The performances of magnesium alloys remain insufficient to further enhance the application potential of ultralight magnesium alloys.In this work,a Mg-8Li-3Y-2Zn alloy was prepared through vacuum melting and subsequent...The performances of magnesium alloys remain insufficient to further enhance the application potential of ultralight magnesium alloys.In this work,a Mg-8Li-3Y-2Zn alloy was prepared through vacuum melting and subsequent heat treatment at 300,450,and 500°C.The material properties of the resulting samples were assessed through microstructural observation,tensile testing,electrical conductivity measurements,and electromagnetic shielding effectiveness(EMI-SE)testing.The influence of the Mg-8Li-3Y-2Zn alloy microstructure on its mechanical and electromagnetic shielding properties in different states was investigated.It was found that the as-cast alloy containsα-Mg,β-Li,Mg_(3)Zn_(3)Y_(2),and Mg_(12)ZnY phases.Following heat treatment at 500℃(HT500),the blockα-Mg phase transformedfine needle-shapes,its tensile strength increased to 263.7 MPa,and its elongation reached 45.3%.The mechanical properties of the alloy were significantly improved by the synergistic effects imparted by the needle-shapedα-Mg phase,solid solution strengthening,and precipitation strengthening.The addition of Y and Zn improved the EMI-SE of Mg-8Li-1Zn alloy,wherein the HT500 sample exhibits the highest SE,maintaining a value of 106.7–76.9 dB in the frequency range of 30–4500 MHz;this performance has rarely been reported for electromagnetically shielded alloys.This effect was mainly attributed to the multiple reflections of electromagnetic waves caused by the severe impedance mismatch of the abundant phase boundaries,which were in turn provided by the dual-phase(α/β)and secondary phases.Furthermore,the presence of nano-precipitation was also believed to enhance the absorption of electromagnetic waves.展开更多
Temporal interference(TI)is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain,a technique that has been validated in mice.Yet,the thin cranial bone...Temporal interference(TI)is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain,a technique that has been validated in mice.Yet,the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals.Based on this,we carried out TI stimulation experiments on rats.Following the TI intervention,analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens(depth,8.5 mm)in rats.Our findings affirm the viability of the TI methodology in the presence of thick cranial bones,furnishing efficacious parameters for profound stimulation with TI administered under such conditions.This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.展开更多
Clinical advances in the treatment of intracranial hemorrhage(ICH)are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury.Acrolein is a highly active unsaturat...Clinical advances in the treatment of intracranial hemorrhage(ICH)are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury.Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases.Our results indicated a significant increase in the level of acrolein after ICH in mouse brain.In primary neurons,acrolein induced an increase in mitochondrial fragmentation,loss of mitochondrial membrane potential,generation of reactive oxidative species,and release of mitochondrial cytochrome c.Mechanistically,acrolein facilitated the translocation of dynaminrelated protein 1(Drpl)from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission.Further studies found that treatment with hydralazine(an acrolein scavenger)significantly reversed Drpl translocation and the morphological damage of mitochondria after ICH.In parallel,the neural apoptosis,brain edema,and neurological functional deficits induced by ICH were also remarkably alleviated.In conclusion,our results identify acrolein as an important contributor to the secondary brain injury following ICH.Meanwhile,we uncovered a novel mechanism by which Drpl-mediated mitochondrial oxidative damage is involved in acroleininduced brain injury.展开更多
Traumatic brain injury(TBI)triggers the activation of the endogenous coagulation mechanism,and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors,also known as protease-a...Traumatic brain injury(TBI)triggers the activation of the endogenous coagulation mechanism,and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors,also known as protease-activated receptors(PARs).However,thrombin is one of the most critical factors in secondary brain injury.Thus,the PARs may be effective targets against hemorrhagic brain injury.Since the PAR1 antagonist has an increased bleeding risk in clinical practice,PAR4 blockade has been suggested as a more promising treatment.Here,we explored the expression pattern of PAR4 in the brain of mice after TBI,and explored the effect and possible mechanism of BMS-986120(BMS),a novel selective and reversible PAR4 antagonist on secondary brain injury.Treatment with BMS protected against TBI in mice.mRNA-seq analysis,Western blot,and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes,and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process.Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI,and suggest that BMS has a potential clinical application in the management of TBI.展开更多
