Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and mammals.Its biological functions range from ion homeostas...Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and mammals.Its biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated T-cells.CN is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate Cna1p.The calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.展开更多
The technology for green and macro-conversion of solid waste biomass to prepare high-quality activated carbon demands urgent development.This study proposes a technique for synthesizing carbon adsorbents using trace K...The technology for green and macro-conversion of solid waste biomass to prepare high-quality activated carbon demands urgent development.This study proposes a technique for synthesizing carbon adsorbents using trace KOH-catalyzed CO_(2) activation.Comprehensive investigations were conducted on three aspects:physicochemical structure evolution of biochar,mechanistic understanding of trace KOH-facilitated CO_(2) activation processes,and application characteristics for CO_(2) adsorption.Results demonstrate that biochar activated by trace KOH(<10%)and CO_(2) achieves comparable specific surface area(1244.09 m^(2)/g)to that obtained with 100%KOH activation(1425.10 m^(2)/g).The pore structure characteristics(specific surface area and pore volume)are governed by CO and CH4 generated through K-salt catalyzed reactions between CO_(2) and biochar.The optimal CO_(2) adsorption capacities of KBC adsorbent reached 4.70 mmol/g(0℃)and 7.25 mmol/g(25℃),representing the maximum values among comparable carbon adsorbents.The 5%KBC-CO_(2) sample exhibited CO_(2) adsorption capacities of 3.19 and 5.01 mmol/g under respective conditions,attaining current average performance levels.Notably,CO_(2)/N_(2) selectivity(85∶15,volume ratio)reached 64.71 at 0.02 bar with robust cycling stability.Molecular dynamics simulations revealed that oxygen-containing functional groups accelerate CO_(2) adsorption kinetics and enhance micropore storage capacity.This technical route offers simplicity,environmental compatibility,and scalability,providing critical references for large-scale preparation of high-quality carbon materials.展开更多
Lowering the synthesis temperature of boron nitride nanotubes(BNNTs)is crucial for their development.The primary reason for adopting a high temperature is to enable the effective activation of highmelting-point solid ...Lowering the synthesis temperature of boron nitride nanotubes(BNNTs)is crucial for their development.The primary reason for adopting a high temperature is to enable the effective activation of highmelting-point solid boron.In this study,we developed a novel approach for efficiently activating boron by introducing alkali metal compounds into the conventional MgO–B system.This approach can be adopted to form various low-melting-point AM–Mg–B–O growth systems.These growth systems have improved catalytic capability and reactivity even under low-temperature conditions,facilitating the synthesis of BNNTs at temperatures as low as 850℃.In addition,molecular dynamics simulations based on density functional theory theoretically demonstrate that the systems maintain a liquid state at low temperatures and interact with N atoms to form BN chains.These findings offer novel insights into the design of boron activation and are expected to facilitate research on the low-temperature synthesis of BNNTs.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19...Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.展开更多
The use of carbon from waste biomass has the potential to eliminate the drawbacks of Li-S batteries and improve their overall performance.Chrome-tanned-leather-shavings(CTLS)are a readily available waste product that ...The use of carbon from waste biomass has the potential to eliminate the drawbacks of Li-S batteries and improve their overall performance.Chrome-tanned-leather-shavings(CTLS)are a readily available waste product that can be transformed into porous carbon.We prepared an ac-tivated carbon by microwave pyrolysis combined with KOH activator using the CTLS as starting materials.The carbon had a specific surface area of 556 m^(2)g^(-1) and a honeycomb-like structure.Two kinds of N-doped activated carbons were then synthesized by thermal decomposition of the activated carbon,either combined with urea,or impregnated with eth-anolamine.Both N-doped activated carbons have an in-creased number of nitrogen and amine surface groups.However,only the urea treatment was effective in improv-ing the initial capacity of the cell(1363 mAh g^(-1)),which is probably linked to the sorption of long-chain polysulfides.This investigation confirms that it is possible to use the thermal de-composition of urea to obtain carbon materials from CTLS for use as the sulfur-host cathode in Li-S batteries and improve their performance.A radial basis function neural network was fitted to provide statistical support for the experimental results,which confirmed the importance of the nitrogen content of the carbons in determining the discharge capacity of the cells.展开更多
Advanced oxidation processes(AOPs)governed by peroxide activation to produce highly oxidative active species have been extensively explored for environmental remediation.Nevertheless,the low diffusion rates,inadequate...Advanced oxidation processes(AOPs)governed by peroxide activation to produce highly oxidative active species have been extensively explored for environmental remediation.Nevertheless,the low diffusion rates,inadequate interactions of the reactants,and limited active site exposure hinder treatment efficiency.Porous carbocatalysts with high specific surface area,tunable pore size,and programmable active sites demonstrate outstanding performance in activating diverse types of peroxides to generate active species for treatment of aqueous organic pollutants.The pore-rich structures enhance reaction kinetics for peroxide activation by facilitating diffusion of the reactants and their interactions.Additionally,the structural flexibility of porous structures favors the accommodation of highly dispersed metal species and allows for precise tuning of the microenvironment around the active sites,which further enhances the catalytic activity.This review critically summarizes the recent research progress in the applications of engineered porous carbocatalysts for peroxide activation and outlines the prevailing pore construction methods in carbocatalysts.Moreover,engineering strategies to regulate the mass transfer efficiency and fine-tune the microenvironment around the active sites are systematically addressed to enhance their catalytic peroxide activation performances.Challenges and future research opportunities pertaining to the design,optimization,mechanistic investigation,and practical application of porous carbocatalysts in peroxide activation are also proposed.展开更多
Reproductive hormones associated with the hypothalamic-pituitary-gonadal(HPG)axis are closely linked to bone homeostasis.In this study,we demonstrate that Gonadotropin inhibitory hormone(GnIH,one of the key reproducti...Reproductive hormones associated with the hypothalamic-pituitary-gonadal(HPG)axis are closely linked to bone homeostasis.In this study,we demonstrate that Gonadotropin inhibitory hormone(GnIH,one of the key reproductive hormones upstream of the HPG axis)plays an indispensable role in regulating bone homeostasis and maintaining bone mass.We find that deficiency of GnIH or its receptor Gpr147 leads to a significant reduction in bone mineral density(BMD)in mice primarily by enhancement of osteoclast activation in vivo and in vitro.Mechanistically,GnIH/Gpr147 inhibits osteoclastogenesis by the PI3K/AKT,MAPK,NF-κB and Nfatc1 signaling pathways.Furthermore,GnIH treatment was able to alleviate bone loss in aging,ovariectomy(OVX)or LPS-induced mice.Moreover,the therapy using green light promotes the release of GnIH and rescues OVX-induced bone loss.In humans,serum GnIH increases and bone resorption markers decrease after green light exposure.Therefore,our study elucidates that GnIH plays an important role in maintaining bone homeostasis via modulating osteoclast differentiation and demonstrates the potential of GnIH therapy or green light therapy in preventing osteoporosis.展开更多
