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1.
Adv Mater ; : e2103882, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510576

RESUMO

To date, the scope of single-atom catalysts (SAC) in liquid-phase transformations is rather limited owing to stability issues and the inability to activate complex substances. This calls for a better design of the catalyst support that can provide a dynamic coordination environment needed for catalytic action, and yet retain robustness against leaching or aggregation. In addition, the chemical orthogonality of SAC is useful for designing tandem or multicomponent reactions, in which side reactions common to metal nanoparticles are suppressed. In this review, the intrinsic mechanism will be highlighted that controls reaction efficiency and selectivity in SAC-catalyzed pathways, as well as the structural dynamism of SAC under complex liquid-phase conditions. These mechanistic insights are helpful for the development of next-generation SAC systems for the synthesis of high-value pharmaceuticals through late-stage functionalization, sequential and multicomponent strategies.

2.
Br J Neurosurg ; : 1-8, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524042

RESUMO

OBJECTIVE: This retrospective study investigated the clinical and radiographic outcomes following temporary transpedicular posterior instrumentation between two cohorts of patients with thoracolumbar fractures (TLF) who underwent selective or bi-segments intervertebral articular process fusion. METHODS: Patients with TLF who underwent the temporary posterior fixation with selective fusion (Group SF), or bi-segments fusion (Group BF) were studied. Superior intervertebral articular process and interlaminar fusion were performed in Group SF, whereas in Group BF, the patients underwent bi-segments fusion in both superior and inferior articular processes, as well as interlaminar fusion. We measured the distal and proximal intervertebral mobility, regional kyphotic angle, and vertebral height before and after surgery in both groups. Greenough Low-Back Outcome Score was used to assess the clinical outcomes. RESULTS: Sixty-five patients with TLF from T12 to L2 fractures were enrolled in the study period: 33 patients in the Group SF and 32 patients in the Group BF. All the patients experienced fracture healing (mean follow-up time: 19.7 months). The mean postoperative functional outcomes were 65.0 ± 2.0 points for the Low-Back Outcome Score in the Group SF and 65.2 ± 1.8 for the Group BF. A progressive regional kyphotic angle was observed with time regardless of fusion but was not significantly different between the two groups. There was a statistical difference between unfused inferior proximal adjacent and inferior distal adjacent segment regardless of fracture segments. CONCLUSIONS: The strategy of selective fusion is reported to be useful for the treatment of patients with TLF. The motion in the un-fused and adjacent segment could be better regained after instrumentation removal in the selective fusion group. LEVEL OF EVIDENCE: Level 3.

3.
Front Immunol ; 12: 722027, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489971

RESUMO

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals who mounted a detectable antibody response with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients did. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections.


Assuntos
Anticorpos Antivirais/sangue , Infecções Assintomáticas/epidemiologia , COVID-19/imunologia , Imunidade Humoral , SARS-CoV-2/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Formação de Anticorpos , COVID-19/epidemiologia , China , Monitoramento Epidemiológico , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/patogenicidade , Adulto Jovem
4.
Photodiagnosis Photodyn Ther ; : 102537, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536608

RESUMO

BACKGROUND: Acne vulgaris is a chronic inflammatory skin disease around pilosebaceous unit. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for severe acne vulgaris. However, its specific treatment mechanism remains unclear. In the present study, we investigated the potential mechanism of how ALA-PDT induced lipid secretion inhibition in acne vulgaris. METHODS: Primary human sebocytes and sebaceous gland of golden hamster were treated with/without ALA-PDT. Cell viability was evaluated by Live/Dead Cell assay. Fluorescence microscope was used to observe lipids secretion in sebocytes after Nile red staining. The expression of SREBP-1 after ALA-PDT was evaluated by qRT-PCR. Regulation of ALA-PDT on AMPK/SREBP-1 was evaluated by western blot. RESULTS: The results showed that ALA-PDT suppressed lipid secretion of primary human sebocytes. In addition, ALA-PDT could inhibit the expression of SREBP-1 in vitro. We also found that ALA-PDT activated AMPK pathway, down-regulating the expression of SREBP-1 in sebocytes after ALA-PDT. CONCLUSIONS: These findings elucidate that ALA-PDT suppresses lipid secretion through AMPK/SREBP-1 pathway in treatment of acne vulgaris.

