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We consider Majorana lattices with two-site interactions consisting of a general function of the fermion bilinear. The models are exactly solvable in the limit of a large number of on-site fermions. The four-site chain exhibits a quantum phase transition controlled by the hopping parameters and manifests itself in a discontinuous entanglement entropy, obtained by constraining the one-sided modular Hamiltonian. Inspired by recent work within the AdS/CFT correspondence, we identify transitions between types of von Neumann operator algebras throughout the phase diagram. We find transitions of the form II_{1}âIIIâI_{∞} that reduce to II_{1}âI_{∞} in the strongly interacting limit, where they connect nonfactorized and factorized ground states. Our results provide novel realizations of such transitions in a controlled many-body model.
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Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested caseâcontrol study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.
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Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.
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WRN helicase is a critical protein involved in maintaining genomic stability, utilizing ATP hydrolysis to dissolve DNA secondary structures. It has been identified as a promising synthetic lethal target for microsatellite instable (MSI) cancers. However, few WRN helicase inhibitors have been discovered, and their potential binding sites remain unexplored. In this study, we analyzed potential binding sites for WRN inhibitors and focused on the ATP-binding site for screening new inhibitors. Through molecular dynamics-enhanced virtual screening, we identified two compounds, h6 and h15, which effectively inhibited WRN's helicase and ATPase activity in vitro. Importantly, these compounds selectively targeted WRN's ATPase activity, setting them apart from other non-homologous proteins with ATPase activity. In comparison to the homologous protein BLM, h6 exhibits some degree of selectivity towards WRN. We also investigated the binding mode of these compounds to WRN's ATP-binding sites. These findings offer a promising strategy for discovering new WRN inhibitors and present two novel scaffolds, which might be potential for the development of MSI cancer treatment.
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Trifosfato de Adenosina , Antineoplásicos , Inibidores Enzimáticos , Simulação de Dinâmica Molecular , Helicase da Síndrome de Werner , Trifosfato de Adenosina/química , Sítios de Ligação , Helicase da Síndrome de Werner/antagonistas & inibidores , Helicase da Síndrome de Werner/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/química , Antineoplásicos/farmacologia , Instabilidade de Microssatélites/efeitos dos fármacos , Neoplasias/genética , HumanosRESUMO
Pulmonary fibrosis (PF) threatens millions of people worldwide with its irreversible progression. Although the underlying pathogenesis of PF is not fully understood, there is evidence to suggest that the disease can be blocked at various stages. Inhalation therapy has been applied for lung diseases such as asthma and chronic obstructive pulmonary disease, and its application for treating PF is currently under consideration. New techniques in inhalation therapy, such as the application of microparticles and nanoparticles, traditional Chinese medicine monomers, gene therapy, inhibitors, or agonists of signaling pathways, extracellular vesicle interventions, and other specific drugs, are effective in treating PF. However, the safety and effectiveness of these therapeutic techniques are influenced by the properties of inhaled particles, biological and pathological barriers, and the type of inhalation device used. This review provides a comprehensive overview of the pharmacological, pharmaceutical, technical, preclinical, and clinical experimental aspects of novel inhalation therapy for treating PF and focus on therapeutic methods that significantly improve existing technologies or expand the range of drugs that can be administered via inhalation. Although inhalation therapy for PF has some limitations, the advantages are significant, and further research and innovation about new inhalation techniques and drugs are encouraged.
