Distribution transformers operating in modern system grids or in industrial networks are subjected to many switching transients,which may occur due to routine operations,network reconfigurations or as reaction on prot...Distribution transformers operating in modern system grids or in industrial networks are subjected to many switching transients,which may occur due to routine operations,network reconfigurations or as reaction on protection signals.Depending on the network configuration and parameters,such events may lead to external overvoltages and result in additional stresses on the insulation system.This paper presents the influence of a series choke on damping of switching transients in distribution transformers.The impact of the choke is assessed by both amplitude and rise time reduction.The suppression of the transient rise time is shown for a test configuration involving distribution transformers connected to low loss cable lines and a medium voltage breaker.Such phenomena are especially typical for industrial networks where switching operations are very frequent.Both simulation and experiment results are given.Simulation results as well as measurement results confirmed that switching events can lead to high dU/dt and in consequence,can have adverse impacts on insulation system.Voltage escalation during switching event is strongly related with system conditions.The results obtained for presented mitigation method are promising and indicate significant dU/dt reduction as well as number of ignitions and voltage peak value.The protection of distribution transformers with a series choke is a new approach dedicated to environments prone to the occurrence of transients with high steepness.Experimental results show that the application of serial choke with suitable parameters realizes the reduction of dU/dt at the machines terminal from 24 kV/μs to 5 kV/μs,as well as the reduction of voltage peak value from 10 kV to 5 kV.The number of ignitions is also reduced.展开更多
This paper discusses the current state of the art of diagnostics at power transformers. A special focus is set on the UHF-PD-measurement （ultra-high-frequency partial discharge measurement） because at power transfor...This paper discusses the current state of the art of diagnostics at power transformers. A special focus is set on the UHF-PD-measurement （ultra-high-frequency partial discharge measurement） because at power transformers, this diagnostic method has become more important in recent years. The current state, basics and principles of operations, proceedings as well as advantages of PD-measurement methods are covered. Furthermore problems and proposed solutions are discussed. Bushings and tap changers are not discussed in detail. In many cases, one single diagnostic method does not have the ability to sufficiently evaluate a power transformer. Therefore, a variety of diagnostic methods came up over times, which are commonly used by now. To expand the evaluation opportunities of power transformers, science strives to develop new diagnostic methods as well as to improve the existing ones. Furthermore, environmentally friendly and hardly inflammable ester liquids are examined for the use at power transformers and PD-measurement at HVDC （high voltage direct current） converter transformers as well. Potential diagnostic options and respectively current developments and findings in the field of oil-paper-insulation systems are outlined conclusively.展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probi...BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.展开更多
Developing a chiral material as versatile and universal chiral stationary phase(CSP) for chiral separation in diverse chromatographic techniques simultaneously is of great significance.In this study,we demonstrated fo...Developing a chiral material as versatile and universal chiral stationary phase(CSP) for chiral separation in diverse chromatographic techniques simultaneously is of great significance.In this study,we demonstrated for the first time that a chiral metal-organic cage(MOC),[Zn_(6)M_(4)],as a universal chiral recognition material for both multi-mode high-performance liquid chromatography(HPLC) and capillary gas chromatography(GC) enantioseparation.Two novel HPLC CSPs with different bonding arms(CSP-A with a cationic imidazolium bonding arm and CSP-B with an alkyl chain bonding arm) were prepared by clicking of functionalized chiral MOC [Zn_(6)M_(4)] onto thiolated silica via thiol-ene click chemistry.Meanwhile,a capillary GC column statically coated with the chiral MOC [Zn_(6)M_(4)] was also fabricated.The results showed that the chiral MOC exhibits excellent enantioselectivity not only in normal phase HPLC(NP-HPLC) and reversed phase(RP-HPLC) but also in GC,and various racemates were well separated,including alcohols,diols,esters,ketones,ethers,amines,and epoxides.Importantly,CSP-A and CSP-B are complementary to commercially available Chiralcel OD-H and Chiralpak AD-H columns in enantioseparation,which can separate some racemates that could not be or could not well be separated by the two widely used commercial columns,suggesting the great potential of the two prepared CSPs in enantioseparation.This work reveals that the chiral MOC is potential versatile chiral recognition materials for both HPLC and GC,and also paves the way to expand the potential applications of MOCs.展开更多
