Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role ...Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role in PD.Mesenchymal stem cells(MSCs)have emerged as a promising therapeutic approach for various nerve injuries,but there are limited reports on their use in PD and the underlying mechanisms remain unclear.Methods:We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa(hOM)-MSCs on neural functional recovery in both PD models and patients,as well as the preventive effects on mouse models of PD.To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure,we employed single-cell RNA sequencing(scRNA-seq),assay for transposase accessible chromatin with high-throughput sequencing(ATAC-seq)combined with full-length transcriptome isoform-sequencing(ISO-seq),and functional assay.Furthermore,we present the findings from an initial cohort of patients enrolled in a phaseⅠfirstinhuman clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients.Results:A functional assay identified that transforming growth factor-β1(TGF-β1),secreted from hOM-MSCs,played a critical role in modulating mitochondrial function recovery in dopaminergic neurons.This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN,which are closely associated with neuroinflammatory responses.Mechanistically,exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B(ALK/PI3K/Akt)signaling pathway in microglia located in the SN of PD patients.Furthermore,intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD.Conclusions:These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD.Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD.Additionally,TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.展开更多
BACKGROUND Natural killer(NK)/T-cell non-Hodgkin's lymphoma(NHL)in the nasal cavities and paranasal sinuses accounts for approximately 10%of all lymphomas,and the occurrence of nasal NHL is related to Epstein-Barr...BACKGROUND Natural killer(NK)/T-cell non-Hodgkin's lymphoma(NHL)in the nasal cavities and paranasal sinuses accounts for approximately 10%of all lymphomas,and the occurrence of nasal NHL is related to Epstein-Barr virus infection.AIM To explore the anxiety and depression status of patients with NK/T-cell NHL in the nasal cavities and paranasal sinuses and analyzes the relevant influencing factors.METHODS A retrospective analysis was performed,which included 30 patients with primary nasal NK/T-cell NHL treated in Shaanxi Provincial People’s Hospital from January 2017 to January 2023.An additional 50 healthy volunteers were selected as the control group.Both groups were assessed using the self-rating anxiety scale(SAS)and Self-rating(SDS).SDS and SAS scores of patients with NHL at different disease stages were analyzed,and they were further grouped into negative emotion(NE)(n=19)and non-NE(n=11)groups based on their depression and anxiety.Factors affecting the occurrence of NEs in patients with NHL were analyzed using univariate and multivariate logistic regression models.RESULTS Patients with NHL exhibited higher SDS and SAS scores than healthy controls.Moreover,patients with NHL at stages III and IV had higher SDS and SAS scores than those in stage I.Among the 30 patients,there were 13 patients with depression(43.3%),16 patients with anxiety(53.3%),and 10 patients with both anxiety and depression(33.3%).Univariate analysis identified a higher proportion of people in the NE group with stage III-IV NHL,an educational level≤high school,and a monthly household income<5000 yuan compared with the non-NE group.Multiple logistic regression analysis further revealed that stage III-IV was a risk factor for NEs in patients with NHL.CONCLUSION The stage of NK/T-cell NHL in nasal cavities and paranasal sinuses is closely related to patient anxiety and depression.The higher the staging,the greater the incidence of anxiety and depression.展开更多
Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.I...Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.Inhibiting ferroptosis has shown great promise as a therapeutic strategy for these diseases,underscoring the urgent need to develop effective ferroptosis inhibitors.Although Ferrostatin-1(Fer-1)is a potent ferroptosis inhibitor,its susceptibility to oxidation and metabolic inactivation limits its clinical utility.In this study,the accumulation of peroxides and the resulting oxidative damage in the cellular microenvironment during ferroptosis were utilized to design Ferrostatin-1 prodrugs with reactive oxygen species-responsive features.This approach led to the development of a series of ferroptosis inhibitors that were capable of recognizing oxidative damage in diseased areas,allowing for targeted release and improved stability.The novel compounds demonstrated significant inhibitory effects and selectivity against RSL-3-induced ferroptosis in HK-2 cells,with compound a1 exhibiting an EC50 of 15.4�0.7μM,outperforming Fer-1.These compounds effectively identify the oxidative microenvironment associated with ferroptosis,enabling the targeted release of Fer-1,which prevents lipid peroxide accumulation and inhibits ferroptosis.This strategy holds promise for treating diseases related to ferroptosis,offering a targeted and intelligent therapeutic approach.展开更多