Electrocatalytic CO_(2)reduction reaction(CO_(2)RR)to ethylene(C_(2)H_(4))represents a promising approach to reducing CO_(2)emissions and producing high-value chemicals.The ethylene productivity is always limited by t...Electrocatalytic CO_(2)reduction reaction(CO_(2)RR)to ethylene(C_(2)H_(4))represents a promising approach to reducing CO_(2)emissions and producing high-value chemicals.The ethylene productivity is always limited by the slow reaction kinetics and the high-performance catalysts are significantly desired.Many efforts have been made to develop a catalyst to activate CO_(2)molecules.However,as another reactant,H2O activation does not receive the attention it deserves.In particular,slow H2O dissociation kinetics limit the rate of proton supply,severely impairing the production of C_(2)H_(4).Here,we designed a MgO-modified CuO catalyst(MgO/CuO),which can promote H2O dissociation and enhance CO_(2)adsorption at the same time to realize the efficient ethylene production.The optimal catalyst exhibits a Faraday efficiency for C_(2)H_(4)reached 54.4%at−1.4 V vs.RHE in an H-cell,which is 1.4 times that of pure CuO(37.9%),and it was further enhanced to a 56.7%in a flow cell,with a high current density of up to 535.9 mA cm−2 at−1.0 V vs.RHE.Experimental and theoretical calculations show that MgO/CuO plays a bifunctional role in the CO_(2)RR,which facilitates the adsorption and activation of CO_(2)by CuO and simultaneously accelerates H2O dissociation by MgO doping.The in situ XRD experiments demonstrate that the introduction of MgO protects CuO active phase to avoid overreduction and preserves the active centers for CO_(2)RR.In combination with in situ FTIR and DFT calculations,the protonation process from*CO to*COH and asymmetric C–C coupling step are promoted by the enhanced water activation and proton coupling on MgO/CuO.This work provides new insights into the CO_(2)and H_(2)O coactivation mechanism in CO_(2)RR and a potential universal strategy to design ethylene production electrocatalysts.展开更多
BACKGROUND Pain in the back or pelvis or fear of back pain may affect the timing or cocontraction of the core muscles.In both static and dynamic movements,the Sahrmann core stability test provides an assessment of cor...BACKGROUND Pain in the back or pelvis or fear of back pain may affect the timing or cocontraction of the core muscles.In both static and dynamic movements,the Sahrmann core stability test provides an assessment of core muscle activation and a person's ability to stabilize the lumbopelvic complex.Preparatory cues and images can be used to increase the activation of these muscles.To attain optimal movement patterns,it will be necessary to determine what cueing will give the most effective results for core stability.AIM To investigate the effects of external and internal cues on core muscle activation during the Sahrmann five-level core stability test.METHODS Total 68 participants(21.83±3.47 years)were randomly allocated to an external(n=35)or internal cue group(n=33).Participants performed the Sahrmann fivelevel core stability test without a cue as baseline and the five-level stability exercises with an internal or external cue.External cue group received a pressure biofeedback unit(PBU),and the internal cue group received an audio cue.A Delsys Trigno^(TM)surface electromyography unit was used for muscle activation from the rectus abdominis,external oblique,and transverse abdominis/internal oblique muscles.RESULTS Linear mixed effects model analysis showed that cueing had a significant effect on core muscle activation(P=0.001);however,there was no significant difference between cue types(internal or external)(P=0.130).CONCLUSION Both external and internal cueing have significant effects on core muscle activation during the Sahrmann five-level core stability test and the PBU does not create higher muscle activation than internal cueing.展开更多
The activation of the N≡N triple bond in N_(2) is a fascinating topic in nitrogen chemistry.The transition metals have been demonstrated to effectively modulate the reactivity of N_(2) molecules under high pressure,l...The activation of the N≡N triple bond in N_(2) is a fascinating topic in nitrogen chemistry.The transition metals have been demonstrated to effectively modulate the reactivity of N_(2) molecules under high pressure,leading to nitrogen-rich compounds.However,their use often results in a significant reduction in energy density.In this work,we propose a series of low-enthalpy nitrogen-rich phases in CN_(x)(x=3,...,7)compounds using a first-principles crystal structure search method.The results of calculations reveal that all these CN compounds are assembled from both CN_(4) tetrahedra and N_(x)(x=1,2,or 5)species.Strikingly,we find that the CN_(4) tetrahedron can effectively activate the N≡N bond through weakening of the π orbital of N_(2) under a pressure of 40 GPa,leading to stable CN polynitrides.The robust structural framework of CN polynitrides containing C-N and N-N bonds plays a crucial role in enhancing their structural stability,energy density,and hardness.Among these polynitrides,CN_(6) possesses not only a very high mass density of 3.19 g/cm^(3),but also an ultrahigh energy density of 28.94 kJ/cm^(3),which represents a significant advance in the development of energetic materials using high-pressure methods.This work provides new insights into the mechanism of N_(2) activation under high pressure,and offers a promising pathway to realize high-performance energetic materials.展开更多
This study documents pioneering results in marginal wells in Texas,where the application of RDV-00■restored production through delayed protonic activation catalyzed by reservoir energy.The product,based on RDV■(Vaso...This study documents pioneering results in marginal wells in Texas,where the application of RDV-00■restored production through delayed protonic activation catalyzed by reservoir energy.The product,based on RDV■(Vasoactive Dynamic Reactor)technology,operates via:Controlled protonation of molecular structures;Release of energetic carbocations;Autonomous transformation without external inputs.(a)Case 1(Well#E2-Starr County):Certified as“dry”by RRC(2022)after 48 months at 0 BPD;8 months post-injection of 5 gal RDV-00■(Fluid column:37 bbl;Wellhead pressure:80 psi(vs.0 psi initially)).(b)Case 2(Well#P1-Luling Field):Historical stripper well(0.25-0.5 BPD);23 months of immobilization with 15 gal RDV-00■;Critical results:(1)Initial production:42 BPD(8,400%above baseline);(2)Shut-in wellhead pressure:40 psi(neighboring wells=0-3 psi);(3)Current behavior:Continuous recharge from reservoir(well shut-in due to lack of storage).(c)Technically Significant Observations:(1)First case of self-sustaining reactivation in depleted wells;(2)Mechanism validated by Autonomous pressure generation(0→40-80 psi),and Continuous flow without additional stimulation;(3)No documented precedents in SPE/OnePetro literature to our knowledge.展开更多
