The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arth...The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.展开更多
Intercalated transition metal dichalcogenides(TMDCs)attract much attention due to their rich properties and potential applications.In this article,we grew successfully high-quality V_(1/3)TaS_(2) crystals by a vapor t...Intercalated transition metal dichalcogenides(TMDCs)attract much attention due to their rich properties and potential applications.In this article,we grew successfully high-quality V_(1/3)TaS_(2) crystals by a vapor transport method.We measured the magnetization,longitudinal resistivityρxx(T,H),Hall resistivityρxy(T,H),as well as performed calculations of the electronic band structure.It was found that V_(1/3)TaS_(2) is an A-type antiferromagnet with the Neel temperature T_(N)=6.20 K,and exhibits a negative magnetoresistance(MR)near T_(N).Both band structure calculations and Hall resistivity measurements demonstrated it is a magnetic semimetal.展开更多
Poly(glycidyl methacrylates)(PGMA) was grafted from zinc oxide(ZnO) nanowires via surface-initiated atom transfer radical polymerization(SI-ATRP) technique.Firstly,the ZnO nanowires were synthesized by the one-pot hyd...Poly(glycidyl methacrylates)(PGMA) was grafted from zinc oxide(ZnO) nanowires via surface-initiated atom transfer radical polymerization(SI-ATRP) technique.Firstly,the ZnO nanowires were synthesized by the one-pot hydrothermal technique.Subsequently,the ZnO was functionalized with 3-aminopropyl triethoxysilane,which was converted to macroinitiator by the esterification of them with 2-bromopropionyl bromide.PGMA grafted ZnO nanowires(PGMA-ZnO) were then synthesized in an ATRP of the GMA with CuCl/2,2`-bipyridine as the catalyst system.Kinetics studies revealed an approximate linear increase in weight of polymer with reaction time,indicating that the polymerization process owned some "living" character.The structure and composition of PGMA-ZnO were characterized with scanning electron microscope(SEM),energy-dispersive X-ray(EDX) spectrometer,fourier transform infrared spectroscopy(FT-IR) and thermogravimetric analysis(TGA).展开更多
三磷酸腺苷结合盒式(ATP-binding cassette,ABC)输出转运体是一类典型的蛋白质分子机器,这类分子机器通过门控运动进行“向外打开”(outward-facing,OF)和“向内打开”(inward-facing,IF)构象态之间转换,从而把底物转运输出生物膜外。...三磷酸腺苷结合盒式(ATP-binding cassette,ABC)输出转运体是一类典型的蛋白质分子机器,这类分子机器通过门控运动进行“向外打开”(outward-facing,OF)和“向内打开”(inward-facing,IF)构象态之间转换,从而把底物转运输出生物膜外。尽管结构和功能的研究已取得重大进展,但对ABC输出转运体构象门控的分子机制还没有完全理解。由于全原子分子动力学存在长时间尺度问题,因此对ABC蛋白质分子构象变化不能进行完全描述。本文应用粗粒化分子动力学(CG-MD)结合改善的抽样方法,对细菌ABC输出转运体MsbA进行计算模拟研究。本文计算得到的平均力势(potential of mean force,PMF)表明,从OF构象态到IF构象态之间的转变需要经过一个“阻塞态”(occluded state,OC),即MsbA的内门和外门都是关闭的状态。这种阻塞状态对ABC输出功能的方向单一性具有重要意义。我们的CG-MD计算模拟结果显示,随着MsbA的核苷酸结合域(nucleotide binding domain,NBD)的分离,外门的关闭和内门的打开是采用高度协作的方式。基于本文的计算模拟结果,我们提出了一个与目前文献中发表的有很大不同的机械力学模型,揭示了ABC输出转运体通过构象门控运动输运底物的分子机制。展开更多
Dear Editor,Autophagy is an evolutionarily conserved catabolic process that involves the sequestration and transport of organelles,macromolecules,or invading microorganisms to lysosomes for degradation[1].Sequestosome...Dear Editor,Autophagy is an evolutionarily conserved catabolic process that involves the sequestration and transport of organelles,macromolecules,or invading microorganisms to lysosomes for degradation[1].Sequestosome 1(p62/SQSTM1)was the first protein shown to bind target-associated ubiquitin(Ub)and LC3 conjugated to the phagophore membrane,thus,acting as an important autophagy receptor for ubiquitinated targets[2].展开更多
The passive radiative cooling technology shows a great potential application on reducing the enormous global energy consumption.The multilayer metamaterials could enhance the radiative cooling performance.However,it i...The passive radiative cooling technology shows a great potential application on reducing the enormous global energy consumption.The multilayer metamaterials could enhance the radiative cooling performance.However,it is a challenge to design the radiative cooler.In this work,based on the particle swarm optimization(PSO)evolutionary algorithm,we develop an intelligent workflow in designing photonic radiative cooling metamaterials.Specifically,we design two 10-layer SiO_(2) radiative coolers doped by cylindrical MgF_(2) or air impurities,possessing high emissivity within the selective(8–13μm)and broadband(8–25μm)atmospheric transparency windows,respectively.Our two kinds of coolers demonstrate power density as high as 119 W/m^(2) and 132 W/m^(2) at the room temperature(300 K).Our scheme does not rely on the usage of special materials,forming high-performing metamaterials with conventional poor-performing components.This significant improvement of the emission spectra proves the effectiveness of our inverse design algorithm in boosting the discovery of high-performing functional metamaterials.展开更多
Solid solution strengthening(SSS)is one of the main contributions to the desired tensile properties of nickel-based superalloys for turbine blades and disks.The value of SSS can be calculated by using Fleischer’s and...Solid solution strengthening(SSS)is one of the main contributions to the desired tensile properties of nickel-based superalloys for turbine blades and disks.The value of SSS can be calculated by using Fleischer’s and Labusch’s theories,while the model parameters are incorporated without fitting to experimental data of complex alloys.In thiswork,four diffusionmultiples consisting of multicomponent alloys and pure Niare prepared and characterized.The composition and microhardness of singleγphase regions in samples are used to quantify the SSS.Then,Fleischer’s and Labusch’s theories are examined based on high-throughput experiments,respectively.The fitted solid solution coefficients are obtained based on Labusch’s theory and experimental data,indicating higher accuracy.Furthermore,six machine learning algorithms are established,providing a more accurate prediction compared with traditional physical models and fitted physical models.The results show that the coupling of highthroughput experiments and machine learning has great potential in the field of performance prediction and alloy design.展开更多
