Quinoxalin-2(1H)-ones are unique nitrogen-containing organic compounds with wide applications in the agrochemical,pharmaceutical,and chemical industries as well as in material science.During the last decades,visible-l...Quinoxalin-2(1H)-ones are unique nitrogen-containing organic compounds with wide applications in the agrochemical,pharmaceutical,and chemical industries as well as in material science.During the last decades,visible-light-promoted photoredox catalysis has emerged as a versatile platform for constructing quinoxalin-2(1H)-one scaffolds under exceptionally mild conditions.In this review,we provide an overview of recent advances in photocatalytic direct C(3)–H functionalization of quinoxaline-2(1H)-ones,including the construction of C(3)–C bonds and C(3)–R_(F)/C/O/N/Cl/S/D bonds,as well as the related reaction mechanisms.We aim to enhance the methods for the reaction of quinoxalin-2(1H)-ones at the C-3 position,which have extensive applications in organic synthesis and medicinal chemistry.展开更多
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a stoichiometric oxidant that is frequently used in traditional organic synthesis. Recently, the rapid development of organic electrochemistry has led to new advancem...2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a stoichiometric oxidant that is frequently used in traditional organic synthesis. Recently, the rapid development of organic electrochemistry has led to new advancements in DDQ-catalyzed C—H bonds functionalization. Moreover, the challenging C—H functionalization of electron-deficient arenes has been achieved through the merger of electrochemical DDQ catalysis and photoirradiation. In addition, the synthetic utility of electrophotochemical DDQ catalysis was further demonstrated by the nucleophilic aromatic substitution (SNAr) reaction of unactivated aryl fluorides. The recent developments in electro- and electrophotochemical DDQ-catalyzed C—H/C—F func- tionalizations with attention to their strategies and mechanistic insights are summarized. It is hoped that this not only deepens the understanding of this field, but also helps relevant researchers expand the application scope of DDQ catalysis.展开更多
Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and hi...Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.展开更多
Listeria monocytogenes(LM)is a dangerous foodborne pathogen for humans.One emerging and validated method of indirectly assessing LM in food is detecting 3-hydroxy-2-butanone(3H2B)gas.In this study,the synthesis of 3-(...Listeria monocytogenes(LM)is a dangerous foodborne pathogen for humans.One emerging and validated method of indirectly assessing LM in food is detecting 3-hydroxy-2-butanone(3H2B)gas.In this study,the synthesis of 3-(2-aminoethylamino)propyltrimethoxysilane(AAPTMS)functionalized hierarchical hollow TiO_(2)nanospheres was achieved via precise controlling of solvothermal reaction temperature and post-grafting route.The sensors based on as-prepared materials exhibited excellent sensitivity(480 Hz@50 ppm),low detection limit(100 ppb),and outstanding selectivity.Moreover,the evaluation of LM with high sensitivity and specificity was achieved using the sensors.Such stable three-dimensional spheres,whose distinctive hierarchical and hollow nanostructure simultaneously improved both sensitivity and response/recovery speed dramatically,were spontaneously assembled by nanosheets.Meanwhile,the moderate loadings of AAPTMS significantly improved the selectivity of sensors.Then,the gas-sensing mechanism was explored by utilizing thermodynamic investigation,Gaussian 16 software,and in situ diffuse reflectance infrared transform spectroscopy,illustrating the weak chemisorption between the-NHgroup and 3H2B molecules.These portable sensors are promising for real-time assessment of LM at room temperature,which will make a magnificent contribution to food safety.展开更多
Soybean mosaic virus(SMV)is a worldwide disease significantly decreasing soybean yield and seed quality.In this study,a genome-wide association study(GWAS)for SMV-SC3 resistance was conducted by using a deep re-sequen...Soybean mosaic virus(SMV)is a worldwide disease significantly decreasing soybean yield and seed quality.In this study,a genome-wide association study(GWAS)for SMV-SC3 resistance was conducted by using a deep re-sequencing dataset of 547 soybean accessions.A total of 11,405 SNPs and 1566 InDels were significantly associated with disease index(DI)at seedling stage and eight yield-and seed quality-related traits to SC3 resistance under eight environments.Among these genetic loci,952 SNPs and 118 InDels were firstly identified to control SC3 resistance,and 52.42% and 42.37% of them were pleiotropic loci across multiple environments.Notably,the 8.47-8.89 Mb genomic region on chromosome 