Interparticle frictional interactions are ubiquitous in colloidal systems,exerting a profound influence on their structural and physical attributes.In this study,we employed Brownian dynamics simulations to explore th...Interparticle frictional interactions are ubiquitous in colloidal systems,exerting a profound influence on their structural and physical attributes.In this study,we employed Brownian dynamics simulations to explore the non-equilibrium dynamics in colloidal systems,focusing particularly on the role of tangential friction and its influence on the macroscopic physical properties of colloids.We found that the disruption of instantaneous time-reversal symmetry by tangential frictional interactions can trigger the self-assembly of colloidal systems into intricate network configurations,and these novel structures exhibit unique depletion force and rheological properties that set them apart from traditional colloidal gel systems.These findings not only help deepen our comprehension of the self-assembly phenomena in non-equilibrium colloidal systems but also offer fresh insights for the development of colloidal materials with tailored characteristics.展开更多
目的:探讨宫颈弹性成像技术在自发性早产孕妇孕期检查中的应用价值。方法:选取2021年8月—2023年8月在徐州市中心医院超声科进行常规产检的431例孕妇为研究对象,所有孕妇均随访至分娩,且在孕期内定期进行超声检查。利用宫颈弹性成像技...目的:探讨宫颈弹性成像技术在自发性早产孕妇孕期检查中的应用价值。方法:选取2021年8月—2023年8月在徐州市中心医院超声科进行常规产检的431例孕妇为研究对象,所有孕妇均随访至分娩,且在孕期内定期进行超声检查。利用宫颈弹性成像技术对所有孕妇进行产前超声检查并记录宫颈在孕期内的变化。根据孕妇孕周及分娩时间,将孕妇分为足月产组和早产组,回顾性比较两组孕妇宫颈参数的变化。结果:两组孕妇在入组时的一般资料差异无统计学意义,在孕20~24周,早产组孕妇的宫颈长度低于足月产组(3.67±0.55 vs 4.21±0.61),差异有统计学意义,且这种现象在孕晚期持续存在(3.34±0.71 vs 3.94±0.52)。早产组孕妇的宫颈硬度比(76.54±6.21)在孕20~24周也低于足月产组(83.34±5.14),差异有统计学意义(P<0.05)。早产组孕妇的对比指数和宫颈内口应变平均值在孕20~24周和孕28~35周也与足月产组比较差异有统计学意义(P<0.05)。结论:宫颈弹性成像技术可以在孕中晚期对孕妇宫颈状况进行筛查,提示可能出现的自发性早产的发生,在临床中具有一定的研究价值。展开更多
Photocatalytic activation of peroxymonosulfate (PMS) has garnered a lot of interest in the field of wastewater treatment. Herein, a plasmonic Ag nanoparticles decorated MIL-101(Fe) hybrid was synthesized through a pho...Photocatalytic activation of peroxymonosulfate (PMS) has garnered a lot of interest in the field of wastewater treatment. Herein, a plasmonic Ag nanoparticles decorated MIL-101(Fe) hybrid was synthesized through a photodeposition process. Upon light irradiation, the Ag/MIL-101(Fe) exhibit reinforced photocatalytic activities for elimination of bisphenol A (BPA) with PMS. The optimized 2.0% Ag/MIL-101(Fe) composite presented the highest photocatalytic activity with kinetic constant k of 0.102 min-1, which was about 10-fold of the pristine MIL-101(Fe). Loading of plasmonic Ag into MIL-101(Fe) boosts photoinduced carrier separation and accelerates PMS activation to generate strong oxidative radicals. Photoelectrochemical tests and multiple spectroscopic studies confirmed the promoted charge carrier separation and transfer capability of Ag/MIL-101(Fe). Combining the results of radical trapping experiments and electron spin resonance (ESR), the formed SO4·-, ·OH, ·O2- and 1O2 had a significant role in the photocatalytic process. According to intermediate study, the degradation pathway was studied, and the possible mechanism was proposed.展开更多
Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target ...Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.展开更多
BACKGROUND Mutations in mitochondrial tRNA(mt-tRNA)genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus(T2DM).We previously reported a large Chinese pedigree with maternally ...BACKGROUND Mutations in mitochondrial tRNA(mt-tRNA)genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus(T2DM).We previously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA^(Trp)A5514G and tRNA^(Ser(AGY))C12237T variants,however,the effects of these mt-tRNA variants on T2DM progression are largely unknown.AIM To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic,molecular,and biochemical levels.METHODS Cytoplasmic hybrid(cybrid)cells carrying both m.A5514G and m.C12237T variants,and healthy control cells without these mitochondrial DNA(mtDNA)variants were generated using trans-mitochondrial technology.Mitochondrial features,including mt-tRNA steady-state level,levels of adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),reactive oxygen species(ROS),mtDNA copy number,nicotinamide adenine dinucleotide(NAD+)/NADH ratio,enzymatic activities of respiratory chain complexes(RCCs),8-hydroxy-deoxyguanine(8-OhdG),malondialdehyde(MDA),and superoxide dismutase(SOD)were examined in cell lines with and without these mt-tRNA variants.RESULTS Compared with control cells,the m.A5514G variant caused an approximately 35%reduction in the steady-state level of mt-tRNA^(Trp)(P<0.0001);however,the m.C12237T variant did not affect the mt-tRNA^(Ser(AGY))steady-state level(P=0.5849).Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells:ATP,MMP,NAD+/NADH ratio,enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells(P<0.05 for all measures).By contrast,the levels of ROS,8-OhdG and MDA were significantly increased(P<0.05 for all measures),but mtDNA copy number was not affected by m.A5514G and m.C12237T variants(P=0.5942).CONCLUSION The m.A5514G variant impaired mt-tRNA^(Trp)metabolism,which subsequently caused mitochondrial dysfunction.The m.C12237T variant did not alter the steady-state level of mt-tRNA^(Ser(AGY)),indicating that it may be a modifier of the m.A5514G variant.The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.展开更多