Nutritional characteristics determine tree stock quality to a considerable extent. Exponential fertilization can induce nutrient reserves within juvenile trees, but its validity on poplar is contingent on interaction ...Nutritional characteristics determine tree stock quality to a considerable extent. Exponential fertilization can induce nutrient reserves within juvenile trees, but its validity on poplar is contingent on interaction with a scientific irrigation regime due to limited water resources under global warming. In the present study, we raised 3200 Populus 9 euramericana cv. ‘74/76' cuttings under four irrigation regimes of 0(I0), 60 %(I60), 80 %(I80), and100 %(I100) of field capacity for soil moisture content with or without(control) the employment of nitrogen(N) addition delivered as exponential fertilization at the rate of 8 g N cutting^(-1)(E8) in an open-air nursery in Beijing, China. Both height and diameter increased with the increment of soil moisture ratio or in response to exponential fertilization(EF) without any interactive effects. In general, concentrations of N, phosphorus(P),and potassium(K) declined with time in stem but foliar N concentration did not change. Under the I100 regime, EF increased foliar N concentration relative to the control but failed to affect N concentration in stem in September, when both N concentration and N content were increased by EF under the I80 regime. Stem-K content and concentration by EF under the I80 regime also increased in September,therefore EF-treated cuttings had a higher ratio of K content in stem to that in whole plant(%ANAR). Vector diagnosis for nutritional status indicated that EF resulted in dilution of K concentration but induced a steady-state P uptake in leaves under all irrigation regimes. Therefore, EF of N addition could promote N uptake to leaves of P. 9 euramericana cv. ‘74/76' cuttings, but it had a null effect on N and P reserves in stem and impaired K reserves.In conclusion, the irrigation regime of 80 % field capacity of soil moisture content was suggested for the culture of juvenile P. 9 euramericana cv. ‘74/76' cuttings. As the interactive meaning, EF was also suggested for its excellent promotion on both N and K uptakes.展开更多
BACKGROUND Due to the special clinical features and biologic characteristics of adolescent and young adult(AYA)cancers,AYA cancers are different from cancers in children and elderly individuals.However,there are few r...BACKGROUND Due to the special clinical features and biologic characteristics of adolescent and young adult(AYA)cancers,AYA cancers are different from cancers in children and elderly individuals.However,there are few reports on AYA hepatocellular carcinoma(HCC).AIM To investigate the overall survival(OS)of AYA(15-39 years)and elderly(40-74 years)patients with HCC.METHODS The data of all the HCC cases were extracted from the Surveillance,Epidemiology,and End Results database from 2004 to 2015 and were then divided into two groups based on age:AYA group(15-39 years)and older group(40-74 years).Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups.Propensity score matching(PSM)was employed to analyze the OS difference between the two groups.The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTS Compared to elderly cancer patients,AYA patients with HCC had a worse Surveillance,Epidemiology,and End Results stage,including the distant stage(22.1%vs 15.4%,P<0.001),and a more advanced American Joint Committee on Cancer(AJCC)stage,including AJCC III and IV(49.2%vs 38.3%,P<0.001),and were more likely to receive surgery(64.5%vs 47.5%,P<0.001).Before PSM,the AYA group had a longer survival in months(median:20.00,interquartile range[IQR]:5.00-62.50)than the older group(median:15.00,IQR:4.00-40.00)(P<0.001).After PSM,the AYA group still had a longer survival in months(median:21.00,IQR:5.00-64.50)than the older group(median:18.00,IQR:6.00-53.00)(P<0.001).The Cox proportional hazards regression model showed that advanced age(hazard ratio[HR]=1.405,95%CI:1.218-1.621,P<0.001)was a risk factor for OS of HCC patients.In the subgroup analysis,the Cox proportional hazards regression model showed that in AJCC I/II HCC patients,advanced age(HR=1.749,95%CI:1.352-2.263,P<0.001)was a risk factor for OS,while it was not a risk factor in AJCC III/IV HCC patients(HR=1.186,95%CI:0.997-1.410,P=0.054)before PSM.After PSM,advanced age(HR=1.891,95%CI:1.356-2.637,P<0.001)was still a risk factor for OS in AJCC I/II HCC patients,but was not a risk factor for OS in AJCC III/IV HCC patients(HR=1.192,95%CI:0.934-1.521,P=0.157)after PSM.CONCLUSION AYA patients with HCC have different clinical characteristics from older adults.In different AJCC stages,the two groups of patients have different OS:In AJCC I/II HCC patients,advanced age is a risk factor for OS,but it is not a risk factor for OS in the AJCC III/IV HCC patient group.展开更多
Heat stress(HS)reaction can lead to serious physiological dysfunction associated with cardiovascular and various organ diseases.Ginsenoside Rg3(G-Rg3)is a representative component of ginseng rare saponin and can prote...Heat stress(HS)reaction can lead to serious physiological dysfunction associated with cardiovascular and various organ diseases.Ginsenoside Rg3(G-Rg3)is a representative component of ginseng rare saponin and can protect against multiple organs,also used as functional food to adjust the balance of the human body,but the therapeutic effect and molecular mechanism of G-Rg3 on male diseases under HS are underexplored.The aim of the present study,G-Rg3 was prepared through the efficient conversion of ginsenoside Rd and investigate the contribution of G-Rg3 to testicular injury induced exposure to HS.All mice were divided into four groups as follows:normal group,HS group,and HS+G-Rg3(5 and 10 mg/kg)groups.G-Rg3 was administered orally for 14 days,then exposed to a single scrotal heat treatment(43°C,18min)on