18 was firstly discovvered to associate with DI at seedling stage and four related traits at adult stage across multiple environments.Furthermore,the causal gene Gm18GRSC3 was identified and validated in this stable and pleiotropic locus for resistance to SC3 via positive and negative transgenic strategies.Overexpression of Gm18GRSC3 significantly decreased the accumulation of SC3 in transgenic soybean hairy roots,while silencing of Gm18GRSC3 significantly increased SC3 accumulation in soybean leaves.A functional marker,FM18GSC3,was developed based on the allelic variation of Gm18GRSC3,and the detection efficiency reached to 76% in another 100 soybean accessions.These findings provide valuable genetic loci and a functional gene for the improvement of SMV resistance in soybean.展开更多
Background Reproductive efficiency in goats is closely linked to the healthy development of follicles,with the proliferation of ovarian granulosa cells(GCs)playing a crucial role in this process.Sirtuin 3(SIRT3),an en...Background Reproductive efficiency in goats is closely linked to the healthy development of follicles,with the proliferation of ovarian granulosa cells(GCs)playing a crucial role in this process.Sirtuin 3(SIRT3),an enzyme that catalyzes post-translational modifications(PTMs)of proteins,is known to regulate a variety of mitochondrial metabolic pathways,thereby affecting cell fate.However,the specific effect of SIRT3 on the follicular development process remains unclear.Therefore,this study aimed to investigate the regulatory role of SIRT3 in the mitochondrial function and proliferation of goat GCs,as well as the underlying mechanisms involved.Results In this study,GCs from small follicles in goat ovaries presented increased proliferative potential and elevated SIRT3 expression levels compared with those from large follicles.In vitro,SIRT3 overexpression enhanced mitochondrial function,promoted proliferation and inhibited apoptosis in GCs.Correspondingly,the inhibition of SIRT3 led to the opposite effects.Notably,SIRT3 interacted with carnitine palmitoyl transferase 2(CPT2)and stabilized the CPT2 protein by mediating delactylation,which prolonged the half-life of CPT2 and prevented its degradation.Further investigation revealed that CPT2 overexpression enhanced fatty acidβ-oxidation and mitochondrial function in GCs.Additionally,CPT2 promoted the proliferation of GCs by increasing the protein levels ofβ-catenin and its downstream target,cyclin D1(CCND1).However,this effect was reversed by 3-TYP(a SIRT3 inhibitor).Conclusions SIRT3 stabilizes CPT2 protein expression through delactylation,thereby enhancing mitochondrial function and the proliferative capacity of GCs in goats.This study provides novel insights into the molecular mechanisms and regulatory pathways involved in mammalian follicular development.展开更多
Aluminum alloys are widely used in industry due to their light weight.These alloys are generally exposed to abrasive wear,which diminishes their effective lifespan.The wear resistance of these alloys is enhanced by ad...Aluminum alloys are widely used in industry due to their light weight.These alloys are generally exposed to abrasive wear,which diminishes their effective lifespan.The wear resistance of these alloys is enhanced by adding various reinforcements,however,this enhancement comes at the cost of reduced fracture toughness.This paradox of increased wear resistance versus decreased fracture toughness in aluminum alloys can be resolved by using functionally graded materials (FGMs).This study focuses on the abrasive wear behavior of functional graded aluminum matrix composites reinforced with Al_(3)Ti particles.The wear properties of the composites were investigated by considering the characteristics of the composite such as matrix type and various composite zones,as well as the wear parameters such as abrasive particle diameter,load,sliding speed and distance.Taguchi method was used in the abrasive wear tests in order to get more reliable results in a timeefficient manner.Experiment recipes were created based on the L_(27)(3^(6)) orthogonal series.As a result of the study,it is observed that the wear resistance of the composites increases with an increase in Al_(3)Ti reinforcement content and hardness of the matrix.In addition,the size of abrasive particles and the applied load are significant factors affecting abrasive wear.展开更多
Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate...Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate the role of the Shank3 gene,known to be associated with monogenic causes of autism,in early developmental processes to inform the timing and mechanisms for poten-tial interventions for ASD.Utilizing the Shank3B knockout(KO)mouse model,we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex(ACC)across different postnatal stages.Our longitudinal analysis revealed that,while Shank3B KO mice displayed normal neuronal morphology at one week postnatal,signifi-cant impairments in dendritic growth and synaptic activity emerged by two to three weeks.These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.展开更多