Hydrogen as an interstitial solute at grain boundaries(GBs)can have a catastrophic impact on the mechanical properties of many metals.Despite the global research effort,the underlying hydrogen-GB interactions in polyc...Hydrogen as an interstitial solute at grain boundaries(GBs)can have a catastrophic impact on the mechanical properties of many metals.Despite the global research effort,the underlying hydrogen-GB interactions in polycrystals remain inadequately understood.In this study,using Voronoi tessellations and atomistic simulations,we elucidate the hydrogen segregation energy spectrum at the GBs of polycrystalline nickel by exploring all the topologically favorable segregation sites.Three distinct peaks in the energy spectrum are identified,corresponding to different structural fingerprints.The first peak(-0.205 eV)represents the most favorable segregation sites at GB core,while the second and third peaks account for the sites at GB surface.By incorporating a thermodynamic model,the spectrum enables the determination of the equilibrium hydrogen concentrations at GBs,unveiling a remarkable two to three orders of magnitude increase compared to the bulk hydrogen concentration reported in experimental studies.The identified structures from the GB spectrum exhibit vastly different behaviors in hydrogen segregation and diffusion,with the low-barrier channels inside GB core contributing to short-circuit diffusion,while the high energy gaps between GB and neighboring lattice serving as on-plane diffusion barriers.Mean square displacement analysis further confirms the findings,and shows that the calculated GB diffusion coefficient is three orders of magnitude greater than that of lattice.The present study has a significant implication for practical applications since it offers a tool to bridge the gap between atomic-scale interactions and macroscopic behaviors in engineering materials.展开更多
The second-to-fourth digit(2D:4D)ratio is thought to be associated with prenatal androgen exposure.However,the relationship between the 2D:4D ratio and hypospadias is poorly understood,and its molecular mechanism is n...The second-to-fourth digit(2D:4D)ratio is thought to be associated with prenatal androgen exposure.However,the relationship between the 2D:4D ratio and hypospadias is poorly understood,and its molecular mechanism is not clear.In this study,by analyzing the hand digit length of 142 boys with hypospadias(23 distal,68 middle,and 51 proximal)and 196 controls enrolled in Shanghai Children’s Hospital(Shanghai,China)from December 2020 to December 2021,we found that the 2D:4D ratio was significantly increased in boys with hypospadias(P<0.001)and it was positively correlated with the severity of the hypospadias.This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene(dynein axonemal heavy chain 8[DNAH8])associated with hypospadias.Furthermore,the discrepancy was mainly caused by a shift in 4D.Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D.Comprehensive mechanistic explorations revealed that during the androgen-sensitive window,the downregulation of the androgen receptor(AR)caused by low testosterone levels,as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a(Wnt5a),Wnt5b,Smad family member 2(Smad2),and Smad3;mitochondrial function-related genes in cartilage such as AMP-activated protein kinase(AMPK)and nuclear respiratory factor 1(Nrf-1);and vascular development-related genes such as myosin light chain(MLC),notch receptor 3(Notch3),and sphingosine kinase 1(Sphk1),are responsible for the limitation of 4D growth,which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification.This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.展开更多