The synergetic technology of hydrodynamic cavitation(HC)and peroxydisulfate(PDS)has been adopted for the treatment of organic pollutants,while the rationale behind the thermal-activation of PDS in this process remains...The synergetic technology of hydrodynamic cavitation(HC)and peroxydisulfate(PDS)has been adopted for the treatment of organic pollutants,while the rationale behind the thermal-activation of PDS in this process remains lacking.This paper presented investigation on the degradation of tetracycline under two types of operating conditions,including“internal reaction conditions”(pH value and TC/PDS molar ratio)and“external physical conditions”(hole shape,solution temperature and inlet pressure).Special emphasis was paid on the analysis of thermal effects through a robust modeling approach.The results showed that a synergy index of 6.26 and a degradation rate of 56.71%could be obtained by the HC-PDS process,respectively,when the reaction conditions were optimized.Quenching experiment revealed that·OH and·SO_(4)^(-)were the predominant free radicals and their contribution to the degradation was 75.4%and 24.6%respectively,since a part of·SO_(4)^(-)was transformed into·OH in the solution.The thermal activation of PDS mainly occurred near the hole where the fitting temperature was around 340 K,while·OH was generated in the bubble collapse region downstream the hole,where the temperature was much higher and favorable for the cleavage of water molecular.The average temperature under different external physical conditions was in good consistence with the degradation rates.This research developed a useful method to effectively evaluate the activation extent of PDS by HC and could provide reliable guidance for further development of cavitational reactors to treat organic pollutants based on this hybrid approach.展开更多
In-situ exploration of deep-sea seabed resources is a valuable research direction.Neutron activation-based in-situ exploration methods for seabed polymetallic nodules or crust resources are theoretically feasible beca...In-situ exploration of deep-sea seabed resources is a valuable research direction.Neutron activation-based in-situ exploration methods for seabed polymetallic nodules or crust resources are theoretically feasible because of the high content and high neutron capture cross-section of manganese in these nodules or crusts.However,to date,only a few relevant studies have been conducted.In this study,a prototype deep-sea in-situ neutron activation spectrometer(DINAS)was designed for resource exploration.Through an analysis of the principles of the spectrometer combined with Monte Carlo simulations of the physical principles and finite element simulations of deep-sea pressure,the structure and fundamental components of the spectrometer were determined.The inner core of the spectrometer comprised three components:a compact neutron generator for neutron production,gamma-ray detectors,and an electronics system.The gamma-ray detector array of the spectrometer consisted of LaBr_(3)and Bi_(4)Ge_(3)O_(12)scintillation crystals coupled with silicon photomultiplier arrays.The electronics system was divided into two modules to implement the SiPM readout and digital signal analysis along the modular design lines.The experimental activation of neutron beamlines at the China Spallation Neutron Source demonstrated the capability of the spectrometer detectors to detect activated gamma-rays and showed that the spectrometer achieved an energy resolution of 2.8%at 847 keV for the LaBr_(3)detector and 6.7%at 2.113 MeV for the BGO detector.The laboratory model experiment tested the functionality of the spectrometer prototype,whereas the Geant4 simulation verified the reliability of the Monte Carlo method.The method and prototype proposed in this study proved feasible for the in-situ detection of polymetallic nodules or crusts in deep-sea environments.展开更多
NLRP3 inflammasome activation is pivotal for cytokine secretion and pyroptosis in response to diverse stimuli,playing a crucial role in innate immunity.While extensively studied in mammals,the regulatory mechanisms go...NLRP3 inflammasome activation is pivotal for cytokine secretion and pyroptosis in response to diverse stimuli,playing a crucial role in innate immunity.While extensively studied in mammals,the regulatory mechanisms governing NLRP3 activation in non-mammalian vertebrates remain largely unexplored.Teleosts,as basal vertebrates,represent an ideal model for exploring the evolutionary trajectory of inflammasome regulation.In this study,ABE assays,confocal microscopy,and biochemical analyses were applied to systematically characterize the mechanisms underlying NLRP3 inflammasome in teleosts,using large yellow croakers(Larimichthys crocea,Lc)and zebrafish(Danio rerio,Dr)as representative models.Our findings revealed a previously unrecognized palmitoylation-dependent regulatory mechanism essential for teleost NLRP3 activation.Specifically,zDHHC18-mediated palmitoylation at a teleost-specific cysteine residue(C946 in LcNLRP3,C1037 in DrNLRP3)was required for the translocation of NLRP3 to the dispersed trans-Golgi network,facilitating its subsequent recruitment to the microtubule-organizing center.This membrane trafficking was crucial for inflammasome assembly and downstream inflammatory responses.These findings provide new insights into the distinct regulatory mechanisms of NLRP3 activation in teleosts,highlighting an evolutionary divergence that contributes to innate immunity adaptation in early vertebrates.展开更多
Rotenone is a lipophilic herbicide extensively utilized in experimental neurodegenerative models because of its capacity to disrupt complex I of the mitochondrial electron transport chain.This inhibition results in re...Rotenone is a lipophilic herbicide extensively utilized in experimental neurodegenerative models because of its capacity to disrupt complex I of the mitochondrial electron transport chain.This inhibition results in reduced ATP synthesis,elevated reactive oxygen species(ROS)formation,and mitochondrial malfunction,which instigates oxidative stress and cellular damage,critical elements in neurodegenerative disorders like Parkinson’s disease(PD),amyotrophic lateral sclerosis(ALS),and Alzheimer’s disease(AD).In addition to causing direct neuronal injury,rotenone significantly contributes to the activation of glial cells,specifically microglia and astrocytes.Activated microglia assumes a proinflammatory(M1)phenotype,distinguished by the secretion of inflammatory cytokines including tumor necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6),with the generation of nitric oxide and ROS,which exacerbate the neuronal injury.Astrocytes can intensify neuroinflammation by secreting proinflammatory molecules and impairing their neuroprotective roles.Our hypothesis is that rotenone is posited to elicit a neuroinflammatory response via mitochondrial malfunction,ROS generation,and the activation of proinflammatory pathways in microglia and astrocytes.This mechanism leads to accelerated neuronal impair-ment,promoting neurodegeneration.Comprehending the inflammatory pathways activated by rotenone is crucial for pinpointing therapeutic targets to regulate glial responses and mitigate the advancement of neurodegenerative disorders linked to mitochondrial malfunction and chronic inflammation.This review examines the function of glial cells and critical inflammatory pathways,namely Nuclear factor kappaβ(NF-κB),Phosphoinositide 3-kinase/Protein kinase B/Mammalian target of rapamycin(PI3K/AKT/mTOR),and Wnt/β-catenin signaling pathway in Parkinson’s disease,Alzheimer’s disease,and ALS,emphasizing illness-specific responses and the translational constraints of rotenone-based models.The objective is to consolidate existing understanding regarding the role of rotenone-induced mitochondrial failure in promoting glial activation and neuroinflammation,highlighting the necessity for additional research into these pathways.Despite the prevalent application of rotenone in experimental models,its specific effects on glial-mediated inflammation are inadequately comprehended,necessitating further investigation to guide the formulation of targeted therapeutic strategies.展开更多