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Asma , Doença Pulmonar Obstrutiva Crônica , Fibrose Pulmonar , Humanos , Fibrose Pulmonar/tratamento farmacológico , Administração por Inalação , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Asma/tratamento farmacológico , Terapia RespiratóriaRESUMO
OBJECTIVE: The purpose of this research was to ascertain the effectiveness of the newly established criteria for classifying IgG4-related disease (IgG4-RD), as applied to a large Chinese cohort in real-world clinical settings. METHODS: Patient data were procured from the digital health records of 4 prominent academic hospitals. The criterion standard for identifying IgG4-RD patients was from a seasoned rheumatologist. The control group consisted of individuals with other ailments such as cancer, other forms of pancreatitis, infectious diseases, and illnesses that mimic IgG4-RD. RESULTS: A total of 605 IgG4-RD patients and 760 mimickers were available for analysis. The 2019 EULAR/ACR criteria have a sensitivity of 69.1% and a specificity of 90.9% in this large Chinese cohort. IgG4-RD had a greater proportion of males (55.89% vs 36.25%, p < 0.001), an older average age at diagnosis (54.91 ± 13.44 vs 48.91 ± 15.71, p < 0.001), more pancreatic (29.59% vs 6.12%, p < 0.001) and salivary gland (63.30% vs 27.50%, p < 0.001) involvement, and a larger number of organ involvement (3.431 ± 2.054 vs 2.062 ± 1.748, p < 0.001) compared with mimickers. CONCLUSIONS: The 2019 EULAR/ACR criteria are effective in classifying IgG4-RD in Chinese patients, demonstrating high specificity and moderate sensitivity.
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Doença Relacionada a Imunoglobulina G4 , Pancreatite , Humanos , Masculino , Povo Asiático , China , Doença Relacionada a Imunoglobulina G4/diagnóstico , Pancreatite/diagnóstico , Glândulas Salivares , FemininoRESUMO
Mosquitoes (Diptera: Culicidae) are one of the most studied groups of arthropods worldwide due to their high transmission capacity for pathogens, including viruses and parasites. During June to October 2022, the prevalence of mosquito species in 12 intensive pig farms from 12 representative administrative regions in Hunan province of China was investigated using traps with ultraviolet light. All collected mosquitoes were counted and identified to species according to morphological and molecular methods. A total of 4,443 mosquito specimens were collected in the pig farms, and they represented one family, four genera and nine species. Culex pipiens pipiens (24%) was the most common mosquito species, followed by Armigeres subalbatus (23.4%) and Culex tritaeniorhynchus (20.6%). Phylogenetic analyses based on mitochondrial cox1 sequences revealed all mosquito species from present study grouping into distinct monophyletic groups corresponding to nine known mosquito species with strongly supported. The results of the present investigation have implications for the ongoing control of mosquito infestation in pig farms in Hunan province, China. This is the first report of mosquito populations in intensive pig farms in Hunan province, China.
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Culicidae , Filogenia , Animais , China/epidemiologia , Culicidae/fisiologia , Culicidae/classificação , Suínos , Fazendas , Criação de Animais Domésticos , Sus scrofaRESUMO
Objective: This study aims to investigate the agreement between the Huaxi Emotional Index (HEI) and the Nurses' Global Assessment of Suicide Risk (NGASR) in assessing high suicide risk and to explore the predictive value of HEI in identifying high suicide risk among patients with depression. Methods: Convenience sampling was used and 386 inpatients with depression were included in this cross-sectional study. All patients were admitted to the Mental Health Center, West China Hospital between June and December 2023. The inclusion criteria were as follows, a diagnosis of depression according to the International Classification of Diseases, Tenth Revision (ICD-10), age over 18, and completion of both NGASR and HEI assessments. According to the exclusion criteria, depression patients who had other comorbid mental disorders or those who had severe cognitive impairments and were unable to communicate effectively were excluded. The study was approved by the Biomedical Ethics Review Committee of West China Hospital (Approval No. 647, 2021). Demographic data such as age, sex, ethnicity, marital status, and educational attainment were collected using a self-designed questionnaire. Both the HEI and NGASR were applied to evaluate the patients. We conducted statistical analyses with SPSS 27, employing Spearman's rank correlation for correlation analysis, Kappa tests for consistency between the two instruments, and receiver operating characteristic (ROC) curves for evaluating the predictive performance of HEI scores for high suicide risk, with the optimal HEI cutoff value determined on the basis of the Youden Index. Results: The study included 386 depression inpatients with an average age of 32 years and an average length-of-stay of 14 days. Of these participants, 252 were female (65.3%) and 134 were male (34.7%). Regarding ethnicity, most of the