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1.
Int J Med Sci ; 21(7): 1366-1377, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818469

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) leads to coronavirus disease-2019 (COVID-19) which can cause severe cardiovascular complications including myocardial injury, arrhythmias, acute coronary syndrome and others. Among these complications, arrhythmias are considered serious and life-threatening. Although arrhythmias have been associated with factors such as direct virus invasion leading to myocardial injury, myocarditis, immune response disorder, cytokine storms, myocardial ischemia/hypoxia, electrolyte abnormalities, intravascular volume imbalances, drug interactions, side effects of COVID-19 vaccines and autonomic nervous system dysfunction, the exact mechanisms of arrhythmic complications in patients with COVID-19 are complex and not well understood. In the present review, the literature was extensively searched to investigate the potential mechanisms of arrhythmias in patients with COVID-19. The aim of the current review is to provide clinicians with a comprehensive foundation for the prevention and treatment of arrhythmias associated with long COVID-19.


Assuntos
Arritmias Cardíacas , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/imunologia , COVID-19/virologia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/virologia , Arritmias Cardíacas/fisiopatologia
2.
Biomacromolecules ; 24(12): 5836-5846, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-37940601

RESUMO

By thermal embedding of the commercially available enzyme Humicola insolens cutinase (HiC), this study successfully enhanced the biodegradability of various polyesters (PBS, PBSA, PCL, PBAT) in seawater, which otherwise show limited environmental degradability. Melt extrusion above the melting temperature was used for embedding HiC in the polyesters. The overall physical properties of the HiC-embedded films remained almost unchanged compared to those of the neat films. In the buffer, embedding HiC allowed rapid polymer degradation into water-soluble hydrolysis products. Biochemical oxygen demand tests showed that the HiC-embedded polyester films exhibited similar or much higher biodegradability than the biodegradable cellulose standard in natural seawater. Thermal embedding of HiC aims to accelerate the biodegradation of plastics that are already biodegradable but have limited environmental biodegradability, potentially reducing their contribution to environmental problems such as marine microplastics.


Assuntos
Plásticos , Poliésteres , Poliésteres/química , Água do Mar , Biodegradação Ambiental
3.
Mar Drugs ; 20(12)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36547897

RESUMO

α-conotoxin AuIB is the only one of the 4/6 type α-conotoxins (α-CTxs) that inhibits the γ-aminobutyric acid receptor B (GABABR)-coupled N-type calcium channel (CaV2.2). To improve its inhibitory activity, a series of variants were synthesized and evaluated according to the structure-activity relationships of 4/7 type α-CTxs targeting GABABR-coupled CaV2.2. Surprisingly, only the substitution of Pro7 with Arg results in a 2-3-fold increase in the inhibition of GABABR-coupled CaV2.2 (IC50 is 0.74 nM); substitutions of position 9-12 with basic or hydrophobic amino acid and the addition of hydrophobic amino acid Leu or Ile at the second loop to mimic 4/7 type α-CTxs all failed to improve the inhibitory activity of AuIB against GABABR-coupled CaV2.2. Interestingly, the most potent form of AuIB[P7R] has disulfide bridges of "1-4, 2-3" (ribbon), which differs from the "1-3, 2-4" (globular) in the isoforms of wildtype AuIB. In addition, AuIB[P7R](globular) displays potent analgesic activity in the acetic acid writhing model and the partial sciatic nerve injury (PNL) model. Our study demonstrated that 4/6 type α-CTxs, with the disulfide bridge connectivity "1-4, 2-3," are also potent inhibitors for GABABR-coupled CaV2.2, exhibiting potent analgesic activity.


