Aging is characterized by a decreased autophagic activity contributing to the intracellular deposition of damaged organelles and macromolecules.Autophagy is particularly challenging in neurons since autophagic vesicle...Aging is characterized by a decreased autophagic activity contributing to the intracellular deposition of damaged organelles and macromolecules.Autophagy is particularly challenging in neurons since autophagic vesicles are formed at the axonal tip and must be transported to the soma where final degradation occurs.Here,we examined if axonal transport of autophagic vesicles is altered during aging.We employed two-photon microscopy for in vivo imaging in the optic nerve of young and aged rats.In old animals(>18 months old),retrograde autophagic vesicle transport was significantly reduced with regard to motility and velocity.While activation of autophagy was decreased,expression of key proteins of the autophagy-lysosomal pathway including p62 and procathepsin D and the number of autophagolysosomes was increased.Maturation of autophagic vesicles was shifted to more distal regions of the axon and axonal lysosomal clearing was impaired.In a pull-down assay,the protein binding between dynein and dynactin was decreased by half,which could explain the retrograde axonal transport effects.Taken together,retrograde axonal autophagic vesicle transport in vivo is diminished during aging accompanied by decreased autophagy activation,alterations of the lysosomal pathway,and a reduced dynein-dynactin binding.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
Oncology Research Editorial Office Published:23 March 2026 The published article titled“MicroRNA 125a-5p Inhibits Cell Proliferation and Induces Apoptosis in Hepatitis B Virus-Related Hepatocellular Carcinoma by Down...Oncology Research Editorial Office Published:23 March 2026 The published article titled“MicroRNA 125a-5p Inhibits Cell Proliferation and Induces Apoptosis in Hepatitis B Virus-Related Hepatocellular Carcinoma by Downregulation of ErbB3”has been retracted from Oncology Research,Vol.27,No.4,2019,pp.449-458.DOI:10.3727/096504017X15016337254623 URL:https://www.techscience.com/or/v27n4/48558.展开更多
High-pressure hydrides have emerged as promising superconducting materials,attracting considerable attention in recent years.In this work,by combining the stochastic self-consistent harmonic approximation with first-p...High-pressure hydrides have emerged as promising superconducting materials,attracting considerable attention in recent years.In this work,by combining the stochastic self-consistent harmonic approximation with first-principles calculations,we elucidate crucial corrections to the vibrational and superconducting properties arising from quantum and anharmonic ionic vibrations of SnH4 in P63/mmc phase at 150–240 GPa.Compared with the classical harmonic approximation,inclusion of these effects results in a pronounced softening(over 500 cm^(−1))of hydrogen-derived optical phonon modes,and increases the superconducting critical temperature(Tc)from 65 K to 79 K(μ^(*)=0.1;isotropic Migdal–Eliashberg theory),corresponding to a 22%enhancement.For μ^(*)=0.13,the predicted Tc is approximately 70 K.Analysis of the Eliashberg spectral function confirms that hydrogen vibrational modes constitute the dominant tuning mechanism.These results provide quantitative insights into quantum ionic effects in hydride superconductors.展开更多
Let p be a prime. For any finite p-group G, the deep transfers T H,G ' : H / H ' → G ' / G " from the maximal subgroups H of index (G:H) = p in G to the derived subgroup G ' are introduced as an ...Let p be a prime. For any finite p-group G, the deep transfers T H,G ' : H / H ' → G ' / G " from the maximal subgroups H of index (G:H) = p in G to the derived subgroup G ' are introduced as an innovative tool for identifying G uniquely by means of the family of kernels ùd(G) =(ker(T H,G ')) (G: H) = p. For all finite 3-groups G of coclass cc(G) = 1, the family ùd(G) is determined explicitly. The results are applied to the Galois groups G =Gal(F3 (∞)/ F) of the Hilbert 3-class towers of all real quadratic fields F = Q(√d) with fundamental discriminants d > 1, 3-class group Cl3(F) □ C3 × C3, and total 3-principalization in each of their four unramified cyclic cubic extensions E/F. A systematic statistical evaluation is given for the complete range 1 d 7, and a few exceptional cases are pointed out for 1 d 8.展开更多
BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in m...BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in many biological processes that supports cellular homeostasis,including the inhibition of apoptosis by preventing mitochondrial BAX localization(Lin et al.,2022)and the promotion of the degradation of hyperphosphorylated tau aggregates by its interactions with SQSTM1(p62)(Hamano and Mutoh,2022).展开更多
Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues...Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.展开更多
Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effec...Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects,and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models.Here,we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta(CaMKKβ)/adenosine 5′-monophosphate-activated protein kinase(AMPK)/suppressor of cytokine signaling-3(SOCS3)signaling in microglia.Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation.Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia,which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain,thereby suppressing neuroinflammation.The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia.The results suggested that focal repetitive trans-spinal magnetic stimulation inhibits spinal neuroinflammation and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia.This mechanism provides an effective noninvasive treatment for neuropathic pain caused by peripheral nerve injury.展开更多
Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration vi...Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.展开更多
Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibi...Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investigation in ongoing clinical trials. Investigation has also been demonstrating that combinatorial therapies of growth inhibitors with other therapies, such as growth factors or stem-cell therapies, produce stronger results and their potential application in the clinics opens new venues in spinal cord injury treatment.展开更多
Let F be a number field and p be a prime. In the successive approximation theorem, we prove that, for each integer n ≥ 1, finitely many candidates for the Galois group of the nth stage of the p-class tower over F are...Let F be a number field and p be a prime. In the successive approximation theorem, we prove that, for each integer n ≥ 1, finitely many candidates for the Galois group of the nth stage of the p-class tower over F are determined by abelian type invariants of p-class groups C1pE of unramified extensions E/F with degree [E : F] = pn-1. Illustrated by the most extensive numerical results available currently, the transfer kernels (TE, F) of the p-class extensions TE, F : C1pF → C1pE from F to unramified cyclic degree-p extensions E/F are shown to be capable of narrowing down the number of contestants significantly. By determining the isomorphism type of the maximal subgroups S G of all 3-groups G with coclass cc(G) = 1, and establishing a general theorem on the connection between the p-class towers of a number field F and of an unramified abelian p-extension E/F, we are able to provide a theoretical proof of the realization of certain 3-groups S with maximal class by 3-tower groups of dihedral fields E with degree 6, which could not be realized up to now.展开更多
Many labdane-related diterpenoids(LRDs)exhibit high values in drug development.Their diversity in structure and bioactivity,to a large extent,arise from oxidative modifications which are mainly catalyzed by cytochrome...Many labdane-related diterpenoids(LRDs)exhibit high values in drug development.Their diversity in structure and bioactivity,to a large extent,arise from oxidative modifications which are mainly catalyzed by cytochrome P450s(CYPs).The medicinal plant Euphorbia fischeriana Steud.is rich in LRDs with distinct scaffolds.Herein,we characterized three cytochrome P450s involved in LRD biosynthesis from this plant.Notably,CYP71D450 and CYP701A148 are two substrate-promiscuity CYPs.The former is the first example of CYPs which can oxidize C-3 of ent-atisane skeleton and ent-isopimara-7(8),15-diene,and the latter is the first example of CYPs which can oxidize C-19 of ent-abietane and ent-pimarane skeletons.This study expands the toolkit for bioproduction of diverse LRDs.展开更多
Green manuring is essential for improving soil quality and nutrient uptake.With the gradual depletion of phosphorus(P)resources,more attention is being paid to the role of green manures in cultivation systems,such as ...Green manuring is essential for improving soil quality and nutrient uptake.With the gradual depletion of phosphorus(P)resources,more attention is being paid to the role of green manures in cultivation systems,such as maize-green manure intercropping,to find possible pathways for enhancing soil P utilization.A maize-green manure intercropping experiment was started in 2009 to investigate the effects and mechanisms for enhancing P uptake and yield in maize.Three species of green manures(hairy vetch(HV),needle leaf pea(NP),sweet pea(SP))and a sole maize treatment(CK)were used,resulting in four treatments(CK,HVT,NPT,and SPT)in the experiment.During 2020-2023,the intercropping treatments enhanced maize yields in 2020 and 2021,particularly in HVT with increases of 13.7%(1.96 t ha^(-1))and 13.0%(2.13 t ha^(-1))compared with CK,respectively.Grain P accumulation of maize was significantly higher in the intercropping treatments than CK in 2020,2021,and 2023,and with an average increase of 10.6%over the four years(5.2% for NPT,10.8% for SPT and 15.9% for HVT)compared with CK.Intercropping promoted maize growth with a greater root length density and a higher organic acid release rate.HVT changed the soil properties more dramatically than the other treatments,with increases in the acid phosphatase and alkaline phosphatase activities of 29.8 and 38.5%,respectively,in the topsoil(0-15 cm),while the soil p H was reduced by 0.37 units compared to CK(p H=8.44).Intercropping treatments facilitated the conversion of non-labile P to mod-labile P and stimulated the growth of soil bacteria in the topsoil.Compared with CK,the relative abundance of Gemmatimonadota,known for accumulating polyphosphate,and Actinobacteriota,a prominent source of bioactive compounds,increased significantly in the intercropping treatments,especially in HVT and SPT.A PLS-PM analysis showed that intercropping promoted soil P mobilization and the enrichment of beneficial bacteria by regulating maize root morphology and physiology.Our results highlight that maize-green manure intercropping optimizes root traits,soil properties and bacterial composition,which contribute to greater maize P uptake and yield,providing an effective strategy for sustainable crop production.展开更多
In this article,we prove the boundedness for commutators of fractional Hardy and Hardy-Littlewood-Pólya operators on grand p-adic variable Herz spaces,where the symbols of the commutators belong to Lipschitz spaces.