participants were Han Chinese (89.4%), Tibetans accounted for 7.3%, and other minorities, 3.3%. Regarding marital status, 51.3% of the participants were married, 41.2% single, 6.5% divorced, and 1.0% widowed. Regarding educational attainment, 26.2% had an undergraduate or graduate education, 20.7% had junior college education, 24.8% had high school or secondary technical school education, and 28.2% had middle school education or less. The NGASR identified 57.3% of the participants as being at high suicide risk, while the HEI identified 53.6% as having severe emotional distress. There was a moderate agreement between the HEI and the NGASR scores, with a Kappa value of 0.518 ( P<0.001), indicating statistically significant differences. At an HEI score of 17, the Youden Index peaked at 0.52, predicting high suicide risk with a specificity of 76.36%, a sensitivity of 76.02%, and an area under the ROC curve of 0.829 (95% CI: 0.787-0.871), demonstrating statistically significant differences. Conclusion: HEI and NGASR demonstrate moderate agreement in assessing high suicide risk among depression patients. The HEI questionnaire effectively predicts high suicide risk in patients with depression, with 17 being the optimal cutoff value for assessing high suicide risk.
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Depressão , Pacientes Internados , Suicídio , Humanos , Feminino , Masculino , Depressão/diagnóstico , Depressão/etiologia , Estudos Transversais , Inquéritos e Questionários , Suicídio/psicologia , Suicídio/estatística & dados numéricos , China/epidemiologia , Medição de Risco/métodos , Emoções , Adulto , Fatores de Risco , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
The abnormal immunomodulatory functions of mesenchymal stem cells (MSCs) have been implicated in the development of immune thrombocytopenia (ITP). Recent studies have suggested important effects of complement on immune cell function. However, whether complement modulates bone marrow MSCs function in ITP is poorly defined. Tacrolimus has recently been applied to the treatment of autoimmune diseases. Here, we explored whether impaired ITP-MSCs could be targeted by tacrolimus. Our results showed that the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome was activated in ITP MSCs with complement deposition (MSCs-C+ ) and initiated caspase-1-dependent pyroptosis. Transcriptome sequencing results showed abnormal fatty acid metabolism in MSCs-C+ . Enhanced fatty acid ß-oxidation and reactive oxygen species production activated the NLRP3 inflammasome. Adipocytes derived from MSCs-C+ secreted less adiponectin. Adiponectin promoted the differentiation of megakaryocytes and inhibited the destruction of platelets. Tacrolimus inhibited NLRP3 inflammasome activation and MSCs-C+ pyroptosis in vitro and in vivo. Tacrolimus plus danazol elicited a higher sustained response than danazol monotherapy in corticosteroid-resistant patients with ITP. Our findings demonstrate that the activation of the NLRP3 inflammasome in ITP MSCs mediated by complement could be inhibited by tacrolimus, which might be a potential new therapy for ITP.
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Células-Tronco Mesenquimais , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Tacrolimo/farmacologia , Proteínas NLR/metabolismo , Púrpura Trombocitopênica Idiopática/metabolismo , Adiponectina/metabolismo , Adiponectina/farmacologia , Piroptose , Complemento C3/metabolismo , Complemento C3/farmacologia , Danazol , Domínio Pirina , Células-Tronco Mesenquimais/metabolismo , Trombocitopenia/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos/farmacologiaRESUMO
Atherosclerosis is a risk factor for various cardiovascular diseases, and is linked to high rates of morbidity and mortality across the globe. Although numerous complex processes are involved in the development and progression of atherosclerosis, the exact mechanisms behind its pathogenesis remain unclear. Inflammation and endothelial cell damage exert a lasting effect on atherosclerosis, causing lipid and fibrous tissue accumulation in the intima of the artery to form plaques, and subsequently promoting atherosclerosis. Nod-like receptor protein 3 (NLRP3) inflammatory corpuscle is thought to be the link between lipid metabolism and inflammation. Long Potassium outflow is a vital activator of NLRP3, with a simultaneous effect as a start-up and adjustment. The majority of existing drugs for atherosclerosis targeting the NLRP3 signaling pathway target IL-1, whereas drugs targeting the critical link of potassium efflux are relatively new. This review discusses the NLRP3 inflammatory corpuscle as a critical regulator of the immunological inflammatory pathway in atherosclerosis. Moreover, current knowledge on NLRP3 inflammatory corpuscle start and activation pathways were integrated, emphasizing potassium-involved outflow-related proteins. We highlight potential treatment approaches for NLRP3 inflammatory corpuscle pathways, specifically targeting potassium outflow channels of targeted drugs. Collectively, these insights indicate that targeting the NLRP3 inflammatory corpuscle is a vital anti-inflammatory therapy for treating atherosclerosis.
