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
Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A complet...Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.展开更多
Background: The objective of this study was to determine the effects of supplementing Cu on growth performance, Cu metabolism and Cu-related enzyme activities of weanling pigs fed diets with two different Cu sources, ...Background: The objective of this study was to determine the effects of supplementing Cu on growth performance, Cu metabolism and Cu-related enzyme activities of weanling pigs fed diets with two different Cu sources, and to estimate optimal Cu requirements and relative bioavailability from these two sources for pigs.Methods: Weanling pigs were allocated to 14 treatments arranged factorially, including 6 added Cu levels(5, 10,20, 40, 80, 160 mg/kg), and 2 mineral sources(tribasic Cu chloride, TBCC and copper proteinate, Cu Pro), as well as one negative control(0 mg/kg added Cu level) and one maximum allowed level treatment(200 mg/kg TBCC) for the entire 38-d experiment. Growth performance, mineral status and enzyme activities were measured at the end of this study.Results: Increasing levels of Cu showed linear and quadratic responses(P < 0.01) for final BW, ADG and FCR regardless of the sources. Supplementation with TBCC(> 80 mg/kg) and Cu Pro(> 20 mg/kg) significantly decreased(P < 0.05) diarrhea incidence of weanling pigs. There were linear and quadratic increases(P < 0.01) in bile, hepatic,and intestinal Cu concentrations, fecal Cu contents, and plasma enzyme activities(alkaline phosphatase,ceruloplasmin, Cu, Zn-Superoxide dismutase(Cu/Zn SOD), and glutathione peroxidase), whereas plasma malondialdehyde decreased(P < 0.01) linearly and quadratically as dietary Cu level increased. Similarly, pigs fed Cu Pro absorbed and retained more Cu and excreted less Cu than those fed TBCC when supplemented 80 mg/kg and above. Optimal dietary Cu requirements for pigs from 28 to 66 d of age estimated based on fitted broken-line models(P < 0.05) of bile Cu, plasma Cu/Zn SOD and growth performance were 93–140 mg/kg from TBCC, and 63–98 mg/kg from Cu Pro accordingly. According to slope ratios from multiple linear regression, the bioavailability value of Cu Pro relative to TBCC(100%) was 156–263%(P < 0.01).Conclusion: The findings indicated that Cu recommendation from current NRC(5–6 mg/kg) was not sufficient to meet the high requirement of weanling pigs. Cu from Cu Pro was significantly more bioavailable to weanling pigs than TBCC in stimulating growth and enzyme activities, decreasing diarrhea frequency and fecal Cu contents to the environment.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
Biological nitrogen fixation(BNF)and photosynthetic carbon fixation underpin food production and climate mitigation,yet natural systems are constrained by oxygen sensitivity,high energy demand,and inefficient catalyst...Biological nitrogen fixation(BNF)and photosynthetic carbon fixation underpin food production and climate mitigation,yet natural systems are constrained by oxygen sensitivity,high energy demand,and inefficient catalysts.This review synthesizes advances that recast these processes as engineering targets and proposes a conceptual roadmap that bridges synthetic symbioses with the synthetic biology of enzymes and pathways.For BNF,progress spans cross-kingdom strategies—from refactoring nif gene sets and targeting nitrogenase assembly to eukaryotic organelles,to engineering plant-associated diazotrophs,rhizosphere control circuits,and emerging nodule-like microenvironments.For carbon assimilation,new-to-nature CO_(2)-fixation modules and photorespiratory bypasses illustrate how pathway redesign and alternative carboxylases can circumvent key Calvin–Benson–Bassham limitations,and expanding photosynthetic light capture offers additional leverage.Across these domains,we extract common design principles:(i)nitrogenase output is increasingly governed by carbon/energy supply and electron delivery as much as by oxygen protection;(ii)robust function requires compartment-aware enzyme–chassis coordination,substrate channeling,and dynamic regulation using sensors and control circuits;and(iii)scalable implementation may benefit from distributing metabolic labor across engineered consortia rather than forcing all functions into a single host.We discuss enabling technologies—including AI-guided protein design and directed evolution,cell-free prototyping,chassis toolkits,and materials/bioelectrochemical interfaces—that can accelerate design–build–test–learn cycles and reduce barriers to deployment.Together,these insights define a path toward integrated nitrogen and carbon fixation systems for low-emission agriculture and biomanufacturing.展开更多
The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,p...The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