The selective electrochemical conversion of glycerol into value-added products is a green and sustainable strategy for the biomass utilization.In this work,Au nanowires(Au-NW)modified with polyethyleneimine(PEI)molecu...The selective electrochemical conversion of glycerol into value-added products is a green and sustainable strategy for the biomass utilization.In this work,Au nanowires(Au-NW)modified with polyethyleneimine(PEI)molecule(Au-NW@PEI)is obtained by an up-bottom post-modification approach.Physical characterization,molecular dynamics simulation and density functional theory demonstrate that the loose-packed PEI monolayer firmly and uniformly distribute on the Au-NW surface due to the strong Au-N interaction.Electrochemical experiments and product analysis display that PEI modification significantly enhance the electro-activity of Au-NW for the glycerol electro-oxidation reaction(GEOR)due to the electronic effect.Meanwhile,the steric hindrance and electrostatic effect of PEI layer make the optimizing adsorption of intermediates possible.Therefore,the selectivity of C3 product glyceric acid over Au-NW@PEI is increased by nearly 20%.The work thus indicates that the rational design of metal-organic interface can effectively elevate the electro-activity and selectivity of Au nanostructures,which may have wide application in biomass development.展开更多
Nonpolar(11–20) a-plane p-type GaN films were successfully grown on r-plane sapphire substrate with the metal–organic chemical vapor deposition(MOCVD) system. The effects of Mg-doping temperature on the structural a...Nonpolar(11–20) a-plane p-type GaN films were successfully grown on r-plane sapphire substrate with the metal–organic chemical vapor deposition(MOCVD) system. The effects of Mg-doping temperature on the structural and electrical properties of nonpolar p-type GaN films were investigated in detail. It is found that all the surface morphology, crystalline quality, strains, and electrical properties of nonpolar a-plane p-type GaN films are interconnected, and are closely related to the Mg-doping temperature. This means that a proper performance of nonpolar p-type GaN can be expected by optimizing the Mg-doping temperature. In fact, a hole concentration of 1.3×10^(18)cm^(-3), a high Mg activation efficiency of 6.5%,an activation energy of 114 me V for Mg acceptor, and a low anisotropy of 8.3% in crystalline quality were achieved with a growth temperature of 990℃. This approach to optimizing the Mg-doping temperature of the nonpolar a-plane p-type GaN film provides an effective way to fabricate high-efficiency optoelectronic devices in the future.展开更多
Selenopeptides may be a valuable bioactive compound to promote gut microbiota-targeted therapeutic methods for intestinal disease and hepatopathy.However,limited information is available on the utilization of selenope...Selenopeptides may be a valuable bioactive compound to promote gut microbiota-targeted therapeutic methods for intestinal disease and hepatopathy.However,limited information is available on the utilization of selenopeptides by gut microbiota,especially Selenium(Se)function.For this purpose,the present study aimed to investigate the protective effect of selenopeptide(RYNA(Se)MNDYT,Se-P2,purity of≥95%)and its original peptide(RYNAMNDYT,P2,purity of≥95%)in vivo by the microbiota-metabolite axis and further analyze the potential contribution of Se biofortification to Se-P2 bioactivity.The results showed that Se-P2 exhibits a higher protective effect on lipopolysaccharide(LPS)-induced inflammation than P2,including pathology of the colon and liver,which suggested that the bioactivity of P2 was promoted by the organic combination of Se.Notably,gut microbiota composition tended to be a healthy structure by Se-P2 pretreatment in LPS-injured mice,which had a positive effect on LPS-induced gut microbiota dysbacteriosis.Additionally,only Se-P2 promoted an increase in the relative abundance of Lactobacillus,Alistipes,and Roseburia and a decrease in the relative abundance of Akkermansia,Erysipelatoclostridium,and Bacteroides in LPS-injured mice.The changes in gut microbiota were obviously correlated with the changes in metabolites and affected the metabolic pathways of valine,leucine,isoleucine,phenylalanine,tyrosine,and tryptophan biosynthesis and phenylalanine metabolism.This may be one of the key reasons for Se-P2 to exert bioactivity through the microbiota-metabolite axis.Furthermore,Se-biofortification in Se-enriched Cordyceps militaris affected the parental proteins of Se-P2 to modulate mitogen-activated protein kinase,GPI anchored protein,and carbohydrate metabolism,translation,folding,sorting and degradation,which may contribute to the bioactivity of Se-P2.Our study provides information on the effect of Se on selenopeptides in vivo,which further promotes the prospective applications of selenopeptides as dietary supplements.展开更多
基金supported by the Key Research and Development Program of Hunan Province of China(2020SK2102)the Hunan Provincial Natural Science Foundation of China(2023JJ40420)+5 种基金the Changsha Municipal Natural Science Foundation(kq2208154)the Scientific Research Project of Hunan Provincial Health Commission(B202304088074)the Scientific Research Project of Hunan Provincial Health Commission(202203105045)the National Natural Science Foundation of China(82301435,82201484)the Hunan Provincial Natural Science Foundation of China(2024JJ4083)the Graduate Research and Innovation Project of Hunan Education Department(CX20220528).