This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitu...This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitus(T2DM).We question the necessity of excluding patients with severe cataract(unable to complete fundus exams),as the focus on T2DM-MASLD correlation may render other T2DM complications less relevant.We emphasize vitamin D3’s multifaceted relevance:It associates with T2DM(high-dose supplementation reduces onset risk),MASLD(serum levels predict risk),smooth muscle function,immunity,and T2DM-related fractures via advanced glycation end products.We propose correlating MASLD severity with vitamin D3 levels and diabetic gastric motility disorders in validation analyses(e.g.,correlation,area under the curve)to refine factor analysis.Additionally,based on the authors’note of vitamin D3-tryptophan metabolism links,we call for deeper integration of metabolic pathways to clarify vitamin D3’s role in smooth muscle electrophysiology,leveraging the team’s prior research insights.展开更多
This study systematically investigates the cyclization reaction mechanisms between n-C_(4)H_(3)(1-buten-3-yn-1-yl)and i-C_(4)H_(3)(2-buten-3-yn-1-yl)radicals with acetylene(C_(2)H_(2))using density functional theory(D...This study systematically investigates the cyclization reaction mechanisms between n-C_(4)H_(3)(1-buten-3-yn-1-yl)and i-C_(4)H_(3)(2-buten-3-yn-1-yl)radicals with acetylene(C_(2)H_(2))using density functional theory(DFT)and transition state theory(TST).The results reveal that the reaction of n-C_(4)H_(3)with acetylene proceeds via a radical chain mechanism through an additioncyclization pathway,yielding phenyl(sixmembered ring),fulvenyl(five-membered ring),and four-membered ring intermediates.The product formation rates follow the order:fulvenyl(five-membered ring)>phenyl(six-membered ring)>four-membered ring.For i-C_(4)H_(3),the intermediate structures depend on the carbon position of i-C_(4)H_(3)where acetylene addition occurs:addition at the C2 position predominantly generates fulvenyl(five-membered ring)as the primary product,whereas addition at the C4 position may lead to phenyl(six-membered ring),fulvenyl(five-membered ring),or four-membered ring intermediates,with the four-membered ring forming most rapidly and the six-membered ring the slowest.Theoretical analyses demonstrate that the selectivity of reaction pathways is primarily governed by structural differences between the isomers.This work provides atomic-scale insights into the cyclization processes between acetylene and C_(4)H_(3)species,establishing a foundation for refining models of soot precursor formation.展开更多
Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In th...Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In this study,we investigated the potential therapeutic effects of MCC950,a selective NOD-like receptor family pyrin domain-containing protein 3 inhibitor,on cerebral small vessel disease pathogenesis and cognitive decline in spontaneously hypertensive rats.Our results showed that chronic administration of MCC950(10 mg/kg)to spontaneously hypertensive rats inhibited NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation,thereby considerably suppressing the production of pyroptosis executive protein gasdermin D and pro-inflammatory factors,including interleukin-1βand-18.A decrease in astrocytic and microglial activation was also observed.We also found that MCC950 significantly inhibited autophagy.More importantly,behavioral assessment indicated that MCC950 administration ameliorated impaired neurocognitive function,which was associated with improvements in neuropathological hallmarks in the cerebral small vessel disease brain,such as blood‒brain barrier breakdown,white matter damage,and endothelial dysfunction.Thus,our findings revealed that the NOD-like receptor family pyrin domain-containing protein 3 inflammasome is a key contributor to the onset or progression of cerebral small vessel disease and suggested the potential of NOD-like receptor family pyrin domain-containing protein 3-based therapy as a potential novel strategy for treating cerebral small vessel disease.展开更多
基金support from the National Natural Science Foundation of China(No.22101267)the China Postdoctoral Science Foundation(Nos.2021M692905 and 2024T170832)+2 种基金Natural Science Foundation of Henan Province,China(No.242300421123)Scientific Research Project of Hubei Provincial Education Department,China(No.Q20233104)Hubei Provincial Natural Science Foundation,China(No.2024AFB946).