the 7th day.After HS treatment,the morphology of testis and epididymis changes,and caused a significant loss of multinucleated giant cells,desquamation of germ cells in destructive seminiferous tubules,and degenerative Leydig cells,further destroying the production of sperm.After administration G-Rg3(5 and 10 mg/kg/day)for 2 weeks,the spermatogenic-related indexes of testosterone levels and superoxide dismutase(SOD)activity,glutathione(GSH)content significantly(p<0.01)increase compared with the HS group.Moreover,G-Rg3 treatment effectively ameliorated the production of malondialdehyde(MDA)(p<0.05 or p<0.01).Importantly,G-Rg3 exhibited the protective potential against HS-induced injury not only suppressing the protein levels of heme oxygenase-1(HO-1),hypoxia-inducible factor-1α(HIF-1α),and heat shock protein 70(HSP70)but also modulating the Bcl-2 family(p<0.01 or p<0.001)and activation of mitogen-activated protein kinase(MAPK)signaling pathways(p<0.01).For most of the parameters tested,the HS+G-Rg3(10 mg/kg)group exhibited potent effects compared with those exhibited by the low dose(5 mg/kg)group.In conclusion,the present study demonstrated that G-Rg3 exerted protective effects against HS-induced testicular dysfunction via inhibiting the MAPK-mediated oxidative stress and apoptosis in mice.展开更多
High-quality source rocks in saline lacustrine or marine sedimentary environments often show early peak petroleum generation and enhanced hydrocarbon yields,which have conventionally been attributed to organosulfur-en...High-quality source rocks in saline lacustrine or marine sedimentary environments often show early peak petroleum generation and enhanced hydrocarbon yields,which have conventionally been attributed to organosulfur-enhanced thermal decomposition of kero gen.However,there is increasing awareness that the coexisting inorganic salts,particularly sulfates,might also contribute to the acceleration of petroleum generation.In this study,we investigated the influence of sulfates on the thermal decomposition of kerogen sampled from the Pingliang Formation in the Ordos Basin.Our results demonstrate that the kerogen samples mixed with sulfate generate more hydrocarbons with a lower peak production temperature than their sulfate-free counterparts.Detailed chemical analysis revealed that the presence of sulfates significantly facilitated the generation of resins and asphaltenes at temperatures below 350℃,corresponding in our simulations to the early stage of petroleum generation(Easy%R_o <1.0%).We hypothesize that sulfates can promote the fragmentation of kerogen via direct thermochemical oxidation into a complex mixture of bitumen components that consist mostly of compounds typically encountered in the classical resin and asphaltene fractions.The findings reveal a new reaction paradigm between sulfates and organic macromolecules that could offer useful guidance in the exploration for low-maturity oils.展开更多
Ginsenoside Rb3(G-Rb3)is one of the primary active compounds isolated from Panax ginseng Meyer,which belongs to protopanaxadiol ginsenosides(PPD).Based on the structure-activity relationship(SAR)of ginsenosides,the pe...Ginsenoside Rb3(G-Rb3)is one of the primary active compounds isolated from Panax ginseng Meyer,which belongs to protopanaxadiol ginsenosides(PPD).Based on the structure-activity relationship(SAR)of ginsenosides,the pentose structure of G-Rb3 limited itself to possess more pharmacological activity to a certain extent.However,pharmacokinetics show that G-Rb3 is processed through deglycosylation in the intestinal tract and converted into more active rare saponins,such as Compound K,F2,etc.A series of studies focused on neuroprotection and the cardiovascular system demonstrating its therapeutic potentials,which was achieved by diminishing oxidative stress and apoptosis.Therefore,more systematic and in-depth studies are needed to complete the pharmaceutical value and to promote its clinical applications.This article highlights the multiple pharmacological effects and mechanisms of G-Rb3 and prospects for its development.展开更多
Objective The aim of the study was to use dynamic magnetic resonance imaging(MRI) to compare quantitative parameters of small bowel motility between healthy volunteers and patients with small bowel diseases in order t...Objective The aim of the study was to use dynamic magnetic resonance imaging(MRI) to compare quantitative parameters of small bowel motility between healthy volunteers and patients with small bowel diseases in order to investigate the characteristics of normal and impaired bowel peristalsis. Methods A total of 44 healthy volunteers(20 men, 24 women; mean age: 36 years; range: 20–61 years) and 42 patients(28 men, 14 women; mean age: 44 years; range: 15–72 years) with organic small bowel disease were recruited in our hospital(Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) in this prospective study approved by the hospital institutional review board. Imaging was performed using a 3.0-T scanner 45 minutes after standardized oral administration of 1500 m L non-absorbable fluid(2.5% mannitol). A serial coronal scan was performed at selected planes for two minutes without breath-hold. Time-caliber curves were plotted at two well-distended small bowel loops in both healthy and patient groups regardless of location. Luminal diameter(LD), contraction period(CP), frequency of contraction(FC), and amplitude-diameter ratio(ADR) were measured based on the graph. Results The characteristics of abnormal peristaltic parameters were assessed in different patients and compared to normal curves from healthy volunteers. A total of 37 segments with abnormal motility were confirmed by two readers in consensus, based on curve patterns and the presence of a stationary phase. Compared to normal peristalsis in healthy volunteers, five different patterns of impaired peristalsis were identified: I, consecutive; II, slow; III, giant type; IV, uncoordinated; and V, akinetic. Dilated LDs were detected in all instances of abnormal peristalsis(P < 0.05). Increased frequency was found in type I [(8.73 ± 1.15) /min], while decreased frequency was detected in type III peristalsis [(0.67 ± 0.29) /min]. There were no significant differences in frequency between type II [(3.19 ± 0.43) /min] and normal peristalsis [(3.45 ± 0.57) /min]. Apart from type I [(8.70 ± 0.75) /min], increased FCs were found in all other abnormal patterns. In type II peristalsis, the average ADR value was 0.82 ± 0.08, comparable to the ADR value in the healthy group(0.83 ± 0.13). Conclusion MR cine is an effective method for differentiating normal and abnormal small bowel peristalsis. Plotting time-caliber curves and measuring quantitative MR cine parameters such as LD, CP, FC, and ADR offers more precise information about small bowel motility.展开更多