OBJECTIVE: To assess whether dietary fat intake influences Parkinson’s disease risk. DATA SOURCES: We systematically surveyed the Embase and PubMed databases, reviewing manuscripts published prior to October 2018. Th...OBJECTIVE: To assess whether dietary fat intake influences Parkinson’s disease risk. DATA SOURCES: We systematically surveyed the Embase and PubMed databases, reviewing manuscripts published prior to October 2018. The following terms were used:(“Paralysis agitans” OR “Parkinson disease” OR “Parkinson” OR “Parkinson’s” OR “Parkinson’s disease”) AND (“fat” OR “dietary fat” OR “dietary fat intake”). DATA SELECTION: Included studies were those with both dietary fat intake and Parkinson’s disease risk as exposure factors. The Newcastle-Ottawa Scale was adapted to investigate the quality of included studies. Stata V12.0 software was used for statistical analysis. OUTCOME MEASURES: The primary outcomes included the relationship between high total energy intake, high total fat intake, and Parkinson’s disease risk. The secondary outcomes included the relationship between different kinds of fatty acids and Parkinson’s disease risk. RESULTS: Nine articles met the inclusion criteria and were incorporated into this meta-analysis. Four studies scored 7 and the other five studies scored 9 on the Newcastle-Ottawa Scale, meaning that all studies were of high quality. Meta-analysis results showed that high total energy intake was associated with an increased risk of Parkinson’s disease (P = 0.000, odds ratio (OR)= 1.49, 95% confidence interval (CI): 1.26–1.75);in contrast, high total fat intake was not associated with Parkinson’s disease risk (P = 0.123, OR = 1.07, 95% CI: 0.91–1.25). Subgroup analysis revealed that polyunsaturated fatty acid intake (P = 0.010, OR = 1.03, 95% CI: 0.88–1.20) reduced the risk of Parkinson’s disease, while arachidonic acid (P = 0.026, OR = 1.15, 95% CI: 0.97–1.37) and cholesterol (P = 0.002, OR = 1.09, 95% CI: 0.92–1.29) both increased the risk of Parkinson’s disease. Subgroup analysis also demonstrated that, although the results were not significant, consumption of n-3 polyunsaturated fatty acids (P = 0.071, OR = 0.88, 95% CI: 0.73–1.05),α-linolenic acid (P = 0.06, OR = 0.86, 95% CI: 0.72–1.02), and the n-3 to n-6 ratio (P = 0.458, OR = 0.89, 95% CI: 0.75–1.06) were all linked with a trend toward reduced Parkinson’s disease risk. Monounsaturated fatty acid (P = 0.450, OR = 1.06, 95% CI: 0.91–1.23), n-6 polyunsaturated fatty acids (P = 0.100, OR = 1.15, 95% CI: 0.96–1.36) and linoleic acid (P = 0.053, OR = 1.11, 95% CI: 0.94–1.32) intakes were associated with a non-significant trend toward higher PD risk. Saturated fatty acid (P = 0.619, OR = 1.01, 95% CI: 0.87–1.18) intake was not associated with Parkinson’s disease. CONCLUSION: Dietary fat intake affects Parkinson’s disease risk, although this depends on the fatty acid subtype. Higher intake of polyunsaturated fatty acids may reduce the risk of Parkinson’s disease, while higher cholesterol and arachidonic acid intakes may elevate Parkinson’s disease risk. However, further studies and evidence are needed to validate any link between dietary fat intake and Parkinson’s disease.展开更多
Although multitudinous nanoscale drug-delivery systems(DDSs)have been recommended to improve anti-ulcerative colitis(UC)outcomes,to enhance the mucoadhesion of nanosystems on the colon and specifically release the loa...Although multitudinous nanoscale drug-delivery systems(DDSs)have been recommended to improve anti-ulcerative colitis(UC)outcomes,to enhance the mucoadhesion of nanosystems on the colon and specifically release the loaded drugs in response to the colon micro-environment would be critical factors.The application of curcumin(Cur),an acknowledged anti-UC phytochemical compound,for UC therapy requires more efficient nano-carriers to improve its therapeutic outcome.Herein,we developed the colon-targeted nano-micelles with mucoadhesive effect and Azo reductase-triggered drug release profiles for Cur delivery in UC treatment.Specifically,the amphiphilic block polymer containing the Azo-reductase sensitive linkage(PEG-Azo-PLGA),and catechol-modified TPGS(Cat-TPGS)were synthesized respectively.Based on the self-assembly of the mixed polymers,Cur-micelles(142.7±1.7 nm of average size,72.36%±1.54%of DEE)were obtained.Interestingly,the Cur-micelles exhibited the Azo-reductase sensitive particle dissociation and drug release,the enhanced cellular uptake and the prolonged retention on colonic mucosa,mediated by the strong mucoadhesion of catechol structure.Ultimately,Cur-micelles significantly mitigated colitis symptoms and accelerated colitis repair in DSS-treated mice by regulating the intestinal flora and the levels of pro-inflammatory factors(MPO,IL-6,IL-1β,and TNF-α)related to TLR4/MyD88/NF-κB signaling pathway.This work provides an effective drug delivery strategy for anti-UC drugs by oral administration.展开更多
Traumatic brain injury(TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes,but the pathogenesis remains poorly understood.In this study,we aimed to investigate the...Traumatic brain injury(TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes,but the pathogenesis remains poorly understood.In this study,we aimed to investigate the causal role of acrolein,a typical lipid peroxidation product,in TBI-induced coagulopathy,and further explore the underlying molecular mechanisms.We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy.Using a controlled cortical impact mouse model,we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor(VWF).Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion.mRNA sequencing(mRNA-seq)and transcriptome analysis indicated that acrolein over-activated autophagy,and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway.In addition,we demonstrated that acrolein was produced in the perilesional cortex,affected endothelial cell integrity,and disrupted the blood-brain barrier.In conclusion,in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage,providing an alternative therapeutic target.展开更多