Mechanical activation (MA) is a significant pretreatment technique for enhancing the dissolution of mineral;however, its promotion effect on the role of pyrite during chalcopyrite bioleaching has not been elucidated u...Mechanical activation (MA) is a significant pretreatment technique for enhancing the dissolution of mineral;however, its promotion effect on the role of pyrite during chalcopyrite bioleaching has not been elucidated up to now. In this study, the effect of MA on the role of pyrite on chalcopyrite bioleaching mediated by Acidithiobacillus ferroxidans was investigated by X-ray diffraction, scanning electron microscopy, particle size distribution analysis, and electrochemical measurement. The results showed MA could significantly reduce the minerals particle size, and increase the specific surface area and surface energy of minerals. For example, the d50 of chalcopyrite reduced from 13.40 to 0.31 μm after MA. The copper extraction of mixed MA-chalcopyrite and MA-pyrite system was 63.4%, which exhibited a 51.8% enhancement compared to the non-activated mixed system. Electrochemical experiments identified that the strengthening effect of pyrite on chalcopyrite dissolution was negligible before MA. After MA, the dissolution mechanism of chalcopyrite was not changed, and pyrite could not only provide additional oxidants (acids and iron) but also act as the cathode in the galvanic couple. In this case, the bioleaching of chalcopyrite was accelerated. Therefore, a model of the promotion effect of mechanical activation on the role of pyrite on chalcopyrite bioleaching was proposed.展开更多
The thermal effect has a significant impact on the activation and slip characteristics of fractures.In this study,four pairs of granite fractures were treated by temperatures T ranging from 25℃to 900℃.The fractures ...The thermal effect has a significant impact on the activation and slip characteristics of fractures.In this study,four pairs of granite fractures were treated by temperatures T ranging from 25℃to 900℃.The fractures were then employed to carry out triaxial unloading-induced shear slip experiments.The step unloading of confining pressure σ_(3) was used as a disturbed stress to activate fractures that were in a near-critical stress state.The slip characteristics,frictional behaviors,as well as damage modes of fractures with different T,were systematically investigated.The results show that at T=25℃ and 300℃,no stick-slip events were observed,and the slipping process of the fractures was characterized by aseismic slip and creep,respectively.For T=600℃ and 900℃,the fractures slipped stably,with occasional interruptions by episodic stick-slip events.Ultimately,they entered the dynamic slip stage after a series of consecutive stick-slip episodes.With increasing T,the number of sheared-off asperities increases due to thermal damage,which in turn leads to an increase in the occurrence of stick-slip events.The slip modes of the fractures transited from friction strengthening to friction weakening.As T increased from 300℃to 900℃,a considerable quantity of generated gouge layer acted as a lubricant for the slipping of fractures.This resulted in a notable increase in the proportion of aseismic slip,which rose from 24%to 54%.As the temperature increased from 25℃to 900℃,the crack length increased exponentially from 2.975 mm to 45.349 mm.For T=600℃ and 900℃,the duration between stick-slip events decreased as stick-slip events occurred more frequently.展开更多
Neutron-induced gamma-ray imaging is a spectroscopic technique that uses characteristic gamma rays to infer the elemental distribution of an object.Currently,this technique requires the use of large facilities to supp...Neutron-induced gamma-ray imaging is a spectroscopic technique that uses characteristic gamma rays to infer the elemental distribution of an object.Currently,this technique requires the use of large facilities to supply a high neutron flux and a time-consuming detection procedure involving direct collimating measurements.In this study,a new method based on low neutron flux was proposed.A single-pixel gamma-ray detector combined with random pattern gamma-ray masks was used to measure the characteristic gamma rays emitted from the sample.Images of the elemental distribution in the sample,comprising 30×30 pixels,were reconstructed using the maximum-likelihood expectation-maximization algorithm.The results demonstrate that the elemental imaging of the sample can be accurately determined using this method.The proposed approach,which eliminates the need for high neutron flux and scanning measurements,can be used for in-field imaging applications.展开更多
Ferroptosis in combination with immune therapy emerges as a promising approach for cancer therapy.Herein,dual-responsive metal-polyphenol coordinated nanomedicines were developed for pH/glutathione(GSH)-responsive syn...Ferroptosis in combination with immune therapy emerges as a promising approach for cancer therapy.Herein,dual-responsive metal-polyphenol coordinated nanomedicines were developed for pH/glutathione(GSH)-responsive synergistic ferroptosis and immunotherapy.Our innovative strategy involves the development of a manganese-polyphenol coordinated nanostructure,leveraging the biocompatibility of bovine serum albumin(BSA)as a template to encapsulate the anticancer drug sorafenib.The tumor microenvironment(pH/GSH)prompts the disassembly of MnO_(2)and epigallocatechin gallate(EGCG),thereby releases the anticancer payload.Concurrently,MnO_(2)acts to deplete intracellular GSH,which in turn suppresses glutathione peroxidase activity,leading to an accumulation of lipid peroxides with cell ferroptosis.Additionally,the release of Mn^(2+)ions bolster the cyclic guanosine monophosphlic acid(GMP)-adenosine monophosphlic acid(AMP)synthase-stimulator of interferon gene(cGAS-STING)pathway,which,in conjunction with the immunogenic cell death(ICD)effect induced by tumor cell apoptosis,significantly promotes dendritic cell(DC)maturation and enhances the presentation of tumor antigens.This successively ignites a robust innate and adaptive immune response.Both in vitro and in vivo experiments have demonstrated that the concurrent administration of ferroptosis-inducing and immune-stimulating therapies can significantly inhibit tumor growth.展开更多
Designing and synthesizing nanomedicines with multi-modal tumor therapeutic capabilities is the key to cancer treatment.Herein,we prepared MICG nanoparticles(NPs)by assembling glucose oxidase(GOx)and indocyanine green...Designing and synthesizing nanomedicines with multi-modal tumor therapeutic capabilities is the key to cancer treatment.Herein,we prepared MICG nanoparticles(NPs)by assembling glucose oxidase(GOx)and indocyanine green(ICG)with manganese carbonate(MnCO_(3))NPs for starvation therapy cascaded chemodynamic therapy,enhanced phototherapy and immune activation.In MICG NPs,the GOx consumes intratumoral glucose resulting in starvation therapy,and simultaneously produces H_(2)O_(2)and decreases p H in tumor.The intensified acidic tumor environment promotes the decomposition of MnCO_(3)NPs to release Mn^(2+).The Mn^(2+)further catalyzes H_(2)O_(2)to generate hydroxyl radical for chemodynamic therapy.While ICG can generate singlet oxygen(^(1)O_(2))and heat to kill cancer cells through phototherapy mechanism.The hydroxyl radical and ^(1)O_(2) will further accelerate the oxidative stress,intensify immunogenic cell death,induce dendritic cell maturation,and thus activate systemic immunity.This work provides a new therapeutic platform for combining therapy of tumor.展开更多
文摘Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and mammals.Its biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated T-cells.CN is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate Cna1p.The calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.