文摘Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role in PD.Mesenchymal stem cells(MSCs)have emerged as a promising therapeutic approach for various nerve injuries,but there are limited reports on their use in PD and the underlying mechanisms remain unclear.Methods:We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa(hOM)-MSCs on neural functional recovery in both PD models and patients,as well as the preventive effects on mouse models of PD.To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure,we employed single-cell RNA sequencing(scRNA-seq),assay for transposase accessible chromatin with high-throughput sequencing(ATAC-seq)combined with full-length transcriptome isoform-sequencing(ISO-seq),and functional assay.Furthermore,we present the findings from an initial cohort of patients enrolled in a phaseⅠfirstinhuman clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients.Results:A functional assay identified that transforming growth factor-β1(TGF-β1),secreted from hOM-MSCs,played a critical role in modulating mitochondrial function recovery in dopaminergic neurons.This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN,which are closely associated with neuroinflammatory responses.Mechanistically,exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B(ALK/PI3K/Akt)signaling pathway in microglia located in the SN of PD patients.Furthermore,intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD.Conclusions:These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD.Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD.Additionally,TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.
文摘BACKGROUND Natural killer(NK)/T-cell non-Hodgkin's lymphoma(NHL)in the nasal cavities and paranasal sinuses accounts for approximately 10%of all lymphomas,and the occurrence of nasal NHL is related to Epstein-Barr virus infection.AIM To explore the anxiety and depression status of patients with NK/T-cell NHL in the nasal cavities and paranasal sinuses and analyzes the relevant influencing factors.METHODS A retrospective analysis was performed,which included 30 patients with primary nasal NK/T-cell NHL treated in Shaanxi Provincial People’s Hospital from January 2017 to January 2023.An additional 50 healthy volunteers were selected as the control group.Both groups were assessed using the self-rating anxiety scale(SAS)and Self-rating(SDS).SDS and SAS scores of patients with NHL at different disease stages were analyzed,and they were further grouped into negative emotion(NE)(n=19)and non-NE(n=11)groups based on their depression and anxiety.Factors affecting the occurrence of NEs in patients with NHL were analyzed using univariate and multivariate logistic regression models.RESULTS Patients with NHL exhibited higher SDS and SAS scores than healthy controls.Moreover,patients with NHL at stages III and IV had higher SDS and SAS scores than those in stage I.Among the 30 patients,there were 13 patients with depression(43.3%),16 patients with anxiety(53.3%),and 10 patients with both anxiety and depression(33.3%).Univariate analysis identified a higher proportion of people in the NE group with stage III-IV NHL,an educational level≤high school,and a monthly household income<5000 yuan compared with the non-NE group.Multiple logistic regression analysis further revealed that stage III-IV was a risk factor for NEs in patients with NHL.CONCLUSION The stage of NK/T-cell NHL in nasal cavities and paranasal sinuses is closely related to patient anxiety and depression.The higher the staging,the greater the incidence of anxiety and depression.
基金supported by the Natural Science Foundation of Liaoning Province(2023-MSBA-020)the Fundamental Research Funds for Central Universities(DUT24MS020)Science and Technology Innovation Fund of Dalian(2022JJ13SN073).
文摘Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.Inhibiting ferroptosis has shown great promise as a therapeutic strategy for these diseases,underscoring the urgent need to develop effective ferroptosis inhibitors.Although Ferrostatin-1(Fer-1)is a potent ferroptosis inhibitor,its susceptibility to oxidation and metabolic inactivation limits its clinical utility.In this study,the accumulation of peroxides and the resulting oxidative damage in the cellular microenvironment during ferroptosis were utilized to design Ferrostatin-1 prodrugs with reactive oxygen species-responsive features.This approach led to the development of a series of ferroptosis inhibitors that were capable of recognizing oxidative damage in diseased areas,allowing for targeted release and improved stability.The novel compounds demonstrated significant inhibitory effects and selectivity against RSL-3-induced ferroptosis in HK-2 cells,with compound a1 exhibiting an EC50 of 15.4�0.7μM,outperforming Fer-1.These compounds effectively identify the oxidative microenvironment associated with ferroptosis,enabling the targeted release of Fer-1,which prevents lipid peroxide accumulation and inhibits ferroptosis.This strategy holds promise for treating diseases related to ferroptosis,offering a targeted and intelligent therapeutic approach.