5.
J Agric Food Chem ; 69(37): 10989-10998, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34516110

RESUMO

The alkaloid 1-deoxynojirimycin (DNJ) is one of the major bioactive compounds in mulberry leaves (Morus alba L.). Previously, we discovered four key genes involved in the pathway from lysine to piperidine in the biosynthesis of DNJ in mulberry leaves, MaLDC (MG727866), MaCAO (MH205733), MaSDR1 (MT989445), and MaSDR2 (MT989446), which encoded lysine decarboxylase, copper amine oxidase, and short-chain dehydrogenase/reductase 1 and 2, respectively. However, the in vivo functions of these four genes have not been verified yet. Here, these four genes were successfully cloned and used for the establishment of C58C1 Agrobacterium rhizogenes mediated overexpression genetic transformation systems and GV3101 Agrobacterium-mediated virus-induced gene silencing transformation systems in order to verify the influence of these four genes on the biosynthetic content of DNJ in mulberry leaves. The results showed that the content of DNJ increased after the four genes were overexpressed. When these four genes were silenced, the gene expression was blocked, which affected the biosynthesis of DNJ, and the DNJ content decreased. The above results indicated that these four genes participated in DNJ biosynthesis. This study provided a foundation for further elucidating the regulatory mechanisms of DNJ biosynthesis in mulberry leaves.

6.
J Int Med Res ; 49(9): 3000605211029808, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34488485

RESUMO

OBJECTIVE: Endoscopic submucosal excavation (ESE) has been established as an effective method for removal of gastric submucosal tumors (SMTs). The aim of the present study was to explore risk factors for technical difficulties in ESE. METHODS: In this retrospective study, we collected clinical data from patients who underwent ESE for gastric SMTs. Difficult ESE was defined as a procedure time ≥90 minutes, piecemeal resection, and/or occurrence of major adverse events. Univariate and multivariate analyses were performed to explore the risk factors for a difficult ESE. RESULTS: ESE was successfully performed in 96.5% (195/202) of patients from April 2011 to December 2019. The average tumor size was 17.41 mm, and en bloc resection was achieved in 97.4% of patients (190/195). Five patients (2.56%, 5/195) had complications, including two with delayed bleeding, two with fever, and one with chest pain accompanying ST-T changes in an electrocardiogram. Twenty-four patients (11.88%, 24/202) had a difficult ESE. Logistic analysis showed that outgrowth behavior and an inexperienced surgeon were risk factors for a difficult ESE. CONCLUSION: ESE may be safe and effective to treat patients with gastric SMTs. Outgrowth behavior and an inexperienced surgeon were risk factors for a difficult ESE.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Mucosa Gástrica/cirurgia , Gastroscopia , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
7.
Front Public Health ; 9: 670889, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490178

RESUMO

COVID-19, the coronavirus disease 2019; SARS-CoV-2, the coronavirus 2; ACE2, angiotensin converting enzyme 2; S protein, spiked glycoprotein; TMPRSS2, transmembrane serine protease 2; WHO, World Health Organization. Purpose: Although the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2, has been viably controlled in China, a new normal in healthcare strategies has become standard in China and worldwide. We conducted a questionnaire study to disseminate the experience from China in terms of urology outpatient prevention and control measures under standardized prevention policies against COVID-19. Participants and Methods: From May 3, 2020 to June 25, 2020, we conducted an anonymous cross-sectional questionnaire study, focused on the status of and experiences with outpatient urology prevention and control measures during the COVID-19 pandemic. The targeted respondents were urologists in mainland China, covering all levels of hospitals and clinics. Results: A total of 216 (97%) valid responses were collected. We found that 183 (85%) respondents were from outside of Hubei province in China. One-hundred-and-fifty-eight (73%) respondents believed that SARS-CoV-2 could be detected in urine, and that protection against urine exposure was needed. Over 80% of respondents recommended WeChat application or similar online video meetings for virtual outpatient consultations. The suggested flowcharts and recommendations to prevent new cases were easy to understand and approved by most physicians, which could provide reference for outpatient prevention and control. We still need to make adequate preparations under the new normal of the COVID-19 Epidemic, especially for those suspected of being infected. Conclusions: Although the scientific validation of the questionnaire is limited, it provides a first snapshot of the experiences relating to the prevention and control measures in urology clinics in China, and can inform future policies in this field.