基金supported by the National Natural Science Foundation of China(52376103,542B2081).
文摘The technology for green and macro-conversion of solid waste biomass to prepare high-quality activated carbon demands urgent development.This study proposes a technique for synthesizing carbon adsorbents using trace KOH-catalyzed CO_(2) activation.Comprehensive investigations were conducted on three aspects:physicochemical structure evolution of biochar,mechanistic understanding of trace KOH-facilitated CO_(2) activation processes,and application characteristics for CO_(2) adsorption.Results demonstrate that biochar activated by trace KOH(<10%)and CO_(2) achieves comparable specific surface area(1244.09 m^(2)/g)to that obtained with 100%KOH activation(1425.10 m^(2)/g).The pore structure characteristics(specific surface area and pore volume)are governed by CO and CH4 generated through K-salt catalyzed reactions between CO_(2) and biochar.The optimal CO_(2) adsorption capacities of KBC adsorbent reached 4.70 mmol/g(0℃)and 7.25 mmol/g(25℃),representing the maximum values among comparable carbon adsorbents.The 5%KBC-CO_(2) sample exhibited CO_(2) adsorption capacities of 3.19 and 5.01 mmol/g under respective conditions,attaining current average performance levels.Notably,CO_(2)/N_(2) selectivity(85∶15,volume ratio)reached 64.71 at 0.02 bar with robust cycling stability.Molecular dynamics simulations revealed that oxygen-containing functional groups accelerate CO_(2) adsorption kinetics and enhance micropore storage capacity.This technical route offers simplicity,environmental compatibility,and scalability,providing critical references for large-scale preparation of high-quality carbon materials.
基金supported by the National Natural Science Foundation of China(No.51972162)the Fundamental Research Funds for the Central Universities(No.2024300440).
文摘Lowering the synthesis temperature of boron nitride nanotubes(BNNTs)is crucial for their development.The primary reason for adopting a high temperature is to enable the effective activation of highmelting-point solid boron.In this study,we developed a novel approach for efficiently activating boron by introducing alkali metal compounds into the conventional MgO–B system.This approach can be adopted to form various low-melting-point AM–Mg–B–O growth systems.These growth systems have improved catalytic capability and reactivity even under low-temperature conditions,facilitating the synthesis of BNNTs at temperatures as low as 850℃.In addition,molecular dynamics simulations based on density functional theory theoretically demonstrate that the systems maintain a liquid state at low temperatures and interact with N atoms to form BN chains.These findings offer novel insights into the design of boron activation and are expected to facilitate research on the low-temperature synthesis of BNNTs.
基金supported by GILO Foundation.This research is in part supported by Korea Drug Development Fund funded by Ministry of Science and ICT,Ministry of Trade,Industry,and Energy,and Ministry of Health and Welfare(RS-2023-00282595,Republic of Korea).
文摘Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.
文摘The use of carbon from waste biomass has the potential to eliminate the drawbacks of Li-S batteries and improve their overall performance.Chrome-tanned-leather-shavings(CTLS)are a readily available waste product that can be transformed into porous carbon.We prepared an ac-tivated carbon by microwave pyrolysis combined with KOH activator using the CTLS as starting materials.The carbon had a specific surface area of 556 m^(2)g^(-1) and a honeycomb-like structure.Two kinds of N-doped activated carbons were then synthesized by thermal decomposition of the activated carbon,either combined with urea,or impregnated with eth-anolamine.Both N-doped activated carbons have an in-creased number of nitrogen and amine surface groups.However,only the urea treatment was effective in improv-ing the initial capacity of the cell(1363 mAh g^(-1)),which is probably linked to the sorption of long-chain polysulfides.This investigation confirms that it is possible to use the thermal de-composition of urea to obtain carbon materials from CTLS for use as the sulfur-host cathode in Li-S batteries and improve their performance.A radial basis function neural network was fitted to provide statistical support for the experimental results,which confirmed the importance of the nitrogen content of the carbons in determining the discharge capacity of the cells.
基金supports from the National Natural Science Foundation of China(Nos.22478426 and 22278436)Young Elite Scientists Sponsorship Program by BAST(No.1101020370359)Science Foundation of China University of Petroleum,Beijing(No.2462021QNXZ009)。
文摘Advanced oxidation processes(AOPs)governed by peroxide activation to produce highly oxidative active species have been extensively explored for environmental remediation.Nevertheless,the low diffusion rates,inadequate interactions of the reactants,and limited active site exposure hinder treatment efficiency.Porous carbocatalysts with high specific surface area,tunable pore size,and programmable active sites demonstrate outstanding performance in activating diverse types of peroxides to generate active species for treatment of aqueous organic pollutants.The pore-rich structures enhance reaction kinetics for peroxide activation by facilitating diffusion of the reactants and their interactions.Additionally,the structural flexibility of porous structures favors the accommodation of highly dispersed metal species and allows for precise tuning of the microenvironment around the active sites,which further enhances the catalytic activity.This review critically summarizes the recent research progress in the applications of engineered porous carbocatalysts for peroxide activation and outlines the prevailing pore construction methods in carbocatalysts.Moreover,engineering strategies to regulate the mass transfer efficiency and fine-tune the microenvironment around the active sites are systematically addressed to enhance their catalytic peroxide activation performances.Challenges and future research opportunities pertaining to the design,optimization,mechanistic investigation,and practical application of porous carbocatalysts in peroxide activation are also proposed.
基金National Key Research and Development Program of China(2023YFB3810200 to J.L.)National Natural Science Foundation of China(92168204,82225030 to J.L.)Fundamental Research Funds for the Central Universities(22120210586 to J.L.)。
文摘Reproductive hormones associated with the hypothalamic-pituitary-gonadal(HPG)axis are closely linked to bone homeostasis.In this study,we demonstrate that Gonadotropin inhibitory hormone(GnIH,one of the key reproductive hormones upstream of the HPG axis)plays an indispensable role in regulating bone homeostasis and maintaining bone mass.We find that deficiency of GnIH or its receptor Gpr147 leads to a significant reduction in bone mineral density(BMD)in mice primarily by enhancement of osteoclast activation in vivo and in vitro.Mechanistically,GnIH/Gpr147 inhibits osteoclastogenesis by the PI3K/AKT,MAPK,NF-κB and Nfatc1 signaling pathways.Furthermore,GnIH treatment was able to alleviate bone loss in aging,ovariectomy(OVX)or LPS-induced mice.Moreover,the therapy using green light promotes the release of GnIH and rescues OVX-induced bone loss.In humans,serum GnIH increases and bone resorption markers decrease after green light exposure.Therefore,our study elucidates that GnIH plays an important role in maintaining bone homeostasis via modulating osteoclast differentiation and demonstrates the potential of GnIH therapy or green light therapy in preventing osteoporosis.
