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BACKGROUND: Being in a state of high occupational stress may disrupt the metabolic balance of the body, thus increasing the risk of metabolic diseases. However, the evidence about the relationship between occupational stress and metabolic syndrome was limited. OBJECTIVES: To explore the association between occupational stress and metabolic syndrome (MetS) in employees of a power grid enterprise. METHODS: A total of 1091 employees were recruited from a power grid enterprise in China. Excluding those who failed to complete the questionnaire and those who had incomplete health check-ups, 945 subjects were included in the study. Assessment of occupational stress was used by job demand-control (JDC) and effort-reward imbalance (ERI) questionnaires, respectively. The information on body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were collected. The levels of high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and fasting blood glucose (FBG) in the fasting venous blood samples were measured. Logistic regression analysis and multiple linear regression methods were used to analyze the correlation between JDC and ERI models of occupational stress, metabolic syndrome, and its components, respectively. RESULTS: The prevalence of MetS was 8.4% and 9.9% in JDC and ERI model high occupational stress employees, respectively. ERI model occupational stress and smoking are significantly associated with the risk of MetS. ERI ratio was significantly associated with lower HDL-C levels. Gender, age, marital status, smoking, high-temperature and high-altitude work were significantly associated with metabolic component levels. CONCLUSION: Our study revealed a high detection rate of occupational stress in both JDC and ERI models among employees of a power grid enterprise. ERI model occupational stress, demanding more attention, was associated with the risk of MetS as well as its components such as HDL-C.
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BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.
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Infecções por Henipavirus , Vírus Nipah , Vírus Nipah/fisiologia , Infecções por Henipavirus/epidemiologia , Infecções por Henipavirus/transmissão , Humanos , Animais , Quirópteros/virologia , Sudeste Asiático/epidemiologia , Filogenia , Zoonoses/epidemiologia , Zoonoses/virologiaRESUMO
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterised by progressive degeneration of motor neurons. Genetic factors have a substantial impact on ALS. Therefore, this study aimed to explore the correlation between genotype (SOD1, TARDBP, FUS, C9orf72) and phenotype in ALS. METHODS: Genetic analysis was performed on 2038 patients with ALS, among which 1696 patients with sporadic ALS (SALS) as controls for genotype-phenotype analysis, and 1602 SALS as controls for survival analysis. Logistic regression and Cox proportional hazards models were used for statistical analysis. RESULTS: A total of 172 patients with ALS with the gene mutations were included in the statistical analysis (SOD1, n=65; FUS, n=43; TARDBP, n=27; C9orf72, n=37). SOD1 mutations were more frequent in flail leg phenotype (OR 7.317, p=0.001) and less in bulbar phenotype (OR 0.222, p=0.038). C9orf72 expansions exhibited higher frequency in bulbar phenotype (OR 2.770, p=0.008). SOD1 and FUS mutations were significantly associated with earlier age of onset (HR 2.039, p<0.001; HR 1.762, p=0.001). The patients with SOD1 mutations, C9orf72 expansions and those carrying pathogenic FUS mutations had significantly increased death risk (HR 2.217, p<0.001; HR 1.694, p=0.008; HR 1.652, p=0.036). The increased risk of death in ALS with C9orf72 expansions was significant in females (HR 2.419, p=0.014) but not in males (HR 1.442, p=0.128). CONCLUSION: Our study revealed distinct motor phenotypic tendencies in patients with ALS with different genotypes, indicating variations in the vulnerability of motor neurons during the disease's progression. Furthermore, we made novel discoveries regarding survival of different gene mutations, warranting further investigation.