In this study,electrochemical C-H carboxylation of benzylamines with CO_(2) was reported.This linear paired electrolysis system enables efficient and economical synthesis of value-added α-amino acids(α-AAs) under mi...In this study,electrochemical C-H carboxylation of benzylamines with CO_(2) was reported.This linear paired electrolysis system enables efficient and economical synthesis of value-added α-amino acids(α-AAs) under mild conditions.Various substituted benzylamines containing diverse functional groups and even highly reactive moieties,such as cyano,amide and alkene groups could be successfully transformed to the carboxylated products.Notably,this method proved to be applicable to the late-stage modification of biorelevant compounds,highlighting its potential for synthetic chemistry.Mechanistic studies such as radical trapping experiments,kinetic isotope effect(KIE) tests and cyclic voltammetry(CV) studies provided useful insight into this transformation.展开更多
Vortex-induced vibration(VIV)of an underwater manipulator in pulsating flow presents a notable engineering problem in precise control due to the velocity variation in the flow.This study investigates the VIV response ...Vortex-induced vibration(VIV)of an underwater manipulator in pulsating flow presents a notable engineering problem in precise control due to the velocity variation in the flow.This study investigates the VIV response of an underwater manipulator subjected to pulsating flow,focusing on how different postures affect the behavior of the system.The effects of pulsating parameters and manipulator arrangement on the hydrodynamic coefficient,vibration response,motion trajectory,and vortex shedding behaviors were analyzed.Results indicated that the cross flow vibration displacement in pulsating flow increased by 32.14%compared to uniform flow,inducing a shift in the motion trajectory from a crescent shape to a sideward vase shape.In the absence of interference between the upper and lower arms,the lift coefficient of the manipulator substantially increased with rising pulsating frequency,reaching a maximum increment of 67.0%.This increase in the lift coefficient led to a 67.05%rise in the vibration frequency of the manipulator in the in-line direction.As the pulsating amplitude increased,the drag coefficient of the underwater manipulator rose by 36.79%,but the vibration frequency in the cross-flow direction decreased by 56.26%.Additionally,when the upper and lower arms remained in a state of mutual interference,the cross-flow vibration amplitudes of the upper and lower arms were approximately 1.84 and 4.82 times higher in a circular-elliptical arrangement compared to an elliptical-circular arrangement,respectively.Consequently,the flow field shifted from a P+S pattern to a disordered pattern,disrupting the regularity of the motion trajectory.展开更多
Bicyclo[2.1.1]hexanes(BCHs) are structurally unique C(sp^(3))-rich bicyclic hydrocarbons that are gaining prominence in the field of medicinal chemistry as bioisosteres of benzenoids.The nitrile is an important functi...Bicyclo[2.1.1]hexanes(BCHs) are structurally unique C(sp^(3))-rich bicyclic hydrocarbons that are gaining prominence in the field of medicinal chemistry as bioisosteres of benzenoids.The nitrile is an important functionality in drug development due to its ability to improve physicochemical and pharmacokinetic properties and facilitate potential noncovalent interactions with drug targets.Consequently,cyanoarene motifs are commonly found in drug development.The introduction of cyano-BCHs as potential bioisosteres of cyano-arenes shows great promise;however,there are currently no catalytic methods available for their synthesis.Herein,we report a palladium-catalyzed enantioselective [2σ+2π] cycloadditions of bicyclo[1.1.0]butanes with arylidenemalononitriles for the preparation of chiral cyano-BCHs.This method accommodated a wide range of substrates and tolerated various functional groups.The cyano-BCH products could be transformed to molecules with diverse functionality.Control experiments suggest that the reaction proceeds via a zwitterionic intermediate generated by palladium-mediated ring opening of vinyl-carbonyl bicyclo[1.1.0]butanes followed by stereoselective 1,2-addition and intramolecular allylic substitution reactions.展开更多
Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually wit...Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.展开更多
Cmyc,a proto-oncogene,is expressed at extremely low levels in mature neurons and is traditionally thought to have no function in these cells.However,recent studies suggest that Cmyc may play a crucial role in maintain...Cmyc,a proto-oncogene,is expressed at extremely low levels in mature neurons and is traditionally thought to have no function in these cells.However,recent studies suggest that Cmyc may play a crucial role in maintaining the health and function of mature dopaminergic neurons.This study assessed the role of Cmyc in dopaminergic neurons and its significance in Parkinson’s disease.We used a conditional knockout approach to specifically delete Cmyc in substantia nigra dopaminergic neurons of adult mice.Our findings showed that Cmyc deletion led to progressive neuron loss,Parkinson’s disease-like symptoms,downregulation of Klotho,and upregulation of senescence-associated inflammatory factors,along with enhanced oxidative stress and nitrated alpha-synuclein accumulation,ultimately causing neuronal death.In vitro experiments confirmed increased senescence in C-MYC knockout cells,which was partially reversible by KLOTHO overexpression.We conclude that low-level Cmyc expression is essential for maintaining the health of mature dopaminergic neurons and preventing neurodegeneration,and suggest the c-Myc/Klotho axis as a potential therapeutic target for age-related neurodegenerative diseases,including Parkinson’s disease.Our study introduces a novel mouse model for Parkinson’s disease that replicates a condition associated with normal aging,offering a valuable tool for future research into disease mechanisms and therapeutic strategies.展开更多
Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynam...Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynamic size and slower degradation.It is key to develop facile methods to large-scale synthesis of polymer rings with tunable compositions and microstructures.Recent progresses in large-scale synthesis of polymer rings against single-chain dynamic nanoparticles,and the example applications in synchronous enhancing toughness and strength of polymer nanocomposites are summarized.Once there is the breakthrough in rational design and effective large-scale synthesis of polymer rings and their functional derivatives,a family of cyclic functional hybrids would be available,thus providing a new paradigm in developing polymer science and engineering.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
Innovative use of HfO_(2)-based high-dielectric-permittivity materials could enable their integration into few-nanometre-scale devices for storing substantial quantities of electrical charges,which have received wides...Innovative use of HfO_(2)-based high-dielectric-permittivity materials could enable their integration into few-nanometre-scale devices for storing substantial quantities of electrical charges,which have received widespread applications in high-storage-density dynamic random access memory and energy-efficient complementary metal-oxide-semiconductor devices.During bipolar high electric-field cycling in numbers close to dielectric breakdown,the dielectric permittivity suddenly increases by 30 times after oxygen-vacancy ordering and ferroelectric-to-nonferroelectric phase transition of near-edge plasma-treated Hf_(0.5)Zr_(0.5)O_(2) thin-film capacitors.Here we report a much higher dielectric permittivity of 1466 during downscaling of the capacitor into the diameter of 3.85μm when the ferroelectricity suddenly disappears without high-field cycling.The stored charge density is as high as 183μC cm^(−2) at an operating voltage/time of 1.2 V/50 ns at cycle numbers of more than 10^(12) without inducing dielectric breakdown.The study of synchrotron X-ray micro-diffraction patterns show missing of a mixed tetragonal phase.The image of electron energy loss spectroscopy shows the preferred oxygen-vacancy accumulation at the regions near top/bottom electrodes as well as grain boundaries.The ultrahigh dielectric-permittivity material enables high-density integration of extremely scaled logic and memory devices in the future.展开更多
Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological prop...Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.展开更多
Ceramic cells promise ideal energy conversion and storage devices,making the development of efficient and robust air electrodes crucial for their application.In this study,a Ba_(0.4)Sr_(0.5)Cs_(0.1)Co_(0.7)Fe_(0.2)Nb_...Ceramic cells promise ideal energy conversion and storage devices,making the development of efficient and robust air electrodes crucial for their application.In this study,a Ba_(0.4)Sr_(0.5)Cs_(0.1)Co_(0.7)Fe_(0.2)Nb_(0.1)O_(3−δ)(BSCCFN)air electrode,based on Ba_(0.5)Sr_(0.5)Co_(0.8)Fe_(0.2)O_(3−δ)(BSCF),is designed using a perovskite A-B-site ionic Lewis acid strength(ISA)polarization distribution strategy and is successfully applied in both oxygen-ion conducting solid oxide fuel cells(O-SOFCs)and proton-conducting reversible protonic ceramic cells(R-PCCs).When BSCCFN is used as the air electrode in O-SOFCs,a peak power density(PPD)of 1.45 W cm^(−2)is achieved at 650°C,whereas in R-PCCs,a PPD of 1.13 W cm^(−2)and a current density of−1.8 A cm^(−2)at 1.3 V are achieved at the same temperature and show stable reversibility over 100 h.Experimental measurements and theoretical calculations demonstrate that low-ISA Cs+doping accelerates the reaction kinetics of both oxygen ions and protons,while high-ISA Nb^(5+)doping enhances electrode stability.The synergistic effect of Cs^(+)and Nb^(5+)co-doping in the BSCCFN electrode lies in the ISA polarization distribution,which weakens the Co/Fe–O bond covalency,thereby promoting oxygen vacancy formation and facilitating the conduction of oxygen ions and protons.展开更多
Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs sur...Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.展开更多
The transformer is one of the main components in the power network and transformer windings are one of the most expensive elements in the power transformer. Optimisation of winding distances is one of the most importa...The transformer is one of the main components in the power network and transformer windings are one of the most expensive elements in the power transformer. Optimisation of winding distances is one of the most important parameters during the manufacturing of transformer. The distance between the windings in the two winding transformers is well known to transformer designers and manufacturers. However, insulation of the high voltage transformer with additional winding and tap winding is still a major problem for transformer designers. In this study, the additional winding to tap winding distance optimisation is made for a high voltage power transformer. Optimisation of the transformer's windings just not minimises the cost of the transformer but also increases the lifetime of the transformer. With additional winding and tap winding in high-voltage transformers, insulation distance is a major concern for minimising the cost and size of the high voltage transformer. In this study, an approach is made to balance the cost, size, and safety of high voltage transformers. The optimised distance and position between tap winding and additional winding are determined by using the finite element analysis. The finite element method results were also verified by making a prototype transformer.展开更多