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NLRP3 inflammasome activation plays an important role in the development of pancreatic fibrosis. However, it is unclear whether the activation of the NLRP3 inflammasome is directly involved in the activation of Pancreatic stellate cells (PSCs). The aim of this study was to investigate the role and mechanism of the NLRP3 inflammasome in the activation of PSCs. In vivo, a rat model of chronic pancreatitis (CP) was induced by intravenous injection of dibutyltin dichloride (DBTC). In vitro, rat primary PSCs were isolated from pancreatic tissues and incubated with the NLRP3 inflammasome activator LPS, the NLRP3 inhibitor MCC950, or NLRP3 siRNA. The results showed that the expression of NLRP3, pro-Caspase-1, Caspase-1 and IL-18 was increased in the rat model of CP and during PSCs activation. LPS increased the protein levels of NLRP3, ASC, Caspase-1, IL-1ß and IL-18 accompanied by the upregulation of α-SMA, Col I and FN expression. Moreover, MCC950 or NLPR3 siRNA decreased the expression of α-SMA, Col I, FN, TGF-ß1 and p-Smad3. Furthermore, MCC950 reversed the LPS-induced upregulation of α-SMA, FN and Col â expression in PSCs. This study revealed that the NLRP3 inflammasome is directly involved in the activation of PSCs in vivo and in vitro. Inhibiting NLRP3 suppresses the activation of PSCs through the TGF-ß1/Smad3 pathway.
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Fibrose/metabolismo , Inflamassomos/metabolismo , Lipopolissacarídeos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células Estreladas do Pâncreas/metabolismo , Animais , Caspase 1/metabolismo , Células Cultivadas , Fibrose/induzido quimicamente , Ratos Wistar , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Ultraviolet (UV)/chlorine draws increasing attention for the abatement of recalcitrant organic pollutants. Herein, it was found that TiO2 would significantly promote the degradation of dimethyl phthalate (DMP) in the UV/chlorine system (from 19 to 84%). Hydroxyl radicals (HOâ¢) and chlorine radicals (Clâ¢) were the dominant reactive species for DMP degradation in the UV/chlorine/TiO2 system. Chlorine decayed much faster in UV/chlorine/TiO2 compared with UV/chlorine, which is possibly because photogenerated electrons (ecb-) and superoxide radicals (O2â¢-) have high reactivity with chlorine. As a result, the recombination of photogenerated holes (hvb+) and ecb- was inhibited and the accumulation of HO⢠and Cl⢠was facilitated. A kinetic model was established to simulate the reaction process, and it was found that the concentrations of HO⢠and Cl⢠were several times to dozens of times higher in UV/chlorine/TiO2 than that in UV/chlorine. The contributions of HO⢠and Cl⢠to DMP degradation were 70.3 and 29.7% by model simulation, respectively, and were close to the probe experiment result. In the UV/chlorine/TiO2 system, the degradation of DMP did not follow pseudo-first-order kinetics but the degradation of benzoate fitted well with pseudo-first-order kinetics. This phenomenon was elucidated by the structure of the pollutant and TiO2 and further tested by calculating the adsorption energy (Eads)/binding energy (Eb) with density functional theory. Due to faster decay of chlorine, lower amounts of disinfection byproducts formed in UV/chlorine/TiO2 compared with UV/chlorine. Adding TiO2 into the UV/chlorine system can promote the degradation of recalcitrant organic pollutants in an aqueous environment.