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BACKGROUND: The sorghum aphid Melanaphis sacchari (Zehntner) (Homoptera: Aphididae) is an important insect in the late growth phase of sorghum (Sorghum bicolor L.). However, the mechanisms of sorghum response to aphid infestation are unclear. RESULTS: In this paper, the mechanisms of aphid resistance in different types of sorghum varieties were revealed by studying the epidermal cell structure and performing a transcriptome and metabolome association analysis of aphid-resistant and aphid-susceptible varieties. The epidermal cell results showed that the resistance of sorghum to aphids was positively correlated with epidermal cell regularity and negatively correlated with the intercellular space and leaf thickness. Transcriptome and metabolomic analyses showed that differentially expressed genes in the resistant variety HN16 and susceptible variety BTX623 were mainly enriched in the flavonoid biosynthesis pathway and differentially expressed metabolites were mainly related to isoflavonoid biosynthesis and flavonoid biosynthesis. The q-PCR results of key genes were consistent with the transcriptome expression results. Meanwhile, the metabolome test results showed that after aphidinfestation, naringenin and genistein were significantly upregulated in the aphid-resistant variety HN16 and aphid-susceptible variety BTX623 while luteolin was only significantly upregulated in BTX623. These results show that naringenin, genistein, and luteolin play important roles in plant resistance to aphid infestation. The results of exogenous spraying tests showed that a 1 concentration of naringenin and genistein is optimal for improving sorghum resistance to aphid feeding. CONCLUSIONS: In summary, the physical properties of the sorghum leaf structure related to aphid resistance were studied to provide a reference for the breeding of aphid-resistant varieties. The flavonoid biosynthesis pathway plays an important role in the response of sorghum aphids and represents an important basis for the biological control of these pests. The results of the spraying experiment provide insights for developing anti-aphid substances in the future.
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Afídeos , Metaboloma , Sorghum , Transcriptoma , Sorghum/genética , Sorghum/parasitologia , Sorghum/metabolismo , Afídeos/fisiologia , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Folhas de Planta/metabolismo , Folhas de Planta/genéticaRESUMO
BACKGROUND: Cognitive decline is among the most common non-motor symptoms in Parkinson's disease (PD), while its physiological mechanisms remain poorly understood. Genetic factors constituted a fundamental determinant in the heterogeneity of cognitive decline among PD patients. However, the underlying genetic background was still less studied. METHODS: To explore the genetic determinants contributing to cognitive decline in PD, we performed genome-wide survival analysis using a Cox proportional hazards model in a longitudinal cohort of 450 Chinese patients with PD, and further explored the functional effect of the target variant. Additionally, we built a clinical-genetic model by incorporating clinical characteristics and polygenic risk score (PRS) to predict cognitive decline in PD. RESULTS: The cohort was followed up for an average of 5.25 (SEâ =â 2.46) years, with 95 incidents of cognitive impairment. We identified significant association between locus rs75819919 (DPP6) and accelerated cognitive decline (pâ =â 8.63E-09, betaâ =â 1.74, SEâ =â 0.30). Dual-luciferase reporter assay suggested this locus might be involved in the regulation of DPP6 expression. Using data set from the UK Biobank, we identified rs75819919 was associated with cognitive performance in the general population. Incorporation of PRS increased the model's predictability, achieving an average AUC of 75.6% through fivefold cross-validation in 1 000 iterations. CONCLUSIONS: These findings improve the current understanding of the genetic etiology of cognitive impairment in PD, and provide a novel target DPP6 to explore therapeutic options. Our results also demonstrate the potential to develop clinical-genetic model to identify patients susceptible to cognitive impairment and thus provide personalized clinical guidance.
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Disfunção Cognitiva , Dipeptidil Peptidases e Tripeptidil Peptidases , Estudo de Associação Genômica Ampla , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doença de Parkinson/complicações , Masculino , Feminino , Disfunção Cognitiva/genética , Idoso , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Predisposição Genética para Doença , Pessoa de Meia-Idade , Fatores de Risco , Polimorfismo de Nucleotídeo Único , Estudos Longitudinais , Modelos de Riscos Proporcionais , China/epidemiologia , Proteínas do Tecido Nervoso , Canais de PotássioRESUMO
Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.