Let G be a group and H;K be subgroups of G.H is called a TI-subgroup of G if H∩H^(g)=1 or H for every g∈G.K is called P-subnormal in G if there is a chain of subgroups K=K_(0)≤K_(1)≤K_(2)≤…≤K_(n-1)≤K_(n)=G suc...Let G be a group and H;K be subgroups of G.H is called a TI-subgroup of G if H∩H^(g)=1 or H for every g∈G.K is called P-subnormal in G if there is a chain of subgroups K=K_(0)≤K_(1)≤K_(2)≤…≤K_(n-1)≤K_(n)=G such that|K_(i):K_(i-1)|∈P for i∈{1;2;…;n}.Furthermore,K is called K-P-subnormal in G if there is a chain of subgroups K=K_(0)≤K_(1)≤K_(2)≤…≤K_(n-1)≤K_(n)=G such that either K_(i-1)is normal in Ki or|K_(i):K_(i-1)|∈P for i∈{1;2;…;n}.In this paper,some properties of a nite group in which some particular subgroups are TI-subgroups or P-subnormal subgroups or K-P-subnormal subgroups are given.展开更多
基金China Scholarship Council(CSCto XL)and a generous heritage donation from Bettina Fischer,Germany(to JCK).
文摘Aging is characterized by a decreased autophagic activity contributing to the intracellular deposition of damaged organelles and macromolecules.Autophagy is particularly challenging in neurons since autophagic vesicles are formed at the axonal tip and must be transported to the soma where final degradation occurs.Here,we examined if axonal transport of autophagic vesicles is altered during aging.We employed two-photon microscopy for in vivo imaging in the optic nerve of young and aged rats.In old animals(>18 months old),retrograde autophagic vesicle transport was significantly reduced with regard to motility and velocity.While activation of autophagy was decreased,expression of key proteins of the autophagy-lysosomal pathway including p62 and procathepsin D and the number of autophagolysosomes was increased.Maturation of autophagic vesicles was shifted to more distal regions of the axon and axonal lysosomal clearing was impaired.In a pull-down assay,the protein binding between dynein and dynactin was decreased by half,which could explain the retrograde axonal transport effects.Taken together,retrograde axonal autophagic vesicle transport in vivo is diminished during aging accompanied by decreased autophagy activation,alterations of the lysosomal pathway,and a reduced dynein-dynactin binding.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
文摘Oncology Research Editorial Office Published:23 March 2026 The published article titled“MicroRNA 125a-5p Inhibits Cell Proliferation and Induces Apoptosis in Hepatitis B Virus-Related Hepatocellular Carcinoma by Downregulation of ErbB3”has been retracted from Oncology Research,Vol.27,No.4,2019,pp.449-458.DOI:10.3727/096504017X15016337254623 URL:https://www.techscience.com/or/v27n4/48558.
基金supported by the Scientific Research Program Funded by Shaanxi Provincial Education Department (Grant No.24JP126)the National Natural Science Foundation of China (Grant No.62174136)the Natural Science Basic Research Program of Shaanxi Province (Grant No.2025JC-YBMS-063)。
文摘High-pressure hydrides have emerged as promising superconducting materials,attracting considerable attention in recent years.In this work,by combining the stochastic self-consistent harmonic approximation with first-principles calculations,we elucidate crucial corrections to the vibrational and superconducting properties arising from quantum and anharmonic ionic vibrations of SnH4 in P63/mmc phase at 150–240 GPa.Compared with the classical harmonic approximation,inclusion of these effects results in a pronounced softening(over 500 cm^(−1))of hydrogen-derived optical phonon modes,and increases the superconducting critical temperature(Tc)from 65 K to 79 K(μ^(*)=0.1;isotropic Migdal–Eliashberg theory),corresponding to a 22%enhancement.For μ^(*)=0.13,the predicted Tc is approximately 70 K.Analysis of the Eliashberg spectral function confirms that hydrogen vibrational modes constitute the dominant tuning mechanism.These results provide quantitative insights into quantum ionic effects in hydride superconductors.