Assuntos
COVID-19 , Urologia , China/epidemiologia , Estudos Transversais , Humanos , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
8.
Elife ; 102021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491895

RESUMO

Inducible regulatory T (iTreg) cells play a central role in immune suppression. As iTreg cells are differentiated from activated T (Th0) cells, cell metabolism undergoes dramatic changes, including a shift from fatty acid synthesis (FAS) to fatty acid oxidation (FAO). Although the reprogramming in fatty acid metabolism is critical, the mechanism regulating this process during iTreg differentiation is still unclear. Here we have revealed that the enzymatic activity of ATP-citrate lyase (ACLY) declined significantly during iTreg differentiation upon transforming growth factor ß1 (TGFß1) stimulation. This reduction was due to CUL3-KLHL25-mediated ACLY ubiquitination and degradation. As a consequence, malonyl-CoA, a metabolic intermediate in FAS that is capable of inhibiting the rate-limiting enzyme in FAO, carnitine palmitoyltransferase 1 (CPT1), was decreased. Therefore, ACLY ubiquitination and degradation facilitate FAO and thereby iTreg differentiation. Together, we suggest TGFß1-CUL3-KLHL25-ACLY axis as an important means regulating iTreg differentiation and bring insights into the maintenance of immune homeostasis for the prevention of immune diseases.

9.
Acta Derm Venereol ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515803

RESUMO

Persistent eruption occurs in a subset of patients with adult-onset Still's disease. In our experience, a considerable proportion of these patients present with peripheral eosinophilia. The aims of this study were to summarize the clinical and histological features of patients with adult-onset Still's disease with persistent eruption in the current study cohort, and to assess the association between peripheral eosinophil levels and disease characteristics. A total of 21 patients with adult-onset Still's disease with persistent eruption were included in this retrospective study. Koebner signs, an important diagnostic clue, were found in 85.7% of patients. The proportion of patients presenting with eosinophilia within the disease course was 57.1%. Skin histology revealed infiltration of eosinophils in 90.5% of patients. Peripheral eosinophil levels were positively associated with involved body surface area. Patients with normal peripheral eosinophil counts were more likely to achieve complete remission than those with abnormal peripheral eosinophil counts. Eosinophils may be involved in the pathogenesis of skin eruption. Abnormal peripheral eosinophil counts in these patients may indicate a more refractory disease course.

10.
Int J Psychophysiol ; 169: 63-70, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34499961

RESUMO

EEG microstate analysis involves the examination of topographies of the scalp potential fields to indicate the temporal dynamics of resting-state networks on a millisecond time scale, through which we can investigate the subsecond brain dynamics of stress in individuals. The present study implemented the EEG microstate method to explore the temporal dynamic changes of the large-scale brain networks induced by acute stress. The participants (n = 51) were randomly exposed to a stress condition (n = 25) (induced by Trier Social Stress Test, TSST) or a control condition (n = 26). Two 4-min blocks of resting EEG data were recorded before and after the stress/control test to reflect the stress effect on temporal dynamics of EEG microstates. The results showed that the stress group had larger occurrences and coverage of microstate class C during the post-test session than during the pre-test session. This pattern was reversed in the control group. Further, the microstate class C showed positive correlations with negative affect and perceived stress levels following acute stress. The transition probability between the microstates C and D was larger during the post-test session than during the pre-test session in the stress group, but not different in the control group. In addition, the microstate pairs C and D were positively correlated with negative affect and perceived stress levels. The proportion and sequence of EEG microstates class C and D reflected deviations of salience and executive functions following acute stress. We further proposed that the coordination between salience and executive functions was promoted by acute stress.

11.
Medicine (Baltimore) ; 100(36): e27186, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516520

RESUMO

ABSTRACT: The emergence of carbapenem-resistant Enterobacteriaceae made the treatment difficult, which has become a significant issue of public health. A sharp increase of carbapenem-resistance rate in Klebsiella pneumoniae was observed in a maternity and child health care hospital in Zunyi, China, in 2014.In 2015 to 2016, carbapenem-resistant Klebsiella pneumoniae (CRKp) isolated from all the clinical samples were analyzed to identify the carbapenem-resistance genes. They were then fingerprinted in order to determine their genetic relationship. Clinical data such as usage of imipenem in 2012 to 2016 and the nosocomial infection surveillance data were analyzed.Thirty-five isolates of CRKp out of 4328 various pathogens were obtained, and blaNDM-1 was identified to be the most common resistant gene present in the CRKp isolates. The fingerprint analysis identified 15 major clusters of CRKp isolates. The bacteria with close proximity relationship tended to be from the same wards. However, a few CRKp isolates from different wards were found to be genetically highly related. The clinical data showed a significantly higher usage of carbapenems in 2012 to 2013 before the CRKp rate sharply increased in 2014. The nosocomial infection surveillance showed an unexpectedly high rate of failures to meet the requirement of the hospital environment hygiene and hand hygiene in the neonatal ward.The increasing isolation rate of CRKp was associated with poorly regulated usage of carbapenems, impropriate medical practices, and the poor hospital environmental hygiene and hand hygiene.


Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana , Imipenem/uso terapêutico , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/isolamento & purificação , Adulto , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Criança , Pré-Escolar , China/epidemiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Feminino , Humanos , Imipenem/farmacologia , Lactente , Recém-Nascido , Controle de Infecções , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Serviços de Saúde Materno-Infantil , Gravidez
12.
J Med Internet Res ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34543228

RESUMO

BACKGROUND: The COVID-19 pandemic has raised the importance of the deployment of digital detection surveillance systems to support early warning and monitoring of infectious diseases (ID). These opportunities create a "double-edge sword" as the ethical governance of such approaches often lag behind technological achievements. OBJECTIVE: The aim was to investigate ethical issues identified from utilizing AI-augmented surveillance or early warning systems to monitor and detect common or novel ID outbreaks. METHODS: We searched relevant articles in a number of databases that addressed ethical issues of using artificial intelligence, digital surveillance systems, early warning systems and/or big data analytics technology for detecting, monitoring, or tracing ID according to PRISMA guidelines, and further identified and analysed them with a theoretical framework. RESULTS: This systematic review identified 29 articles presented in six major themes clustered under individual, organizational and societal levels, including: awareness of implementing digital surveillance, digital integrity, trust, privacy and confidentiality, civil rights, and governance. Whilst these measures were understandable during a pandemic, the public were concerned about receiving inadequate information, unclear governance frameworks, and lack of privacy protection, data integrity and autonomy when utilizing ID digital surveillance. The barriers to engagement could widen existing healthcare disparities or digital divides by underrepresenting vulnerable and at-risk populations, and expose patients' highly sensitive data such as their movements and contacts to outside sources, impinging significantly upon basic human and civil rights. CONCLUSIONS: Our findings inform ethical considerations for service delivery models for medical practitioners and policymakers implicated in the use of digital surveillance for ID spread and a basis for the global governance structure.

13.
J Magn Reson Imaging ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34545977

RESUMO

BACKGROUND: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. PURPOSE: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. ANIMAL MODEL: Established PBDL models. POPULATION: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group. FIELD STRENGTH/SEQUENCE: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging. ASSESSMENT: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. STATISTICAL TESTS: One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. DATA CONCLUSION: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

14.
mSystems ; : e0020121, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546069

RESUMO

Genes belonging to the same functional group may include numerous and variable gene sequences, making characterizing and quantifying difficult. Therefore, high-throughput design tools are needed to simultaneously create primers for improved quantification of target genes. We developed MetaFunPrimer, a bioinformatic pipeline, to design primers for numerous genes of interest. This tool also enables gene target prioritization based on ranking the presence of genes in user-defined references, such as environment-specific metagenomes. Given inputs of protein and nucleotide sequences for gene targets of interest and an accompanying set of reference metagenomes or genomes, MetaFunPrimer generates primers for ranked genes of interest. To demonstrate the usage and benefits of MetaFunPrimer, a total of 78 primer pairs were designed to target observed ammonia monooxygenase subunit A (amoA) genes of ammonia-oxidizing bacteria (AOB) in 1,550 publicly available soil metagenomes. We demonstrate computationally that these amoA-AOB primers can cover 94% of the amoA-AOB genes observed in the 1,550 soil metagenomes compared with a 49% estimated coverage by previously published primers. Finally, we verified the utility of these primer sets in incubation experiments that used long-term nitrogen fertilized or unfertilized soils. High-throughput quantitative PCR (qPCR) results and statistical analyses showed significant differences in relative quantification patterns between the two soils, and subsequent absolute quantifications also confirmed that target genes enumerated by six selected primer pairs were significantly more abundant in the nitrogen-fertilized soils. This new tool gives microbial ecologists a new approach to assess functional gene abundance and related microbial community dynamics quickly and affordably. IMPORTANCE Amplification-based gene characterization allows for sensitive and specific quantification of functional genes. There is often a large diversity of genes represented for functional gene groups, and multiple primers may be necessary to target associated genes. Current primer design tools are limited to designing primers for only a few genes of interest. MetaFunPrimer allows for high-throughput primer design for various genes of interest and also allows for ranking gene targets by their presence and abundance in environmental data sets. Primers designed by this tool improve the characterization and quantification of functional genes in broad gene amplification platforms and can be powerful with high-throughput qPCR approaches.

