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Objective: Expanding on previous investigations, this study aims to elucidate the role of lipid metabolism disorders in the development of intracranial atherosclerotic stenosis (ICAS) and the determination of stroke risk. The primary objective is to explore the connections between lipid parameters and acute ischemic stroke (AIS), while also examining the potential mediating influence of fasting glucose levels. Methods: Retrospectively, we collected data from symptomatic ICAS patients at the First Affiliated Hospital of Soochow University, including their baseline information such as medical histories and admission blood biochemical parameters. Stenotic conditions were evaluated using magnetic resonance imaging, computed tomography angiography, or digital subtraction angiography. The associations between lipid parameters and AIS risks were investigated via multivariate logistic regression analysis. Results: A total of 1103 patients with symptomatic ICAS were recruited, among whom 441 (40.0%) suffered new ischemic events during hospitalization. After adjusting for confounding factors, the RCS curves exhibited a dose-response relationship between the atherogenic index of plasma (AIP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and AIS. Further multivariate analysis revealed significant associations between these parameters and AIS. Furthermore, mediation analysis indicated that fasting blood glucose (FBG) acted as a mediator in the association between lipid parameters (AIP, TC, and TG) and AIS. Conclusion: Higher lipid parameters in ICAS patients, particularly AIP, TC, and TG, were associated with an increased AIS risk. Additionally, FBG may mediate stroke risk in ICAS patients, highlighting the need for further exploration of underlying mechanisms.
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Glucemia , Arteriosclerosis Intracraneal , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Arteriosclerosis Intracraneal/sangre , Arteriosclerosis Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/complicaciones , Persona de Mediana Edad , Estudios Retrospectivos , Glucemia/metabolismo , Glucemia/análisis , Anciano , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , Lípidos/sangre , Constricción Patológica/sangre , Accidente Cerebrovascular Isquémico/sangre , Factores de RiesgoRESUMEN
Background: Cutaneous tuberculosis (CTB) and nontuberculous mycobacteria (NTM) infections present considerable diagnostic and therapeutic challenges. This study aims to provide a comprehensive clinicopathological analysis of CTB and NTM infections. Methods: We conducted a retrospective analysis of 103 patients diagnosed with cutaneous tuberculosis (CTB) and nontuberculous mycobacteria (NTM) infections at a Beijing dermatology department from January 2000 to January 2024. Demographic, clinical, histological, and laboratory finding data were collected. Diagnostic methods and histopathological examination were recorded. Treatment regimens and outcomes were reviewed. Descriptive statistics were used to summarize demographic and clinical data, and continuous variables expressed as means and standard deviations (SD), and categorical variables as frequencies and percentages. Statistical analyses were conducted using SPSS version 25.0. Results: The cohort included 103 patients (40.8% males and 59.2% females), with a mean age of 51.86 years. Common clinical manifestations included nodules (97.1%), erythema (74.8%), and plaques (68.9%). Histological examination revealed hyperkeratosis (68.9%), parakeratosis (23.3%), and extensive neutrophil infiltration (95.1%) were observed. Acid fast bacteria (AFB) stains and nucleic acid tests exhibited respective positivity rates of 39.6% and 52.3%, respectively. Most patients were treated with a combination of three drugs; 77.1% of patients showed improvement, with the cure rate for CTB being 20.0%. Discussion: This study highlights the diverse clinical and histological presentations of CTB and NTM infections, emphasizing the need for comprehensive diagnostic approaches. The variability in treatment regimens reflects the complex management of these infections. Conclusion: The implementation of advanced molecular techniques and standardized treatment protocols is imperative for enhancing diagnostic precision and therapeutic outcomes.