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Córnea , Neovascularização da Córnea , Nanopartículas , Soluções Oftálmicas , Neovascularização da Córnea/tratamento farmacológico , Animais , Nanopartículas/química , Soluções Oftálmicas/química , Córnea/metabolismo , Córnea/efeitos dos fármacos , Camundongos , Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/farmacologia , Tamanho da Partícula , Humanos , Masculino , Camundongos Endogâmicos C57BL , CoelhosRESUMO
Nanocomposites combining inorganic nanoparticles with high dielectric constant and polymers with high breakdown strength are promising for the high energy density storage of electricity, and carrier traps can significantly affect the dielectric breakdown process. Nevertheless, there still lacks direct experimental evidence on how nanoparticles affect the trap characteristics of nanocomposites, especially in a spatially resolved manner. Here, a technique is developed to image the trap distribution based on sequential Kelvin probe force microscopy (KPFM) in combination with the isothermal surface potential decay (ISPD) technique, wherein both shallow and deep trap densities and the corresponding energy levels can be mapped with nanoscale resolution. The technique is first validated using the widely-used commercial biaxially oriented polypropylene, yielding consistent results with macroscopic ISPD. The technique is then applied to investigate polyvinylidene fluoride-based nanocomposites filled with barium titanate nanoparticles, revealing higher deep trap density around surface-modified nanoparticles, which correlates well with its increased breakdown strength. This technique thus provides a powerful spatially resolved tool for understanding the microscopic mechanism of dielectric breakdown of nanocomposites.
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Accurate estimates of fossil fuel CO2 (FFCO2) emissions are of great importance for climate prediction and mitigation regulations but remain a significant challenge for accounting methods relying on economic statistics and emission factors. In this study, we employed a regional data assimilation framework to assimilate in situ NO2 observations, allowing us to combine observation-constrained NOx emissions coemitted with FFCO2 and grid-specific CO2-to-NOx emission ratios to infer the daily FFCO2 emissions over China. The estimated national total for 2016 was 11.4 PgCO2·yr-1, with an uncertainty (1σ) of 1.5 PgCO2·yr-1 that accounted for errors associated with atmospheric transport, inversion framework parameters, and CO2-to-NOx emission ratios. Our findings indicated that widely used "bottom-up" emission inventories generally ignore numerous activity level statistics of FFCO2 related to energy industries and power plants in western China, whereas the inventories are significantly overestimated in developed regions and key urban areas owing to exaggerated emission factors and inexact spatial disaggregation. The optimized FFCO2 estimate exhibited more distinct seasonality with a significant increase in emissions in winter. These findings advance our understanding of the spatiotemporal regime of FFCO2 emissions in China.
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Dióxido de Carbono , Monitoramento Ambiental , Combustíveis Fósseis , Dióxido de Nitrogênio , Dióxido de Carbono/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Dióxido de Nitrogênio/análise , Estações do AnoRESUMO
Importance: The association of endovascular therapy (EVT) with outcomes is unclear for patients with very low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) within 24 hours of stroke onset. Objective: To explore the association of EVT with functional and safety outcomes among patients with ASPECTS of 0 to 2 scored with noncontrast computed tomography. Design, Setting, and Participants: This cohort study used data from an ongoing, prospective, observational, nationwide registry including all patients treated at 38 stroke centers in China with an occlusion in the internal carotid artery or M1 or M2 segment of the middle cerebral artery within 24 hours of witnessed symptom onset. Patients with ASPECTS of 0 to 2 between November 1, 2021, and February 8, 2023, were included in analysis. Data were analyzed October to November 2023. Exposures: EVT vs standard medical treatment (SMT). Main Outcomes and Measures: The primary outcome was favorable functional outcome, defined as modified Rankin Scale score (mRS) of 0 to 3, at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 48 hours and mortality at 90 days. Results: A total of 245 patients (median [IQR] age, 71 [63-78] years; 118 [48%] women) with ASPECTS of 0 to 2 were included, of whom 111 patients (45.1%) received SMT and 135 patients (54.9%) received EVT. The EVT group had significantly greater odds of favorable functional outcome at 90 days than the SMT group (30 patients [22.2%] vs 11 patients [9.9%]; P = .01; adjusted odds ratio [aOR], 3.07 [95% CI, 1.29-7.31]; P = .01). Patients in the EVT group, compared with the SMT group, had significantly greater odds of any ICH (56 patients [41.5%] vs 16 patients [11.4%]; P < .001; aOR, 4.27 [95% CI, 2.19-8.35]; P < .001) and sICH (24 patients [17.8%] vs 1 patient [0.9%]; P < .001; aOR, 23.07 [95% CI, 2.99-177.79]; P = .003) within 48 hours. There were no differences between groups for 90-day mortality (80 patients [59.3%] vs 59 patients [53.2%]; P = .34; aOR, 1.38 [95% CI, 0.77-2.47]; P = .28). The results remained robust in the propensity score-matched analysis. Conclusions and Relevance: In this cohort study of patients with very low ASPECTS based on NCCT within 24 hours of stroke onset, those treated with EVT had higher odds of a favorable functional outcome compared with those who received SMT. Randomized clinical trials are needed to assess these findings.
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Procedimentos Endovasculares , AVC Isquêmico , Humanos , Feminino , Masculino , Procedimentos Endovasculares/métodos , Idoso , Pessoa de Meia-Idade , AVC Isquêmico/terapia , AVC Isquêmico/mortalidade , AVC Isquêmico/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Sistema de Registros , China/epidemiologia , Tomografia Computadorizada por Raios X , Estudos de CoortesRESUMO
AIM: To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography (SS-OCT). METHODS: According to the body mass index (BMI) results, the adults enrolled in the cross-sectional study were divided into the normal group (18.50≤BMI<25.00 kg/m2), the overweight group (25.00≤BMI<30.00 kg/m2), and the obesity group (BMI≥30.00 kg/m2). The one-way ANOVA and the Chi-square test were used for comparisons. Pearson's correlation analysis was used to evaluate the relationships between the measured variables. RESULTS: This research covered the left eyes of 3 groups of 434 age- and sex-matched subjects each: normal, overweight, and obesity. The mean BMI was 22.20±1.67, 26.82±1.38, and 32.21±2.35 kg/m2 in normal, overweight and obesity groups, respectively. The choroid was significantly thinner in both the overweight and obesity groups compared to the normal group (P<0.05 for all), while the retinal thickness of the three groups did not differ significantly. Pearson's correlation analysis showed that BMI was significantly negatively correlated with choroidal thickness, but no significant correlation was observed between BMI and retinal thickness. CONCLUSION: Choroidal thickness is decreased in people with overweight or obesity. Research on changes in choroidal thickness contributes to the understanding of the mechanisms of certain ocular disorders in overweight and obese adults.
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Introduction: Tirofiban is a non-peptide selective glycoprotein IIb/IIIa receptor inhibitor with a short half-life. The research assesses the efficacy and safety of continuous intravenous tirofiban in patients with acute ischemic stroke (AIS) undergoing endovascular therapy (ET). Methods: A systematic search of Pubmed, Embase, Web of Science, and Cochrane Library databases is conducted from inception until January 26, 2024. Eligible studies are included based on predefined selection criteria. Efficacy outcomes (favorable functional outcome and excellent functional outcome) and safety outcomes (symptomatic intracranial hemorrhage [sICH], any intracranial hemorrhage [ICH], and 90-day mortality) are calculated using odds ratios (OR) and 95% confidence intervals (CI). Results: A total of 4,329 patients from 15 studies are included in the analysis. The results indicate a significant trend toward favorable functional outcomes in the tirofiban group (OR, 1.24; 95% CI, 1.09-1.42; p = 0.001). In terms of safety outcomes, tirofiban does not increase the risk of sICH (OR, 0.90; 95% CI, 0.71-1.13; p = 0.35) or any ICH (OR, 0.97; 95% CI, 0.70-1.34; p = 0.85), but it significantly decreases 90-day mortality (OR, 0.75; 95% CI, 0.64-0.88; p = 0.0006). A subgroup analysis suggests that continuous intravenous tirofiban demonstrates better efficacy (OR, 1.24; 95% CI, 1.09-1.42; p = 0.001) for patients with AIS undergoing rescue ET with even better results when used in combination with intra-arterial and intravenous administration (OR, 1.25; 95% CI, 1.07-1.451; p = 0.005). Conclusion: Continuous intravenous tirofiban is effective and safe for patients with AIS undergoing rescue ET, particularly when combined with intra-arterial tirofiban. Systematic review registration: PROSPERO, identifier CRD42023385695.