The virulent factors of Escherichia coil （E.cofi） play an important role in the process of pathopoiesis. The study aimed to compare drug-resistant genes and virulence genes between extended spectrum β-1actamases （...The virulent factors of Escherichia coil （E.cofi） play an important role in the process of pathopoiesis. The study aimed to compare drug-resistant genes and virulence genes between extended spectrum β-1actamases （ESBLs）-producing E.coli and non-ESBLs-producing E.cofi to provide a reference for physicians in management of hospital infection. From October 2010 to August 2011,96 drug-resistant strains of E. coli isolated were collected from the specimens in Qingdao Municipal Hospital, Qingdao, China. These bacteria strains were divided into a ESBLs-producing group and a non-ESBLs-producing group. Drug sensitivity tests were performed using the Kirby-Bauer （K-B） method. Disinfectant gene, qacEAl-sull and 8 virulence genes （CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1） were tested by polymerase chain reaction （PCR）. Among the 96 E.coli isolates, the ESBLs-producing E.coli comprised 46 （47.9%） strains and the non-ESBLs-producing E.cofi consisted of 50 （52.1%） strains. The detection rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA,VT1, est, bfpA, elt, and CNF1 in 46 ESBLs-producing E.coli isolates were 89.1%, 76.1%, 6.5%, 69.6%, 69.6%, 89.1%, 10.9%, 26.1%, 8.7%, and 19.6%, respectively. In the non-ESBLs-producing E.cofi strains, the positive rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1 were 62.0%, 80.0%, 16.0%, 28.0%, 64.0%, 38.0%, 6.0%, 34.0%, 10.0%, and 24.0%, respectively. The difference in the detection rates of multiple drug-resistant strain, hlyA and VT1 between the ESBLs-producing E.cofi strains and the non-ESBLs-producing E.cofi strains was statistically significant （P〈0.05）. The positive rate of multiple drug-resistant strains is higher in the ESBLs-producing strains than in the non-ESBLs-producing strains. The expression of some virulence genes hlyA and VT1 varies between the ESBLs-producing strains and the non-ESBLs-producing strains. Increased awareness of clinicians and enhanced testing by laboratories are required to reduce treatment failures and prevent the spread of multiple drug-resistant strains.展开更多
Four new monoterpenoid indole alkaloids,alstrostines C-F together with thirteen known alkaloids were isolated from the leaves and twigs of Alstonia rostrata.All structures of new compounds were elucidated based on NMR...Four new monoterpenoid indole alkaloids,alstrostines C-F together with thirteen known alkaloids were isolated from the leaves and twigs of Alstonia rostrata.All structures of new compounds were elucidated based on NMR,FTIR,UV,and MS spectroscopic data.Alstrostines C-E might originate from keto-enol tautomerism of preakummicine during biogenetic pathway of akummicine.展开更多
BACKGROUND Tofacitinib is an oral Janus kinase(JAK)inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis(RA).Varicella zoster virus reactivati...BACKGROUND Tofacitinib is an oral Janus kinase(JAK)inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis(RA).Varicella zoster virus reactivation leading to herpes zoster(HZ)is an adverse effect of this drug;however,recurrent HZ at the same site is a rare clinical condition.CASE SUMMARY A 70-year-old female RA patient had undergone 1-year of tofacitinib treatment(10 mg daily).About 1 mo after initiation of oral tofacitinib,she developed blisters on the left flank and abdomen and was diagnosed with HZ;antiviral therapy with acyclovir was resolutory.However,5 d prior to presentation at our hospital,erythema and blisters with severe pain recurred at the same site.Small clustered blisters and bullous were visible on the left lumbar abdomen and perineum,with a pain score of 8(visual analogue scale).Antiviral,nutritional supplement,analgesic and other treatments led to healing but over an atypically long period(approximately 26 d,vs approximately 1 wk).HZ is a common and serious adverse reaction of JAK inhibitors,but it rarely recurs.Our patient’s experience of HZ recurrence at the same site,with a wider affected area,more severe pain and longer healing period,is inconsistent with previous reports.CONCLUSION Same-anatomical site HZ recurrence may occur during oral tofacitinib treatment,with more severe clinical manifestations than in the initial occurrence.展开更多
Heat shock protein 70（HSP70） maintains Ca^2＋ homeostasis in PC12 cells,which may protect against apoptosis;however,the mechanisms of neuroprotection are unclear.Therefore,in this study,we examined Ca^2＋ levels in ...Heat shock protein 70（HSP70） maintains Ca^2＋ homeostasis in PC12 cells,which may protect against apoptosis;however,the mechanisms of neuroprotection are unclear.Therefore,in this study,we examined Ca^2＋ levels in PC12 cells transfected with an exogenous lentiviral HSP70 gene expression construct,and we subsequently subjected the cells to ischemia-hypoxia/reoxygenation injury.HSP70 overexpression increased neuronal viability and ATPase activity,and it decreased cellular reactive oxygen species levels and intracellular Ca^2＋ concentration after hypoxia/reoxygenation.HSP70 overexpression enhanced the protein and m RNA expression levels of sarcoplasmic/endoplasmic reticulum Ca^2＋-ATPase（SERCA）,but it decreased the protein and m RNA levels of inositol 1,4,5-trisphosphate receptor（IP3R）,thereby leading to decreased intracellular Ca^2＋concentration after ischemia-hypoxia/reoxygenation.These results suggest that exogenous HSP70 protects against ischemia-hypoxia/reoxygenation injury,at least in part,by maintaining cellular Ca^2＋ homeostasis,by upregulating SERCA expression and by downregulating IP_3 R expression.展开更多