In this study,thyme essential oil(TEO)nanoemulsion(tPTNs)was constructed with transglutaminase(TGase)-modified potato protein,and its antibacterial activity and mechanism of action were evaluated and explored.Results ...In this study,thyme essential oil(TEO)nanoemulsion(tPTNs)was constructed with transglutaminase(TGase)-modified potato protein,and its antibacterial activity and mechanism of action were evaluated and explored.Results indicated that tPTNs exhibited great antibacterial activity against both Staphylococcus aureus and Escherichia coli,with minimal inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of 2.5 and 5.0 mg/mL,respectively.Also,the antibacterial effects of tPTNs were concentration-dependent.We observed a significant decrease in the absolute value of the zeta potential,and significant increases in particle size,cell membrane hydrophobicity,conductivity,the release of metal ions,and the leakage of nucleic acid as the concentration of tPTNs increased from 0 mg/mL to MBC.Furthermore,sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)demonstrated that protein synthesis was inhibited or even disrupted.Analysis by liquid chromatography-mass spectrometry(LC-MS)indicated that treatment with tPTNs caused significant changes in bacterial metabolites,1117 and 692 differential metabolites being found for S.aureus and E.coli,respectively.The differential metabolites were involved in nucleotide metabolism,amino acid metabolism,tricarboxylic acid cycle and other metabolic pathways.These findings provide valuable insights for the application of thyme essential oil as an efficient antibacterial agent and for the understanding of its mechanism of action.展开更多
Age-related macular degeneration(AMD)is the leading cause of irreversible vision loss in older adults,with early-stage features including subretinal lipid deposits and progressing to retinal geographic atrophy and cho...Age-related macular degeneration(AMD)is the leading cause of irreversible vision loss in older adults,with early-stage features including subretinal lipid deposits and progressing to retinal geographic atrophy and choroidal neovascularization in advanced stages.The dysregulation of ocular lipid metabolism,oxidative stress,and inflammation are critical risk factors for AMD pathogenesis.7-ketocholesterol(7-KC),a hallmark of ocular lipid metabolism disorders,is a significant component of subretinal lipid deposits in AMD patients,exhibiting toxicity to retinal cells and exacerbating lipotoxic aging.This review elaborates on the biosynthesis and metabolism of 7-KC in the retina,investigates its detoxification mechanisms by examining its binding proteins,and summarizes recent progress on kinase signaling pathways induced by 7-KC through inflammatory cytokines and intracellular effectors.The aim is to pinpoint potential pharmacological targets,nutritional compounds,and synthetic molecules to explore the potential of targeting 7-KC for AMD treatment.展开更多
Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et a...Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et al.,2022).This molecular event is believed to lead to activation of stress pathways ultimately resulting in cellular dysfunction(Eldeeb et al.,2022).Accordingly,many lines of research investigations focused on dampening the formation of protein aggregates or augmenting the clearance of protein aggregates as a potential therapeutic strategy to counteract the progression of neurodegenerative diseases,albeit with little success(Costa-Mattioli and Walter,2020).Cell stress cues such as the accumulation of protein aggregates lead to the activation of stress response pathways that aid cells in responding to the damage.Despite the notion that the transient activation of these pathways helps cells cope with stressors,persistent activation can induce unwanted apoptosis of cells and reduce overall tissue strength as well as lead to an accumulation of aggregation-prone proteins(Hetz and Papa,2018).Mutations in proteins involved in stress signaling termination can cause conditions like ataxia and early-onset dementia(Conroy et al.,2014).Therefore,it is crucial for stress response signaling to be turned off once conditions have improved.Nevertheless,the mechanisms by which cells silence these signals are still elusive.展开更多
Autophagy is well-known for delivering cargo materials to lysosomes for proteolytic digestion.Recently,autophagy has emerged as a key mechanism in unconventional protein secretion(UPS).This perspective introduces unco...Autophagy is well-known for delivering cargo materials to lysosomes for proteolytic digestion.Recently,autophagy has emerged as a key mechanism in unconventional protein secretion(UPS).This perspective introduces unconventional secretion pathways,focusing on secretory autophagy and its role in secreting protein aggregates associated with neurodegenerative disorders.We also explore additional neuronal functions of secretory autophagy beyond the release of protein aggregates.We propose autophagosomes as transport organelles that deliver cargo material directly from the endoplasmatic reticulum(ER)to the plasma membrane rather than solely to lysosomes.展开更多
CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Althou...CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Although a limited investigation depicted that CRD310 contained higher levels of glutelin and some essential amino acids,detailed biochemical,molecular,and cellular mechanisms remain to be studied.As one of the means to identify the proteins and understand the underlying mechanism of higher proteins accumulation in grains of CRD310,the comparative proteomics was undertaken on grains of CRD310 and NV at the yellow ripening stage.展开更多
Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological...Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological functions and,importantly,disease-related roles of the prion protein(PrP),a relatively broadly expressed membrane-anchored glycoprotein with high levels in several cell types of the nervous and immune system and with well-established key roles in different progressive and fatal neurodegenerative protein misfolding diseases(proteopathies).展开更多
Oat milk has gained widespread consumer acceptance for its creamy texture,β-glucan content,and environmental sustainability.However,its relatively low protein content(typically 2-3 g/serving)presents a nutritional li...Oat milk has gained widespread consumer acceptance for its creamy texture,β-glucan content,and environmental sustainability.However,its relatively low protein content(typically 2-3 g/serving)presents a nutritional limitation,largely due to poor protein solubility.This study investigated how processing conditions influence protein content and functional stability in oat-based systems by applying two treatments:(1)α-amylase enzymatic hydrolysis,and(2)pH-shifting(from pH 7 to 12 and back)with mild heating(50℃for 10 or 30 min).Oat protein solutions were formulated from two sources:oat flour(OF)and oat protein isolate(OPI).Results suggests that α-amylase pretreatment effectively reduced starch-driven viscosity in OF,facilitating better sample handling and centrifugation.Following pH-shifting and heat treatment,both OF and OPI solutions showed significantly improved protein solubility,with protein content increased from 2.0 to~6.5 g/serving.These changes were accompanied by reduced precipitation,smaller particle sizes,and more negative zeta potential values,indicating enhanced colloidal stability.SDS-PAGE analysis revealed the presence of low-molecular-weight protein fractions,supporting increased solubilization.Fluorescence microscopy confirmed the formation of smaller,more uniformly dispersed particles in treated samples compared to controls.However,noticeable darkening or browning occurred under high-pH heating,indicating potential challenges in color control.The findings provide useful information for future industrial applications and product innovation in the plant-based beverage sector.展开更多
Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a na...Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a natural inhibitor of recombinant tissue plasminogen activator,neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia.However,the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear.In this study,we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models,respectively.The models were used to investigate the neuroprotective effects of neuroserpin.Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia,initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis,which was followed by a later apoptotic response.Notably,ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons.Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules,the reduction in protein synthesis,and the upregulation of apoptotic transcription factors.This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion,as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion.However,the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin.Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.展开更多
Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance protei...Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance proteins are a diverse group of molecules that play crucial roles in axon and dendrite growth during nervous system development.Increasing evidence highlights their regulatory functions in spinal cord injury.This review provides a brief overview of the modulation patterns of key neuronal guidance proteins in neuronal axon growth during nervous system formation and subsequently focuses on their roles in neuronal regeneration and functional recovery following spinal cord injury.Neuronal guidance proteins include,but are not limited to,semaphorins and their receptors,plexins;netrins and their receptors,deleted in colorectal cancer and UNC5;Eph receptors and their ligands,ephrins;Slit and its receptor,Robo;repulsive guidance molecules and their receptor,neogenin;Wnt proteins and their receptor,Frizzled;and protocadherins.Localized Netrin-1 at the injury site inhibits motor axon regeneration after adult spinal cord injury while promoting oligodendrocyte growth.Slit2 enhances synapse formation in the injured spinal cord of rats.EphA7 regulates acute apoptosis in the early pathophysiological stages of spinal cord injury,while ephrinA1 plays a role in the nervous system’s injury response,with its reduced expression leading to impaired motor function in rats.EphA3 is upregulated following spinal cord injury,promoting an inhibitory environment for axonal regeneration.After spinal cord injury,bidirectional activation of ephrinB2 and EphB2 in astrocytes and fibroblasts results in the formation of a dense astrocyte-meningeal fibroblast scar.EphB1/ephrinB1 signaling mediates pain processing in spinal cord injury by regulating calpain-1 and caspase-3 in neurons.EphB3 expression increases in white matter after spinal cord injury,further inhibiting axon regeneration.Sema3A,expressed by neurons and fibroblasts in the scar surrounding the injury,inhibits motor neuron and sensory nerve growth after spinal cord injury.Sema4D suppresses neuronal axon myelination and axon regeneration,while its inhibition significantly enhances axon regeneration and motor recovery.Sema7A is involved in glial scar formation and may influence serotonin channel remodeling,thereby affecting motor coordination.Given these findings,the local or systemic application of neuronal guidance proteins represents a promising avenue for spinal cord injury treatment.展开更多