15.
Fungal Biol ; 125(10): 776-784, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34537173

RESUMO

The mannosyltransferase Alg9 plays a vital role in N-linked protein glycosylation in Saccharomyces cerevisiae, but its function in most filamentous fungi is not clear. The present study characterized BbAlg9 (an ortholog of S. cerevisiae Alg9) in Beauveria bassiana to determine the roles of N-mannosyltransferase in biological control potential of the filamentous entomopathogenic fungus. The disruption of BbAlg9 led to slower fungal growth in media with various nutrition compositions. The conidiation of ΔBbAlg9 was less than that of the wild type from the third to the fifth day but showed no significant difference on the sixth day, suggesting that BbAlg9 affects the development of conidia rather than conidial yield of late stage. ΔBbAlg9 showed defects in conidial germination, multiple stress tolerances and the yield of blastospores, with altered size and density, and virulence in hosts infected via the immersion and injection methods. The deletion of BbAlg9 resulted in defects in cell wall integrity, including increased mannoprotein and glucan content and decreased chitin content, which were accompanied by transcriptional activation or suppression of genes related to cell wall component biosynthesis. Notably, deletion of the N-mannosyltransferase BbAlg9 altered the transcription levels of O-mannosyltransferase genes (Pmt and Ktr family). These data show that BbAlg9 is involved in the fungal development, conidial stress tolerance, cell wall integrity and virulence of B. bassiana.

16.
Oxid Med Cell Longev ; 2021: 5530907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484563

RESUMO

Although taurine is known to exert an antihypertensive effect, it is unclear whether it is involved in the mechanism for hypertension-related target organ injury. To reveal the role of endogenous taurine in renal injury formation during salt-sensitive hypertension and clarify its mechanisms, both salt-sensitive Dahl rats and salt-resistant SS-13BN rats were fed a high-salt diet (8% NaCl) and given 2% taurine for 6 weeks. Rat systolic blood pressure (SBP) was measured by the tail-cuff method and artery catheterization. Kidney ultrastructure was observed under an electron microscope. Taurine content and mRNA and protein levels of taurine synthases, cysteine dioxygenase type 1 (CDO1) and cysteine sulfinic acid decarboxylase (CSAD), were decreased in Dahl rats fed a high-salt diet. However, taurine supplementation and the resulting increase in renal taurine content reduced the increased SBP and improved renal function and structural damage in high-salt diet-fed Dahl rats. In contrast, taurine did not affect SS-13BN SBP and renal function and structure. Taurine intervention increased the renal H2S content and enhanced cystathionine-ß-synthase (CBS) expression and activity in Dahl rats fed a high-salt diet. Taurine reduced the renin, angiotensin II, and aldosterone contents and the levels of oxidative stress indices in Dahl rat renal tissues but increased antioxidant capacity, antioxidant enzyme activity, and protein expression. However, taurine failed to achieve this effect in the renal tissue of SS-13BN rats fed a high-salt diet. Pretreatment with the CBS inhibitor HA or renal CBS knockdown inhibited H2S generation and subsequently blocked the effect of taurine on renin, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) levels in high-salt-stimulated Dahl renal slices. In conclusion, the downregulation of endogenous taurine production resulted in a decrease in the renal CBS/H2S pathway. This decrease subsequently promoted renin-angiotensin-aldosterone system (RAAS) activation and oxidative stress in the kidney, ultimately contributing to renal injury in salt-sensitive Dahl rats.

17.
Cardiol J ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34490603

RESUMO

BACKGROUND: High D-dimer (DD) is associated with short-term adverse outcomes in patients with acute coronary syndrome (ACS). In ACS patients who underwent percutaneous coronary intervention (PCI), however, the value of DD (or combined with neutrophil to lymphocyte ratio [NLR]) to predict long-term major adverse cardiovascular events (MACEs) has not been fully evaluated. METHODS: Patients diagnosed with ACS and receiving PCI were included. The primary outcome was MACEs. Cox proportional hazards regression and logistic regression was used to illustrate the relationship between clinical risk factors, biomarkers and MACEs. Survival models were developed based on significant factors and evaluated by the Concordance-index (C-index). RESULTS: The final study cohort was comprised of 650 patients (median age, 64 years; 474 males), including 98 (15%) with MACEs during a median follow-up period of 40 months. According to the cut-off value of DD and NLR, the patients were separated into four groups: high DD or nonhigh DD with high or nonhigh NLR. After adjusting for confounding variables, DD (adjusted hazard ratio [aHR]: 2.39, 95% confidence interval [CI]: 1.52-3.76) and NLR (aHR: 2.71, 95% CI: 1.78-4.11) were independently associated with long-term MACEs. Moreover, patients with both high DD and NLR had a significantly higher risk in MACEs when considering patients with nonhigh DD and NLR as reference (aHR: 6.19, 95% CI: 3.30-11.61). The area under curve (AUC) increased and reached 0.70 in differentiating long-term MACEs when DD and NLR were combined, and survival models incorporating the two exhibited a stronger predictive power (C-index: 0.75). CONCLUSIONS: D-dimer (or combined with NLR) can be used to predict long-term MACEs in ACS patients undergoing PCI.