We use a semi-analytic galaxy formation model to study the co-evolution of supermassive black holes(SMBHs) with their host galaxies.Although the coalescence of SMBHs is not important,the quasarmode accretion induced b...We use a semi-analytic galaxy formation model to study the co-evolution of supermassive black holes(SMBHs) with their host galaxies.Although the coalescence of SMBHs is not important,the quasarmode accretion induced by mergers plays a dominant role in the growth of SMBHs.Mergers play a more important role in the growth of SMBH host galaxies than in the SMBH growth.It is the combined contribution from quasar mode accretion and mergers to the SMBH growth and the combined contribution from starburst and mergers to their host galaxy growth that determine the observed scaling relation between the SMBH masses and their host galaxy masses.We also find that mergers are more important in the growth of SMBH host galaxies compared to normal galaxies which share the same stellar mass range as the SMBH host galaxies.展开更多
Objective:To analyze the effect of implementing a comprehensive nursing management program for rabies vaccination patients.Methods:100 cases of rabies vaccination patients were selected as observation objects from Jan...Objective:To analyze the effect of implementing a comprehensive nursing management program for rabies vaccination patients.Methods:100 cases of rabies vaccination patients were selected as observation objects from January 2022 to December 2023,and after enrollment,they were grouped according to the different nursing management programs,with 50 cases in each group.The control group was only given routine nursing management,and the observation group was combined with comprehensive nursing management on the basis of routine nursing management.The completion rate of vaccination,the rate of adverse reactions,and the satisfaction rate were assessed,comparing the clinical effects of different nursing management programs.Results:The completion rate of the 5th shot of rabies vaccination in the observation group was 82.00%higher than 64.00%in the control group(χ^(2)=4.1096,P<0.05);the rate of adverse reaction of vaccination in the observation group was 4.00%lower than 18.00%in the control group(χ^(2)=5.0051,P<0.05);the vaccination satisfaction in the observation group was 98.00%higher than 86.00%in the control group(χ^(2)=4.8913,P<0.05).Conclusion:The application of comprehensive nursing management program can help rabies vaccination patients to improve the completion rate of vaccination and reduce the incidence of adverse reactions to vaccination,with clear effects.展开更多
We perform a set of non-radiative hydro-dynamical(NHD)simulations of a rich cluster sized dark matter halo from the Phoenix Project with three different numerical resolutions,to investigate the effect of hydrodynamics...We perform a set of non-radiative hydro-dynamical(NHD)simulations of a rich cluster sized dark matter halo from the Phoenix Project with three different numerical resolutions,to investigate the effect of hydrodynamics alone on the subhalo population in the halo.Compared to dark matter only(DMO)simulations of the same halo,subhaloes are less abundant for relatively massive subhaloes(Msub>2.5×109h 1M⊙,or Vmax>70 km s 1)but more abundant for less massive subhaloes in the NHD simulations.This results in different shapes in the subhalo mass/Vmax function in two different sets of simulations.At given subhalo mass,the subhaloes less massive than 1010h 1M⊙have larger Vmax in the NHD than DMO simulations,while Vmax is similar for the subhaloes more massive than the mass value.This is mainly because the progenitors of present day low mass subhaloes have larger concentration parameters in the NHD than DMO simulations.The survival number fraction of the accreted low mass progenitors of the main halo at redshift 2 is about 50 percent higher in the NHD than DMO simulations.展开更多
[Objective]This study aimed to investigate the leaf anatomical structures of P.tunicoides populations under water-limited conditions.[Method]2-year-old seedlings of herbaceous perennial P.tunicoides that was introduce...[Objective]This study aimed to investigate the leaf anatomical structures of P.tunicoides populations under water-limited conditions.[Method]2-year-old seedlings of herbaceous perennial P.tunicoides that was introduced into the experi-mental field were selected as the research objects.Under the well-watered and wa-ter-limited conditions,we conducted the comparative observation of leaf anatomical structure and stomatal characteristics of two populations by using paraffin slice method and imprinting method.[Result]The result showed that the upper cuticle of P.tunicoides leaves were thickened,the palisade tissue/spongy tissue ratio,vascular bundle diameter and number of xylem vessels in main vein had increased,the stomatal opening became smaller and the stomatal density had increased in winter-spring drought period under water-limited conditions.The plasticity of above traits could be regarded as the important indicators for detecting the responses of P.tunicoides populations to water-limited conditions.Meanwhile,variation amplitudes of these indicators were different among populations.Leaf anatomical structure and stomatal characteristics in Lijiang Axi population under water-limited conditions varied significantly,which might cause the stronger adaptability of this population to drought conditions.[Conclusion]This research provided a reference for the selection of drought-resistant P.tunicoides germplasm and exploration of the adaptive differentia-tion of P.tunicoides populations under natural drought conditions.展开更多
基金supported by the National Natural Sci-ence Foundation of China[No.51564032]Yunnan Provin-cial Department of Education Science Research Fund Project[KKPH202132005]the Analysis and Testing Founda-tion of Kunming University of Science and Technology[2022M20212130086].