文摘Let p be a prime. For any finite p-group G, the deep transfers T H,G ' : H / H ' → G ' / G " from the maximal subgroups H of index (G:H) = p in G to the derived subgroup G ' are introduced as an innovative tool for identifying G uniquely by means of the family of kernels ùd(G) =(ker(T H,G ')) (G: H) = p. For all finite 3-groups G of coclass cc(G) = 1, the family ùd(G) is determined explicitly. The results are applied to the Galois groups G =Gal(F3 (∞)/ F) of the Hilbert 3-class towers of all real quadratic fields F = Q(√d) with fundamental discriminants d > 1, 3-class group Cl3(F) □ C3 × C3, and total 3-principalization in each of their four unramified cyclic cubic extensions E/F. A systematic statistical evaluation is given for the complete range 1 d 7, and a few exceptional cases are pointed out for 1 d 8.
基金supported by the award W81XWH1910309 (to HF) from the Department of Defensethe award R01-AG075092-01 (to HF)+2 种基金the award RF1AG063521 from the National Institute of Aging at the National Institutes of Healththe Neurological Research Institute Seed grant (to HF) from The Ohio State Universitythe Summer Undergraduate Research Fellowship (to NS) from The Ohio State University Chronic Brain Injury Discovery Theme
文摘BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in many biological processes that supports cellular homeostasis,including the inhibition of apoptosis by preventing mitochondrial BAX localization(Lin et al.,2022)and the promotion of the degradation of hyperphosphorylated tau aggregates by its interactions with SQSTM1(p62)(Hamano and Mutoh,2022).
基金supported by the Joint Funds for the Innovation of Science and Technology,Fujian Province,No.2023Y9233(to HH)the QuanzhouScience and Technology Project,No.2022C036R(to HH)+1 种基金the Science and Technology Bureau of Quanzhou,No.2020CT003(to SL)the Quanzhou MunicipalMedical and Health Guiding Science and Technology Project,No.2023N066S(to YZhou).
文摘Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.
基金National Natural Science Foundation of China,Nos.82302877(to QW),82172541(to TW)the Natural Science Foundation of Hunan Province,No.2023JJ30549(to QW)Clinical Medical Technology Innovation Guidance Project of Hunan Provincial Science and Technology Department,No.2021SK51815(to QW).
文摘Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects,and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models.Here,we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta(CaMKKβ)/adenosine 5′-monophosphate-activated protein kinase(AMPK)/suppressor of cytokine signaling-3(SOCS3)signaling in microglia.Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation.Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia,which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain,thereby suppressing neuroinflammation.The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia.The results suggested that focal repetitive trans-spinal magnetic stimulation inhibits spinal neuroinflammation and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia.This mechanism provides an effective noninvasive treatment for neuropathic pain caused by peripheral nerve injury.
基金supported by the National Natural Science Foundation of China,No.81571211(to FL)the Natural Science Foundation of Shanghai,No.22ZR1476800(to CH)。
文摘Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.
基金a Ph D fellowship by FCT-Fundacao para a Ciência Tecnologia (SFRH/BD/135868/2018)(to SSC)。
文摘Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investigation in ongoing clinical trials. Investigation has also been demonstrating that combinatorial therapies of growth inhibitors with other therapies, such as growth factors or stem-cell therapies, produce stronger results and their potential application in the clinics opens new venues in spinal cord injury treatment.
文摘Let F be a number field and p be a prime. In the successive approximation theorem, we prove that, for each integer n ≥ 1, finitely many candidates for the Galois group of the nth stage of the p-class tower over F are determined by abelian type invariants of p-class groups C1pE of unramified extensions E/F with degree [E : F] = pn-1. Illustrated by the most extensive numerical results available currently, the transfer kernels (TE, F) of the p-class extensions TE, F : C1pF → C1pE from F to unramified cyclic degree-p extensions E/F are shown to be capable of narrowing down the number of contestants significantly. By determining the isomorphism type of the maximal subgroups S G of all 3-groups G with coclass cc(G) = 1, and establishing a general theorem on the connection between the p-class towers of a number field F and of an unramified abelian p-extension E/F, we are able to provide a theoretical proof of the realization of certain 3-groups S with maximal class by 3-tower groups of dihedral fields E with degree 6, which could not be realized up to now.
