-albumin ratio(CAR)as biomarkers for assessing systemic inflammation and predicting the development and severity of diabetic chronic microvascular complications.Elevated levels of CRP and hs-CRP have been consistently associated with increased risk of these complications,reflecting ongoing inflammatory processes that contribute to endothelial dysfunction and tissue damage.Furthermore,CAR and CLR,which combine CRP with albumin and lymphocyte counts respectively,offer a more nuanced understanding of the inflammatory and immune response in T2DM patients.While individual studies have demonstrated the clinical relevance of these biomarkers in predicting disease onset and progression,further investigation is needed to establish their utility in clinical practice.This review highlights the potential of these biomarkers for enhancing early detection,risk stratification,and personalized management of diabetic patients,ultimately aiming to improve outcomes and reduce the burden of diabetic chronic microvascular complications.
文摘Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes pathology.This condition could be protected by the upregulation of the gene encoding polycytosine RNA-binding protein 1(PCBP1).Additionally,Ma et al used a lentivirus infection system to express PCBP1.As the authors’method of administration can be improved in terms of stability and cost,we propose delivering PCBP1 to treat type 2 diabetic osteoporosis by encapsulating it in protein nanoparticles.First,PCBP1 is small and druggable.Second,intravenous injection can help deliver PCBP1 across the mucosa while avoiding acid and enzyme-catalyzed degradation.Furthermore,incorporating PCBP1 into nanoparticles prevents its interaction with water or oxygen and protects PCBP1’s structure and activity.Notably,the safety of the protein materials and the industrialization techniques for large-scale production of protein nanoparticles must be comprehensively investigated before clinical application.
基金Major State BasicResearch (973) Program of China, (G1999053905).
文摘Trail, a tumor necrosis factor-related apoptosis-inducing ligand, is a novel potent endogenous activator of the cell death pathway through the activation of cell surface death receptors Trail-R1 and Trail-R2. Its role, like FasL in activation-induced cell death (AICD), has been demonstrated in immune system. However the mechanism of Trail induced apoptosis remains unclear. In this report, the recombinant Trail protein was expressed and purified. The apoptosis-inducing activity and the regulation mechanism of recombinant Trail on Jurkat T cells were explored in vitro. Trypan blue exclusion assay demonstrated that the recombinant Trail protein actively killed Jurkat T cells in a dose-dependent manner. Trail-induced apoptosis in Jurkat T cells were remarkably reduced by Bcl-2 over expression in Bcl-2 gene transfected cells. Treatment with PMA (phorbol 12-myristate 13-acetate), a PKC activator, suppressed Trail-induced apoptosis in Jurkat T cells. The inhibition of apoptosis by PMA was abolished by pretreatment with Bis, a PKC inhibitor. Taken together, it was suggested that Bcl-2 over-expression and PMA activated PKC actively down-regulated the Trail-mediated apoptosis in Jurkat T cell.
文摘The events of cell death and the expression of nuclear matrix protein (NMP) have been investigated in a promyelocytic leukemic cell line HL-60 induced with etoposide. By means of TUNEL assay, the nuclei displayed a characteristic morphology change, and the amount of apoptotic cells increased early and reached maximun about 39% after treatment with etoposide for 2 h. Nucleosomal DNA fragmentation was observed after treatment for 4 h. The morphological change of HL-60 cells, thus, occurred earlier than the appearance of DNA ladder. Total nuclear matrix proteins were analyzed by 2-dimensional gel electrophoresis. Differential expression of 59 nuclear matrix proteins was found in 4 h etoposide treated cells. Western blotting was then performed on three nuclear matrix acssociated proteins, PML, HSC70 and NuMA. The expression of the suppressor PML protein and heat shock protein HSC70 were significantly upregulated after etoposide treatment, while NuMA, a nuclear mitotic apparatus protein, was down regulated. These results demonstrate that significant biochemical alterations in nuclear matrix proteins take place during the apoptotic process.
基金supported by the National Key Research and Development Program of China(2021YFD1200703 and 2022YFF1001602)the National Science Foundation of China(32272024 and 32171940)+2 种基金the Pinduoduo-China Agricultural University Research Fund(PC2023B01001)the Chinese Universities Scientific Fund(2022TC142)the 2115 Talent Development Program of China Agricultural University。
文摘Maize(Zea mays),which is a vital source of food,feed,and energy feedstock globally,has significant potential for higher yields.However,environmental stress conditions,including drought and salt stress,severely restrict maize plant growth and development,leading to great yield losses.Leucine-rich repeat receptor-like kinases(LRR-RLKs)function in biotic and abiotic stress responses in the model plant Arabidopsis(Arabidopsis thaliana),but their roles in abiotic stress responses in maize are not entirely understood.In this study,we determine that the LRR-RLK ZmMIK2,a homolog of the Arabidopsis LRR-RK MALE DISCOVERER 1(MDIS1)-INTERACTING RECEPTOR LIKE KINASE 2(MIK2),functions in resistance to both drought and salt stress in maize.Zmmik2 plants exhibit enhanced resistance to both stresses,whereas overexpressing ZmMIK2 confers the opposite phenotypes.Furthermore,we identify C2-DOMAIN-CONTAINING PROTEIN 1(ZmC2DP1),which interacts with the intracellular region of ZmMIK2.Notably,that region of ZmMIK2 mediates the phosphorylation of ZmC2DP1,likely by increasing its stability.Both ZmMIK2 and ZmC2DP1 are mainly expressed in roots.As with ZmMIK2,knockout of ZmC2DP1 enhances resistance to both drought and salt stress.We conclude that ZmMIK2-ZmC2DP1 acts as a negative regulatory module in maize drought-and salt-stress responses.