文摘The performances of magnesium alloys remain insufficient to further enhance the application potential of ultralight magnesium alloys.In this work,a Mg-8Li-3Y-2Zn alloy was prepared through vacuum melting and subsequent heat treatment at 300,450,and 500°C.The material properties of the resulting samples were assessed through microstructural observation,tensile testing,electrical conductivity measurements,and electromagnetic shielding effectiveness(EMI-SE)testing.The influence of the Mg-8Li-3Y-2Zn alloy microstructure on its mechanical and electromagnetic shielding properties in different states was investigated.It was found that the as-cast alloy containsα-Mg,β-Li,Mg_(3)Zn_(3)Y_(2),and Mg_(12)ZnY phases.Following heat treatment at 500℃(HT500),the blockα-Mg phase transformedfine needle-shapes,its tensile strength increased to 263.7 MPa,and its elongation reached 45.3%.The mechanical properties of the alloy were significantly improved by the synergistic effects imparted by the needle-shapedα-Mg phase,solid solution strengthening,and precipitation strengthening.The addition of Y and Zn improved the EMI-SE of Mg-8Li-1Zn alloy,wherein the HT500 sample exhibits the highest SE,maintaining a value of 106.7–76.9 dB in the frequency range of 30–4500 MHz;this performance has rarely been reported for electromagnetically shielded alloys.This effect was mainly attributed to the multiple reflections of electromagnetic waves caused by the severe impedance mismatch of the abundant phase boundaries,which were in turn provided by the dual-phase(α/β)and secondary phases.Furthermore,the presence of nano-precipitation was also believed to enhance the absorption of electromagnetic waves.
基金supported by the National Key Research and Development Program Project(2021YFC2400203)the Shaanxi Province Key Research and Development Program Project(2023-YBSF-120)+1 种基金the Shandong Provincial Natural Science Foundation(ZR2024QF287)the National Natural Science Foundation of China(31972907).
文摘Temporal interference(TI)is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain,a technique that has been validated in mice.Yet,the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals.Based on this,we carried out TI stimulation experiments on rats.Following the TI intervention,analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens(depth,8.5 mm)in rats.Our findings affirm the viability of the TI methodology in the presence of thick cranial bones,furnishing efficacious parameters for profound stimulation with TI administered under such conditions.This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
基金This work was supported by grants from the National Natural Science Foundation of China(81630027,81571215)and the Chang Jiang Scholar Program of China.
文摘Clinical advances in the treatment of intracranial hemorrhage(ICH)are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury.Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases.Our results indicated a significant increase in the level of acrolein after ICH in mouse brain.In primary neurons,acrolein induced an increase in mitochondrial fragmentation,loss of mitochondrial membrane potential,generation of reactive oxidative species,and release of mitochondrial cytochrome c.Mechanistically,acrolein facilitated the translocation of dynaminrelated protein 1(Drpl)from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission.Further studies found that treatment with hydralazine(an acrolein scavenger)significantly reversed Drpl translocation and the morphological damage of mitochondria after ICH.In parallel,the neural apoptosis,brain edema,and neurological functional deficits induced by ICH were also remarkably alleviated.In conclusion,our results identify acrolein as an important contributor to the secondary brain injury following ICH.Meanwhile,we uncovered a novel mechanism by which Drpl-mediated mitochondrial oxidative damage is involved in acroleininduced brain injury.
基金This work was supported by grants from the National Natural Science Foundation of China(81630027,81571215)the Chang Jiang Scholar Program of China。
文摘Traumatic brain injury(TBI)triggers the activation of the endogenous coagulation mechanism,and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors,also known as protease-activated receptors(PARs).However,thrombin is one of the most critical factors in secondary brain injury.Thus,the PARs may be effective targets against hemorrhagic brain injury.Since the PAR1 antagonist has an increased bleeding risk in clinical practice,PAR4 blockade has been suggested as a more promising treatment.Here,we explored the expression pattern of PAR4 in the brain of mice after TBI,and explored the effect and possible mechanism of BMS-986120(BMS),a novel selective and reversible PAR4 antagonist on secondary brain injury.Treatment with BMS protected against TBI in mice.mRNA-seq analysis,Western blot,and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes,and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process.Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI,and suggest that BMS has a potential clinical application in the management of TBI.