18.
J Pathol Clin Res ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480529

RESUMO

Myeloproliferative neoplasms (MPNs) are characterized by upregulation of proinflammatory cytokines and immune dysregulation, which provide a reasonable basis for immunotherapy in patients. Megakaryocytes are crucial in the pathogenesis of primary myelofibrosis (PMF), the most clinically aggressive subtype of MPN. In this study, we aimed to explore PD-L1 (programmed death-ligand 1) expression in megakaryocytes and its clinical implications in PMF. We analyzed PD-L1 expression on megakaryocytes in PMF patients by immunohistochemistry and correlated the results with clinicopathological features and molecular aberrations. We employed a two-tier grading system considering both the proportion of cells positively stained and the intensity of staining. Among the 85 PMF patients, 41 (48%) showed positive PD-L1 expression on megakaryocytes with the immune-reactive score ranging from 1 to 12. PD-L1 expression correlated closely with higher white blood cell count (p = 0.045), overt myelofibrosis (p = 0.010), JAK2V617F mutation (p = 0.011), and high-molecular risk mutations (p = 0.045), leading to less favorable overall survival in these patients (hazard ratio 0.341, 95% CI 0.135-0.863, p = 0.023). Our study provides unique insights into the interaction between immunologic and molecular phenotypes in PMF patients. Future work to explore the translational potential of PD-L1 in the clinical setting is needed.

19.
Cell Res ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465913

RESUMO

The outbreak of SARS-CoV-2 (SARS2) has caused a global COVID-19 pandemic. The spike protein of SARS2 (SARS2-S) recognizes host receptors, including ACE2, to initiate viral entry in a complex biomechanical environment. Here, we reveal that tensile force, generated by bending of the host cell membrane, strengthens spike recognition of ACE2 and accelerates the detachment of spike's S1 subunit from the S2 subunit to rapidly prime the viral fusion machinery. Mechanistically, such mechano-activation is fulfilled by force-induced opening and rotation of spike's receptor-binding domain to prolong the bond lifetime of spike/ACE2 binding, up to 4 times longer than that of SARS-S binding with ACE2 under 10 pN force application, and subsequently by force-accelerated S1/S2 detachment which is up to ~103 times faster than that in the no-force condition. Interestingly, the SARS2-S D614G mutant, a more infectious variant, shows 3-time stronger force-dependent ACE2 binding and 35-time faster force-induced S1/S2 detachment. We also reveal that an anti-S1/S2 non-RBD-blocking antibody that was derived from convalescent COVID-19 patients with potent neutralizing capability can reduce S1/S2 detachment by 3 × 106 times under force. Our study sheds light on the mechano-chemistry of spike activation and on developing a non-RBD-blocking but S1/S2-locking therapeutic strategy to prevent SARS2 invasion.

20.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4139-4144, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467725

RESUMO

The purpose of the research is to study the bioactive constituents of Callicarpa nudiflora. From the 65% ethanol extract of C. nudiflora leaves, ten compounds were isolated by macroporous adsorption resin, Sephadex LH-20, ODS, silica gel, and preparative HPLC. These compounds were identified as callicapene M6(1), sterebin A(2), isomartynoside(3), crenatoside(4), luteolin-7-O-neohesperidoside(5), apigenin-7-O-ß-D-neohesperidoside(6), isoacteoside(7), acteoside(8),(7R)-campneoside I(9), and(7S)-campneoside I(10) on the basis of NMR, HR-ESI-MS, and optical rotation data. Compound 1 was obtained as a new compound. Compounds 2 and 4 were isolated from the genus Callicarpa for the first time. Compounds 9 and 10 were isolated from C. nudiflora for the first time.


Assuntos
Callicarpa , Diterpenos , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Folhas de Planta
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