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Objectives: This study aims to elucidate the role of peripheral inflammation in Huntington's disease (HD) by examining the correlation of peripheral inflammatory markers with clinical manifestations and disease prognosis. Methods: This investigation involved 92 HD patients and 92 matched healthy controls (HCs). We quantified various peripheral inflammatory markers and calculated their derived metrics including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). Clinical assessments spanning cognitive, motor, and disease severity were administered. Comparative analysis of inflammatory markers and clinical correlations between HD and controls was performed. Kaplan-Meier survival analysis and Cox regression model were used to assess the effect of inflammatory markers on survival. Results: The study revealed that HD patients had significantly reduced lymphocyte counts, and LMR. Conversely, NLR, PLR, and SII were elevated compared to HCs. Lymphocyte levels inversely correlated with the age of onset and monocyte levels inversely correlated with the UHDRS-total functional capacity (TFC) scores. After adjusting for age, sex, and CAG repeat length, lymphocyte count, NLR, PLR, and SII were significantly correlated with the progression rate of TFC scores. Elevated levels of white blood cells and monocytes were associated with an increased risk of disability and mortality in the HD cohort. Conclusion: Our findings indicate that HD patients display a distinct peripheral inflammatory profile with increased NLR, PLR, and SII levels compared to HCs. The peripheral inflammation appears to be linked with accelerated disease progression and decreased survival in HD.
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Dry eye disease (DED) is a multifactorial condition affecting the ocular surface. It is characterized by loss of tear film homeostasis and accompanied by ocular symptoms that may potentially result in damage to the ocular surface and even vision loss. Unmodifiable risk factors for DED mainly include aging, hormonal changes, and lifestyle issues such as reduced sleep duration, increased screen exposure, smoking, and ethanol consumption. As its prevalence continues to rise, DED has garnered considerable attention, prompting the exploration of potential new therapeutic targets. Recent studies have found that when the production of ROS exceeds the capacity of the antioxidant defense system on the ocular surface, oxidative stress ensues, leading to cellular apoptosis and further oxidative damage. These events can exacerbate inflammation and cellular stress responses, further increasing ROS levels and promoting a vicious cycle of oxidative stress in DED. Therefore, given the central role of reactive oxygen species in the vicious cycle of inflammation in DED, strategies involving antioxidants have emerged as a novel approach for its treatment. This review aims to enhance our understanding of the intricate relationship between oxidative stress and DED, thereby providing directions to explore innovative therapeutic approaches for this complex ocular disorder.