Halide perovskites have emerged as promising materials for X-ray detection with exceptional properties and reasonable costs.Among them,heterostructures between 3D perovskites and low-dimensional perovskites attract in...Halide perovskites have emerged as promising materials for X-ray detection with exceptional properties and reasonable costs.Among them,heterostructures between 3D perovskites and low-dimensional perovskites attract intensive studies of their advantages due to low-level ion migration and decent stability.However,there is still a lack of methods to precisely construct heterostructures and a fundamental understanding of their structure-dependent optoelectronic properties.Herein,a gas-phase method was developed to grow 2D perovskites directly on 3D perovskites with nanoscale accuracy.In addition,the larger steric hindrance of organic layers of 2D perovskites was proved to enable slower ion migration,which resulted in reduced trap states and better stability.Based on MAPbBr_(3)single crystals with the(PA)_(2)PbBr_(4)capping layer,the X-ray detector achieved a sensitivity of 22,245μC Gy_(air)^(−1)cm^(−2),a response speed of 240μs,and a dark current drift of 1.17.10^(–4)nA cm^(−1)s^(−1)V^(−1),which were among the highest reported for state-of-the-art perovskite-based X-ray detectors.This study presents a precise synthesis method to construct perovskite-based heterostructures.It also brings an in-depth understanding of the relationship between lattice structures and properties,which are beneficial for advancing high-performance and cost-effective X-ray detectors.展开更多
Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairme...Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.展开更多
Novel hydrogen storage materials have propelled progress in hydrogen storage technologies.Magnesium hydride(MgH_(2))is a highly promising candidate.Nevertheless,several drawbacks,including the need for elevated therma...Novel hydrogen storage materials have propelled progress in hydrogen storage technologies.Magnesium hydride(MgH_(2))is a highly promising candidate.Nevertheless,several drawbacks,including the need for elevated thermal conditions,sluggish dehydrogena-tion kinetics,and high thermodynamic stability,limit its practical application.One effective method of addressing these challenges is cata-lyst doping,which effectively boosts the hydrogen storage capability of Mg-based materials.Herein,we review recent advancements in catalyst-doped MgH_(2) composites,with particular focus on multicomponent and high-entropy catalysts.Structure-property relationships and catalytic mechanisms in these doping strategies are also summarized.Finally,based on existing challenges,we discuss future research directions for the development of Mg-based hydrogen storage systems.展开更多
文摘Distribution transformers operating in modern system grids or in industrial networks are subjected to many switching transients,which may occur due to routine operations,network reconfigurations or as reaction on protection signals.Depending on the network configuration and parameters,such events may lead to external overvoltages and result in additional stresses on the insulation system.This paper presents the influence of a series choke on damping of switching transients in distribution transformers.The impact of the choke is assessed by both amplitude and rise time reduction.The suppression of the transient rise time is shown for a test configuration involving distribution transformers connected to low loss cable lines and a medium voltage breaker.Such phenomena are especially typical for industrial networks where switching operations are very frequent.Both simulation and experiment results are given.Simulation results as well as measurement results confirmed that switching events can lead to high dU/dt and in consequence,can have adverse impacts on insulation system.Voltage escalation during switching event is strongly related with system conditions.The results obtained for presented mitigation method are promising and indicate significant dU/dt reduction as well as number of ignitions and voltage peak value.The protection of distribution transformers with a series choke is a new approach dedicated to environments prone to the occurrence of transients with high steepness.Experimental results show that the application of serial choke with suitable parameters realizes the reduction of dU/dt at the machines terminal from 24 kV/μs to 5 kV/μs,as well as the reduction of voltage peak value from 10 kV to 5 kV.The number of ignitions is also reduced.
文摘This paper discusses the current state of the art of diagnostics at power transformers. A special focus is set on the UHF-PD-measurement （ultra-high-frequency partial discharge measurement） because at power transformers, this diagnostic method has become more important in recent years. The current state, basics and principles of operations, proceedings as well as advantages of PD-measurement methods are covered. Furthermore problems and proposed solutions are discussed. Bushings and tap changers are not discussed in detail. In many cases, one single diagnostic method does not have the ability to sufficiently evaluate a power transformer. Therefore, a variety of diagnostic methods came up over times, which are commonly used by now. To expand the evaluation opportunities of power transformers, science strives to develop new diagnostic methods as well as to improve the existing ones. Furthermore, environmentally friendly and hardly inflammable ester liquids are examined for the use at power transformers and PD-measurement at HVDC （high voltage direct current） converter transformers as well. Potential diagnostic options and respectively current developments and findings in the field of oil-paper-insulation systems are outlined conclusively.