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Infecciones por Mycobacterium no Tuberculosas , Micobacterias no Tuberculosas , Tuberculosis Cutánea , Humanos , Femenino , Masculino , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/patología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Persona de Mediana Edad , Tuberculosis Cutánea/diagnóstico , Tuberculosis Cutánea/patología , Tuberculosis Cutánea/tratamiento farmacológico , Tuberculosis Cutánea/epidemiología , Estudios Retrospectivos , Adulto , Anciano , Micobacterias no Tuberculosas/aislamiento & purificación , Beijing/epidemiología , China/epidemiología , Adulto Joven , Antituberculosos/uso terapéutico , Piel/patología , Piel/microbiología , Adolescente , Anciano de 80 o más Años , Resultado del TratamientoRESUMEN
Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund's adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Disulfuros , Glicoproteínas Hemaglutininas del Virus de la Influenza , Vacunas contra la Influenza , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Anticuerpos Antivirales/inmunología , Ratones , Disulfuros/química , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Anticuerpos Neutralizantes/inmunología , Femenino , Protección Cruzada/inmunología , Reacciones Cruzadas , Humanos , Gripe Humana/prevención & control , Gripe Humana/inmunología , Gripe Humana/virología , Epítopos/inmunología , Epítopos/genética , Epítopos/química , Multimerización de Proteína , Virus de la Influenza B/inmunología , Virus de la Influenza B/genética , Virus de la Influenza B/químicaRESUMEN
The first dikaryotic genome of Ganoderma cultivar Zizhi S2 (56.76 Mb, 16,681 genes) has been sequenced recently. 98.15% of complete BUSCOs were recovered in this genome assembly and high-confidence annotation rate improved to 91.41%. Collinearity analysis displayed the nuclear genome were 80.2% and 93.84% similar to reference genome of G. sinense at nucleotide and amino acid levels, which presented 8,521 core genes and 880 unique orthologous gene groups. Among that, at least six functional genes (tef1-α, ß-tubulin, rpb2, CaM, Mn-SOD and VeA) and a newly discovered fip gene were highly similar 99.27% â¼100% to those in reference genome. And the mt-LSU, mt-SSU and 13 PCGs in their mitogenome were also highly conserved with 99.27%-99.87% and 99.08%-100% identity, respectively. So that, this cultivar Zizhi S2 is confirmed conspecific with Ganoderma sinense (NCBI: txid1077348). The new fip gene (MN635280.1_336bp) existing a novel mutation which can be reflected on the phylogenetic tree and 3-dimensional model topology structure.
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Solid-state lithium-sulfur batteries (SSLSBs) have attracted a great deal of attention because of their high theoretical energy density and intrinsic safety. However, their practical applications are severely impeded by slow redox kinetics and poor cycling stability. Herein, we revealed the detrimental effect of aggregation of lithium polysulfides (LiPSs) on the redox kinetics and reversibility of SSLSBs. As a paradigm, we introduced a multifunctional hyperbranched ionic conducting (HIC) polymer serving as a solid polymer electrolyte (SPE) and cathode binder for constructing SSLSBs featuring high electrochemical activity and high cycling stability. It is demonstrated that the unique structure of the HIC polymer with numerous flexible ether oxygen dangling chains and fast segmental relaxation enables the dissociation of LiPS clusters, facilitates the conversion kinetics of LiPSs, and improves the battery's performance. A Li|HIC SPE|HIC-S battery, in which the HIC polymer acts as an SPE and cathode binder, exhibits an initial capacity of 910.1 mA h gS-1 at 0.1C and 40 °C, a capacity retention of 73.7% at the end of 200 cycles, and an average Coulombic efficiency of approximately 99.0%, demonstrating high potential for application in SSLSBs. This work provides insights into the electrochemistry performance of SSLSBs and provides a guideline for SPE design for SSLSBs with high specific energy and high safety.
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AIMS: Sex differences in the long-term prognosis of heart failure (HF) remain controversial, and there is a lack of comprehensive pooling of the sex differences in outcomes of HF. This study aims to characterize the sex differences in the long-term prognosis of HF and explore whether these differences vary by age, HF course, left ventricular ejection fraction, region, period of study, study design, and follow-up duration. METHODS AND RESULTS: A systematic review was conducted using Medline, Embase, Web of Science, and the Cochrane Library, from January 1, 1990, to March 31, 2024. The primary outcome was all-cause mortality (ACM), and the secondary outcomes included cardiovascular mortality (CVM), hospitalization for HF (HHF), all-cause hospitalization, a composite of ACM and HHF, and a composite of CVM and HHF. Pooled hazard risks (HRs) with corresponding 95% confidence intervals (CIs) were calculated using random effects meta-analysis. 94 studies (comprising 96 cohorts) were included in the meta-analysis, representing 706,247 participants (56.5% were men, the mean age was 71.0 years). Female HF patients had a lower risk of ACM (HR: 0.83, 95% CI: 0.80, 0.85; I2=84.9%), CVM (HR: 0.84, 95% CI: 0.79, 0.89; I2=70.7%), HHF (HR: 0.94, 95% CI: 0.89, 0.98; I2=84.0%), and composite endpoints (ACM+HHF: HR: 0.89, 95% CI: 0.83, 0.95; I2=80.0%; CVM+HHF: HR: 0.85, 95% CI: 0.77, 0.93; I2=87.9%) compared to males. Subgroup analysis revealed that the lower risk of mortality observed in women was more pronounced among individuals with long-course HF (i.e., chronic HF, follow-up duration >2 years) or recruited in the randomized controlled trials. (P for interaction <0.05). CONCLUSIONS: Female HF patients had a better prognosis compared to males, with lower risks of ACM, CVM, HHF, and composite endpoints. Despite the underrepresentation of female populations in HF clinical trials, their mortality benefits tended to be lower than in real-world settings. REGISTRATION: PROSPERO: CRD42024526100.