In an era of profound changes to global trade,food security,and industrial organization,the ChinaIndonesia“Two Countries,Twin Parks”initiative has emerged as a strategic experiment with farreaching implications.Anch...In an era of profound changes to global trade,food security,and industrial organization,the ChinaIndonesia“Two Countries,Twin Parks”initiative has emerged as a strategic experiment with farreaching implications.Anchored in marine protein processing and advanced food manufacturing,this collaboration reflects not only a convergence of economic interests but also a deliberate rethinking of how China engages with global resources,technology,and partners.展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
Phytophthora blight is a devastating disease of pigeon pea(Cajanus cajan)that severely impacts plant growth and productivity.This study investigates the morphological,anatomical,and biochemical responses of a suscepti...Phytophthora blight is a devastating disease of pigeon pea(Cajanus cajan)that severely impacts plant growth and productivity.This study investigates the morphological,anatomical,and biochemical responses of a susceptible variety(ICPL 11260)and a resistant variety(IPAC-02)following infection by Phytophthora.Morphological analyses showed that infection caused a drastic reduction in root length,shoot length,leaf number,fresh weight,and dry weight in the susceptible ICPL 11260 variety,with reductions ranging from 0.5-to 2-fold compared to non-infected controls.Anatomical observations revealed pronounced cellular damage and mycelial invasion in infected ICPL 11260 plants by 30 days after infection,whereas infected IPAC-02 plants exhibited no fungal colonization.Biochemical analyses further demonstrated that the resistant IPAC-02 variety accumulated higher levels of total soluble sugars,proteins,phenols,and flavonoids,along with increased activities of defense-related enzymes(chitinase andβ-1,3-glucanase),compared with the susceptible ICPL 11260.Under P.cajani stress,IPAC-02 maintained significantly elevated osmolyte concentrations(total sugars 153.7 mg g^(−1)FW;proteins 25.4 mg g^(−1)FW),secondary metabolites(phenols 51.7 mg g^(−1)FW;flavonoids 33.1 mg g^(−1)FW),and PR-enzyme activities(chitinase 11.4 U mg^(−1)protein;β-1,3-glucanase 9.1 U mg^(−1)protein).These responses support a lignification-mediated defense mechanism in IPAC-02 and highlight its potential value for breeding Phytophthora-resistant pigeon pea cultivars.展开更多
Background Fast-growing broilers are poorly adapted to heat.Adjusting feed composition may mitigate heat stress(HS)effects in temperate climates,while maintaining performance and health during cooler days.Methods One ...Background Fast-growing broilers are poorly adapted to heat.Adjusting feed composition may mitigate heat stress(HS)effects in temperate climates,while maintaining performance and health during cooler days.Methods One thousand nine hundred and twenty Ross 308 male broilers were housed in 64 pens in 4 climate-controlled rooms,2 under cyclical HS(d 28–43;32±2℃;60%–70%RH;09:30–15:30)and 2 under thermoneutral(TN)conditions.In the finisher phase,broilers were allocated to 4 dietary treatments,analyzed values are given except for metabolizable energy(ME):low crude protein(CP)and control fat(LowCP-ConF;17.0%CP,5.9%crude fat(CF),2,925 kcal/kg ME),low CP and high fat(LowCP-HighF;17.2%CP,7.9%CF,3,019 kcal/kg ME),control CP and high fat(ConCP-HighF;18.1%CP,8.0%CF,2,992 kcal/kg ME)and a basal control(ConCP-ConF;18.7%CP,6.3%CF,2,913 kcal/kg ME).LowCP diets contained control levels of digestible amino acids.Results During the finisher phase,compared to control CP levels,LowCP increased average daily feed intake(ADFI)(+2.15%;P=0.020)and affected average daily gain(ADG)and feed conversion ratio(FCR)negatively under TN(-3.77%and+6.49%;P=0.003 and P<0.001,respectively),but not during HS.Compared to control CF,HighF decreased ADFI during TN and HS(-3.16%and-3.17%;P<0.001 and P=0.022)and reduced ADG in TN groups(-3.17%;P=0.010),but not during HS.Mortality was higher in broilers receiving HighF during HS(P=0.040).Slaughter weights were unaffected.LowCP decreased plasma uric acid and lactate dehydrogenase levels during TN,but increased plasma glucose during HS.LowCP increased breast meat redness(a*)during TN and HS(P<0.05).HighF decreased fat(-1.68%;P=0.017),but increased protein levels(+1.53%;P<0.001)in breast meat of HS-broilers.Conclusion LowCP and HighF impaired performance under TN but not under HS.HighF increased mortality under HS,yet improved breast meat composition.These findings highlight the challenge of designing an optimal diet for both conditions and underscore the need to better understand amino acid needs and energy-to-protein ratios during HS.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Key International Cooperation Program of the National Natural Science Foundation of China(32120103011)Jiangsu Shuang Chuang Tuan Dui program(JSSCTD202147)+1 种基金Jiangsu Shuang Chuang Ren Cai program(JSSCRC2021541)Initiation Funds of Yangzhou University for Distinguished Scientists.
文摘Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.