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
文摘BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.
基金supported by the National Natural Science Foundation of China (Nos.22064020,22364022,and 22174125)the Applied Basic Research Foundation of Yunnan Province (Nos.202101AT070101 and 202201AT070029)。
文摘Developing a chiral material as versatile and universal chiral stationary phase(CSP) for chiral separation in diverse chromatographic techniques simultaneously is of great significance.In this study,we demonstrated for the first time that a chiral metal-organic cage(MOC),[Zn_(6)M_(4)],as a universal chiral recognition material for both multi-mode high-performance liquid chromatography(HPLC) and capillary gas chromatography(GC) enantioseparation.Two novel HPLC CSPs with different bonding arms(CSP-A with a cationic imidazolium bonding arm and CSP-B with an alkyl chain bonding arm) were prepared by clicking of functionalized chiral MOC [Zn_(6)M_(4)] onto thiolated silica via thiol-ene click chemistry.Meanwhile,a capillary GC column statically coated with the chiral MOC [Zn_(6)M_(4)] was also fabricated.The results showed that the chiral MOC exhibits excellent enantioselectivity not only in normal phase HPLC(NP-HPLC) and reversed phase(RP-HPLC) but also in GC,and various racemates were well separated,including alcohols,diols,esters,ketones,ethers,amines,and epoxides.Importantly,CSP-A and CSP-B are complementary to commercially available Chiralcel OD-H and Chiralpak AD-H columns in enantioseparation,which can separate some racemates that could not be or could not well be separated by the two widely used commercial columns,suggesting the great potential of the two prepared CSPs in enantioseparation.This work reveals that the chiral MOC is potential versatile chiral recognition materials for both HPLC and GC,and also paves the way to expand the potential applications of MOCs.
基金Financial support from National Key R&D Program of China (No.2023YFA1507203)National Natural Science Foundation of China (Nos.22371149 and 22188101)+3 种基金the Fundamental Research Funds for the Central Universities (No.63224098)Frontiers Science Center for New Organic Matter,Nankai University (No.63181206)Nankai University are gratefully acknowledgedthe Haihe Laboratory of Sustainable Chemical Transformations for financial support。
文摘In this study,electrochemical C-H carboxylation of benzylamines with CO_(2) was reported.This linear paired electrolysis system enables efficient and economical synthesis of value-added α-amino acids(α-AAs) under mild conditions.Various substituted benzylamines containing diverse functional groups and even highly reactive moieties,such as cyano,amide and alkene groups could be successfully transformed to the carboxylated products.Notably,this method proved to be applicable to the late-stage modification of biorelevant compounds,highlighting its potential for synthetic chemistry.Mechanistic studies such as radical trapping experiments,kinetic isotope effect(KIE) tests and cyclic voltammetry(CV) studies provided useful insight into this transformation.
基金Supported by the National Natural Science Foundation of China(No.51905211)A Project of the“20 Regulations for New Universities”Funding Program of Jinan(No.202228116).
文摘Vortex-induced vibration(VIV)of an underwater manipulator in pulsating flow presents a notable engineering problem in precise control due to the velocity variation in the flow.This study investigates the VIV response of an underwater manipulator subjected to pulsating flow,focusing on how different postures affect the behavior of the system.The effects of pulsating parameters and manipulator arrangement on the hydrodynamic coefficient,vibration response,motion trajectory,and vortex shedding behaviors were analyzed.Results indicated that the cross flow vibration displacement in pulsating flow increased by 32.14%compared to uniform flow,inducing a shift in the motion trajectory from a crescent shape to a sideward vase shape.In the absence of interference between the upper and lower arms,the lift coefficient of the manipulator substantially increased with rising pulsating frequency,reaching a maximum increment of 67.0%.This increase in the lift coefficient led to a 67.05%rise in the vibration frequency of the manipulator in the in-line direction.As the pulsating amplitude increased,the drag coefficient of the underwater manipulator rose by 36.79%,but the vibration frequency in the cross-flow direction decreased by 56.26%.Additionally,when the upper and lower arms remained in a state of mutual interference,the cross-flow vibration amplitudes of the upper and lower arms were approximately 1.84 and 4.82 times higher in a circular-elliptical arrangement compared to an elliptical-circular arrangement,respectively.Consequently,the flow field shifted from a P+S pattern to a disordered pattern,disrupting the regularity of the motion trajectory.