基金supported by grants from the National Natural Science Foundation of China[Nos.82474024,82293682(82293680),82073953]the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2021-RC350-009)+1 种基金the CAMS Innovation Fund for Medical Sciences(No.2023-I2M-2-006)the Special Fund for the Construction of Qinghai Innovation Platform(No.2024-ZJ-T02)。
文摘Many labdane-related diterpenoids(LRDs)exhibit high values in drug development.Their diversity in structure and bioactivity,to a large extent,arise from oxidative modifications which are mainly catalyzed by cytochrome P450s(CYPs).The medicinal plant Euphorbia fischeriana Steud.is rich in LRDs with distinct scaffolds.Herein,we characterized three cytochrome P450s involved in LRD biosynthesis from this plant.Notably,CYP71D450 and CYP701A148 are two substrate-promiscuity CYPs.The former is the first example of CYPs which can oxidize C-3 of ent-atisane skeleton and ent-isopimara-7(8),15-diene,and the latter is the first example of CYPs which can oxidize C-19 of ent-abietane and ent-pimarane skeletons.This study expands the toolkit for bioproduction of diverse LRDs.
基金supported financially by the National Key Research&Development Program of China(2021YFD1700200)the National Natural Science Foundation of China(32402686)+3 种基金the Earmarked Fund for China Agriculture Research System(CARS-22)the Fundamental Research Funds for Central Non-profit Scientific Institution,China(1610132022013)the Science and Technology Innovation Project of Chinese Academy of Agricultural Sciencesthe China National Crop Germplasm Resources Platform for Green Manure(NICGR-2024-19)。
文摘Green manuring is essential for improving soil quality and nutrient uptake.With the gradual depletion of phosphorus(P)resources,more attention is being paid to the role of green manures in cultivation systems,such as maize-green manure intercropping,to find possible pathways for enhancing soil P utilization.A maize-green manure intercropping experiment was started in 2009 to investigate the effects and mechanisms for enhancing P uptake and yield in maize.Three species of green manures(hairy vetch(HV),needle leaf pea(NP),sweet pea(SP))and a sole maize treatment(CK)were used,resulting in four treatments(CK,HVT,NPT,and SPT)in the experiment.During 2020-2023,the intercropping treatments enhanced maize yields in 2020 and 2021,particularly in HVT with increases of 13.7%(1.96 t ha^(-1))and 13.0%(2.13 t ha^(-1))compared with CK,respectively.Grain P accumulation of maize was significantly higher in the intercropping treatments than CK in 2020,2021,and 2023,and with an average increase of 10.6%over the four years(5.2% for NPT,10.8% for SPT and 15.9% for HVT)compared with CK.Intercropping promoted maize growth with a greater root length density and a higher organic acid release rate.HVT changed the soil properties more dramatically than the other treatments,with increases in the acid phosphatase and alkaline phosphatase activities of 29.8 and 38.5%,respectively,in the topsoil(0-15 cm),while the soil p H was reduced by 0.37 units compared to CK(p H=8.44).Intercropping treatments facilitated the conversion of non-labile P to mod-labile P and stimulated the growth of soil bacteria in the topsoil.Compared with CK,the relative abundance of Gemmatimonadota,known for accumulating polyphosphate,and Actinobacteriota,a prominent source of bioactive compounds,increased significantly in the intercropping treatments,especially in HVT and SPT.A PLS-PM analysis showed that intercropping promoted soil P mobilization and the enrichment of beneficial bacteria by regulating maize root morphology and physiology.Our results highlight that maize-green manure intercropping optimizes root traits,soil properties and bacterial composition,which contribute to greater maize P uptake and yield,providing an effective strategy for sustainable crop production.
基金Supported by Chizhou University High Level Talent Research Start up Fund (No.CZ2025YJRC52)。
文摘In this article,we prove the boundedness for commutators of fractional Hardy and Hardy-Littlewood-Pólya operators on grand p-adic variable Herz spaces,where the symbols of the commutators belong to Lipschitz spaces.
文摘Let G be a group and H;K be subgroups of G.H is called a TI-subgroup of G if H∩H^(g)=1 or H for every g∈G.K is called P-subnormal in G if there is a chain of subgroups K=K_(0)≤K_(1)≤K_(2)≤…≤K_(n-1)≤K_(n)=G such that|K_(i):K_(i-1)|∈P for i∈{1;2;…;n}.Furthermore,K is called K-P-subnormal in G if there is a chain of subgroups K=K_(0)≤K_(1)≤K_(2)≤…≤K_(n-1)≤K_(n)=G such that either K_(i-1)is normal in Ki or|K_(i):K_(i-1)|∈P for i∈{1;2;…;n}.In this paper,some properties of a nite group in which some particular subgroups are TI-subgroups or P-subnormal subgroups or K-P-subnormal subgroups are given.
