The development of enantioselective C-H macrocyclizations to efficiently access structurally diversified macrocycles is highly desirable,but remain a big challenge.Herein,we reported the first rhodium(Ⅲ)-catalyzed as...The development of enantioselective C-H macrocyclizations to efficiently access structurally diversified macrocycles is highly desirable,but remain a big challenge.Herein,we reported the first rhodium(Ⅲ)-catalyzed asymmetric intramolecular C-H macrocyclization,enabling the efficient synthesis of structurally diverse enantioenriched macrocycles.This robust enantioselective C-H macrocyclization has a broad functional group tolerance,excellent enantioselectivities(up to 98.5:1.5 e.r.)and a mild reaction condition,releasing CO_(2)as the single by-product.More significantly,the resulting unique enantioenriched19-membered macrocycle 2f was found to demonstrate a potent in vitro anti-Zika virus(ZIKV)activity without obvious cytotoxicity.Further investigation revealed that the anti-ZIKV activity is presumably attributed to an autophagy inhibition in the early stage of viral infection by down-regulating the expression of autophagy related gene Atg12.展开更多
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
Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]iso...Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.展开更多
Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficientl...Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficiently accomplished from the key intermediate(S)-6 with three contiguous stereocenters in 5 steps and the synthetic 1 induced G2/M-phase cell cycle arrest of HT29 cells and apoptosis of HL60 and NB4 cells by activation of caspase-3 and degradation of PARP.(S)-6,bearing three contiguous chiral centers,was efficiently constructed by a novel Nazarov cyclization reaction containing basic nitrogen,which was less developed,primarily due to the incompatibility of basic nitrogen under acidic reaction conditions.This reaction allows a wide range of pentadienone substrates containing basic nitrogen to undergo Nazarov cyclization in a single regioselective and diastereoselective manner and is capable of generating three stereocenters simultaneously.Furthermore,the mechanism of the Nazarov cyclization and the origin of the regio-and diastereoselectivity were elucidated by DFT calculations and deuteration experiments,providing valuable insights into the reaction and serving as a guide for future applications involving substrates containing basic nitrogen.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
Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the con...Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.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
The Meinwald rearrangement has proven to be one of the most useful tools in organic synthesis.However,examples of asymmetric Meinwald rearrangements are quite scarce,and these reactions have so far been limited to the...The Meinwald rearrangement has proven to be one of the most useful tools in organic synthesis.However,examples of asymmetric Meinwald rearrangements are quite scarce,and these reactions have so far been limited to the use of chiral Br?nsted acids as catalysts.Here,we report a copper-catalyzed asymmetric cascade cyclization/Meinwald rearrangement reaction,allowing the practical and atom-economic synthesis of a range of chiral tricyclic pyrroles bearing a chiral oxa-quaternary carbon stereocenter in high yields and enantioselectivities.Thus,this protocol not only represents the first transition-metal-catalyzed enantioselective Meinwald rearrangement,but also constitutes the first example of asymmetric formal monocarbon insertion into C-O bond of ester.Moreover,theoretical calculations provide further evidence for this multiple cascade cyclization and elucidate the origin of enantioselectivity.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
基金supported by National Natural Science Foundation of China(No.81973166)Science and Technology Commission of Shanghai Municipality(No.22XD1424600)+4 种基金Natural Science Foundation of Shanghai Municipality(No.22ZR1474100)Taishan Scholar Foundation of Shandong Province(No.tsqn202306322)National Key R&D Program of China(No.2021YFC2300700)Shandong Laboratory Program(No.SYS202205)Shandong Provincial Natural Science Foundation(Nos.ZR2023LSW003 and ZR2023JQ028)。
文摘The development of enantioselective C-H macrocyclizations to efficiently access structurally diversified macrocycles is highly desirable,but remain a big challenge.Herein,we reported the first rhodium(Ⅲ)-catalyzed asymmetric intramolecular C-H macrocyclization,enabling the efficient synthesis of structurally diverse enantioenriched macrocycles.This robust enantioselective C-H macrocyclization has a broad functional group tolerance,excellent enantioselectivities(up to 98.5:1.5 e.r.)and a mild reaction condition,releasing CO_(2)as the single by-product.More significantly,the resulting unique enantioenriched19-membered macrocycle 2f was found to demonstrate a potent in vitro anti-Zika virus(ZIKV)activity without obvious cytotoxicity.Further investigation revealed that the anti-ZIKV activity is presumably attributed to an autophagy inhibition in the early stage of viral infection by down-regulating the expression of autophagy related gene Atg12.
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.
文摘Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.
基金supported by the National Natural Science Foundation of China(Nos.81725021,81903461)the National Key R&D Program of China(No.2022YFA1503200)the Natural Science Foundation of Hubei Province(No.ZRMS2023000340)。
文摘Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficiently accomplished from the key intermediate(S)-6 with three contiguous stereocenters in 5 steps and the synthetic 1 induced G2/M-phase cell cycle arrest of HT29 cells and apoptosis of HL60 and NB4 cells by activation of caspase-3 and degradation of PARP.(S)-6,bearing three contiguous chiral centers,was efficiently constructed by a novel Nazarov cyclization reaction containing basic nitrogen,which was less developed,primarily due to the incompatibility of basic nitrogen under acidic reaction conditions.This reaction allows a wide range of pentadienone substrates containing basic nitrogen to undergo Nazarov cyclization in a single regioselective and diastereoselective manner and is capable of generating three stereocenters simultaneously.Furthermore,the mechanism of the Nazarov cyclization and the origin of the regio-and diastereoselectivity were elucidated by DFT calculations and deuteration experiments,providing valuable insights into the reaction and serving as a guide for future applications involving substrates containing basic nitrogen.
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.
文摘Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.
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financial support from the National Natural Science Foundation of China(Nos.22125108,22101238,22331004 and 22121001)Yunnan Fundamental Research Project(No.202401CF070024)+2 种基金Natural Science Foundation of Jiangsu Province(No.BK20211059)the Project of Science and Technology of Xuzhou Government(No.KC22080)NFFTBS(No.J1310024)。
文摘The Meinwald rearrangement has proven to be one of the most useful tools in organic synthesis.However,examples of asymmetric Meinwald rearrangements are quite scarce,and these reactions have so far been limited to the use of chiral Br?nsted acids as catalysts.Here,we report a copper-catalyzed asymmetric cascade cyclization/Meinwald rearrangement reaction,allowing the practical and atom-economic synthesis of a range of chiral tricyclic pyrroles bearing a chiral oxa-quaternary carbon stereocenter in high yields and enantioselectivities.Thus,this protocol not only represents the first transition-metal-catalyzed enantioselective Meinwald rearrangement,but also constitutes the first example of asymmetric formal monocarbon insertion into C-O bond of ester.Moreover,theoretical calculations provide further evidence for this multiple cascade cyclization and elucidate the origin of enantioselectivity.
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.