基金funding support from the National Key R&D Program of China (Nos.2022YFA1503703,2023YFA1506700)the National Natural Science Foundation of China (Nos.22071118,22271162)the Haihe Laboratory of Sustainable Chemical Transformations and the Fundamental Research Funds for the Central Universities for financial support。
文摘Bicyclo[2.1.1]hexanes(BCHs) are structurally unique C(sp^(3))-rich bicyclic hydrocarbons that are gaining prominence in the field of medicinal chemistry as bioisosteres of benzenoids.The nitrile is an important functionality in drug development due to its ability to improve physicochemical and pharmacokinetic properties and facilitate potential noncovalent interactions with drug targets.Consequently,cyanoarene motifs are commonly found in drug development.The introduction of cyano-BCHs as potential bioisosteres of cyano-arenes shows great promise;however,there are currently no catalytic methods available for their synthesis.Herein,we report a palladium-catalyzed enantioselective [2σ+2π] cycloadditions of bicyclo[1.1.0]butanes with arylidenemalononitriles for the preparation of chiral cyano-BCHs.This method accommodated a wide range of substrates and tolerated various functional groups.The cyano-BCH products could be transformed to molecules with diverse functionality.Control experiments suggest that the reaction proceeds via a zwitterionic intermediate generated by palladium-mediated ring opening of vinyl-carbonyl bicyclo[1.1.0]butanes followed by stereoselective 1,2-addition and intramolecular allylic substitution reactions.
基金supported by Hebei Province Natural Science Foundation(H2023423037)The Government Funded Clinical Program of Hebei Province(No.ZF2025287)+1 种基金Special Project of Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation(No.YJY2024001)Chinese Medicine Scientific Research Program of Hebei Province(No.2025222).
文摘Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.
基金supported by the National Natural Science Foundation of China,No.81671263(to XX)Scientific Research and Innovation Team,Education Department of Anhui Province,China,No.2023AH010072(to XX)+1 种基金the Natural Science Foundation of Anhui Province,No.2208085MH221(to XX)The Key Projects for National Science Research of Education Department of Anhui Province,No.KJ2021A0851(to YD).
文摘Cmyc,a proto-oncogene,is expressed at extremely low levels in mature neurons and is traditionally thought to have no function in these cells.However,recent studies suggest that Cmyc may play a crucial role in maintaining the health and function of mature dopaminergic neurons.This study assessed the role of Cmyc in dopaminergic neurons and its significance in Parkinson’s disease.We used a conditional knockout approach to specifically delete Cmyc in substantia nigra dopaminergic neurons of adult mice.Our findings showed that Cmyc deletion led to progressive neuron loss,Parkinson’s disease-like symptoms,downregulation of Klotho,and upregulation of senescence-associated inflammatory factors,along with enhanced oxidative stress and nitrated alpha-synuclein accumulation,ultimately causing neuronal death.In vitro experiments confirmed increased senescence in C-MYC knockout cells,which was partially reversible by KLOTHO overexpression.We conclude that low-level Cmyc expression is essential for maintaining the health of mature dopaminergic neurons and preventing neurodegeneration,and suggest the c-Myc/Klotho axis as a potential therapeutic target for age-related neurodegenerative diseases,including Parkinson’s disease.Our study introduces a novel mouse model for Parkinson’s disease that replicates a condition associated with normal aging,offering a valuable tool for future research into disease mechanisms and therapeutic strategies.
基金Supported by the National Natural Science Foundation of China(Nos.52293472,22473096 and 22471164)。
文摘Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynamic size and slower degradation.It is key to develop facile methods to large-scale synthesis of polymer rings with tunable compositions and microstructures.Recent progresses in large-scale synthesis of polymer rings against single-chain dynamic nanoparticles,and the example applications in synchronous enhancing toughness and strength of polymer nanocomposites are summarized.Once there is the breakthrough in rational design and effective large-scale synthesis of polymer rings and their functional derivatives,a family of cyclic functional hybrids would be available,thus providing a new paradigm in developing polymer science and engineering.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金supported by the National Key Basic Research Program of China (2022YFA1402904)Basic Research Project of Shanghai Science and Technology Innovation Action (grant number 24CL2900900)the National Natural Science Foundation of China (grant number 61904034)
文摘Innovative use of HfO_(2)-based high-dielectric-permittivity materials could enable their integration into few-nanometre-scale devices for storing substantial quantities of electrical charges,which have received widespread applications in high-storage-density dynamic random access memory and energy-efficient complementary metal-oxide-semiconductor devices.During bipolar high electric-field cycling in numbers close to dielectric breakdown,the dielectric permittivity suddenly increases by 30 times after oxygen-vacancy ordering and ferroelectric-to-nonferroelectric phase transition of near-edge plasma-treated Hf_(0.5)Zr_(0.5)O_(2) thin-film capacitors.Here we report a much higher dielectric permittivity of 1466 during downscaling of the capacitor into the diameter of 3.85μm when the ferroelectricity suddenly disappears without high-field cycling.The stored charge density is as high as 183μC cm^(−2) at an operating voltage/time of 1.2 V/50 ns at cycle numbers of more than 10^(12) without inducing dielectric breakdown.The study of synchrotron X-ray micro-diffraction patterns show missing of a mixed tetragonal phase.The image of electron energy loss spectroscopy shows the preferred oxygen-vacancy accumulation at the regions near top/bottom electrodes as well as grain boundaries.The ultrahigh dielectric-permittivity material enables high-density integration of extremely scaled logic and memory devices in the future.