基金the support of the National Natural Science Foundation of China(Grant Nos.12274448,12325405,and 12174390)the National Key R&D Program of China(Grant No.2022YFF0503504)。
文摘Interparticle frictional interactions are ubiquitous in colloidal systems,exerting a profound influence on their structural and physical attributes.In this study,we employed Brownian dynamics simulations to explore the non-equilibrium dynamics in colloidal systems,focusing particularly on the role of tangential friction and its influence on the macroscopic physical properties of colloids.We found that the disruption of instantaneous time-reversal symmetry by tangential frictional interactions can trigger the self-assembly of colloidal systems into intricate network configurations,and these novel structures exhibit unique depletion force and rheological properties that set them apart from traditional colloidal gel systems.These findings not only help deepen our comprehension of the self-assembly phenomena in non-equilibrium colloidal systems but also offer fresh insights for the development of colloidal materials with tailored characteristics.
文摘目的:探讨宫颈弹性成像技术在自发性早产孕妇孕期检查中的应用价值。方法:选取2021年8月—2023年8月在徐州市中心医院超声科进行常规产检的431例孕妇为研究对象,所有孕妇均随访至分娩,且在孕期内定期进行超声检查。利用宫颈弹性成像技术对所有孕妇进行产前超声检查并记录宫颈在孕期内的变化。根据孕妇孕周及分娩时间,将孕妇分为足月产组和早产组,回顾性比较两组孕妇宫颈参数的变化。结果:两组孕妇在入组时的一般资料差异无统计学意义,在孕20~24周,早产组孕妇的宫颈长度低于足月产组(3.67±0.55 vs 4.21±0.61),差异有统计学意义,且这种现象在孕晚期持续存在(3.34±0.71 vs 3.94±0.52)。早产组孕妇的宫颈硬度比(76.54±6.21)在孕20~24周也低于足月产组(83.34±5.14),差异有统计学意义(P<0.05)。早产组孕妇的对比指数和宫颈内口应变平均值在孕20~24周和孕28~35周也与足月产组比较差异有统计学意义(P<0.05)。结论:宫颈弹性成像技术可以在孕中晚期对孕妇宫颈状况进行筛查,提示可能出现的自发性早产的发生,在临床中具有一定的研究价值。
基金Natural Science Foundation of Hebei Province, China (No. B2020202044)the Open Foundation of Key Laboratory of Industrial Ecology and Environmental Engineering, MOE, China (No. KLIEEE-21-04).
文摘Photocatalytic activation of peroxymonosulfate (PMS) has garnered a lot of interest in the field of wastewater treatment. Herein, a plasmonic Ag nanoparticles decorated MIL-101(Fe) hybrid was synthesized through a photodeposition process. Upon light irradiation, the Ag/MIL-101(Fe) exhibit reinforced photocatalytic activities for elimination of bisphenol A (BPA) with PMS. The optimized 2.0% Ag/MIL-101(Fe) composite presented the highest photocatalytic activity with kinetic constant k of 0.102 min-1, which was about 10-fold of the pristine MIL-101(Fe). Loading of plasmonic Ag into MIL-101(Fe) boosts photoinduced carrier separation and accelerates PMS activation to generate strong oxidative radicals. Photoelectrochemical tests and multiple spectroscopic studies confirmed the promoted charge carrier separation and transfer capability of Ag/MIL-101(Fe). Combining the results of radical trapping experiments and electron spin resonance (ESR), the formed SO4·-, ·OH, ·O2- and 1O2 had a significant role in the photocatalytic process. According to intermediate study, the degradation pathway was studied, and the possible mechanism was proposed.
基金supported by Guangdong Basic and Applied Basic Research Foundation(2023A1515010969)Natural Science Foundation of Top Talent of SZTU(GDRC202305).
文摘Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.
基金Supported by the Hangzhou Joint Fund of the Zhejiang Provincial Natural Science Foundation of China,No.LHZY24H020002Hangzhou Municipal Health Commission,No.ZD20220010Quzhou Bureau of Science and Technology,No.2022K51.