文摘Quinoxalin-2(1H)-ones are unique nitrogen-containing organic compounds with wide applications in the agrochemical,pharmaceutical,and chemical industries as well as in material science.During the last decades,visible-light-promoted photoredox catalysis has emerged as a versatile platform for constructing quinoxalin-2(1H)-one scaffolds under exceptionally mild conditions.In this review,we provide an overview of recent advances in photocatalytic direct C(3)–H functionalization of quinoxaline-2(1H)-ones,including the construction of C(3)–C bonds and C(3)–R_(F)/C/O/N/Cl/S/D bonds,as well as the related reaction mechanisms.We aim to enhance the methods for the reaction of quinoxalin-2(1H)-ones at the C-3 position,which have extensive applications in organic synthesis and medicinal chemistry.
文摘2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a stoichiometric oxidant that is frequently used in traditional organic synthesis. Recently, the rapid development of organic electrochemistry has led to new advancements in DDQ-catalyzed C—H bonds functionalization. Moreover, the challenging C—H functionalization of electron-deficient arenes has been achieved through the merger of electrochemical DDQ catalysis and photoirradiation. In addition, the synthetic utility of electrophotochemical DDQ catalysis was further demonstrated by the nucleophilic aromatic substitution (SNAr) reaction of unactivated aryl fluorides. The recent developments in electro- and electrophotochemical DDQ-catalyzed C—H/C—F func- tionalizations with attention to their strategies and mechanistic insights are summarized. It is hoped that this not only deepens the understanding of this field, but also helps relevant researchers expand the application scope of DDQ catalysis.
基金supported by the Innovative Research Group Project of the National Natural Science Foundation of China(T2121004)Key Programme(52235007)National Outstanding Youth Foundation of China(52325504).
文摘Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.
基金supported by the National Natural Science Foundation of China(No.32272399)the Shanghai Natural Science Foundation(No.21ZR1427500).
文摘Listeria monocytogenes(LM)is a dangerous foodborne pathogen for humans.One emerging and validated method of indirectly assessing LM in food is detecting 3-hydroxy-2-butanone(3H2B)gas.In this study,the synthesis of 3-(2-aminoethylamino)propyltrimethoxysilane(AAPTMS)functionalized hierarchical hollow TiO_(2)nanospheres was achieved via precise controlling of solvothermal reaction temperature and post-grafting route.The sensors based on as-prepared materials exhibited excellent sensitivity(480 Hz@50 ppm),low detection limit(100 ppb),and outstanding selectivity.Moreover,the evaluation of LM with high sensitivity and specificity was achieved using the sensors.Such stable three-dimensional spheres,whose distinctive hierarchical and hollow nanostructure simultaneously improved both sensitivity and response/recovery speed dramatically,were spontaneously assembled by nanosheets.Meanwhile,the moderate loadings of AAPTMS significantly improved the selectivity of sensors.Then,the gas-sensing mechanism was explored by utilizing thermodynamic investigation,Gaussian 16 software,and in situ diffuse reflectance infrared transform spectroscopy,illustrating the weak chemisorption between the-NHgroup and 3H2B molecules.These portable sensors are promising for real-time assessment of LM at room temperature,which will make a magnificent contribution to food safety.
基金supported by the Project of Hebei Province Science and Technology Support Program(17927670H)the Science and Technology Innovation Team of Soybean Modern Seed Industry in Hebei(21326313D)。
文摘Soybean mosaic virus(SMV)is a worldwide disease significantly decreasing soybean yield and seed quality.In this study,a genome-wide association study(GWAS)for SMV-SC3 resistance was conducted by using a deep re-sequencing dataset of 547 soybean accessions.A total of 11,405 SNPs and 1566 InDels were significantly associated with disease index(DI)at seedling stage and eight yield-and seed quality-related traits to SC3 resistance under eight environments.Among these genetic loci,952 SNPs and 118 InDels were firstly identified to control SC3 resistance,and 52.42% and 42.37% of them were pleiotropic loci across multiple environments.Notably,the 8.47-8.89 Mb genomic region on chromosome 18 was firstly discovvered to associate with DI at seedling stage and four related traits at adult stage across multiple environments.Furthermore,the causal gene Gm18GRSC3 was identified and validated in this stable and pleiotropic locus for resistance to SC3 via positive and negative transgenic strategies.Overexpression of Gm18GRSC3 significantly decreased the accumulation of SC3 in transgenic soybean hairy roots,while silencing of Gm18GRSC3 significantly increased SC3 accumulation in soybean leaves.A functional marker,FM18GSC3,was developed based on the allelic variation of Gm18GRSC3,and the detection efficiency reached to 76% in another 100 soybean accessions.These findings provide valuable genetic loci and a functional gene for the improvement of SMV resistance in soybean.