This article continues to study the research suggestions in depth made by M.Z.Nashed and G.F.Votruba in the journal"Bull.Amer.Math.Soc."in 1974.Concerned with the pricing of non-reachable"contingent cla...This article continues to study the research suggestions in depth made by M.Z.Nashed and G.F.Votruba in the journal"Bull.Amer.Math.Soc."in 1974.Concerned with the pricing of non-reachable"contingent claims"in an incomplete financial market,when constructing a specific bounded linear operator A:l_(1)^(n)→l_(2) from a non-reflexive Banach space l_(1)^(n) to a Hilbert space l_(2),the problem of non-reachable"contingent claims"pricing is reduced to researching the(single-valued)selection of the(set-valued)metric generalized inverse A■ of the operator A.In this paper,by using the Banach space structure theory and the generalized inverse method of operators,we obtain a bounded linear single-valued selection A^(σ)=A+of A■.展开更多
BACKGROUND The therapeutic effects of a combination of Chinese medicines called Biyu decoction have been clinically verified,although its molecular targets in psoriasis remain unknown.AIM To explore the molecular mech...BACKGROUND The therapeutic effects of a combination of Chinese medicines called Biyu decoction have been clinically verified,although its molecular targets in psoriasis remain unknown.AIM To explore the molecular mechanisms of Biyu decoction for psoriasis treatment.METHODS In this network pharmacology and molecular docking study,the Traditional Chinese Medicine Systems Pharmacology database was searched for Biyu decoction active ingredients.GeneCards,Online Mendelian Inheritance in Man,PharmGkb,Therapeutic Target Database,and DrugBank databases were searched for psoriasis-related genes.The genes targeted by the decoction’s active ingredient and disease genes were intersected to obtain predictive targets of the drug during psoriasis treatment.Cytoscape 3.8.0 was used to construct a drug component/target disease network.The The functional protein association networks database and Cytoscape were used to construct a protein-protein interaction network and streamline the core network.The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for pathway enrichment analysis.Molecular docking technology was used to verify the drug component/target disease network.RESULTS We screened 117 major active ingredients,including quercetin,kaempferol,naringenin,and acetyl-shikonin,and identified 213 gene targets,such as MAPK3,JUN,FOS,MYC,MAPK8,STAT3,and NFKBIA.Using a molecular docking analysis,the main active ingredients demonstrated good binding to the core targets.The Gene Ontology analysis showed that these ingredients were significantly associated with biological activities,such as transcription factor DNA binding,RNA polymerase II-specific DNA binding of transcription factors,and cytokine receptor binding;responses to lipopolysaccharides,molecules of bacterial origin,and oxidative stress;and were mainly distributed in membrane rafts,microdomains,and regions.The Kyoto Encyclopedia of Genes and Genomes analysis showed that decoction ingredients act on Th17 cell differentiation,tumor necrosis factor and mitogen-activated protein signaling pathways,the interleukin-17 signaling pathway,and the PI3K-Akt signaling pathway.CONCLUSION Biyu decoction may be effective against psoriasis through multi-component,multi-target,and multi-channel synergy.展开更多
BACKGROUND Dystrophic epidermolysis bullosa pruriginosa(DEB-Pr)is a rare subtype of DEB,characterized by recurrent pruritus of the extremities,pruritus papules,nodules,and mossy-like plaques.To date,fewer than 100 cas...BACKGROUND Dystrophic epidermolysis bullosa pruriginosa(DEB-Pr)is a rare subtype of DEB,characterized by recurrent pruritus of the extremities,pruritus papules,nodules,and mossy-like plaques.To date,fewer than 100 cases have been reported.We report a misdiagnosed 30-year-old man with sporadic late-onset DEB-Pr who responded well to tacrolimus treatment,thereby serving as a guide to correct diagnosis and treatment.CASE SUMMARY A 30-year-old man presented with recurrent itching plaques of 1-year duration in the left tibia that aggravated and involved both legs and the back.Examination revealed multiple symmetrical,purple,and hyperpigmented papules and nodules with surface exfoliation involving the tibia and dorsum of the neck with negative Nissl's sign,no abnormalities in the skin,mucosa,hair,or fingernail,and no local lymph node enlargement.Blisters were never reported prior to presentation.Serum immunoglobulin E level was 636 IU/mL.Clinical manifestations suggested DEB-Pr.Histological examination showed subepidermal fissure,scar tissue,and milia.Direct immunofluorescence showed no obvious abnormalities.However,we were unable to perform electron microscopy or genetic research following his choice.We treated him with topical tacrolimus.After 2 wk,the itching alleviated,and the skin lesions began to subside.No adverse reactions were observed during treatment.CONCLUSION Topical tacrolimus is a safe treatment option for patients with DEB-Pr and can achieve continuous relief of severe itching.展开更多
基金supported by the National Natural Science Foundation of China,No.82272484(to XC).