基金The financial support from the National Key Research and Development Program of China (2017YFC1600306) is gratefully acknowledged。
文摘Background: The objective of this study was to determine the effects of supplementing Cu on growth performance, Cu metabolism and Cu-related enzyme activities of weanling pigs fed diets with two different Cu sources, and to estimate optimal Cu requirements and relative bioavailability from these two sources for pigs.Methods: Weanling pigs were allocated to 14 treatments arranged factorially, including 6 added Cu levels(5, 10,20, 40, 80, 160 mg/kg), and 2 mineral sources(tribasic Cu chloride, TBCC and copper proteinate, Cu Pro), as well as one negative control(0 mg/kg added Cu level) and one maximum allowed level treatment(200 mg/kg TBCC) for the entire 38-d experiment. Growth performance, mineral status and enzyme activities were measured at the end of this study.Results: Increasing levels of Cu showed linear and quadratic responses(P < 0.01) for final BW, ADG and FCR regardless of the sources. Supplementation with TBCC(> 80 mg/kg) and Cu Pro(> 20 mg/kg) significantly decreased(P < 0.05) diarrhea incidence of weanling pigs. There were linear and quadratic increases(P < 0.01) in bile, hepatic,and intestinal Cu concentrations, fecal Cu contents, and plasma enzyme activities(alkaline phosphatase,ceruloplasmin, Cu, Zn-Superoxide dismutase(Cu/Zn SOD), and glutathione peroxidase), whereas plasma malondialdehyde decreased(P < 0.01) linearly and quadratically as dietary Cu level increased. Similarly, pigs fed Cu Pro absorbed and retained more Cu and excreted less Cu than those fed TBCC when supplemented 80 mg/kg and above. Optimal dietary Cu requirements for pigs from 28 to 66 d of age estimated based on fitted broken-line models(P < 0.05) of bile Cu, plasma Cu/Zn SOD and growth performance were 93–140 mg/kg from TBCC, and 63–98 mg/kg from Cu Pro accordingly. According to slope ratios from multiple linear regression, the bioavailability value of Cu Pro relative to TBCC(100%) was 156–263%(P < 0.01).Conclusion: The findings indicated that Cu recommendation from current NRC(5–6 mg/kg) was not sufficient to meet the high requirement of weanling pigs. Cu from Cu Pro was significantly more bioavailable to weanling pigs than TBCC in stimulating growth and enzyme activities, decreasing diarrhea frequency and fecal Cu contents to the environment.
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.
基金supported by the funds of the Ministry of Science and Technology of China(2019YFA0904700)the National Natural Science Foundation of China(32471477)to Cheng Qi.
文摘Biological nitrogen fixation(BNF)and photosynthetic carbon fixation underpin food production and climate mitigation,yet natural systems are constrained by oxygen sensitivity,high energy demand,and inefficient catalysts.This review synthesizes advances that recast these processes as engineering targets and proposes a conceptual roadmap that bridges synthetic symbioses with the synthetic biology of enzymes and pathways.For BNF,progress spans cross-kingdom strategies—from refactoring nif gene sets and targeting nitrogenase assembly to eukaryotic organelles,to engineering plant-associated diazotrophs,rhizosphere control circuits,and emerging nodule-like microenvironments.For carbon assimilation,new-to-nature CO_(2)-fixation modules and photorespiratory bypasses illustrate how pathway redesign and alternative carboxylases can circumvent key Calvin–Benson–Bassham limitations,and expanding photosynthetic light capture offers additional leverage.Across these domains,we extract common design principles:(i)nitrogenase output is increasingly governed by carbon/energy supply and electron delivery as much as by oxygen protection;(ii)robust function requires compartment-aware enzyme–chassis coordination,substrate channeling,and dynamic regulation using sensors and control circuits;and(iii)scalable implementation may benefit from distributing metabolic labor across engineered consortia rather than forcing all functions into a single host.We discuss enabling technologies—including AI-guided protein design and directed evolution,cell-free prototyping,chassis toolkits,and materials/bioelectrochemical interfaces—that can accelerate design–build–test–learn cycles and reduce barriers to deployment.Together,these insights define a path toward integrated nitrogen and carbon fixation systems for low-emission agriculture and biomanufacturing.
基金supported by the National Natural Science Foundation of China,No.81971031(to ZL)the National Key Research and Development Program of China,No.2022YFE0210100(to JFC)+7 种基金the National Natural Science Foundation of China(Original Exploration Project),No.82151308(to JFC)the National Natural Science Foundation of China(Research Fund for International Senior Scientists),No.82150710558(to JFC)Science&Technology Initiative STI2030-Major Projects,No.2021ZD0203400(to JFC)Key Research and Development Program of Zhejiang Province,No.2023C03079(to JFC)Scientific Research Starting Foundation of Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine,Vision and Brain Health),No.OJQDSP2022007(to JFC)Project of State Key Laboratory of Ophthalmology,Optometry and Visual Science,Wenzhou Medical University,No.J01-20190101(to JFC)Scientific Research Starting Foundation of Wenzhou Medical University,No.QTJ12003(to JFC)Department of Science and Technology of Zhejiang Province,No.2023ZY1011(to JFC)。
文摘The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
文摘In this study,thyme essential oil(TEO)nanoemulsion(tPTNs)was constructed with transglutaminase(TGase)-modified potato protein,and its antibacterial activity and mechanism of action were evaluated and explored.Results indicated that tPTNs exhibited great antibacterial activity against both Staphylococcus aureus and Escherichia coli,with minimal inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of 2.5 and 5.0 mg/mL,respectively.Also,the antibacterial effects of tPTNs were concentration-dependent.We observed a significant decrease in the absolute value of the zeta potential,and significant increases in particle size,cell membrane hydrophobicity,conductivity,the release of metal ions,and the leakage of nucleic acid as the concentration of tPTNs increased from 0 mg/mL to MBC.Furthermore,sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)demonstrated that protein synthesis was inhibited or even disrupted.Analysis by liquid chromatography-mass spectrometry(LC-MS)indicated that treatment with tPTNs caused significant changes in bacterial metabolites,1117 and 692 differential metabolites being found for S.aureus and E.coli,respectively.The differential metabolites were involved in nucleotide metabolism,amino acid metabolism,tricarboxylic acid cycle and other metabolic pathways.These findings provide valuable insights for the application of thyme essential oil as an efficient antibacterial agent and for the understanding of its mechanism of action.