文摘BACKGROUND Mutations in mitochondrial tRNA(mt-tRNA)genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus(T2DM).We previously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA^(Trp)A5514G and tRNA^(Ser(AGY))C12237T variants,however,the effects of these mt-tRNA variants on T2DM progression are largely unknown.AIM To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic,molecular,and biochemical levels.METHODS Cytoplasmic hybrid(cybrid)cells carrying both m.A5514G and m.C12237T variants,and healthy control cells without these mitochondrial DNA(mtDNA)variants were generated using trans-mitochondrial technology.Mitochondrial features,including mt-tRNA steady-state level,levels of adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),reactive oxygen species(ROS),mtDNA copy number,nicotinamide adenine dinucleotide(NAD+)/NADH ratio,enzymatic activities of respiratory chain complexes(RCCs),8-hydroxy-deoxyguanine(8-OhdG),malondialdehyde(MDA),and superoxide dismutase(SOD)were examined in cell lines with and without these mt-tRNA variants.RESULTS Compared with control cells,the m.A5514G variant caused an approximately 35%reduction in the steady-state level of mt-tRNA^(Trp)(P<0.0001);however,the m.C12237T variant did not affect the mt-tRNA^(Ser(AGY))steady-state level(P=0.5849).Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells:ATP,MMP,NAD+/NADH ratio,enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells(P<0.05 for all measures).By contrast,the levels of ROS,8-OhdG and MDA were significantly increased(P<0.05 for all measures),but mtDNA copy number was not affected by m.A5514G and m.C12237T variants(P=0.5942).CONCLUSION The m.A5514G variant impaired mt-tRNA^(Trp)metabolism,which subsequently caused mitochondrial dysfunction.The m.C12237T variant did not alter the steady-state level of mt-tRNA^(Ser(AGY)),indicating that it may be a modifier of the m.A5514G variant.The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.
基金financially supported by the Research Council of Norway under the M-HEAT project(No.294689)the HyLINE Project(No.294739)All simulation resources are provided by the Norwegian Metacenter for Computational Science(Nos.NN9110K and NN9391K).
文摘Hydrogen as an interstitial solute at grain boundaries(GBs)can have a catastrophic impact on the mechanical properties of many metals.Despite the global research effort,the underlying hydrogen-GB interactions in polycrystals remain inadequately understood.In this study,using Voronoi tessellations and atomistic simulations,we elucidate the hydrogen segregation energy spectrum at the GBs of polycrystalline nickel by exploring all the topologically favorable segregation sites.Three distinct peaks in the energy spectrum are identified,corresponding to different structural fingerprints.The first peak(-0.205 eV)represents the most favorable segregation sites at GB core,while the second and third peaks account for the sites at GB surface.By incorporating a thermodynamic model,the spectrum enables the determination of the equilibrium hydrogen concentrations at GBs,unveiling a remarkable two to three orders of magnitude increase compared to the bulk hydrogen concentration reported in experimental studies.The identified structures from the GB spectrum exhibit vastly different behaviors in hydrogen segregation and diffusion,with the low-barrier channels inside GB core contributing to short-circuit diffusion,while the high energy gaps between GB and neighboring lattice serving as on-plane diffusion barriers.Mean square displacement analysis further confirms the findings,and shows that the calculated GB diffusion coefficient is three orders of magnitude greater than that of lattice.The present study has a significant implication for practical applications since it offers a tool to bridge the gap between atomic-scale interactions and macroscopic behaviors in engineering materials.
基金the National Natural Science Foundation of China(Grant No.81870459 and 81970572).
文摘The second-to-fourth digit(2D:4D)ratio is thought to be associated with prenatal androgen exposure.However,the relationship between the 2D:4D ratio and hypospadias is poorly understood,and its molecular mechanism is not clear.In this study,by analyzing the hand digit length of 142 boys with hypospadias(23 distal,68 middle,and 51 proximal)and 196 controls enrolled in Shanghai Children’s Hospital(Shanghai,China)from December 2020 to December 2021,we found that the 2D:4D ratio was significantly increased in boys with hypospadias(P<0.001)and it was positively correlated with the severity of the hypospadias.This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene(dynein axonemal heavy chain 8[DNAH8])associated with hypospadias.Furthermore,the discrepancy was mainly caused by a shift in 4D.Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D.Comprehensive mechanistic explorations revealed that during the androgen-sensitive window,the downregulation of the androgen receptor(AR)caused by low testosterone levels,as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a(Wnt5a),Wnt5b,Smad family member 2(Smad2),and Smad3;mitochondrial function-related genes in cartilage such as AMP-activated protein kinase(AMPK)and nuclear respiratory factor 1(Nrf-1);and vascular development-related genes such as myosin light chain(MLC),notch receptor 3(Notch3),and sphingosine kinase 1(Sphk1),are responsible for the limitation of 4D growth,which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification.This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.