基金supported by the National Natural Science Foundation of China,No.31200868(to XC)
文摘OBJECTIVE: To assess whether dietary fat intake influences Parkinson’s disease risk. DATA SOURCES: We systematically surveyed the Embase and PubMed databases, reviewing manuscripts published prior to October 2018. The following terms were used:(“Paralysis agitans” OR “Parkinson disease” OR “Parkinson” OR “Parkinson’s” OR “Parkinson’s disease”) AND (“fat” OR “dietary fat” OR “dietary fat intake”). DATA SELECTION: Included studies were those with both dietary fat intake and Parkinson’s disease risk as exposure factors. The Newcastle-Ottawa Scale was adapted to investigate the quality of included studies. Stata V12.0 software was used for statistical analysis. OUTCOME MEASURES: The primary outcomes included the relationship between high total energy intake, high total fat intake, and Parkinson’s disease risk. The secondary outcomes included the relationship between different kinds of fatty acids and Parkinson’s disease risk. RESULTS: Nine articles met the inclusion criteria and were incorporated into this meta-analysis. Four studies scored 7 and the other five studies scored 9 on the Newcastle-Ottawa Scale, meaning that all studies were of high quality. Meta-analysis results showed that high total energy intake was associated with an increased risk of Parkinson’s disease (P = 0.000, odds ratio (OR)= 1.49, 95% confidence interval (CI): 1.26–1.75);in contrast, high total fat intake was not associated with Parkinson’s disease risk (P = 0.123, OR = 1.07, 95% CI: 0.91–1.25). Subgroup analysis revealed that polyunsaturated fatty acid intake (P = 0.010, OR = 1.03, 95% CI: 0.88–1.20) reduced the risk of Parkinson’s disease, while arachidonic acid (P = 0.026, OR = 1.15, 95% CI: 0.97–1.37) and cholesterol (P = 0.002, OR = 1.09, 95% CI: 0.92–1.29) both increased the risk of Parkinson’s disease. Subgroup analysis also demonstrated that, although the results were not significant, consumption of n-3 polyunsaturated fatty acids (P = 0.071, OR = 0.88, 95% CI: 0.73–1.05),α-linolenic acid (P = 0.06, OR = 0.86, 95% CI: 0.72–1.02), and the n-3 to n-6 ratio (P = 0.458, OR = 0.89, 95% CI: 0.75–1.06) were all linked with a trend toward reduced Parkinson’s disease risk. Monounsaturated fatty acid (P = 0.450, OR = 1.06, 95% CI: 0.91–1.23), n-6 polyunsaturated fatty acids (P = 0.100, OR = 1.15, 95% CI: 0.96–1.36) and linoleic acid (P = 0.053, OR = 1.11, 95% CI: 0.94–1.32) intakes were associated with a non-significant trend toward higher PD risk. Saturated fatty acid (P = 0.619, OR = 1.01, 95% CI: 0.87–1.18) intake was not associated with Parkinson’s disease. CONCLUSION: Dietary fat intake affects Parkinson’s disease risk, although this depends on the fatty acid subtype. Higher intake of polyunsaturated fatty acids may reduce the risk of Parkinson’s disease, while higher cholesterol and arachidonic acid intakes may elevate Parkinson’s disease risk. However, further studies and evidence are needed to validate any link between dietary fat intake and Parkinson’s disease.
基金supported by the National Natural Science Foundation of China(No.81903811)China Postdoctoral Science Foundation(No.2021M690488)National TCM Multidisciplinary Interdisciplinary Innovation Team Project:Multidisciplinary Evaluation of Southwest Characteristic TCM Resources Multidisciplinary Interdisciplinary Innovation Team(No.ZYYCXTD-D-202209)。
文摘Although multitudinous nanoscale drug-delivery systems(DDSs)have been recommended to improve anti-ulcerative colitis(UC)outcomes,to enhance the mucoadhesion of nanosystems on the colon and specifically release the loaded drugs in response to the colon micro-environment would be critical factors.The application of curcumin(Cur),an acknowledged anti-UC phytochemical compound,for UC therapy requires more efficient nano-carriers to improve its therapeutic outcome.Herein,we developed the colon-targeted nano-micelles with mucoadhesive effect and Azo reductase-triggered drug release profiles for Cur delivery in UC treatment.Specifically,the amphiphilic block polymer containing the Azo-reductase sensitive linkage(PEG-Azo-PLGA),and catechol-modified TPGS(Cat-TPGS)were synthesized respectively.Based on the self-assembly of the mixed polymers,Cur-micelles(142.7±1.7 nm of average size,72.36%±1.54%of DEE)were obtained.Interestingly,the Cur-micelles exhibited the Azo-reductase sensitive particle dissociation and drug release,the enhanced cellular uptake and the prolonged retention on colonic mucosa,mediated by the strong mucoadhesion of catechol structure.Ultimately,Cur-micelles significantly mitigated colitis symptoms and accelerated colitis repair in DSS-treated mice by regulating the intestinal flora and the levels of pro-inflammatory factors(MPO,IL-6,IL-1β,and TNF-α)related to TLR4/MyD88/NF-κB signaling pathway.This work provides an effective drug delivery strategy for anti-UC drugs by oral administration.
基金the National Natural Science Foundation of China(81630027).