基金supported by the National Key Research and Development Program of China(2022YFD1300202)the Technology Innovation and Application Development Special Project of Chongqing(cstc2021jscx-gksbX0008).
文摘Background Reproductive efficiency in goats is closely linked to the healthy development of follicles,with the proliferation of ovarian granulosa cells(GCs)playing a crucial role in this process.Sirtuin 3(SIRT3),an enzyme that catalyzes post-translational modifications(PTMs)of proteins,is known to regulate a variety of mitochondrial metabolic pathways,thereby affecting cell fate.However,the specific effect of SIRT3 on the follicular development process remains unclear.Therefore,this study aimed to investigate the regulatory role of SIRT3 in the mitochondrial function and proliferation of goat GCs,as well as the underlying mechanisms involved.Results In this study,GCs from small follicles in goat ovaries presented increased proliferative potential and elevated SIRT3 expression levels compared with those from large follicles.In vitro,SIRT3 overexpression enhanced mitochondrial function,promoted proliferation and inhibited apoptosis in GCs.Correspondingly,the inhibition of SIRT3 led to the opposite effects.Notably,SIRT3 interacted with carnitine palmitoyl transferase 2(CPT2)and stabilized the CPT2 protein by mediating delactylation,which prolonged the half-life of CPT2 and prevented its degradation.Further investigation revealed that CPT2 overexpression enhanced fatty acidβ-oxidation and mitochondrial function in GCs.Additionally,CPT2 promoted the proliferation of GCs by increasing the protein levels ofβ-catenin and its downstream target,cyclin D1(CCND1).However,this effect was reversed by 3-TYP(a SIRT3 inhibitor).Conclusions SIRT3 stabilizes CPT2 protein expression through delactylation,thereby enhancing mitochondrial function and the proliferative capacity of GCs in goats.This study provides novel insights into the molecular mechanisms and regulatory pathways involved in mammalian follicular development.
基金financially supported by the Scientific Research Project Coordinatorship (BAP) of Yildiz Technical University (YTU) (Project No: FYL-2021-3825)。
文摘Aluminum alloys are widely used in industry due to their light weight.These alloys are generally exposed to abrasive wear,which diminishes their effective lifespan.The wear resistance of these alloys is enhanced by adding various reinforcements,however,this enhancement comes at the cost of reduced fracture toughness.This paradox of increased wear resistance versus decreased fracture toughness in aluminum alloys can be resolved by using functionally graded materials (FGMs).This study focuses on the abrasive wear behavior of functional graded aluminum matrix composites reinforced with Al_(3)Ti particles.The wear properties of the composites were investigated by considering the characteristics of the composite such as matrix type and various composite zones,as well as the wear parameters such as abrasive particle diameter,load,sliding speed and distance.Taguchi method was used in the abrasive wear tests in order to get more reliable results in a timeefficient manner.Experiment recipes were created based on the L_(27)(3^(6)) orthogonal series.As a result of the study,it is observed that the wear resistance of the composites increases with an increase in Al_(3)Ti reinforcement content and hardness of the matrix.In addition,the size of abrasive particles and the applied load are significant factors affecting abrasive wear.
基金supported by the Natural Science Foundation of China(32394032,82201699,and 82221001)the Natural Science Foundation of Zhejiang Province(LTGD24H250001)+1 种基金the Kay R&D Program of Shaanxi Province(2023-YBSF-093),the Young Talent Fund of University Association for Science and Technology in Shaanxi(20220306)the Joint Founding Project of Innovation Research Institute,Xijing Hospital(LHJJ24JH02).