基金supported by the National Natural Science Foundation of China(Grant No.U21B2099,U22A20425,and 22208377)Natural Science Foundation of Shandong Province(ZR2021QE062)Fundamental Research Funds for the Central Universities,Ocean University of China(grant number 202364004)。
文摘Electrocatalytic CO_(2)reduction reaction(CO_(2)RR)to ethylene(C_(2)H_(4))represents a promising approach to reducing CO_(2)emissions and producing high-value chemicals.The ethylene productivity is always limited by the slow reaction kinetics and the high-performance catalysts are significantly desired.Many efforts have been made to develop a catalyst to activate CO_(2)molecules.However,as another reactant,H2O activation does not receive the attention it deserves.In particular,slow H2O dissociation kinetics limit the rate of proton supply,severely impairing the production of C_(2)H_(4).Here,we designed a MgO-modified CuO catalyst(MgO/CuO),which can promote H2O dissociation and enhance CO_(2)adsorption at the same time to realize the efficient ethylene production.The optimal catalyst exhibits a Faraday efficiency for C_(2)H_(4)reached 54.4%at−1.4 V vs.RHE in an H-cell,which is 1.4 times that of pure CuO(37.9%),and it was further enhanced to a 56.7%in a flow cell,with a high current density of up to 535.9 mA cm−2 at−1.0 V vs.RHE.Experimental and theoretical calculations show that MgO/CuO plays a bifunctional role in the CO_(2)RR,which facilitates the adsorption and activation of CO_(2)by CuO and simultaneously accelerates H2O dissociation by MgO doping.The in situ XRD experiments demonstrate that the introduction of MgO protects CuO active phase to avoid overreduction and preserves the active centers for CO_(2)RR.In combination with in situ FTIR and DFT calculations,the protonation process from*CO to*COH and asymmetric C–C coupling step are promoted by the enhanced water activation and proton coupling on MgO/CuO.This work provides new insights into the CO_(2)and H_(2)O coactivation mechanism in CO_(2)RR and a potential universal strategy to design ethylene production electrocatalysts.
文摘BACKGROUND Pain in the back or pelvis or fear of back pain may affect the timing or cocontraction of the core muscles.In both static and dynamic movements,the Sahrmann core stability test provides an assessment of core muscle activation and a person's ability to stabilize the lumbopelvic complex.Preparatory cues and images can be used to increase the activation of these muscles.To attain optimal movement patterns,it will be necessary to determine what cueing will give the most effective results for core stability.AIM To investigate the effects of external and internal cues on core muscle activation during the Sahrmann five-level core stability test.METHODS Total 68 participants(21.83±3.47 years)were randomly allocated to an external(n=35)or internal cue group(n=33).Participants performed the Sahrmann fivelevel core stability test without a cue as baseline and the five-level stability exercises with an internal or external cue.External cue group received a pressure biofeedback unit(PBU),and the internal cue group received an audio cue.A Delsys Trigno^(TM)surface electromyography unit was used for muscle activation from the rectus abdominis,external oblique,and transverse abdominis/internal oblique muscles.RESULTS Linear mixed effects model analysis showed that cueing had a significant effect on core muscle activation(P=0.001);however,there was no significant difference between cue types(internal or external)(P=0.130).CONCLUSION Both external and internal cueing have significant effects on core muscle activation during the Sahrmann five-level core stability test and the PBU does not create higher muscle activation than internal cueing.
基金supported by the Higher Educational Youth Innovation Science and Technology Program Shandong Province(Grant Nos.2022KJ183 and 2022KJ175)the Natural Science Foundation of Shandong Province(Grant Nos.ZR2023MA016 and ZR2023JQ001)+1 种基金the National Natural Science Foundation of China(Grant Nos.11974208 and 12374012)financial support from the award of Taishan Scholar(Grant No.tsqn202211128).
文摘The activation of the N≡N triple bond in N_(2) is a fascinating topic in nitrogen chemistry.The transition metals have been demonstrated to effectively modulate the reactivity of N_(2) molecules under high pressure,leading to nitrogen-rich compounds.However,their use often results in a significant reduction in energy density.In this work,we propose a series of low-enthalpy nitrogen-rich phases in CN_(x)(x=3,...,7)compounds using a first-principles crystal structure search method.The results of calculations reveal that all these CN compounds are assembled from both CN_(4) tetrahedra and N_(x)(x=1,2,or 5)species.Strikingly,we find that the CN_(4) tetrahedron can effectively activate the N≡N bond through weakening of the π orbital of N_(2) under a pressure of 40 GPa,leading to stable CN polynitrides.The robust structural framework of CN polynitrides containing C-N and N-N bonds plays a crucial role in enhancing their structural stability,energy density,and hardness.Among these polynitrides,CN_(6) possesses not only a very high mass density of 3.19 g/cm^(3),but also an ultrahigh energy density of 28.94 kJ/cm^(3),which represents a significant advance in the development of energetic materials using high-pressure methods.This work provides new insights into the mechanism of N_(2) activation under high pressure,and offers a promising pathway to realize high-performance energetic materials.
文摘This study documents pioneering results in marginal wells in Texas,where the application of RDV-00■restored production through delayed protonic activation catalyzed by reservoir energy.The product,based on RDV■(Vasoactive Dynamic Reactor)technology,operates via:Controlled protonation of molecular structures;Release of energetic carbocations;Autonomous transformation without external inputs.(a)Case 1(Well#E2-Starr County):Certified as“dry”by RRC(2022)after 48 months at 0 BPD;8 months post-injection of 5 gal RDV-00■(Fluid column:37 bbl;Wellhead pressure:80 psi(vs.0 psi initially)).(b)Case 2(Well#P1-Luling Field):Historical stripper well(0.25-0.5 BPD);23 months of immobilization with 15 gal RDV-00■;Critical results:(1)Initial production:42 BPD(8,400%above baseline);(2)Shut-in wellhead pressure:40 psi(neighboring wells=0-3 psi);(3)Current behavior:Continuous recharge from reservoir(well shut-in due to lack of storage).(c)Technically Significant Observations:(1)First case of self-sustaining reactivation in depleted wells;(2)Mechanism validated by Autonomous pressure generation(0→40-80 psi),and Continuous flow without additional stimulation;(3)No documented precedents in SPE/OnePetro literature to our knowledge.