文摘Traumatic brain injury(TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes,but the pathogenesis remains poorly understood.In this study,we aimed to investigate the causal role of acrolein,a typical lipid peroxidation product,in TBI-induced coagulopathy,and further explore the underlying molecular mechanisms.We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy.Using a controlled cortical impact mouse model,we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor(VWF).Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion.mRNA sequencing(mRNA-seq)and transcriptome analysis indicated that acrolein over-activated autophagy,and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway.In addition,we demonstrated that acrolein was produced in the perilesional cortex,affected endothelial cell integrity,and disrupted the blood-brain barrier.In conclusion,in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage,providing an alternative therapeutic target.
文摘The virulent factors of Escherichia coil （E.cofi） play an important role in the process of pathopoiesis. The study aimed to compare drug-resistant genes and virulence genes between extended spectrum β-1actamases （ESBLs）-producing E.coli and non-ESBLs-producing E.cofi to provide a reference for physicians in management of hospital infection. From October 2010 to August 2011,96 drug-resistant strains of E. coli isolated were collected from the specimens in Qingdao Municipal Hospital, Qingdao, China. These bacteria strains were divided into a ESBLs-producing group and a non-ESBLs-producing group. Drug sensitivity tests were performed using the Kirby-Bauer （K-B） method. Disinfectant gene, qacEAl-sull and 8 virulence genes （CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1） were tested by polymerase chain reaction （PCR）. Among the 96 E.coli isolates, the ESBLs-producing E.coli comprised 46 （47.9%） strains and the non-ESBLs-producing E.cofi consisted of 50 （52.1%） strains. The detection rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA,VT1, est, bfpA, elt, and CNF1 in 46 ESBLs-producing E.coli isolates were 89.1%, 76.1%, 6.5%, 69.6%, 69.6%, 89.1%, 10.9%, 26.1%, 8.7%, and 19.6%, respectively. In the non-ESBLs-producing E.cofi strains, the positive rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1 were 62.0%, 80.0%, 16.0%, 28.0%, 64.0%, 38.0%, 6.0%, 34.0%, 10.0%, and 24.0%, respectively. The difference in the detection rates of multiple drug-resistant strain, hlyA and VT1 between the ESBLs-producing E.cofi strains and the non-ESBLs-producing E.cofi strains was statistically significant （P〈0.05）. The positive rate of multiple drug-resistant strains is higher in the ESBLs-producing strains than in the non-ESBLs-producing strains. The expression of some virulence genes hlyA and VT1 varies between the ESBLs-producing strains and the non-ESBLs-producing strains. Increased awareness of clinicians and enhanced testing by laboratories are required to reduce treatment failures and prevent the spread of multiple drug-resistant strains.
基金supported by the National Natural Science Foundation of China(21172225,31170334)the 973 Program of Ministry of Science and Technology of China(2009CB522300)the XiBuZhiGuang Project of Chinese Academy of Sciences,and the Young Academic and Technical Leader Raising Foundation of Yunnan Province(No.2010CI049).
文摘Four new monoterpenoid indole alkaloids,alstrostines C-F together with thirteen known alkaloids were isolated from the leaves and twigs of Alstonia rostrata.All structures of new compounds were elucidated based on NMR,FTIR,UV,and MS spectroscopic data.Alstrostines C-E might originate from keto-enol tautomerism of preakummicine during biogenetic pathway of akummicine.
基金Supported by the Doctoral Startup Fund of Affiliated Hospital of Weifang Medical University,No.2021BKQ01.
文摘BACKGROUND Tofacitinib is an oral Janus kinase(JAK)inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis(RA).Varicella zoster virus reactivation leading to herpes zoster(HZ)is an adverse effect of this drug;however,recurrent HZ at the same site is a rare clinical condition.CASE SUMMARY A 70-year-old female RA patient had undergone 1-year of tofacitinib treatment(10 mg daily).About 1 mo after initiation of oral tofacitinib,she developed blisters on the left flank and abdomen and was diagnosed with HZ;antiviral therapy with acyclovir was resolutory.However,5 d prior to presentation at our hospital,erythema and blisters with severe pain recurred at the same site.Small clustered blisters and bullous were visible on the left lumbar abdomen and perineum,with a pain score of 8(visual analogue scale).Antiviral,nutritional supplement,analgesic and other treatments led to healing but over an atypically long period(approximately 26 d,vs approximately 1 wk).HZ is a common and serious adverse reaction of JAK inhibitors,but it rarely recurs.Our patient’s experience of HZ recurrence at the same site,with a wider affected area,more severe pain and longer healing period,is inconsistent with previous reports.CONCLUSION Same-anatomical site HZ recurrence may occur during oral tofacitinib treatment,with more severe clinical manifestations than in the initial occurrence.