Our meta-analysis showed that women were associated with lower risks of all-cause mortality, cardiovascular mortality, hospitalization for HF, and composite endpoints but not all-cause hospitalization. The lower risk of mortality for women was more pronounced among individuals with long-course HF or recruited in the randomized controlled trials. This study highlights the significance of improving women's socio-economic status and addressing the undermanagement of cardiovascular disease among women worldwide.
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BACKGROUND AND AIM: The relationship between walking pace and heart failure (HF) has been recognized, yet the directionality and underlying mediating risk factors remain unclear. METHODS AND RESULTS: This study utilized bidirectional two-sample Mendelian randomization (MR) with genome-wide association studies (GWAS) summary statistics to assess the causal relationships between walking pace and HF. Additionally, we employed a two-step Multivariable Mendelian Randomization (MVMR) to explore potential mediating factors. We further validated our findings by conducting two-sample MR with another available GWAS summary data on heart failure. Results indicated that genetically predicted increases in walking pace were associated with a reduced risk of HF (odds ratio (OR), 0.589, 95% confidence interval (CI): 0.417-0.832). Among the considered mediators, the waist-to-hip ratio (WHR) accounts for the largest proportion of the effect (45.7%, 95% CI: 13.2%, 78.2%). This is followed by type 2 diabetes at 24.4% (95% CI: 6.7%, 42.0%) and triglycerides at 18.6% (95% CI: 4.5%, 32.7%). Furthermore, our findings reveal that genetically predicted HF risk (OR, 0.975, 95% CI: 0.960-0.991) is associated with a slower walking pace. Validated findings were consistent with the main results. CONCLUSIONS: In conclusion, MR analysis demonstrates that a slow walking pace is a reliable indicator of an elevated risk of HF, and the causal relationship is bidirectional. Interventions focusing on waist-to-hip ratio, type 2 diabetes, and triglycerides may provide valuable strategies for HF prevention in individuals with a slow walking pace.
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We present a method for modification of silicon nitride (Si3N4) waveguide resonators using femtosecond laser annealing. The quality (Q) factor of the waveguide resonators can be improved by approximately 1.3 times after annealing. Notably, waveguides that originally had a high Q value maintained their quality after the annealing process. However, those with a lower initial Q value experienced a noticeable improvement post-annealing. To characterize the annealing effect, the surface morphologies of Si3N4 films, both pre- and post-annealing, were analyzed using atomic force microscopy. The findings suggest a potential enhancement in surface refinement. Furthermore, Raman spectroscopy confirmed that the Si3N4 film's composition remains largely consistent with its original state within the annealing power range of 0.6-1.6 W. This research underscores the potential of femtosecond laser annealing as an efficient, cost-effective, and localized technique for fabricating low-loss integrated photonics.
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BACKGROUND: Evodiamine (EVO) is an alkaloid extracted from the dried and nearly ripe fruits of Euodia rutaecarpa and used as an anti-cancer, anti-inflammatory and anti-obesity agent. However, robust evidence of preclinical experiments has been lacking so far. Therefore, the purpose of this article was to investigate the effect of EVO in combination with other treatments on tumors in animal experiments. METHODS: A systematic review and meta-analysis were conducted to assess the anti-tumor effect of evodiamine-combined therapy. The search engine and electronic databases included PubMed, Scopus, China Knowledge Resource Integrated Database (CNKI), and SinoMed. The research method was based on the PRISMA checklist. RESULTS: A total of 7 studies and 108 animals were included. As a result, EVO combined therapy was found to be more effective than EVO monotherapy. The SMD was -25.64(95% CI: -5.77 -3.13) in tumor growth. In tumor weight, the SMD was -8.91(95% CI: -16.37, -1.44). CONCLUSION: EVO has the potential to alleviate the toxicity of chemotherapeutic agents, which increases the translatability to the clinical situation.