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Poluentes Químicos da Água , Purificação da Água , Cloro , Cinética , Oxirredução , Titânio , Raios Ultravioleta , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) significantly increases the mortality of patients with COPD. Guidelines have recommended systemic glucocorticoid as a regular treatment. Recently, evidence has shown that systemic glucocorticoid cannot be a benefit to all of the patients with AECOPD. Thus, the problem that how the clinicians can screen the patients who can benefit from systemic glucocorticoid needs to be solved urgently. This study is aimed to detect the metabolic biomarkers and metabolic pathways that are related to the efficacy of systemic glucocorticoid and contribute to the precise treatment of COPD. METHODS AND DESIGN: In this study, we will utilize ultraperformance liquid chromatography/mass spectrometry (LC-MS) and gas chromatography/mass spectrometry (GC-MS) methods for the analysis of the metabolites in AECOPD patients and compare the metabolites profiles between patients with systemic glucocorticoid treatment success group and treatment failure group. We aim to detect the metabolic biomarkers and metabolic pathways that are related to the efficacy of systemic glucocorticoid and contribute to the precise treatment of COPD. DISCUSSION: Previous studies have found that plasma metabolome changed significantly after dexamethasone treatment in healthy participants. Furthermore, inter-person variability was high and remained uninfluenced by treatment, suggesting the potential of metabolomics for predicting the efficacy and side effects of systemic glucocorticoid. Therefore, we hypothesized that metabolome changes in patients with AECOPD may be associated with the efficacy of systemic glucocorticoid. Trial registration Clinicaltrials.gov registration number NCT04710849. Registered 15 January 2021, https://clinicaltrials.gov/ct2/show/NCT04710849 .
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Glucocorticoides/farmacologia , Metaboloma , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Progressão da Doença , Glucocorticoides/administração & dosagem , Humanos , Estudos Prospectivos , Projetos de Pesquisa , Resultado do TratamentoRESUMO
A simple, rapid, and selective ultra-performance liquid chromatography-tandem mass spectrometry method for determination of l-carnitine (LC) and acetyl-l-carnitine (ALC) in human serum was developed. Acetyl-l-carnitine-d3 (ALC-d3 ) was selected as internal standard (IS). After protein precipitation with acetonitrile-water (1 mL, 2:1, v/v), the analytes and IS were separated on a 2.5-µm XSelect HSS T3 C18 column by gradient elution with methanol-water (containing 0.01% ammonia water) as the mobile phase at a flow rate of 0.2 mL/min. Analytes were detected with multiple reaction monitoring using a positive scan mode with electrospray ionization. Good linearity (R2 > 0.999) was observed in the concentration range for LC and ALC. The inter- and intra-day values of relative error were -10.4% to 10.0% with CVs less than 9.84%. The average recoveries of the two analytes were 91.29%-98.23%. Blood samples containing LC and ALC were stable under various storage conditions. Normal, haemolytic, and hyperlipidaemic serum had no significant effect on the quantification of LC and ALC. This method was successfully applied to study the concentrations of endogenous LC and ALC in the serum of patients with first-episode depression.
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Carnitina/sangue , Cromatografia Líquida de Alta Pressão/métodos , Depressão/sangue , Espectrometria de Massas em Tandem/métodos , Acetilcarnitina/sangue , Humanos , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Double-chambered left ventricle (DCLV) is a rare congenital heart disease. A hypertrophic muscle bundle in the left ventricle may cause varying degrees of obstruction in the middle of the left ventricle, resulting in different clinical symptoms. Here, we report a patient with a history of repeated chest tightness who was misdiagnosed with coronary heart disease and ventricular aneurysm. After repeated ultrasound examinations, the patient was eventually diagnosed with DCLV, which was confirmed by magnetic resonance imaging and coronary angiography. This case highlights the necessity to improve the accuracy of DCLV diagnosis via echocardiogram.