基金supported by the Shenzhen Hong Kong Joint Funding Project,No.SGDX20230116093645007(to LY)the Shenzhen Science and Technology Innovation Committee International Cooperation Project,No.GJHZ20200731095608025(to LY)+7 种基金Shenzhen Development and Reform Commission’s Intelligent Diagnosis,Treatment and Prevention of Adolescent Spinal Health Public Service Platform,No.S2002Q84500835(to LY)Shenzhen Medical Research Fund,No.B2303005(to LY)Team-based Medical Science Research Program,No.2024YZZ02(to LY)Zhejiang Provincial Natural Science Foundation of China,No.LWQ20H170001(to RL)Basic Research Project of Shenzhen Science and Technology from Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324103010029(to BY)Shenzhen Second People’s Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project,Nos.2023yjlcyj029(to BY),2023yjlcyj021(to LL)Guangdong Basic and Applied Basic Research Foundation,No.2022A1515110679(to LL)China Postdoctoral Science Foundation,No.2022M722203(to GL).
文摘Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.
基金funding from the National Natural Science Foundation of China(Award 91745203)supplemented by Central Universities'Basic Research Funds.We gratefully acknowledge the National Synchrotron Radiation Laboratory(NSRL,Hefei,China)for providing MCD-A and MCD-B beamlines for Soft XAS characterization.The authors are grateful to the Instrument and equipment sharing platform,College of Physics,Jilin University,for providing technical assistance in HT-XRD measurements.
文摘Ceramic cells promise ideal energy conversion and storage devices,making the development of efficient and robust air electrodes crucial for their application.In this study,a Ba_(0.4)Sr_(0.5)Cs_(0.1)Co_(0.7)Fe_(0.2)Nb_(0.1)O_(3−δ)(BSCCFN)air electrode,based on Ba_(0.5)Sr_(0.5)Co_(0.8)Fe_(0.2)O_(3−δ)(BSCF),is designed using a perovskite A-B-site ionic Lewis acid strength(ISA)polarization distribution strategy and is successfully applied in both oxygen-ion conducting solid oxide fuel cells(O-SOFCs)and proton-conducting reversible protonic ceramic cells(R-PCCs).When BSCCFN is used as the air electrode in O-SOFCs,a peak power density(PPD)of 1.45 W cm^(−2)is achieved at 650°C,whereas in R-PCCs,a PPD of 1.13 W cm^(−2)and a current density of−1.8 A cm^(−2)at 1.3 V are achieved at the same temperature and show stable reversibility over 100 h.Experimental measurements and theoretical calculations demonstrate that low-ISA Cs+doping accelerates the reaction kinetics of both oxygen ions and protons,while high-ISA Nb^(5+)doping enhances electrode stability.The synergistic effect of Cs^(+)and Nb^(5+)co-doping in the BSCCFN electrode lies in the ISA polarization distribution,which weakens the Co/Fe–O bond covalency,thereby promoting oxygen vacancy formation and facilitating the conduction of oxygen ions and protons.
基金supported by the National Natural Science Foundation of China,Nos.82473334(to LZ),82401629(to XL)the Major Scientific and Technological Achievements Transformation Project of Ningxia Hui Autonomous Region,No.2022CJE09013(to LZ)+4 种基金Mianyang Science and Technology Bureau(Mianyang Science and Technology Program),No.2023ZYDF097(to LZ)NHC Key Laboratory of Nuclear Technology Medical Transformation(Mianyang Central Hospital),No.2023HYX001(to LZ)Spinal Cord Diseases Clinical Medical Center of Yunnan Province,No.2024JSKFKT-16(to BG)the Natural Science Foundation of Sichuan Province,No.2024NSFSC1646(to XL)the China Postdoctoral Science Foundation,Nos.GZC20231811(to XL),2024T170601(to XL)and 2024M76228(to XL).