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Chemical warfare agents (CWAs), epitomized by the notoriously used mustard gas (HD), represent a class of exceptionally toxic chemicals whose airborne removal is paramount for battlefield safety. This study integrates high-throughput computational screening (HTCS) with advanced machine learning (ML) techniques to investigate the efficacy of metal-organic frameworks (MOFs) in adsorbing and capturing trace amounts of HD present in the air. Our approach commenced with a comprehensive univariate analysis, scrutinizing the impact of six distinct descriptors on the adsorption efficiency of MOFs. This analysis elucidated a pronounced correlation between MOF density and the Henry coefficient in the effective capture of HD. Then, four ML algorithms were employed to train and predict the performance of MOFs. The Random Forest (RF) algorithm demonstrates strong model learning and good generalization, achieving the best prediction result of 98.3%. In a novel exploratory stride, we incorporated a 166-bit MACCS molecular fingerprinting (MF) to identify critical functional groups within adsorbents. From the top 100 MOFs analyzed, 22 optimal functional groups were identified. Leveraging these insights, we designed three innovative substructures, grounded in these key functional groups, to enhance HD adsorption efficiency. In this work, the combination of MF and ML could provide a new direction for efficient screening of MOFs for the capture of HD in the air. The outcomes of this study offer substantial potential to revolutionize the domain of CWA capture. This represents a significant stride toward developing practical solutions that enhance both environmental protection and battlefield security.
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Bismuth-based chalcogenides have emerged as promising candidates for next-generation, solution-processable semiconductors, mainly benefiting from their facile fabrication, low cost, excellent stability, and tunable optoelectronic properties. Particularly, the recently developed AgBiS2 solar cells have shown striking power conversion efficiencies. High performance bismuth-based photodetectors have also been extensively studied in the past few years. However, the fundamental properties of these Bi-based semiconductors have not been sufficiently investigated, which is crucial for further improving the device performance. Here, we introduce multiple time-resolved and steady-state techniques to fully characterize the charge carrier dynamics and charge transport of solution-processed Bi-based nanocrystals. It was found that the Ag-Bi ratio plays a critical role in charge transport. For Ag-deficient samples, silver bismuth sulfide thin films behave as localized state induced hopping charge transport, and the Ag-excess samples present band-like charge transport. This finding is crucial for developing more efficient Bi-based semiconductors and optoelectronic devices.
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To investigate the effects of different irrigation and nitrogen application modes on nitrogen gaseous loss in winter wheat farmland, we conducted a field experiment at Changqing Irrigation Experiment Station in Shandong Province, with two irrigation levels (80%-90% θf(I1) and 70%-80% θf(I2)) and three nitrogen application levels (conventional nitrogen application of 240 kg·hm-2(N1), nitrogen reduction of 12.5% (N2), and nitrogen reduction of 25% (N3)). The results showed that ammonia volatilization and nitrous oxide emission rate peak appeared within 2-4 days after fertilization or irrigation. The ammonia volatilization rate during the chasing fertilizer period was significantly higher than that during the basal fertilizer period. Compared with other treatments, the ave-rage ammonia volatilization rate of I2N2 treatment during the chasing fertilizer period was reduced by 10.1%-51.6%, and the average nitrous oxide emission rate over the whole growth period was reduced by 15.4%-52.2%. The ammonia volatilization rate was significantly positively associated with surface soil pH value and ammonium nitrogen content, while the nitrous oxide emission rate was significantly positively associated with nitrate content in topsoil. The accumulation amount of soil ammonia volatilization and nitrous oxide emission ranged from 0.83-1.42 and 0.11-0.33 kg·hm-2, respectively. Moderate reduction of irrigation water and nitrogen input could effectively reduce cumulative amounts of ammonia volatilization and nitrous oxide emission from winter wheat farmland. The cumulative amounts of ammonia volatilization and nitrous oxide emission under I1N3 and I2N2 treatments were signi-ficantly lower than those under other treatments. The highest winter wheat yield (5615.6 kg·hm-2) appeared in I2N2 treatment. The irrigation water utilization efficiency of I2 was significantly higher than that of I1, with the maximum increase rate of 45.2%. Compared with N1 and N3 treatments, the maximum increase rate of nitrogen fertilizer productivity and agricultural utilization efficiency in N2 reached 15.2% and 31.8%, respectively. In conclusion, the treatment with 70%-80% θf irrigation level and 210 kg·hm-2 nitrogen input could effectively improve the utilization efficiency of irrigation water and nitrogen fertilization and reduce gaseous loss from winter wheat farmland.