基金supported by the National Natural Science Foundation of China(Nos.22136003 and 21972073)the Opening foundation of the Engineering Research Center of Ecoenvironment in Three Gorges Reservoir Region,Ministry of Education(No.KF2023-01)the Natural Science Foundation of Yichang City(No.A22-3-005)。
文摘The synergetic technology of hydrodynamic cavitation(HC)and peroxydisulfate(PDS)has been adopted for the treatment of organic pollutants,while the rationale behind the thermal-activation of PDS in this process remains lacking.This paper presented investigation on the degradation of tetracycline under two types of operating conditions,including“internal reaction conditions”(pH value and TC/PDS molar ratio)and“external physical conditions”(hole shape,solution temperature and inlet pressure).Special emphasis was paid on the analysis of thermal effects through a robust modeling approach.The results showed that a synergy index of 6.26 and a degradation rate of 56.71%could be obtained by the HC-PDS process,respectively,when the reaction conditions were optimized.Quenching experiment revealed that·OH and·SO_(4)^(-)were the predominant free radicals and their contribution to the degradation was 75.4%and 24.6%respectively,since a part of·SO_(4)^(-)was transformed into·OH in the solution.The thermal activation of PDS mainly occurred near the hole where the fitting temperature was around 340 K,while·OH was generated in the bubble collapse region downstream the hole,where the temperature was much higher and favorable for the cleavage of water molecular.The average temperature under different external physical conditions was in good consistence with the degradation rates.This research developed a useful method to effectively evaluate the activation extent of PDS by HC and could provide reliable guidance for further development of cavitational reactors to treat organic pollutants based on this hybrid approach.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA22020601)the National Natural Science Foundation of China(No.12075237)。
文摘In-situ exploration of deep-sea seabed resources is a valuable research direction.Neutron activation-based in-situ exploration methods for seabed polymetallic nodules or crust resources are theoretically feasible because of the high content and high neutron capture cross-section of manganese in these nodules or crusts.However,to date,only a few relevant studies have been conducted.In this study,a prototype deep-sea in-situ neutron activation spectrometer(DINAS)was designed for resource exploration.Through an analysis of the principles of the spectrometer combined with Monte Carlo simulations of the physical principles and finite element simulations of deep-sea pressure,the structure and fundamental components of the spectrometer were determined.The inner core of the spectrometer comprised three components:a compact neutron generator for neutron production,gamma-ray detectors,and an electronics system.The gamma-ray detector array of the spectrometer consisted of LaBr_(3)and Bi_(4)Ge_(3)O_(12)scintillation crystals coupled with silicon photomultiplier arrays.The electronics system was divided into two modules to implement the SiPM readout and digital signal analysis along the modular design lines.The experimental activation of neutron beamlines at the China Spallation Neutron Source demonstrated the capability of the spectrometer detectors to detect activated gamma-rays and showed that the spectrometer achieved an energy resolution of 2.8%at 847 keV for the LaBr_(3)detector and 6.7%at 2.113 MeV for the BGO detector.The laboratory model experiment tested the functionality of the spectrometer prototype,whereas the Geant4 simulation verified the reliability of the Monte Carlo method.The method and prototype proposed in this study proved feasible for the in-situ detection of polymetallic nodules or crusts in deep-sea environments.
基金supported by the National Natural Science Foundation of China (32473194)Natural Science Foundation of Zhejiang Province (LY23C190002)+1 种基金Natural Science Foundation of Ningbo City (202003N4011)One Health Interdisciplinary Research Project of Ningbo University (HZ202201)。
文摘NLRP3 inflammasome activation is pivotal for cytokine secretion and pyroptosis in response to diverse stimuli,playing a crucial role in innate immunity.While extensively studied in mammals,the regulatory mechanisms governing NLRP3 activation in non-mammalian vertebrates remain largely unexplored.Teleosts,as basal vertebrates,represent an ideal model for exploring the evolutionary trajectory of inflammasome regulation.In this study,ABE assays,confocal microscopy,and biochemical analyses were applied to systematically characterize the mechanisms underlying NLRP3 inflammasome in teleosts,using large yellow croakers(Larimichthys crocea,Lc)and zebrafish(Danio rerio,Dr)as representative models.Our findings revealed a previously unrecognized palmitoylation-dependent regulatory mechanism essential for teleost NLRP3 activation.Specifically,zDHHC18-mediated palmitoylation at a teleost-specific cysteine residue(C946 in LcNLRP3,C1037 in DrNLRP3)was required for the translocation of NLRP3 to the dispersed trans-Golgi network,facilitating its subsequent recruitment to the microtubule-organizing center.This membrane trafficking was crucial for inflammasome assembly and downstream inflammatory responses.These findings provide new insights into the distinct regulatory mechanisms of NLRP3 activation in teleosts,highlighting an evolutionary divergence that contributes to innate immunity adaptation in early vertebrates.
文摘Rotenone is a lipophilic herbicide extensively utilized in experimental neurodegenerative models because of its capacity to disrupt complex I of the mitochondrial electron transport chain.This inhibition results in reduced ATP synthesis,elevated reactive oxygen species(ROS)formation,and mitochondrial malfunction,which instigates oxidative stress and cellular damage,critical elements in neurodegenerative disorders like Parkinson’s disease(PD),amyotrophic lateral sclerosis(ALS),and Alzheimer’s disease(AD).In addition to causing direct neuronal injury,rotenone significantly contributes to the activation of glial cells,specifically microglia and astrocytes.Activated microglia assumes a proinflammatory(M1)phenotype,distinguished by the secretion of inflammatory cytokines including tumor necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6),with the generation of nitric oxide and ROS,which exacerbate the neuronal injury.Astrocytes can intensify neuroinflammation by secreting proinflammatory molecules and impairing their neuroprotective roles.Our hypothesis is that rotenone is posited to elicit a neuroinflammatory response via mitochondrial malfunction,ROS generation,and the activation of proinflammatory pathways in microglia and astrocytes.This mechanism leads to accelerated neuronal impair-ment,promoting neurodegeneration.Comprehending the inflammatory pathways activated by rotenone is crucial for pinpointing therapeutic targets to regulate glial responses and mitigate the advancement of neurodegenerative disorders linked to mitochondrial malfunction and chronic inflammation.This review examines the function of glial cells and critical inflammatory pathways,namely Nuclear factor kappaβ(NF-κB),Phosphoinositide 3-kinase/Protein kinase B/Mammalian target of rapamycin(PI3K/AKT/mTOR),and Wnt/β-catenin signaling pathway in Parkinson’s disease,Alzheimer’s disease,and ALS,emphasizing illness-specific responses and the translational constraints of rotenone-based models.The objective is to consolidate existing understanding regarding the role of rotenone-induced mitochondrial failure in promoting glial activation and neuroinflammation,highlighting the necessity for additional research into these pathways.Despite the prevalent application of rotenone in experimental models,its specific effects on glial-mediated inflammation are inadequately comprehended,necessitating further investigation to guide the formulation of targeted therapeutic strategies.