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Periodontitis is a chronic oral inflammatory disease with the characteristic of excess oxidative stress in the inflammatory site, dramatically decreasing the quality of life. Studies show that nanozymes can be ideal candidates for ROS scavenging in periodontitis. Here, we design a multipath anti-inflammatory mesoporous polydopamine@cerium oxide nanobowl (mPDA@CeO2 NB) with multienzyme mimicking properties, which combines the advantages of both CeO2 NP and mPDA NB for synergistically eliminating reactive oxygen species (ROS), including hydroxyl radical (â¢OH), hydrogen peroxide (H2O2), and superoxide (O2â¢-). Besides, the erythrocyte-like structure of mNBs makes them a facility for cell uptake, and the mesopores can load both hydrophobic and hydrophilic drugs for combined anti-inflammatory therapy. In vitro and in vivo experiments prove that the combination of CeO2 and mPDA can synergistically achieve multiple complementary ROS eliminations and suppression of ROS-induced inflammation. Moreover, the ROS regulation plus anti-inflammatory drugs in one mPDA@CeO2 NB prevents the progression of periodontitis in a mouse model. Therefore, the design of mPDA@CeO2 NB with these excellent properties provides a therapeutic strategy for inflammatory diseases.
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Cério , Indóis , Teste de Materiais , Tamanho da Partícula , Periodontite , Polímeros , Cério/química , Cério/farmacologia , Periodontite/tratamento farmacológico , Animais , Camundongos , Indóis/química , Indóis/farmacologia , Polímeros/química , Polímeros/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Porosidade , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
Parkinson's disease (PD) is a heterogeneous movement disorder with different motor subtypes including tremor dominant (TD), indeterminate and postural instability, and gait disturbance (PIGD) motor subtypes. Plasma glial fibrillary acidic protein (GFAP) was elevated in PD patients and may be regarded as a biomarker for motor and cognitive progression. Here we explore if there was an association between plasma GFAP and different motor subtypes and whether baseline plasma GFAP level can predict motor subtype conversion. Patients with PD classified as TD, PIGD or indeterminate subtypes underwent neurological evaluation at baseline and 2 years follow-up. Plasma GFAP in PD patients and controls were measured using an ultrasensitive single molecule array. The study enrolled 184 PD patients and 95 control subjects. Plasma GFAP levels were significantly higher in the PIGD group compared to the TD group at 2-year follow-up. Finally, 45% of TD patients at baseline had a subtype shift and 85% of PIGD patients at baseline remained as PIGD subtypes at 2 years follow-up. Baseline plasma GFAP levels were significantly higher in TD patients converted to PIGD than non-converters in the baseline TD group. Higher baseline plasma GFAP levels were significantly associated with the TD motor subtype conversion (OR = 1.283, P = 0.033) and lower baseline plasma GFAP levels in PIGD patients were likely to shift to TD and indeterminate subtype (OR = 0.551, P = 0.021) after adjusting for confounders. Plasma GFAP may serve as a clinical utility biomarker in differentiating motor subtypes and predicting baseline motor subtypes conversion in PD patients.
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With the development of ultra-intense laser technology, the manipulation of relativistic laser pulses has become progressively challenging due to the limitations of damage thresholds for traditional optical devices. In recent years, the generation and manipulation of ultra-intense vortex laser pulses by plasma has attracted a great deal of attention. Here, we propose a new scheme to produce a relativistic vortex laser. This is achieved by using a relativistic Gaussian drive laser to irradiate a plasma binary phase square spiral zone plate (BPSSZP). Based on three-dimensional particle-in-cell (3D-PIC) simulations, we find that the drive laser has a phase difference of π after passing through the BPSSZP, ultimately generating the vortex laser with unique square symmetry. Quantitatively, by employing a drive laser pulse with intensity of 1.3 × 1018~W/cm2, a vortex laser with intensity up to 1.8 × 1019~W/cm2, and energy conversion efficiency of 18.61% can be obtained. The vortex lasers generated using the BPSSZP follow the modulo-4 transmutation rule when varying the topological charge of BPSSZP. Furthermore, the plasma-based BPSSZP has exhibited robustness and the ability to withstand multiple ultra-intense laser pulses. As the vortex laser generated via the BPSSZP has high intensity and large energy conversion efficiency, our scheme may hold potential applications in the community of laser-plasma, such as particles acceleration, intense high-order vortex harmonic generation, and vortex X/γ-ray sources.