文摘The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.
基金Project supported by the National Key Research and Development Program of China(Grant No.2022YFA1403202)the National Natural Science Foundation of China(Grant Nos.NSFC-12074335,11974095,5177115,11974095,and 12188101)the Natural Science Foundation of Shaanxi Province of China(Grant No.2022JM-028).
文摘Intercalated transition metal dichalcogenides(TMDCs)attract much attention due to their rich properties and potential applications.In this article,we grew successfully high-quality V_(1/3)TaS_(2) crystals by a vapor transport method.We measured the magnetization,longitudinal resistivityρxx(T,H),Hall resistivityρxy(T,H),as well as performed calculations of the electronic band structure.It was found that V_(1/3)TaS_(2) is an A-type antiferromagnet with the Neel temperature T_(N)=6.20 K,and exhibits a negative magnetoresistance(MR)near T_(N).Both band structure calculations and Hall resistivity measurements demonstrated it is a magnetic semimetal.
基金the National Natural Science Foundation of China (No.50730008 and 30772434)Shanghai Science & Technology Committee (No.09JC1407400 and 1052nm02000)
文摘Poly(glycidyl methacrylates)(PGMA) was grafted from zinc oxide(ZnO) nanowires via surface-initiated atom transfer radical polymerization(SI-ATRP) technique.Firstly,the ZnO nanowires were synthesized by the one-pot hydrothermal technique.Subsequently,the ZnO was functionalized with 3-aminopropyl triethoxysilane,which was converted to macroinitiator by the esterification of them with 2-bromopropionyl bromide.PGMA grafted ZnO nanowires(PGMA-ZnO) were then synthesized in an ATRP of the GMA with CuCl/2,2`-bipyridine as the catalyst system.Kinetics studies revealed an approximate linear increase in weight of polymer with reaction time,indicating that the polymerization process owned some "living" character.The structure and composition of PGMA-ZnO were characterized with scanning electron microscope(SEM),energy-dispersive X-ray(EDX) spectrometer,fourier transform infrared spectroscopy(FT-IR) and thermogravimetric analysis(TGA).
基金supported by the National Natural Science Foundation of China(21073170,21273209).
文摘三磷酸腺苷结合盒式(ATP-binding cassette,ABC)输出转运体是一类典型的蛋白质分子机器,这类分子机器通过门控运动进行“向外打开”(outward-facing,OF)和“向内打开”(inward-facing,IF)构象态之间转换,从而把底物转运输出生物膜外。尽管结构和功能的研究已取得重大进展,但对ABC输出转运体构象门控的分子机制还没有完全理解。由于全原子分子动力学存在长时间尺度问题,因此对ABC蛋白质分子构象变化不能进行完全描述。本文应用粗粒化分子动力学(CG-MD)结合改善的抽样方法,对细菌ABC输出转运体MsbA进行计算模拟研究。本文计算得到的平均力势(potential of mean force,PMF)表明,从OF构象态到IF构象态之间的转变需要经过一个“阻塞态”(occluded state,OC),即MsbA的内门和外门都是关闭的状态。这种阻塞状态对ABC输出功能的方向单一性具有重要意义。我们的CG-MD计算模拟结果显示,随着MsbA的核苷酸结合域(nucleotide binding domain,NBD)的分离,外门的关闭和内门的打开是采用高度协作的方式。基于本文的计算模拟结果,我们提出了一个与目前文献中发表的有很大不同的机械力学模型,揭示了ABC输出转运体通过构象门控运动输运底物的分子机制。
基金supported by the Ministry of Science and Technology of China (2019YFA0802103)the National Natural Science Foundation of China (31900804, 31960179)+1 种基金the Department of Science and Technology of Zhejiang Province (2021C03104)the Science and Technology Commission of Shanghai Municipality (19140903500)
文摘Dear Editor,Autophagy is an evolutionarily conserved catabolic process that involves the sequestration and transport of organelles,macromolecules,or invading microorganisms to lysosomes for degradation[1].Sequestosome 1(p62/SQSTM1)was the first protein shown to bind target-associated ubiquitin(Ub)and LC3 conjugated to the phagophore membrane,thus,acting as an important autophagy receptor for ubiquitinated targets[2].
基金the National Natural Science Foundation of China(Grant No.11935010)the Opening Project of Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology。
文摘The passive radiative cooling technology shows a great potential application on reducing the enormous global energy consumption.The multilayer metamaterials could enhance the radiative cooling performance.However,it is a challenge to design the radiative cooler.In this work,based on the particle swarm optimization(PSO)evolutionary algorithm,we develop an intelligent workflow in designing photonic radiative cooling metamaterials.Specifically,we design two 10-layer SiO_(2) radiative coolers doped by cylindrical MgF_(2) or air impurities,possessing high emissivity within the selective(8–13μm)and broadband(8–25μm)atmospheric transparency windows,respectively.Our two kinds of coolers demonstrate power density as high as 119 W/m^(2) and 132 W/m^(2) at the room temperature(300 K).Our scheme does not rely on the usage of special materials,forming high-performing metamaterials with conventional poor-performing components.This significant improvement of the emission spectra proves the effectiveness of our inverse design algorithm in boosting the discovery of high-performing functional metamaterials.