基金Project(GZC20233199) supported by the Postdoctoral Fellowship Program of CPSF,ChinaProject(2022YFC2105300) supported by the National Key Research and Development Program of China。
文摘Mechanical activation (MA) is a significant pretreatment technique for enhancing the dissolution of mineral;however, its promotion effect on the role of pyrite during chalcopyrite bioleaching has not been elucidated up to now. In this study, the effect of MA on the role of pyrite on chalcopyrite bioleaching mediated by Acidithiobacillus ferroxidans was investigated by X-ray diffraction, scanning electron microscopy, particle size distribution analysis, and electrochemical measurement. The results showed MA could significantly reduce the minerals particle size, and increase the specific surface area and surface energy of minerals. For example, the d50 of chalcopyrite reduced from 13.40 to 0.31 μm after MA. The copper extraction of mixed MA-chalcopyrite and MA-pyrite system was 63.4%, which exhibited a 51.8% enhancement compared to the non-activated mixed system. Electrochemical experiments identified that the strengthening effect of pyrite on chalcopyrite dissolution was negligible before MA. After MA, the dissolution mechanism of chalcopyrite was not changed, and pyrite could not only provide additional oxidants (acids and iron) but also act as the cathode in the galvanic couple. In this case, the bioleaching of chalcopyrite was accelerated. Therefore, a model of the promotion effect of mechanical activation on the role of pyrite on chalcopyrite bioleaching was proposed.
基金funded by the National Key Research and Development Program of China,(Grant No.2022YFE0128300)the Natural Science Foundation of China(Grant No.52379113)+1 种基金the Fundamental Research Funds for the Central Universities of China(Grant No.2024-10945)the Postgraduate Research&Practice Innovation Program of Jiangsu Province of China.
文摘The thermal effect has a significant impact on the activation and slip characteristics of fractures.In this study,four pairs of granite fractures were treated by temperatures T ranging from 25℃to 900℃.The fractures were then employed to carry out triaxial unloading-induced shear slip experiments.The step unloading of confining pressure σ_(3) was used as a disturbed stress to activate fractures that were in a near-critical stress state.The slip characteristics,frictional behaviors,as well as damage modes of fractures with different T,were systematically investigated.The results show that at T=25℃ and 300℃,no stick-slip events were observed,and the slipping process of the fractures was characterized by aseismic slip and creep,respectively.For T=600℃ and 900℃,the fractures slipped stably,with occasional interruptions by episodic stick-slip events.Ultimately,they entered the dynamic slip stage after a series of consecutive stick-slip episodes.With increasing T,the number of sheared-off asperities increases due to thermal damage,which in turn leads to an increase in the occurrence of stick-slip events.The slip modes of the fractures transited from friction strengthening to friction weakening.As T increased from 300℃to 900℃,a considerable quantity of generated gouge layer acted as a lubricant for the slipping of fractures.This resulted in a notable increase in the proportion of aseismic slip,which rose from 24%to 54%.As the temperature increased from 25℃to 900℃,the crack length increased exponentially from 2.975 mm to 45.349 mm.For T=600℃ and 900℃,the duration between stick-slip events decreased as stick-slip events occurred more frequently.
基金supported by the National Natural Science Foundation of China(Nos.12105143 and 11975121)the China Postdoctoral Science Foundation(No.2023M741453)+1 种基金the Engineering Research Center of Nuclear Technology Application(No.HJSJYB2020-1)the Key Laboratory of Ionizing Radiation Metering and Safety Evaluation for Jiangsu Province Market Regulation,and the Jiangsu Province Excellent Postdoctoral Program(No.JB23057).
文摘Neutron-induced gamma-ray imaging is a spectroscopic technique that uses characteristic gamma rays to infer the elemental distribution of an object.Currently,this technique requires the use of large facilities to supply a high neutron flux and a time-consuming detection procedure involving direct collimating measurements.In this study,a new method based on low neutron flux was proposed.A single-pixel gamma-ray detector combined with random pattern gamma-ray masks was used to measure the characteristic gamma rays emitted from the sample.Images of the elemental distribution in the sample,comprising 30×30 pixels,were reconstructed using the maximum-likelihood expectation-maximization algorithm.The results demonstrate that the elemental imaging of the sample can be accurately determined using this method.The proposed approach,which eliminates the need for high neutron flux and scanning measurements,can be used for in-field imaging applications.
基金supported by the National Key R&D Program of China(No.2022YFC2304205)National Natural Science Foundation of China(Nos.51903062,52273128)the Plan on Enhancing Scientific Research in GMU(No.02-410-2405033).
文摘Ferroptosis in combination with immune therapy emerges as a promising approach for cancer therapy.Herein,dual-responsive metal-polyphenol coordinated nanomedicines were developed for pH/glutathione(GSH)-responsive synergistic ferroptosis and immunotherapy.Our innovative strategy involves the development of a manganese-polyphenol coordinated nanostructure,leveraging the biocompatibility of bovine serum albumin(BSA)as a template to encapsulate the anticancer drug sorafenib.The tumor microenvironment(pH/GSH)prompts the disassembly of MnO_(2)and epigallocatechin gallate(EGCG),thereby releases the anticancer payload.Concurrently,MnO_(2)acts to deplete intracellular GSH,which in turn suppresses glutathione peroxidase activity,leading to an accumulation of lipid peroxides with cell ferroptosis.Additionally,the release of Mn^(2+)ions bolster the cyclic guanosine monophosphlic acid(GMP)-adenosine monophosphlic acid(AMP)synthase-stimulator of interferon gene(cGAS-STING)pathway,which,in conjunction with the immunogenic cell death(ICD)effect induced by tumor cell apoptosis,significantly promotes dendritic cell(DC)maturation and enhances the presentation of tumor antigens.This successively ignites a robust innate and adaptive immune response.Both in vitro and in vivo experiments have demonstrated that the concurrent administration of ferroptosis-inducing and immune-stimulating therapies can significantly inhibit tumor growth.
基金supported by the National Key Research and Development Program of China(No.2022YFA1207600)the National Natural Science Foundation of China(Nos.62375289,62175262)+2 种基金the Science and Technology Innovation Program of Hunan Province(No.2022RC1201)the Scientific Research Fund of Hunan Provincial Education Department(No.22B0081)Postdoctoral Funding Project of Jiangsu Province(No.2019Z156)。
文摘Designing and synthesizing nanomedicines with multi-modal tumor therapeutic capabilities is the key to cancer treatment.Herein,we prepared MICG nanoparticles(NPs)by assembling glucose oxidase(GOx)and indocyanine green(ICG)with manganese carbonate(MnCO_(3))NPs for starvation therapy cascaded chemodynamic therapy,enhanced phototherapy and immune activation.In MICG NPs,the GOx consumes intratumoral glucose resulting in starvation therapy,and simultaneously produces H_(2)O_(2)and decreases p H in tumor.The intensified acidic tumor environment promotes the decomposition of MnCO_(3)NPs to release Mn^(2+).The Mn^(2+)further catalyzes H_(2)O_(2)to generate hydroxyl radical for chemodynamic therapy.While ICG can generate singlet oxygen(^(1)O_(2))and heat to kill cancer cells through phototherapy mechanism.The hydroxyl radical and ^(1)O_(2) will further accelerate the oxidative stress,intensify immunogenic cell death,induce dendritic cell maturation,and thus activate systemic immunity.This work provides a new therapeutic platform for combining therapy of tumor.