文摘Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.
文摘The transformer is one of the main components in the power network and transformer windings are one of the most expensive elements in the power transformer. Optimisation of winding distances is one of the most important parameters during the manufacturing of transformer. The distance between the windings in the two winding transformers is well known to transformer designers and manufacturers. However, insulation of the high voltage transformer with additional winding and tap winding is still a major problem for transformer designers. In this study, the additional winding to tap winding distance optimisation is made for a high voltage power transformer. Optimisation of the transformer's windings just not minimises the cost of the transformer but also increases the lifetime of the transformer. With additional winding and tap winding in high-voltage transformers, insulation distance is a major concern for minimising the cost and size of the high voltage transformer. In this study, an approach is made to balance the cost, size, and safety of high voltage transformers. The optimised distance and position between tap winding and additional winding are determined by using the finite element analysis. The finite element method results were also verified by making a prototype transformer.
基金support from National Key Research and Development Program of China(2024YFE0217100)the National Natural Science Foundation of China(21905006,22261160370,and 62105075)+7 种基金the Guangdong Provincial Science and Technology Plan(2021A0505110003)the Natural Science Foundation of Hunan Province,China(2023JJ50132)Guangxi Department of Science and Technology(2020GXNSFBA159049 and AD19110030)the Shenzhen Science and Technology Program(SGDX20230116093205009,JCYJ20220818100211025 and 2022378670)the Natural Science Foundation of Top Talent of SZTU(GDRC202343)financial support of Innovation and Technology Fund(#GHP/245/22SZ)The University Grant Council of the University of Hong Kong(grant No.2302101786)General Research Fund(grant Nos.17200823 and 17310624)from the Research Grants Council.
文摘Halide perovskites have emerged as promising materials for X-ray detection with exceptional properties and reasonable costs.Among them,heterostructures between 3D perovskites and low-dimensional perovskites attract intensive studies of their advantages due to low-level ion migration and decent stability.However,there is still a lack of methods to precisely construct heterostructures and a fundamental understanding of their structure-dependent optoelectronic properties.Herein,a gas-phase method was developed to grow 2D perovskites directly on 3D perovskites with nanoscale accuracy.In addition,the larger steric hindrance of organic layers of 2D perovskites was proved to enable slower ion migration,which resulted in reduced trap states and better stability.Based on MAPbBr_(3)single crystals with the(PA)_(2)PbBr_(4)capping layer,the X-ray detector achieved a sensitivity of 22,245μC Gy_(air)^(−1)cm^(−2),a response speed of 240μs,and a dark current drift of 1.17.10^(–4)nA cm^(−1)s^(−1)V^(−1),which were among the highest reported for state-of-the-art perovskite-based X-ray detectors.This study presents a precise synthesis method to construct perovskite-based heterostructures.It also brings an in-depth understanding of the relationship between lattice structures and properties,which are beneficial for advancing high-performance and cost-effective X-ray detectors.
基金supported by the National Natural Science Foundation of China,Nos.82374561(to JD),82174490(to JF)the Medical and Health Science and Technology Program of Zhejiang Province,No.2021RC098(to JD)the Research Project of Zhejiang Chinese Medical University,Nos.2022JKZKTS44(to JD),2022FSYYZZ07(to JF).
文摘Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.
基金financially supported by the National Key Research and Development Program of China (No. 2021YFB4000604)the National Natural Science Foundation of China (No. 52271220)+2 种基金the 111 Project (No. B12015)the Fundamental Research Funds for the Central UniversitiesHaihe Laboratory of Sustainable Chemical Transformations, Guangxi Collaborative Innovation Centre of Structure and Property for New Energy and Materials, Science Research and Technology Development Project of Guilin (No. 20210102-4)
文摘Novel hydrogen storage materials have propelled progress in hydrogen storage technologies.Magnesium hydride(MgH_(2))is a highly promising candidate.Nevertheless,several drawbacks,including the need for elevated thermal conditions,sluggish dehydrogena-tion kinetics,and high thermodynamic stability,limit its practical application.One effective method of addressing these challenges is cata-lyst doping,which effectively boosts the hydrogen storage capability of Mg-based materials.Herein,we review recent advancements in catalyst-doped MgH_(2) composites,with particular focus on multicomponent and high-entropy catalysts.Structure-property relationships and catalytic mechanisms in these doping strategies are also summarized.Finally,based on existing challenges,we discuss future research directions for the development of Mg-based hydrogen storage systems.