基金supported by the National Natural Science Foundation of China,Nos.82001178(to LW),81901129(to LH),82001175(to FX)Shanghai Sailing Program,No.20YF1439200(to LW)+1 种基金the Natural Science Foundation of Shanghai,China,No.23ZR1450800(to LH)and the Fundamental Research Funds for the Central Universities,No.YG2023LC15(to ZX)。
文摘Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.
基金funded by NIH-NIA R01AG061708 (to PHO)Patrick Grange Memorial Foundation (to PHO)+1 种基金A Long Swim (to PHO)CureSPG4 Foundation (to PHO)。
文摘Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.
基金supported by the Grand Science and Technology Special Project in Shanxi Province(202201140601025-2)the National Natural Science Foundation of China(32201749)supported by the Agriculture and Food Research Initiative Competitive Grant 2022-68013-36439(WheatCAP)from the USDA National Institute of Food and Agriculture.
文摘The awn can contribute to photosynthesis and carbohydrates,enhancing grain yield in wheat.We mapped QAwn.sxau-5A,a major QTL for awn development in wheat(Triticum aestivum).This QTL was delimited to a 994-kb interval at the B1 locus on chromosome 5A,which included the candidate gene encoding a zinc finger protein(TraesCS5A01G542800)as an awn length inhibitor(ALI).The Ali-A1 allele for the awnless trait showed abundant sequence differences in the promoter regions compared to the ali-A1 allele for the long-awn trait.The results of the swap experiment on the promoters from the two ALI-A1 alleles showed that the two promoters caused a difference in the protein level,indicating the gene was regulated at the transcript level.However,the ali-A1 allele contained an SNP that caused a premature stop codon in its coding region,resulting in a truncated protein compared to the functional Ali-A1 protein.The Ali-A1 protein contained two ethylene-responsive element binding factor-associated amphiphilic repression(EAR)motifs,one at the N terminus(EAR-N)and the other at the C terminus(EAR-C),and they were involved in interactions with the wheat co-repressor protein TOPLESS(TPL1).The ali-A1 protein retained the EAR-N motif but lost the EAR-C motif,resulting in the attenuated ability to interact with TPL1.The tpl1 mutant produced a longer awn compared to the wild type.Ali-A1 repressed the transcription of two downstream genes,TaLRP-A1 and TaARF-B1,involved in endogenous auxin concentrations and auxin responses in wheat.We concluded that the awn length is regulated not only by the ALI-A1 gene at transcript levels but also by Ali-A1 and TPL1 at the protein level in wheat.
基金Supported by National Liver Institute,Menoufia University,and Damietta General Hospital,Damietta,Egypt.
文摘BACKGROUND Neonatal sepsis is a serious health problem,with high morbidity and mortality during the first 28 days of life.Clinical diagnosis at presentation is challenging due to the nonspecific signs and symptoms.Although blood culture is the gold standard for diagnosis,it is not always positive.AIM To evaluate the diagnostic and prognostic utility of D-dimer and heparin-binding protein(HBP)in neonatal sepsis.METHODS This prospective case-control study included 90 neonates in two groups:A sepsis group(n=45)and a control group(n=45)without sepsis.Sepsis group was further subdivided based on blood culture results into proven sepsis(n=28 culturepositive sepsis)and suspected sepsis(n=17 culture-negative sepsis).All neonates underwent complete history taking,thorough clinical examination and investigations[complete blood count,C-reactive protein(CRP),liver and kidney function tests,plasma D-dimer and HBP].RESULTS Levels of CRP,D-dimer and HBP were significantly higher in the sepsis group compared to the controls.At a cutoff value above 517.9 ng/mL,D-dimer outperformed CRP and HBP in distinguishing sepsis group from controls with 95.6%sensitivity and 97.8%specificity.D-dimer was also a better prognostic marker than the neonatal sequential organ failure assessment(nSOFA)for predicting mortality,with 100%sensitivity and 92.5%specificity vs 80%sensitivity and 82.5%specificity.There was a significant positive correlation between CRP,D-dimer and HBP.CONCLUSION D-dimer demonstrated superior diagnostic accuracy compared to CRP and HBP in predicting sepsis,and demonstrated superior prognostic accuracy compared to nSOFA in predicting the outcome of neonatal sepsis.