基金supported by National Science and Technology Major Project (J2019-IV-0003-0070)the Natural Science Foundation of China (91860105,52074366)+4 种基金China Postdoctoral Science Foundation (2019M662799)Natural Science Foundation of Hunan Province of China (2021JJ40757)the Science and Technology Innovation Program of Hunan Province (2021RC3131)Changsha Municipal Natural Science Foundation (kq2014126)Project Supported by State Key Laboratory of Powder Metallurgy,Central South University,Changsha,China.
文摘Solid solution strengthening(SSS)is one of the main contributions to the desired tensile properties of nickel-based superalloys for turbine blades and disks.The value of SSS can be calculated by using Fleischer’s and Labusch’s theories,while the model parameters are incorporated without fitting to experimental data of complex alloys.In thiswork,four diffusionmultiples consisting of multicomponent alloys and pure Niare prepared and characterized.The composition and microhardness of singleγphase regions in samples are used to quantify the SSS.Then,Fleischer’s and Labusch’s theories are examined based on high-throughput experiments,respectively.The fitted solid solution coefficients are obtained based on Labusch’s theory and experimental data,indicating higher accuracy.Furthermore,six machine learning algorithms are established,providing a more accurate prediction compared with traditional physical models and fitted physical models.The results show that the coupling of highthroughput experiments and machine learning has great potential in the field of performance prediction and alloy design.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education(20120014130001)the Eleventh Five-Year Plan Projects of National Science and Technology(Grant No.2006BAD24B01)
文摘Nutritional characteristics determine tree stock quality to a considerable extent. Exponential fertilization can induce nutrient reserves within juvenile trees, but its validity on poplar is contingent on interaction with a scientific irrigation regime due to limited water resources under global warming. In the present study, we raised 3200 Populus 9 euramericana cv. ‘74/76' cuttings under four irrigation regimes of 0(I0), 60 %(I60), 80 %(I80), and100 %(I100) of field capacity for soil moisture content with or without(control) the employment of nitrogen(N) addition delivered as exponential fertilization at the rate of 8 g N cutting^(-1)(E8) in an open-air nursery in Beijing, China. Both height and diameter increased with the increment of soil moisture ratio or in response to exponential fertilization(EF) without any interactive effects. In general, concentrations of N, phosphorus(P),and potassium(K) declined with time in stem but foliar N concentration did not change. Under the I100 regime, EF increased foliar N concentration relative to the control but failed to affect N concentration in stem in September, when both N concentration and N content were increased by EF under the I80 regime. Stem-K content and concentration by EF under the I80 regime also increased in September,therefore EF-treated cuttings had a higher ratio of K content in stem to that in whole plant(%ANAR). Vector diagnosis for nutritional status indicated that EF resulted in dilution of K concentration but induced a steady-state P uptake in leaves under all irrigation regimes. Therefore, EF of N addition could promote N uptake to leaves of P. 9 euramericana cv. ‘74/76' cuttings, but it had a null effect on N and P reserves in stem and impaired K reserves.In conclusion, the irrigation regime of 80 % field capacity of soil moisture content was suggested for the culture of juvenile P. 9 euramericana cv. ‘74/76' cuttings. As the interactive meaning, EF was also suggested for its excellent promotion on both N and K uptakes.
文摘BACKGROUND Due to the special clinical features and biologic characteristics of adolescent and young adult(AYA)cancers,AYA cancers are different from cancers in children and elderly individuals.However,there are few reports on AYA hepatocellular carcinoma(HCC).AIM To investigate the overall survival(OS)of AYA(15-39 years)and elderly(40-74 years)patients with HCC.METHODS The data of all the HCC cases were extracted from the Surveillance,Epidemiology,and End Results database from 2004 to 2015 and were then divided into two groups based on age:AYA group(15-39 years)and older group(40-74 years).Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups.Propensity score matching(PSM)was employed to analyze the OS difference between the two groups.The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTS Compared to elderly cancer patients,AYA patients with HCC had a worse Surveillance,Epidemiology,and End Results stage,including the distant stage(22.1%vs 15.4%,P<0.001),and a more advanced American Joint Committee on Cancer(AJCC)stage,including AJCC III and IV(49.2%vs 38.3%,P<0.001),and were more likely to receive surgery(64.5%vs 47.5%,P<0.001).Before PSM,the AYA group had a longer survival in months(median:20.00,interquartile range[IQR]:5.00-62.50)than the older group(median:15.00,IQR:4.00-40.00)(P<0.001).After PSM,the AYA group still had a longer survival in months(median:21.00,IQR:5.00-64.50)than the older group(median:18.00,IQR:6.00-53.00)(P<0.001).The Cox proportional hazards regression model showed that advanced age(hazard ratio[HR]=1.405,95%CI:1.218-1.621,P<0.001)was a risk factor for OS of HCC patients.In the subgroup analysis,the Cox proportional hazards regression model showed that in AJCC I/II HCC patients,advanced age(HR=1.749,95%CI:1.352-2.263,P<0.001)was a risk factor for OS,while it was not a risk factor in AJCC III/IV HCC patients(HR=1.186,95%CI:0.997-1.410,P=0.054)before PSM.After PSM,advanced age(HR=1.891,95%CI:1.356-2.637,P<0.001)was still a risk factor for OS in AJCC I/II HCC patients,but was not a risk factor for OS in AJCC III/IV HCC patients(HR=1.192,95%CI:0.934-1.521,P=0.157)after PSM.CONCLUSION AYA patients with HCC have different clinical characteristics from older adults.In different AJCC stages,the two groups of patients have different OS:In AJCC I/II HCC patients,advanced age is a risk factor for OS,but it is not a risk factor for OS in the AJCC III/IV HCC patient group.
基金the grants of the Jilin Science&Technology Development Plan(Nos.20170101011JC,20200301037RQ and 20190103092JH)the Open Fund of Key Laboratory of Biotechnology and Bioresources Utilization(KF202004).