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Aneurisma Cardíaco , Cardiopatias Congênitas , Adulto , Ecocardiografia , Cardiopatias Congênitas/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: The northeastern part of the Qinghai-Tibet Plateau (QTP) presents a high number of plateau loach species. As one of the three major groups of fishes distributed on the QTP, plateau loach has high ecological value. However, the taxonomy and systematics of these fish are still controversial, and a large number of new species have been reported. The reason for this phenomenon is that the degree of morphological variation is low, the phylogenetic information provided by morphological and anatomical features used for species identification is relatively poor, and many cryptic species are observed. Based on the high-density sampling points from the biodiversity hotspots surveyed, this study aims to evaluate the biodiversity of plateau loach in the northeastern part of the QTP and reveal the hidden diversity by comparing morphological species with molecular operational taxonomic units (MOTUs). RESULTS: After careful identification and comparison of the morphology and DNA barcoding of 1630 specimens, 22 species were identified, with 20 considered valid local species and two identified as new species that had not been previously described. Based on the combination of morphological and molecular methods, a total of 24 native species were found, two of which were cryptic species: Triplophysa robusta sp1 and Triplophysa minxianensis sp1. Fourteen of the 24 species form clusters of barcodes that allow them to be reliably identified. The remaining cases involved 10 closely related species, including rapidly differentiated species and species that seemed to have experienced incomplete lineage sorting or showed introgressions. CONCLUSIONS: The results highlight the need to combine traditional taxonomies with molecular methods to correctly identify species, especially closely related species, such as the plateau loach. This study provides a basis for protecting the biodiversity of plateau loach.
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Cipriniformes , Código de Barras de DNA Taxonômico , Filogenia , Animais , Cipriniformes/genética , DNA , TibetRESUMO
Insects can produce various antimicrobial peptides (AMPs) upon immune stimulation. One class of AMPs are characterized by their high proline content in certain fragments. They are generally called proline-rich antimicrobial peptides (PrAMPs). We previously reported the characterization of Spodoptera litura lebocin-1 (SlLeb-1), a PrAMP proprotein. Preliminary studies with synthetic polypeptides showed that among the four deductive active fragments, the C-terminal fragment SlLeb-1 (124-158) showed strong antibacterial activities. Here, we further characterized the antibacterial and antifungal activities of 124-158 and its four subfragments: 124-155, 124-149, 127-158, and 135-158. Only 124-158 and 127-158 could agglutinate bacteria, while 124-158 and four subfragments all could agglutinate Beauveria bassiana spores. Confocal microscopy showed that fluorescent peptides were located on the microbial surface. Fragment 135-158 lost activity completely against Escherichia coli and Staphylococcus aureus, and partially against Bacillus subtilis. Only 124-149 showed low activity against Serratia marcescens. Negative staining, transmission, and scanning electron microscopy of 124-158 treated bacteria showed different morphologies. Flow cytometry analysis of S. aureus showed that 124-158 and four subfragments changed bacterial subpopulations and caused an increase of DNA content. These results indicate that active fragments of SlLeb-1 may have diverse antimicrobial effects against different microbes. This study may provide an insight into the development of novel antimicrobial agents.