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Amoníaco , Fertilizantes , Nitrógeno , Óxido Nitroso , Triticum , Agua , Triticum/crecimiento & desarrollo , Triticum/metabolismo , Óxido Nitroso/análisis , Óxido Nitroso/metabolismo , Nitrógeno/análisis , Nitrógeno/metabolismo , Amoníaco/análisis , Amoníaco/metabolismo , China , Agua/análisis , Agua/metabolismo , Riego Agrícola/métodos , Estaciones del Año , Biomasa , Suelo/químicaRESUMEN
The main rice planting areas in the middle and lower reaches of the Yangtze River are primarily affected by two types of rice seedling diseases: bakanae disease and seedling rot disease. These diseases lead to considerable losses. Seed coating technology effectively protects rice from these diseases and mitigates environmental pollution. We determined the antifungal activity of six fungicides, including phenamacril, azoxystrobin, fludioxonil, metconazole, thifluzamide and prothioconazole against Fusarium moniliforme Sheldon and Curvularia lunata in this study. In addition, the impact of fungicides and surfactants on rice seed germination were determined. Furthermore, phenamacril and fludioxonil were selected as the active components of suspension concentrate for seed coating. The antifungal activity of phenamacril against F. moniliforme Sheldon was 0.139 mg/L and fludioxonil against C. lunata was 0.110 mg/L. PEG-2000 was selected as the surfactant due to its promoting effect on rice seedling. Based on the above findings, 6% phenamacril fludioxonil FS was developed via the wet sand grinding method. The toxicity of 6% phenamacril fludioxonil FS to zebrafish was verified, and field experiments were conducted in five different regions of the Yangtze River Basin. The results indicated minimal toxicity of 6% phenamacril fludioxonil FS to zebrafish. Relative to the control agent consisting of 6.25% phenamacril metalaxyl-M FS, 6% phenamacril fludioxonil FS showed better control effect and exhibited superior efficacy in promoting growth and increasing yield in all five regions. Specifically, the control effect of 6% phenamacril fludioxonil FS on bakanae exceeded 84.83% with the highest yield increasing value recorded at 30.48%. Currently, the market offers a limited selection of suspension concentrate for seed coating of rice. The findings of this study may offer a viable alternative formulation and directions for further research concerning the application of suspension concentrate for seed coating of rice.
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BACKGROUND: Toxoplasma gondii and Neospora caninum are closely related protozoan parasites that are considered important causes of abortion in livestock, causing huge economic losses. Hunan Province ranks 12th in the production of beef and mutton in China. However, limited data are available on the seroprevalence, risk factors and molecular characterization of T. gondii and N. caninum in beef cattle and goats in Hunan province, China. METHODS: Sera of 985 beef cattle and 1147 goats were examined for the presence of specific antibodies against T. gondii using indirect hemagglutination test (IHAT) and anti-N. caninum IgG using competitive-inhibition enzyme-linked immunoassay assay (cELISA). Statistical analysis of possible risk factors was performed using PASW Statistics. Muscle samples of 160 beef cattle and 160 goats were examined for the presence of T. gondii DNA (B1 gene) and N. caninum DNA (Nc-5 gene) by nested PCR. The B1 gene-positive samples were genotyped at 10 genetic markers using the multilocus nested PCR-RFLP (Mn-PCR-RFLP). RESULTS: Specific IgG against T. gondii were detected in 8.3% (82/985) and 13.3% (153/1147) and against N. caninum in 2.1% (21/985) and 2.0% (23/1147) of the beef cattle and goats, respectively. Based on statistical analysis, the presence of cats, semi-intensive management mode and gender were identified as significant risk factors for T. gondii infection in beef cattle. Age was a significant risk factor for T. gondii infection in goats (P < 0.05), and age > 3 years was a significant risk factor for N. caninum infection in beef cattle (P < 0.05). PCR positivity for T. gondii was observed in three beef samples (1.9%; 3/160) and seven chevon samples (4.4%; 7/160). Genotyping of PCR positive samples identified one to be ToxoDB#10. The N. caninum DNA was observed in one beef sample (0.6%; 1/160) but was negative in all chevon samples. CONCLUSIONS: To our knowledge, this is the first large-scale serological and molecular investigation of T. gondii and N. caninum and assessment of related risk factors in beef cattle and goats in Hunan Province, China. The findings provide baseline data for executing prevention and control of these two important parasites in beef cattle and goats in China.