基金supported by the National Natural Science Foundation of China,No.81571938 and 81501706the Natural Science Foundation of Shandong Province of China,No.Y2007C133
文摘Heat shock protein 70（HSP70） maintains Ca^2＋ homeostasis in PC12 cells,which may protect against apoptosis;however,the mechanisms of neuroprotection are unclear.Therefore,in this study,we examined Ca^2＋ levels in PC12 cells transfected with an exogenous lentiviral HSP70 gene expression construct,and we subsequently subjected the cells to ischemia-hypoxia/reoxygenation injury.HSP70 overexpression increased neuronal viability and ATPase activity,and it decreased cellular reactive oxygen species levels and intracellular Ca^2＋ concentration after hypoxia/reoxygenation.HSP70 overexpression enhanced the protein and m RNA expression levels of sarcoplasmic/endoplasmic reticulum Ca^2＋-ATPase（SERCA）,but it decreased the protein and m RNA levels of inositol 1,4,5-trisphosphate receptor（IP3R）,thereby leading to decreased intracellular Ca^2＋concentration after ischemia-hypoxia/reoxygenation.These results suggest that exogenous HSP70 protects against ischemia-hypoxia/reoxygenation injury,at least in part,by maintaining cellular Ca^2＋ homeostasis,by upregulating SERCA expression and by downregulating IP_3 R expression.
基金supported by NSFC grants (Nos.11573033,11622325,11425312 and 11988101)supported by NSFC grant (No.11803045)+2 种基金the “Recruitment Program of Global Youth Experts” of China,the NAOC (Grant Y434011V01)supported by the National Key R&D Program of China (No.2017YFB0203300)the Key Program of NFSC (Grant 11733010)。
文摘We use a semi-analytic galaxy formation model to study the co-evolution of supermassive black holes(SMBHs) with their host galaxies.Although the coalescence of SMBHs is not important,the quasarmode accretion induced by mergers plays a dominant role in the growth of SMBHs.Mergers play a more important role in the growth of SMBH host galaxies than in the SMBH growth.It is the combined contribution from quasar mode accretion and mergers to the SMBH growth and the combined contribution from starburst and mergers to their host galaxy growth that determine the observed scaling relation between the SMBH masses and their host galaxy masses.We also find that mergers are more important in the growth of SMBH host galaxies compared to normal galaxies which share the same stellar mass range as the SMBH host galaxies.
文摘Objective:To analyze the effect of implementing a comprehensive nursing management program for rabies vaccination patients.Methods:100 cases of rabies vaccination patients were selected as observation objects from January 2022 to December 2023,and after enrollment,they were grouped according to the different nursing management programs,with 50 cases in each group.The control group was only given routine nursing management,and the observation group was combined with comprehensive nursing management on the basis of routine nursing management.The completion rate of vaccination,the rate of adverse reactions,and the satisfaction rate were assessed,comparing the clinical effects of different nursing management programs.Results:The completion rate of the 5th shot of rabies vaccination in the observation group was 82.00%higher than 64.00%in the control group(χ^(2)=4.1096,P<0.05);the rate of adverse reaction of vaccination in the observation group was 4.00%lower than 18.00%in the control group(χ^(2)=5.0051,P<0.05);the vaccination satisfaction in the observation group was 98.00%higher than 86.00%in the control group(χ^(2)=4.8913,P<0.05).Conclusion:The application of comprehensive nursing management program can help rabies vaccination patients to improve the completion rate of vaccination and reduce the incidence of adverse reactions to vaccination,with clear effects.
文摘We perform a set of non-radiative hydro-dynamical(NHD)simulations of a rich cluster sized dark matter halo from the Phoenix Project with three different numerical resolutions,to investigate the effect of hydrodynamics alone on the subhalo population in the halo.Compared to dark matter only(DMO)simulations of the same halo,subhaloes are less abundant for relatively massive subhaloes(Msub>2.5×109h 1M⊙,or Vmax>70 km s 1)but more abundant for less massive subhaloes in the NHD simulations.This results in different shapes in the subhalo mass/Vmax function in two different sets of simulations.At given subhalo mass,the subhaloes less massive than 1010h 1M⊙have larger Vmax in the NHD than DMO simulations,while Vmax is similar for the subhaloes more massive than the mass value.This is mainly because the progenitors of present day low mass subhaloes have larger concentration parameters in the NHD than DMO simulations.The survival number fraction of the accreted low mass progenitors of the main halo at redshift 2 is about 50 percent higher in the NHD than DMO simulations.
文摘[Objective]This study aimed to investigate the leaf anatomical structures of P.tunicoides populations under water-limited conditions.[Method]2-year-old seedlings of herbaceous perennial P.tunicoides that was introduced into the experi-mental field were selected as the research objects.Under the well-watered and wa-ter-limited conditions,we conducted the comparative observation of leaf anatomical structure and stomatal characteristics of two populations by using paraffin slice method and imprinting method.[Result]The result showed that the upper cuticle of P.tunicoides leaves were thickened,the palisade tissue/spongy tissue ratio,vascular bundle diameter and number of xylem vessels in main vein had increased,the stomatal opening became smaller and the stomatal density had increased in winter-spring drought period under water-limited conditions.The plasticity of above traits could be regarded as the important indicators for detecting the responses of P.tunicoides populations to water-limited conditions.Meanwhile,variation amplitudes of these indicators were different among populations.Leaf anatomical structure and stomatal characteristics in Lijiang Axi population under water-limited conditions varied significantly,which might cause the stronger adaptability of this population to drought conditions.[Conclusion]This research provided a reference for the selection of drought-resistant P.tunicoides germplasm and exploration of the adaptive differentia-tion of P.tunicoides populations under natural drought conditions.