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Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas de Insetos/farmacologia , Spodoptera/química , Animais , Peptídeos Catiônicos Antimicrobianos/química , Bacillus subtilis/efeitos dos fármacos , Beauveria/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Proteínas de Insetos/química , Serratia marcescens/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
BACKGROUND: Stevia has been proposed as a potential antidiabetic sweetener, mainly based on inconsistent results from stevioside or the plant extract, yet lacking relative experimental evidence from individual steviol glycosides (SGs) and their metabolites. RESULTS: The results systematically revealed that the typical SGs and their final metabolite (steviol) presented an antidiabetic effect on streptozotocin (STZ) diabetic mice in all assayed antidiabetic aspects. In general, the performance strength of the samples followed the sequence steviol > steviol glucosyl ester > steviolbioside > rubusoside > stevioside > rebaudioside A, which is opposite to their sweetness strength order, and generally in accordance with the glucosyl group numbers in their molecules. This may imply that the antidiabetic effect of the SGs might be achieved through steviol, which presented antidiabetic performance similar to that of metformin with a dose of 1/20 that of metformin. Moreover, the 18 F-fluorodeoxyglucose traced micro-PET experiment revealed that stevioside and steviol could increase the uptake of glucose in the myocardium and brain of the diabetic mice within 60 min, and decrease the accumulation of glucose in the liver and kidney. CONCLUSIONS: The SGs and steviol presented an antidiabetic effect on STZ diabetic mice in all assayed aspects, with an induction time to start the effect of the SGs. Stevioside and steviol could increase uptake of glucose in the myocardium and brain of the diabetic mice, and decrease accumulation of glucose in the liver and kidney. The performance strength of the SGs is generally in accordance with glucosyl group numbers in their molecules.
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Diabetes Mellitus Experimental/tratamento farmacológico , Diterpenos do Tipo Caurano/administração & dosagem , Glucosídeos/administração & dosagem , Hipoglicemiantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Stevia/química , Animais , Diabetes Mellitus Experimental/metabolismo , Diterpenos do Tipo Caurano/metabolismo , Glucose/metabolismo , Glucosídeos/metabolismo , Humanos , Hipoglicemiantes/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/metabolismo , Folhas de Planta/química , EstreptozocinaRESUMO
Anthracnose is a major leaf disease in tea plant induced by Colletotrichum, which has led to substantial losses in yield and quality of tea. The molecular mechanism with regards to responses or resistance to anthracnose in tea remains unclear. A de novo transcriptome assembly dataset was generated from healthy and anthracnose-infected leaves on tea cultivars "Longjing-43" (LJ43) and "Zhenong-139" (ZN139), with 381.52 million pair-end reads, encompassing 47.78 billion bases. The unigenes were annotated versus Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), National Center for Biotechnology Information (NCBI) non-redundant protein sequences (Nr), evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) and Swiss-prot. The number of differential expression genes (DEGs) detected between healthy and infected leaves was 1621 in LJ43 and 3089 in ZN139. The GO and KEGG enrichment analysis revealed that the DEGs were highly enriched in catalytic activity, oxidation-reduction, cell-wall reinforcement, plant hormone signal transduction and plant-pathogen interaction. Further studies by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and high-performance liquid chromatography (HPLC) showed that expression of genes involved in endogenous salicylic acid biosynthesis and also accumulation of foliar salicylic acid are involved in the response of tea plant to anthracnose infection. This study firstly provided novel insight in salicylic acid acting as a key compound in the responses of tea plant to anthracnose disease. The transcriptome dataset in this study will facilitate to profile gene expression and metabolic networks associated with tea plant immunity against anthracnose.
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Camellia sinensis/genética , Colletotrichum/patogenicidade , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Camellia sinensis/metabolismo , Camellia sinensis/microbiologia , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Folhas de Planta/genética , Proteínas de Plantas/genética , Ácido Salicílico/metabolismoRESUMO
There is epidemiological evidence showing that drinking green tea can lower the risk of esophageal cancer (EC). The effect is mainly attributed to tea polyphenols and their most abundant component, (-)-epigallocatechin-3-gallate (EGCG). The possible mechanisms of tumorigenesis inhibition of EGCG include its suppressive effects on cancer cell proliferation, angiogenesis, DNA methylation, metastasis and oxidant stress. EGCG modulates multiple signal transduction and metabolic signaling pathways involving in EC. A synergistic effect was also observed when EGCG was used in combination with other treatment methods.