文摘Age-related macular degeneration(AMD)is the leading cause of irreversible vision loss in older adults,with early-stage features including subretinal lipid deposits and progressing to retinal geographic atrophy and choroidal neovascularization in advanced stages.The dysregulation of ocular lipid metabolism,oxidative stress,and inflammation are critical risk factors for AMD pathogenesis.7-ketocholesterol(7-KC),a hallmark of ocular lipid metabolism disorders,is a significant component of subretinal lipid deposits in AMD patients,exhibiting toxicity to retinal cells and exacerbating lipotoxic aging.This review elaborates on the biosynthesis and metabolism of 7-KC in the retina,investigates its detoxification mechanisms by examining its binding proteins,and summarizes recent progress on kinase signaling pathways induced by 7-KC through inflammatory cytokines and intracellular effectors.The aim is to pinpoint potential pharmacological targets,nutritional compounds,and synthetic molecules to explore the potential of targeting 7-KC for AMD treatment.
文摘Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et al.,2022).This molecular event is believed to lead to activation of stress pathways ultimately resulting in cellular dysfunction(Eldeeb et al.,2022).Accordingly,many lines of research investigations focused on dampening the formation of protein aggregates or augmenting the clearance of protein aggregates as a potential therapeutic strategy to counteract the progression of neurodegenerative diseases,albeit with little success(Costa-Mattioli and Walter,2020).Cell stress cues such as the accumulation of protein aggregates lead to the activation of stress response pathways that aid cells in responding to the damage.Despite the notion that the transient activation of these pathways helps cells cope with stressors,persistent activation can induce unwanted apoptosis of cells and reduce overall tissue strength as well as lead to an accumulation of aggregation-prone proteins(Hetz and Papa,2018).Mutations in proteins involved in stress signaling termination can cause conditions like ataxia and early-onset dementia(Conroy et al.,2014).Therefore,it is crucial for stress response signaling to be turned off once conditions have improved.Nevertheless,the mechanisms by which cells silence these signals are still elusive.
基金supported by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)grant LU 2347/3-1(to PL).
文摘Autophagy is well-known for delivering cargo materials to lysosomes for proteolytic digestion.Recently,autophagy has emerged as a key mechanism in unconventional protein secretion(UPS).This perspective introduces unconventional secretion pathways,focusing on secretory autophagy and its role in secreting protein aggregates associated with neurodegenerative disorders.We also explore additional neuronal functions of secretory autophagy beyond the release of protein aggregates.We propose autophagosomes as transport organelles that deliver cargo material directly from the endoplasmatic reticulum(ER)to the plasma membrane rather than solely to lysosomes.
基金supported by the director of Indian Council of Agricultural Research and International Rice Research Institute (ICAR-CRRI), Cuttack, Indiathe coordinator of the ICAR-sponsored project ‘C-reactive protein (CRP) in Biofortification in Selected Crops’, India
文摘CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Although a limited investigation depicted that CRD310 contained higher levels of glutelin and some essential amino acids,detailed biochemical,molecular,and cellular mechanisms remain to be studied.As one of the means to identify the proteins and understand the underlying mechanism of higher proteins accumulation in grains of CRD310,the comparative proteomics was undertaken on grains of CRD310 and NV at the yellow ripening stage.
基金supported by the CJD Foundation,USA,the Alzheimer Forschung Initiative(AFI)e.V.,Germany,and Werner-Otto-Stiftung,Germany(all to HCA),ChinaScholarship Council(grant#202108080249 to FS)Deutsche Forschungsgemeinschaft(DFG)CRC877“Proteolysis as a regulatory event in pathophysiology”(project A12 to MG),Slovene Research and InnovationAgency(grant number P4-0176 to VCS).
文摘Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological functions and,importantly,disease-related roles of the prion protein(PrP),a relatively broadly expressed membrane-anchored glycoprotein with high levels in several cell types of the nervous and immune system and with well-established key roles in different progressive and fatal neurodegenerative protein misfolding diseases(proteopathies).