基金supported by the National Natural Science Foundation of China (82272196 and 82272220)。
文摘BACKGROUND: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often difficult to distinguish. Myxovirus resistance protein A(MxA), an essential antiviral factor induced by interferon after viral infection, holds promise for distinguishing between viral and bacterial infections. This study aimed to determine the ability of Mx A to distinguish viral from bacterial infections.METHODS: We quantified MxA in 121 infected patients via dry immunofluorescence chromatography. The Kruskal-Wallis test and receiver operating characteristic(ROC) curve analysis were used to determine the diagnostic value of Mx A, either alone or in combination with C-reactive protein(CRP) or procalcitonin(PCT), in patients with viral, bacterial, or co-infections.RESULTS: The value of MxA(ng/mL) was significantly higher in patients with viral infections than in those with bacterial and co-infections(82.3 [24.5–182.9] vs. 16.4 [10.8–26.5], P<0.0001)(82.3 [24.5–182.9] vs. 28.5 [10.2–106.8], P=0.0237). The area under the curve(AUC) of the ROC curve for distinguishing between viral and bacterial infections was 0.799(95% confidence interval [95% CI] 0.696–0.903), with a sensitivity of 68.9%(95% CI 54.3%–80.5%) and specificity of 90.0%(95% CI 74.4%–96.5%) at the threshold of 50.3 ng/mL. Combining the MxA level with the CRP or PCT level improved its ability. MxA expression was low in cytomegalovirus(15.8 [9.6–47.6] ng/mL) and Epstein-Barr virus(12.9 [8.5–21.0] ng/mL) infections.CONCLUSION: Our study showed the diagnostic efficacy of Mx A in distinguishing between viral and bacterial infections, with further enhancement when it was combined with CRP or PCT. Moreover, EpsteinBarr virus and human cytomegalovirus infections did not elicit elevated Mx A expression.
基金Science and Technology Development Project of Jilin Province:Preparation and Evaluation of an Animal Model of Liverdepression Type Depression (20220505038ZP)Exploring the Material Basis and Action Pathway of the Antipyretic Effect of Baihu Tang based on Histologic Techniques (20240602036RC)。
文摘OBJECTIVE:To clarify the effect of Hamayou(Oviductus Ranae) protein hydrolysate(ORPH) on depression and its exact underlying mechanism from a new perspective. METHODS:We used the Chronic Unpredictable Mild Stress(CUMS) method to prepare a mouse model of depression and lipopolysaccharide(LPS) to prepare a model of BV2 cellular inflammation to investigate the antidepressant effect and mechanism of action of ORPH. Behavioral changes in mice and cerebral blood flow were detected by behavioral experiments and scatter imaging. Levels of corticosterone(CORT), proinflammatory cytokines and neurotransmitter were detected by enzyme-linked immunosorbent assay. Furthermore, hematoxylin-eosin staining, Tunel staining were used to evaluate the effect of ORPH. The distribution and expression of ionized calcium bindingadaptor molecule-1(Iba-1) in mouse hippocampal tissue and BV2 cells were detected by immunofluorescence. Mitogen-activated protein kinase(MAPK) pathway related protein expression was detected by Western blot. RESULTS:ORPH improved depression-like behavior, ameliorated brain tissue damage and apoptosis, and inhibited microglia activation in brain tissue in mice. In addition, ORPH reduced expression of B-cell lymphoma-2(Bcl-2)-associated X(Bax), cysteinyl aspartate specific proteinase 3(Caspase3), cysteinyl aspartate specific proteinase 9(Caspase9), nuclear factor-kappa B(NF-κB), phosphorylation-p38(p-p38), phosphorylation-Jun Nterminal kinase(p-JNK) proteins, and increased expression of Bcl-2, inhibitory kappa B alpha(IκB-α), phosphorylation-extracellular regulated protein kinases 1/2(p-ERK1/2) proteins. On the other hand, there were fewer Iba-1-positive cells, lower expression of NF-κB, pp38, p-JNK and p-ERK1/2 proteins, and higher expression of IκB-α proteins in BV2 cells in the ORPH group. In addition, ORPH increased 5-hydroxytryptamine, norepinephrine levels and decreased CORT, interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) levels. CONCLUSION:ORPH was able to improve depressionlike behaviors and that it took effects by promoting cerebral blood flow, inhibition of hypothalamic-pituitaryadrenal axis overactivation, improving the structural damage of hippocampal tissues, and inhibiting the inflammatory response. ORPH can reduced neuronal damage and inhibiting apoptosis by promoting the MAPK pathway.