文摘Heat stress(HS)reaction can lead to serious physiological dysfunction associated with cardiovascular and various organ diseases.Ginsenoside Rg3(G-Rg3)is a representative component of ginseng rare saponin and can protect against multiple organs,also used as functional food to adjust the balance of the human body,but the therapeutic effect and molecular mechanism of G-Rg3 on male diseases under HS are underexplored.The aim of the present study,G-Rg3 was prepared through the efficient conversion of ginsenoside Rd and investigate the contribution of G-Rg3 to testicular injury induced exposure to HS.All mice were divided into four groups as follows:normal group,HS group,and HS+G-Rg3(5 and 10 mg/kg)groups.G-Rg3 was administered orally for 14 days,then exposed to a single scrotal heat treatment(43°C,18min)on the 7th day.After HS treatment,the morphology of testis and epididymis changes,and caused a significant loss of multinucleated giant cells,desquamation of germ cells in destructive seminiferous tubules,and degenerative Leydig cells,further destroying the production of sperm.After administration G-Rg3(5 and 10 mg/kg/day)for 2 weeks,the spermatogenic-related indexes of testosterone levels and superoxide dismutase(SOD)activity,glutathione(GSH)content significantly(p<0.01)increase compared with the HS group.Moreover,G-Rg3 treatment effectively ameliorated the production of malondialdehyde(MDA)(p<0.05 or p<0.01).Importantly,G-Rg3 exhibited the protective potential against HS-induced injury not only suppressing the protein levels of heme oxygenase-1(HO-1),hypoxia-inducible factor-1α(HIF-1α),and heat shock protein 70(HSP70)but also modulating the Bcl-2 family(p<0.01 or p<0.001)and activation of mitogen-activated protein kinase(MAPK)signaling pathways(p<0.01).For most of the parameters tested,the HS+G-Rg3(10 mg/kg)group exhibited potent effects compared with those exhibited by the low dose(5 mg/kg)group.In conclusion,the present study demonstrated that G-Rg3 exerted protective effects against HS-induced testicular dysfunction via inhibiting the MAPK-mediated oxidative stress and apoptosis in mice.
基金supported by National Natural Science Foundation of China (No. 41403049)the Foundation of State Key Laboratory of Petroleum Resources and Prospecting, China University of Petroleum (Beijing) (No. PRP/indep-3-1715)National Science and Technology Major Project during the 13th Five-Year Plan Period (2016ZX05007-002)。
文摘High-quality source rocks in saline lacustrine or marine sedimentary environments often show early peak petroleum generation and enhanced hydrocarbon yields,which have conventionally been attributed to organosulfur-enhanced thermal decomposition of kero gen.However,there is increasing awareness that the coexisting inorganic salts,particularly sulfates,might also contribute to the acceleration of petroleum generation.In this study,we investigated the influence of sulfates on the thermal decomposition of kerogen sampled from the Pingliang Formation in the Ordos Basin.Our results demonstrate that the kerogen samples mixed with sulfate generate more hydrocarbons with a lower peak production temperature than their sulfate-free counterparts.Detailed chemical analysis revealed that the presence of sulfates significantly facilitated the generation of resins and asphaltenes at temperatures below 350℃,corresponding in our simulations to the early stage of petroleum generation(Easy%R_o <1.0%).We hypothesize that sulfates can promote the fragmentation of kerogen via direct thermochemical oxidation into a complex mixture of bitumen components that consist mostly of compounds typically encountered in the classical resin and asphaltene fractions.The findings reveal a new reaction paradigm between sulfates and organic macromolecules that could offer useful guidance in the exploration for low-maturity oils.
基金This work was funded by the grant of Jilin Science&Technology Development Plan(No.20200301037RQ).
文摘Ginsenoside Rb3(G-Rb3)is one of the primary active compounds isolated from Panax ginseng Meyer,which belongs to protopanaxadiol ginsenosides(PPD).Based on the structure-activity relationship(SAR)of ginsenosides,the pentose structure of G-Rb3 limited itself to possess more pharmacological activity to a certain extent.However,pharmacokinetics show that G-Rb3 is processed through deglycosylation in the intestinal tract and converted into more active rare saponins,such as Compound K,F2,etc.A series of studies focused on neuroprotection and the cardiovascular system demonstrating its therapeutic potentials,which was achieved by diminishing oxidative stress and apoptosis.Therefore,more systematic and in-depth studies are needed to complete the pharmaceutical value and to promote its clinical applications.This article highlights the multiple pharmacological effects and mechanisms of G-Rb3 and prospects for its development.