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The effectiveness and safety of human urinary kallidinogenase (HUK) in acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) due to large vessel occlusion (LVO) was unclear. A pooled analysis was performed using individual data from the DEVT and RESCUE BT trials. Patients were divided into two groups based on HUK treatment. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH) within 48 hours. A total of 1174 patients were included in the study. Of these, 150 (12.8%) patients received HUK. The adjusted common odds ratio (OR) of the mRS score was 1.458 (95% confidence interval [CI] = 1.072-1.983; p = 0.016) favoring HUK. The incidence of sICH (2.0% vs. 8.6%; adjusted OR: 0.198; 95% CI: 0.061-0.638; p = 0.007) and mortality (11.3% vs.18.5%; adjusted OR: 0.496; 95% CI: 0.286-0.862; p = 0.013) was lower in HUK group than non-HUK group. This association was consistent with propensity score-matching and the inverse probability of treatment weighting analysis. In conclusion, HUK was safe and associated with a preferable prognosis in AIS patients due to LVO in the anterior circulation.
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Male infertility has emerged as a global issue, partly attributed to psychological stress. However, the cellular and molecular mechanisms underlying the adverse effects of psychological stress on male reproductive function remain elusive. We created a psychologically stressed model using terrified-sound and profiled the testes from stressed and control rats using single-cell RNA sequencing. Comparative and comprehensive transcriptome analyses of 11,744 testicular cells depicted the cellular landscape of spermatogenesis and revealed significant molecular alterations of spermatogenesis suffering from psychological stress. At the cellular level, stressed rats exhibited delayed spermatogenesis at the spermatogonia and pachytene phases, resulting in reduced sperm production. Additionally, psychological stress rewired cellular interactions among germ cells, negatively impacting reproductive development. Molecularly, we observed the down-regulation of anti-oxidation-related genes and up-regulation of genes promoting reactive oxygen species (ROS) generation in the stress group. These alterations led to elevated ROS levels in testes, affecting the expression of key regulators such as ATF2 and STAR, which caused reproductive damage through apoptosis or inhibition of testosterone synthesis. Overall, our study aimed to uncover the cellular and molecular mechanisms by which psychological stress disrupts spermatogenesis, offering insights into the mechanisms of psychological stress-induced male infertility in other species and promises in potential therapeutic targets.
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In a hierarchical caching system, a server is connected to multiple mirrors, each of which is connected to a different set of users, and both the mirrors and the users are equipped with caching memories. All the existing schemes focus on single file retrieval, i.e., each user requests one file. In this paper, we consider the linear function retrieval problem, i.e., each user requests a linear combination of files, which includes single file retrieval as a special case. We propose a new scheme that reduces the transmission load of the first hop by jointly utilizing the two layers' cache memories, and we show that our scheme achieves the optimal load for the second hop in some cases.
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The fabrication of reliable, reusable and efficient catalyst is crucial for the conversion of nitroaromatic compounds into more chemically valuable amine-based molecules. In this study, a series of chitin supported platinum (Pt) catalysts with high catalytic activity, stability, and reusability were developed by using chitin derived from seafood waste as raw materials. The catalytic performance differences among these catalysts activated by different methods were investigated by hydrogenation of nitroaromatic compounds. The results showed that the multilayer hierarchical pore structure and abundance of hydroxyl and acetamido groups in chitin provided ample anchoring sites for Pt nanoparticles (NPs), ensuring the high dispersion of Pt NPs. Moreover, the interconnected channels between chitin nanofibrous microspheres facilitated rapid transport of reaction substrates. The best Pt/Chitin catalyst exhibited excellent catalytic activity and broad substrate applicability in hydrogenation of nitroaromatic compounds. Significantly, even after 20 runs, no discernible deactivation of activity was observed, demonstrating exceptional catalytic reusability. The application of seafood waste-based catalysts is conducive to the development of a green/sustainable society.