基金supported by the USDA National Institute of Food and Agriculture,Hatch project 7009323.
文摘Oat milk has gained widespread consumer acceptance for its creamy texture,β-glucan content,and environmental sustainability.However,its relatively low protein content(typically 2-3 g/serving)presents a nutritional limitation,largely due to poor protein solubility.This study investigated how processing conditions influence protein content and functional stability in oat-based systems by applying two treatments:(1)α-amylase enzymatic hydrolysis,and(2)pH-shifting(from pH 7 to 12 and back)with mild heating(50℃for 10 or 30 min).Oat protein solutions were formulated from two sources:oat flour(OF)and oat protein isolate(OPI).Results suggests that α-amylase pretreatment effectively reduced starch-driven viscosity in OF,facilitating better sample handling and centrifugation.Following pH-shifting and heat treatment,both OF and OPI solutions showed significantly improved protein solubility,with protein content increased from 2.0 to~6.5 g/serving.These changes were accompanied by reduced precipitation,smaller particle sizes,and more negative zeta potential values,indicating enhanced colloidal stability.SDS-PAGE analysis revealed the presence of low-molecular-weight protein fractions,supporting increased solubilization.Fluorescence microscopy confirmed the formation of smaller,more uniformly dispersed particles in treated samples compared to controls.However,noticeable darkening or browning occurred under high-pH heating,indicating potential challenges in color control.The findings provide useful information for future industrial applications and product innovation in the plant-based beverage sector.
基金supported in part by the National Key Research&Development Program of China,No.2022YFA1104900(to LS)the National Natural Science Foundation of China,Nos.82371175,82071535(both to LS),82101614(to YP)+5 种基金the International Science and Technology Cooperation Projects of Guangdong Province,No.2023A0505050121(to LS)Guangdong Basic and Applied Basic Research Foundation,Nos.2022B1515130007(to LS),2023A1515030012(to SZ),2022A1515010666(to WL)the Science and Technology Program of Guangzhou,Nos.202102070001(to LS),202201010041(to YP)Shenzhen Basic Research Grant,Nos.JCYJ20200109140414636,JCYJ20230807145103007(both to WL)awarded a Royal Society Newton Advanced Fellowship,No.AOMS-NAF0051003in collaboration with Zoltán Molnár,Department of Physiology,Anatomy and Genetics,University of Oxford(2017–2021)。
文摘Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a natural inhibitor of recombinant tissue plasminogen activator,neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia.However,the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear.In this study,we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models,respectively.The models were used to investigate the neuroprotective effects of neuroserpin.Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia,initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis,which was followed by a later apoptotic response.Notably,ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons.Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules,the reduction in protein synthesis,and the upregulation of apoptotic transcription factors.This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion,as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion.However,the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin.Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.
基金supported by Shenzhen University General Hospital Scientific Research Project,No.SUGH2019QD002Shenzhen Science and Technology Development Foundation,No.20220810173216001(both to ZS).
文摘Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance proteins are a diverse group of molecules that play crucial roles in axon and dendrite growth during nervous system development.Increasing evidence highlights their regulatory functions in spinal cord injury.This review provides a brief overview of the modulation patterns of key neuronal guidance proteins in neuronal axon growth during nervous system formation and subsequently focuses on their roles in neuronal regeneration and functional recovery following spinal cord injury.Neuronal guidance proteins include,but are not limited to,semaphorins and their receptors,plexins;netrins and their receptors,deleted in colorectal cancer and UNC5;Eph receptors and their ligands,ephrins;Slit and its receptor,Robo;repulsive guidance molecules and their receptor,neogenin;Wnt proteins and their receptor,Frizzled;and protocadherins.Localized Netrin-1 at the injury site inhibits motor axon regeneration after adult spinal cord injury while promoting oligodendrocyte growth.Slit2 enhances synapse formation in the injured spinal cord of rats.EphA7 regulates acute apoptosis in the early pathophysiological stages of spinal cord injury,while ephrinA1 plays a role in the nervous system’s injury response,with its reduced expression leading to impaired motor function in rats.EphA3 is upregulated following spinal cord injury,promoting an inhibitory environment for axonal regeneration.After spinal cord injury,bidirectional activation of ephrinB2 and EphB2 in astrocytes and fibroblasts results in the formation of a dense astrocyte-meningeal fibroblast scar.EphB1/ephrinB1 signaling mediates pain processing in spinal cord injury by regulating calpain-1 and caspase-3 in neurons.EphB3 expression increases in white matter after spinal cord injury,further inhibiting axon regeneration.Sema3A,expressed by neurons and fibroblasts in the scar surrounding the injury,inhibits motor neuron and sensory nerve growth after spinal cord injury.Sema4D suppresses neuronal axon myelination and axon regeneration,while its inhibition significantly enhances axon regeneration and motor recovery.Sema7A is involved in glial scar formation and may influence serotonin channel remodeling,thereby affecting motor coordination.Given these findings,the local or systemic application of neuronal guidance proteins represents a promising avenue for spinal cord injury treatment.