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Anticuerpos Antiprotozoarios , Enfermedades de los Bovinos , Coccidiosis , Enfermedades de las Cabras , Cabras , Neospora , Toxoplasma , Toxoplasmosis Animal , Animales , Cabras/parasitología , Neospora/genética , Neospora/inmunología , Neospora/aislamiento & purificación , Toxoplasma/genética , Toxoplasma/inmunología , Toxoplasma/aislamiento & purificación , Toxoplasmosis Animal/epidemiología , Toxoplasmosis Animal/parasitología , China/epidemiología , Bovinos , Estudios Seroepidemiológicos , Coccidiosis/veterinaria , Coccidiosis/epidemiología , Coccidiosis/parasitología , Enfermedades de las Cabras/epidemiología , Enfermedades de las Cabras/parasitología , Anticuerpos Antiprotozoarios/sangre , Femenino , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/parasitología , Masculino , Factores de Riesgo , Inmunoglobulina G/sangre , ADN Protozoario/genética , Ensayo de Inmunoadsorción Enzimática/veterinaria , Genotipo , Reacción en Cadena de la Polimerasa/veterinariaRESUMEN
The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing (NGS). Our findings showed that a TP_rate cut-off of 0.033 demonstrated superior diagnostic performance for syphilis, with a specificity of 92.3% and a sensitivity of 71.4% (AUROC = 0.92). This diagnosis model predicted that 20 out of 92 serofast patients had a persistent low-level infection. Based on these predictions, re-treatment was administered to these patients and its efficacy was evaluated. The results showed a statistically significant decrease in RPR titers in the prediction-positive group compared to the prediction-negative group after re-treatment (p < 0.05). These findings provide evidence for the existence of T. pallidum under serofast status and support the use of intensive treatment for serofast patients at higher risk in clinical practice.
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Many BF2 complexes of heteroaromatics are well known for their dual-state emission (DSE) properties. However, AIE and ACQ effects have also been observed in certain cases. To date, no rational explanations have been proposed for these uncommon photoluminescence (PL) behaviours. The current research prepared four BF2 complexes of N-benzoyl 2-aminobenzothiazoles with diversified photoluminescence (PL) properties as model compounds and utilized quantum chemical calculation tools to address this issue. Theoretical calculations revealed that the electron-donating groups (EDGs) at the para-position of the exocyclic phenyl ring exert significant influence on their ground-state electronic structures and vertical excitation features. Potential energy curve (PEC) analysis showed that the exocyclic phenyl ring and NMe2 could not function as effective rotors due to elevated energy barriers. Only the NPh2 of BFBB-3 could spontaneously rotate â¼60° to induce the formation of an emissive twisted intramolecular charge transfer (TICT) state. The two-channel model involving both vibronic relaxation and S0/S1 surface crossing revealed that the drastic narrowing of the S1/S0 energy gap in the region approaching minimun energy conical intersection (MECI) led to the generation of a dark state in BFBB-1. The small energy barrier to access the dark-state region makes the resulting fast internal conversion a competitive channel for excited-state deactivation. In contrast, the presence of EDGs in BFBB-2 and 4 inhibits this pathway, thereby resulting in intense fluorescence emissions in solution. In addition, crystallographic analysis illustrated that the F atoms perpendicular to the polyheterocycle promoted a slipped face-to-face packing mode and enhanced intermolecular interactions. The efficiencies of their solid-state emissions are mainly affected by the degree of π-π overlaps.