基金Supported by a grant of the National Natural Science Foundation of China(No.81371524)
文摘Objective The aim of the study was to use dynamic magnetic resonance imaging(MRI) to compare quantitative parameters of small bowel motility between healthy volunteers and patients with small bowel diseases in order to investigate the characteristics of normal and impaired bowel peristalsis. Methods A total of 44 healthy volunteers(20 men, 24 women; mean age: 36 years; range: 20–61 years) and 42 patients(28 men, 14 women; mean age: 44 years; range: 15–72 years) with organic small bowel disease were recruited in our hospital(Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) in this prospective study approved by the hospital institutional review board. Imaging was performed using a 3.0-T scanner 45 minutes after standardized oral administration of 1500 m L non-absorbable fluid(2.5% mannitol). A serial coronal scan was performed at selected planes for two minutes without breath-hold. Time-caliber curves were plotted at two well-distended small bowel loops in both healthy and patient groups regardless of location. Luminal diameter(LD), contraction period(CP), frequency of contraction(FC), and amplitude-diameter ratio(ADR) were measured based on the graph. Results The characteristics of abnormal peristaltic parameters were assessed in different patients and compared to normal curves from healthy volunteers. A total of 37 segments with abnormal motility were confirmed by two readers in consensus, based on curve patterns and the presence of a stationary phase. Compared to normal peristalsis in healthy volunteers, five different patterns of impaired peristalsis were identified: I, consecutive; II, slow; III, giant type; IV, uncoordinated; and V, akinetic. Dilated LDs were detected in all instances of abnormal peristalsis(P < 0.05). Increased frequency was found in type I [(8.73 ± 1.15) /min], while decreased frequency was detected in type III peristalsis [(0.67 ± 0.29) /min]. There were no significant differences in frequency between type II [(3.19 ± 0.43) /min] and normal peristalsis [(3.45 ± 0.57) /min]. Apart from type I [(8.70 ± 0.75) /min], increased FCs were found in all other abnormal patterns. In type II peristalsis, the average ADR value was 0.82 ± 0.08, comparable to the ADR value in the healthy group(0.83 ± 0.13). Conclusion MR cine is an effective method for differentiating normal and abnormal small bowel peristalsis. Plotting time-caliber curves and measuring quantitative MR cine parameters such as LD, CP, FC, and ADR offers more precise information about small bowel motility.
基金supported by the National Science Foundation (12001142)Harbin Normal University doctoral initiation Fund (XKB201812)supported by the Science Foundation Grant of Heilongjiang Province (LH2019A017)
文摘This article continues to study the research suggestions in depth made by M.Z.Nashed and G.F.Votruba in the journal"Bull.Amer.Math.Soc."in 1974.Concerned with the pricing of non-reachable"contingent claims"in an incomplete financial market,when constructing a specific bounded linear operator A:l_(1)^(n)→l_(2) from a non-reflexive Banach space l_(1)^(n) to a Hilbert space l_(2),the problem of non-reachable"contingent claims"pricing is reduced to researching the(single-valued)selection of the(set-valued)metric generalized inverse A■ of the operator A.In this paper,by using the Banach space structure theory and the generalized inverse method of operators,we obtain a bounded linear single-valued selection A^(σ)=A+of A■.
基金Supported by the National Natural Science Foundation of China(NSFC),No.81874393.
文摘BACKGROUND The therapeutic effects of a combination of Chinese medicines called Biyu decoction have been clinically verified,although its molecular targets in psoriasis remain unknown.AIM To explore the molecular mechanisms of Biyu decoction for psoriasis treatment.METHODS In this network pharmacology and molecular docking study,the Traditional Chinese Medicine Systems Pharmacology database was searched for Biyu decoction active ingredients.GeneCards,Online Mendelian Inheritance in Man,PharmGkb,Therapeutic Target Database,and DrugBank databases were searched for psoriasis-related genes.The genes targeted by the decoction’s active ingredient and disease genes were intersected to obtain predictive targets of the drug during psoriasis treatment.Cytoscape 3.8.0 was used to construct a drug component/target disease network.The The functional protein association networks database and Cytoscape were used to construct a protein-protein interaction network and streamline the core network.The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for pathway enrichment analysis.Molecular docking technology was used to verify the drug component/target disease network.RESULTS We screened 117 major active ingredients,including quercetin,kaempferol,naringenin,and acetyl-shikonin,and identified 213 gene targets,such as MAPK3,JUN,FOS,MYC,MAPK8,STAT3,and NFKBIA.Using a molecular docking analysis,the main active ingredients demonstrated good binding to the core targets.The Gene Ontology analysis showed that these ingredients were significantly associated with biological activities,such as transcription factor DNA binding,RNA polymerase II-specific DNA binding of transcription factors,and cytokine receptor binding;responses to lipopolysaccharides,molecules of bacterial origin,and oxidative stress;and were mainly distributed in membrane rafts,microdomains,and regions.The Kyoto Encyclopedia of Genes and Genomes analysis showed that decoction ingredients act on Th17 cell differentiation,tumor necrosis factor and mitogen-activated protein signaling pathways,the interleukin-17 signaling pathway,and the PI3K-Akt signaling pathway.CONCLUSION Biyu decoction may be effective against psoriasis through multi-component,multi-target,and multi-channel synergy.
基金National Natural Science Foundation of China,No.81874393.
文摘BACKGROUND Dystrophic epidermolysis bullosa pruriginosa(DEB-Pr)is a rare subtype of DEB,characterized by recurrent pruritus of the extremities,pruritus papules,nodules,and mossy-like plaques.To date,fewer than 100 cases have been reported.We report a misdiagnosed 30-year-old man with sporadic late-onset DEB-Pr who responded well to tacrolimus treatment,thereby serving as a guide to correct diagnosis and treatment.CASE SUMMARY A 30-year-old man presented with recurrent itching plaques of 1-year duration in the left tibia that aggravated and involved both legs and the back.Examination revealed multiple symmetrical,purple,and hyperpigmented papules and nodules with surface exfoliation involving the tibia and dorsum of the neck with negative Nissl's sign,no abnormalities in the skin,mucosa,hair,or fingernail,and no local lymph node enlargement.Blisters were never reported prior to presentation.Serum immunoglobulin E level was 636 IU/mL.Clinical manifestations suggested DEB-Pr.Histological examination showed subepidermal fissure,scar tissue,and milia.Direct immunofluorescence showed no obvious abnormalities.However,we were unable to perform electron microscopy or genetic research following his choice.We treated him with topical tacrolimus.After 2 wk,the itching alleviated,and the skin lesions began to subside.No adverse reactions were observed during treatment.CONCLUSION Topical tacrolimus is a safe treatment option for patients with DEB-Pr and can achieve continuous relief of severe itching.