文摘In an era of profound changes to global trade,food security,and industrial organization,the ChinaIndonesia“Two Countries,Twin Parks”initiative has emerged as a strategic experiment with farreaching implications.Anchored in marine protein processing and advanced food manufacturing,this collaboration reflects not only a convergence of economic interests but also a deliberate rethinking of how China engages with global resources,technology,and partners.
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
基金supported and funded by the Deanship of Scientific Research,Vice Presidency for Graduate Studies and Scientific Research,King Faisal University,Saudi Arabia,grant number(KFU252909).
文摘Phytophthora blight is a devastating disease of pigeon pea(Cajanus cajan)that severely impacts plant growth and productivity.This study investigates the morphological,anatomical,and biochemical responses of a susceptible variety(ICPL 11260)and a resistant variety(IPAC-02)following infection by Phytophthora.Morphological analyses showed that infection caused a drastic reduction in root length,shoot length,leaf number,fresh weight,and dry weight in the susceptible ICPL 11260 variety,with reductions ranging from 0.5-to 2-fold compared to non-infected controls.Anatomical observations revealed pronounced cellular damage and mycelial invasion in infected ICPL 11260 plants by 30 days after infection,whereas infected IPAC-02 plants exhibited no fungal colonization.Biochemical analyses further demonstrated that the resistant IPAC-02 variety accumulated higher levels of total soluble sugars,proteins,phenols,and flavonoids,along with increased activities of defense-related enzymes(chitinase andβ-1,3-glucanase),compared with the susceptible ICPL 11260.Under P.cajani stress,IPAC-02 maintained significantly elevated osmolyte concentrations(total sugars 153.7 mg g^(−1)FW;proteins 25.4 mg g^(−1)FW),secondary metabolites(phenols 51.7 mg g^(−1)FW;flavonoids 33.1 mg g^(−1)FW),and PR-enzyme activities(chitinase 11.4 U mg^(−1)protein;β-1,3-glucanase 9.1 U mg^(−1)protein).These responses support a lignification-mediated defense mechanism in IPAC-02 and highlight its potential value for breeding Phytophthora-resistant pigeon pea cultivars.
基金funded by VLAIO(Flemish Innovation&Entrepreneurship),grant number HBC.2020.3165。
文摘Background Fast-growing broilers are poorly adapted to heat.Adjusting feed composition may mitigate heat stress(HS)effects in temperate climates,while maintaining performance and health during cooler days.Methods One thousand nine hundred and twenty Ross 308 male broilers were housed in 64 pens in 4 climate-controlled rooms,2 under cyclical HS(d 28–43;32±2℃;60%–70%RH;09:30–15:30)and 2 under thermoneutral(TN)conditions.In the finisher phase,broilers were allocated to 4 dietary treatments,analyzed values are given except for metabolizable energy(ME):low crude protein(CP)and control fat(LowCP-ConF;17.0%CP,5.9%crude fat(CF),2,925 kcal/kg ME),low CP and high fat(LowCP-HighF;17.2%CP,7.9%CF,3,019 kcal/kg ME),control CP and high fat(ConCP-HighF;18.1%CP,8.0%CF,2,992 kcal/kg ME)and a basal control(ConCP-ConF;18.7%CP,6.3%CF,2,913 kcal/kg ME).LowCP diets contained control levels of digestible amino acids.Results During the finisher phase,compared to control CP levels,LowCP increased average daily feed intake(ADFI)(+2.15%;P=0.020)and affected average daily gain(ADG)and feed conversion ratio(FCR)negatively under TN(-3.77%and+6.49%;P=0.003 and P<0.001,respectively),but not during HS.Compared to control CF,HighF decreased ADFI during TN and HS(-3.16%and-3.17%;P<0.001 and P=0.022)and reduced ADG in TN groups(-3.17%;P=0.010),but not during HS.Mortality was higher in broilers receiving HighF during HS(P=0.040).Slaughter weights were unaffected.LowCP decreased plasma uric acid and lactate dehydrogenase levels during TN,but increased plasma glucose during HS.LowCP increased breast meat redness(a*)during TN and HS(P<0.05).HighF decreased fat(-1.68%;P=0.017),but increased protein levels(+1.53%;P<0.001)in breast meat of HS-broilers.Conclusion LowCP and HighF impaired performance under TN but not under HS.HighF increased mortality under HS,yet improved breast meat composition.These findings highlight the challenge of designing an optimal diet for both conditions and underscore the need to better understand amino acid needs and energy-to-protein ratios during HS.