文摘Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate the role of the Shank3 gene,known to be associated with monogenic causes of autism,in early developmental processes to inform the timing and mechanisms for poten-tial interventions for ASD.Utilizing the Shank3B knockout(KO)mouse model,we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex(ACC)across different postnatal stages.Our longitudinal analysis revealed that,while Shank3B KO mice displayed normal neuronal morphology at one week postnatal,signifi-cant impairments in dendritic growth and synaptic activity emerged by two to three weeks.These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
基金Supported by Fujian Provincial Science and Technology Innovation Joint Fund Project,No.2024Y9555Youth Research Project of the Science and Technology Plan of Fujian Provincial Health Commission,No.2024QNB005+1 种基金Fujian Provincial Natural Science Foundation Project,No.2024J011124Fujian Provincial Medical Project for Creating Dual High-Quality Development(High Level and High Standard),No.ETK2025004.
文摘This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitus(T2DM).We question the necessity of excluding patients with severe cataract(unable to complete fundus exams),as the focus on T2DM-MASLD correlation may render other T2DM complications less relevant.We emphasize vitamin D3’s multifaceted relevance:It associates with T2DM(high-dose supplementation reduces onset risk),MASLD(serum levels predict risk),smooth muscle function,immunity,and T2DM-related fractures via advanced glycation end products.We propose correlating MASLD severity with vitamin D3 levels and diabetic gastric motility disorders in validation analyses(e.g.,correlation,area under the curve)to refine factor analysis.Additionally,based on the authors’note of vitamin D3-tryptophan metabolism links,we call for deeper integration of metabolic pathways to clarify vitamin D3’s role in smooth muscle electrophysiology,leveraging the team’s prior research insights.
基金Supported by the National Key Research and Development Program of China(2022YFB4301400)the Basic Science(Natural Science)Research Project for Higher Education Institutions in Jiangsu Province(24KJD580001)。
文摘This study systematically investigates the cyclization reaction mechanisms between n-C_(4)H_(3)(1-buten-3-yn-1-yl)and i-C_(4)H_(3)(2-buten-3-yn-1-yl)radicals with acetylene(C_(2)H_(2))using density functional theory(DFT)and transition state theory(TST).The results reveal that the reaction of n-C_(4)H_(3)with acetylene proceeds via a radical chain mechanism through an additioncyclization pathway,yielding phenyl(sixmembered ring),fulvenyl(five-membered ring),and four-membered ring intermediates.The product formation rates follow the order:fulvenyl(five-membered ring)>phenyl(six-membered ring)>four-membered ring.For i-C_(4)H_(3),the intermediate structures depend on the carbon position of i-C_(4)H_(3)where acetylene addition occurs:addition at the C2 position predominantly generates fulvenyl(five-membered ring)as the primary product,whereas addition at the C4 position may lead to phenyl(six-membered ring),fulvenyl(five-membered ring),or four-membered ring intermediates,with the four-membered ring forming most rapidly and the six-membered ring the slowest.Theoretical analyses demonstrate that the selectivity of reaction pathways is primarily governed by structural differences between the isomers.This work provides atomic-scale insights into the cyclization processes between acetylene and C_(4)H_(3)species,establishing a foundation for refining models of soot precursor formation.
基金supported by the National Natural Science Foundation of China,No.82201626(to CC)the Natural Science Foundation of LiaoningProvince,No.2022-MS-442(to CC)the Dalian Municipal Medical Key Specialty Climbing Project,No.2024ZZ040(to MZ).
文摘Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In this study,we investigated the potential therapeutic effects of MCC950,a selective NOD-like receptor family pyrin domain-containing protein 3 inhibitor,on cerebral small vessel disease pathogenesis and cognitive decline in spontaneously hypertensive rats.Our results showed that chronic administration of MCC950(10 mg/kg)to spontaneously hypertensive rats inhibited NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation,thereby considerably suppressing the production of pyroptosis executive protein gasdermin D and pro-inflammatory factors,including interleukin-1βand-18.A decrease in astrocytic and microglial activation was also observed.We also found that MCC950 significantly inhibited autophagy.More importantly,behavioral assessment indicated that MCC950 administration ameliorated impaired neurocognitive function,which was associated with improvements in neuropathological hallmarks in the cerebral small vessel disease brain,such as blood‒brain barrier breakdown,white matter damage,and endothelial dysfunction.Thus,our findings revealed that the NOD-like receptor family pyrin domain-containing protein 3 inflammasome is a key contributor to the onset or progression of cerebral small vessel disease and suggested the potential of NOD-like receptor family pyrin domain-containing protein 3-based therapy as a potential novel strategy for treating cerebral small vessel disease.