基金sponsored by National Natural Science Foundation of China(No.22202130)China Postdoctoral Science Foundation(No.2022M710088)+3 种基金Science and Technology Innovation Team of Shaanxi Province(Nos.2023-CX-TD-27 and 2022TD-35)Fundamental Research Funds for the Central Universities(Nos.GK202202001 and GK202101005)Open Funds of the State Key Laboratory of Electroanalytical Chemistry(No.SKLEAC202207)the 111 Project(No.B14041)。
文摘The selective electrochemical conversion of glycerol into value-added products is a green and sustainable strategy for the biomass utilization.In this work,Au nanowires(Au-NW)modified with polyethyleneimine(PEI)molecule(Au-NW@PEI)is obtained by an up-bottom post-modification approach.Physical characterization,molecular dynamics simulation and density functional theory demonstrate that the loose-packed PEI monolayer firmly and uniformly distribute on the Au-NW surface due to the strong Au-N interaction.Electrochemical experiments and product analysis display that PEI modification significantly enhance the electro-activity of Au-NW for the glycerol electro-oxidation reaction(GEOR)due to the electronic effect.Meanwhile,the steric hindrance and electrostatic effect of PEI layer make the optimizing adsorption of intermediates possible.Therefore,the selectivity of C3 product glyceric acid over Au-NW@PEI is increased by nearly 20%.The work thus indicates that the rational design of metal-organic interface can effectively elevate the electro-activity and selectivity of Au nanostructures,which may have wide application in biomass development.
基金Project supported by the National Key Research and Development Program of China (Grant Nos.2021YFB3601000 and 2021YFB3601002)the National Natural Science Foundation of China (Grant Nos.62074077,61921005,61974062,62204121,and 61904082)+1 种基金Leading-edge Technology Program of Jiangsu Natural Science Foundation (Grant No.BE2021008-2)the China Postdoctoral Science Foundation (Grant No.2020M671441)。
文摘Nonpolar(11–20) a-plane p-type GaN films were successfully grown on r-plane sapphire substrate with the metal–organic chemical vapor deposition(MOCVD) system. The effects of Mg-doping temperature on the structural and electrical properties of nonpolar p-type GaN films were investigated in detail. It is found that all the surface morphology, crystalline quality, strains, and electrical properties of nonpolar a-plane p-type GaN films are interconnected, and are closely related to the Mg-doping temperature. This means that a proper performance of nonpolar p-type GaN can be expected by optimizing the Mg-doping temperature. In fact, a hole concentration of 1.3×10^(18)cm^(-3), a high Mg activation efficiency of 6.5%,an activation energy of 114 me V for Mg acceptor, and a low anisotropy of 8.3% in crystalline quality were achieved with a growth temperature of 990℃. This approach to optimizing the Mg-doping temperature of the nonpolar a-plane p-type GaN film provides an effective way to fabricate high-efficiency optoelectronic devices in the future.
基金Guangzhou Basic and Applied Basic Research Project(202201010197)State Key Laboratory of Applied Microbiology Southern China(SKLAM011-2021)+1 种基金National Natural Science Foundation of China(32202014),Guangdong Provincial Key Laboratory(2020B121201009)Guangdong Province Academy of Sciences Special Project for Capacity Building of Innovation Driven Development(2020GDASYL-20200401002).
文摘Selenopeptides may be a valuable bioactive compound to promote gut microbiota-targeted therapeutic methods for intestinal disease and hepatopathy.However,limited information is available on the utilization of selenopeptides by gut microbiota,especially Selenium(Se)function.For this purpose,the present study aimed to investigate the protective effect of selenopeptide(RYNA(Se)MNDYT,Se-P2,purity of≥95%)and its original peptide(RYNAMNDYT,P2,purity of≥95%)in vivo by the microbiota-metabolite axis and further analyze the potential contribution of Se biofortification to Se-P2 bioactivity.The results showed that Se-P2 exhibits a higher protective effect on lipopolysaccharide(LPS)-induced inflammation than P2,including pathology of the colon and liver,which suggested that the bioactivity of P2 was promoted by the organic combination of Se.Notably,gut microbiota composition tended to be a healthy structure by Se-P2 pretreatment in LPS-injured mice,which had a positive effect on LPS-induced gut microbiota dysbacteriosis.Additionally,only Se-P2 promoted an increase in the relative abundance of Lactobacillus,Alistipes,and Roseburia and a decrease in the relative abundance of Akkermansia,Erysipelatoclostridium,and Bacteroides in LPS-injured mice.The changes in gut microbiota were obviously correlated with the changes in metabolites and affected the metabolic pathways of valine,leucine,isoleucine,phenylalanine,tyrosine,and tryptophan biosynthesis and phenylalanine metabolism.This may be one of the key reasons for Se-P2 to exert bioactivity through the microbiota-metabolite axis.Furthermore,Se-biofortification in Se-enriched Cordyceps militaris affected the parental proteins of Se-P2 to modulate mitogen-activated protein kinase,GPI anchored protein,and carbohydrate metabolism,translation,folding,sorting and degradation,which may contribute to the bioactivity of Se-P2.Our study provides information on the effect of Se on selenopeptides in vivo,which further promotes the prospective applications of selenopeptides as dietary supplements.