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Correlating the microscopic structural characteristics with the macroscopic electrochemical performance in electrode materials is critical for developing excellent-performance lithium-ion batteries, which however remains largely unexplored. Here, we show that the Zn2SnO4 (ZTO) nanowires (NWs) with smaller diameters (d < 5 nm) exhibit slower capacity fade rate and better cycling stability, as compared with the NWs with larger diameters ranging from tens to hundreds of nanometers. By applying in situ transmission electron microscopy (TEM), we discover a strong correlation of cracking behavior with the NW diameter. Upon the first lithiation, there exists a critical diameter of â¼80 nm, below which the NWs neither crack nor fracture, and above which the cracks could easily nucleate and propagate along the specific planes, resulting in the deteriorated cycling stability in larger sized electrodes. Further theoretical calculations based on the finite element model and the climbing image nudged elastic band method faithfully predict the size-dependent cracking behaviors, which may result from the synergistic effect of axial stress evolution as well as preferential Li-ion migration directions during the first lithiation. This work provides a real-time tracking of the tempo-spatial structural evolution of a single ZTO NW, which facilitates a fundamental understanding of how the sample size affects the electrochemical behavior and thus offers a reference for future battery design and application strategy.
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BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE-/- mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.
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Aterosclerosis , Proteínas Proto-Oncogénicas c-akt , Humanos , Ratones , Animales , Becaplermina/genética , Becaplermina/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Músculo Liso Vascular/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Movimiento Celular , Transducción de Señal , Proliferación Celular , Serina-Treonina Quinasas TOR/metabolismo , Aterosclerosis/patología , Miocitos del Músculo Liso/patología , Fenotipo , Células Cultivadas , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
BACKGROUND: Azvudine has clinical benefits and acceptable safety against COVID-19, including in patients with comorbidities, but there is a lack of available data for its use in older adult patients. This study explored the effectiveness and safety of azvudine in older adults with mild or moderate COVID-19. METHODS: This retrospective cohort study included patients aged ≥80 diagnosed with COVID-19 at the Central Hospital of Shaoyang between October and November 2022. According to the therapies they received, the eligible patients were divided into the azvudine, nirmatrelvir/ritonavir, and standard-of-care (SOC) groups. The outcomes were the proportion of patients progressing to severe COVID-19, time to nucleic acid negative conversion (NANC), and the 5-, 7-, 10-, and 14-day NANC rates from admission. RESULTS: The study included 55 patients treated with azvudine (n = 14), nirmatrelvir/ritonavir (n = 18), and SOC (n = 23). The median time from symptom onset to NANC of the azvudine, nirmatrelvir/ritonavir, and SOC groups was 14 (range, 6-25), 15 (range, 11-24), and 19 (range, 18-23) days, respectively. The median time from treatment initiation to NANC of the azvudine and nirmatrelvir/ritonavir groups was 8 (range, 4-20) and 9 (range, 5-16) days, respectively. The median length of hospital stay in the three groups was 10.5 (range, 5-23), 13.5 (range, 10-21), and 17 (range, 10-23) days, respectively. No treatment-related adverse events or serious adverse events were reported. CONCLUSION: Azvudine showed satisfactory effectiveness and acceptable safety in older adults with mild or moderate COVID-19. Therefore, azvudine could be a treatment option for this special patient population.
Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Anciano , Humanos , Antivirales/efectos adversos , Estudios Retrospectivos , RitonavirRESUMEN
Soil salinity results in oxidative stress and heavy losses to crop production. The S-acylated protein SALT TOLERANCE RECEPTOR-LIKE CYTOPLASMIC KINASE 1 (STRK1) phosphorylates and activates CATALASE C (CatC) to improve rice (Oryza sativa L.) salt tolerance, but the molecular mechanism underlying its S-acylation involved in salt signal transduction awaits elucidation. Here, we show that the DHHC-type zinc finger protein DHHC09 S-acylates STRK1 at Cys5, Cys10, and Cys14 and promotes salt and oxidative stress tolerance by enhancing rice H2O2-scavenging capacity. This modification determines STRK1 targeting to the plasma membrane or lipid nanodomains and is required for its function. DHHC09 promotes salt signaling from STRK1 to CatC via transphosphorylation, and its deficiency impairs salt signal transduction. Our findings demonstrate that DHHC09 S-acylates and anchors STRK1 to the plasma membrane to promote salt signaling from STRK1 to CatC, thereby regulating H2O2 homeostasis and improving salt stress tolerance in rice. Moreover, overexpression of DHHC09 in rice mitigates grain yield loss under salt stress. Together, these results shed light on the mechanism underlying the role of S-acylation in RLK/RLCK-mediated salt signal transduction and provide a strategy for breeding highly salt-tolerant rice.