Assuntos
Conotoxinas , Receptores Nicotínicos , Aminoácidos , Conotoxinas/química , Analgésicos/farmacologia , Analgésicos/química , Canais de Cálcio Tipo N/metabolismo , Dissulfetos/química , Ácido gama-Aminobutírico , Receptores Nicotínicos/metabolismo
4.
BMC Cancer ; 21(1): 1130, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34670513

RESUMO

BACKGROUND: To aid clinicians strategizing treatment for upper esophageal squamous cell carcinoma (ESCC), this retrospective study investigated associations between primary gross tumor volume (GTVp) and prognosis in patients given surgical resection, radiotherapy, or both resection and radiotherapy. METHODS: The population comprised 568 patients with upper ESCC given definitive treatment, including 238, 216, and 114 who underwent surgery, radiotherapy, or combined radiotherapy and surgery. GTVp as a continuous variable was entered into the multivariate Cox model using penalized splines (P-splines) to determine the optimal cutoff value. Propensity score matching (PSM) was used to adjust imbalanced characteristics among the treatment groups. RESULTS: P-spline regression revealed a dependence of patient outcomes on GTVp, with 30 cm3 being an optimal cut-off for differences in overall and progression-free survival (OS, PFS). GTVp ≥30 cm3 was a negative independent prognostic factor for OS and PFS. PSM analyses confirmed the prognostic value of GTVp. For GTVp < 30 cm3, no significant survival differences were observed among the 3 treatments. For GTVp ≥30 cm3, the worst 5-year OS rate was experienced by those given surgery. The 5-year PFS rate of patients given combined radiotherapy and surgery was significantly better than that of patients given radiotherapy. The surgical complications of patients given the combined treatment were comparable to those who received surgery, but radiation side effects were significantly lower. CONCLUSION: GTVp is prognostic for OS and PFS in upper ESCC. For patients with GTVp ≥30 cm3, radiotherapy plus surgery was more effective than either treatment alone.


Assuntos
Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Terapia Combinada/métodos , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Esofagite/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Intervalo Livre de Progressão , Pontuação de Propensão , Modelos de Riscos Proporcionais , Lesões por Radiação/epidemiologia , Pneumonite por Radiação/epidemiologia , Análise de Regressão , Estudos Retrospectivos
5.
Mar Drugs ; 19(12)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34940704

RESUMO

α-Conotoxins GI and MI belong to the 3/5 subfamily of α-conotoxins and potently inhibit muscular nicotinic acetylcholine receptors (nAChRs). To date, no 3/4- or 3/6-subfamily α-conotoxins have been reported to inhibit muscular nAChRs. In the present study, a series of new 3/4-, 3/6-, and 3/7-subfamily GI and MI variants were synthesized and functionally characterized by modifications of loop2. The results show that the 3/4-subfamily GI variant GI[∆8G]-II and the 3/6-subfamily variants GI[+13A], GI[+13R], and GI[+13K] displayed potent inhibition of muscular nAChRs expressed in Xenopus oocytes, with an IC50 of 45.4-73.4 nM, similar to or slightly lower than that of wild-type GI (42.0 nM). The toxicity of these GI variants in mice appeared to be about a half to a quarter of that of wild-type GI. At the same time, the 3/7-subfamily GI variants showed significantly lower in vitro potency and toxicity. On the other hand, similar to the 3/6-subfamily GI variants, the 3/6-subfamily MI variants MI[+14R] and MI[+14K] were also active after the addition of a basic amino acid, Arg or Lys, in loop2, but the activity was not maintained for the 3/4-subfamily MI variant MI[∆9G]. Interestingly, the disulfide bond connectivity "C1-C4, C2-C3" in the 3/4-subfamily variant GI[∆8G]-II was significantly more potent than the "C1-C3, C2-C4" connectivity found in wild-type GI and MI, suggesting that disulfide bond connectivity is easily affected in the rigid 3/4-subfamily α-conotoxins and that the disulfide bonds significantly impact the variants' function. This work is the first to demonstrate that 3/4- and 3/6-subfamily α-conotoxins potently inhibit muscular nAChRs, expanding our knowledge of α-conotoxins and providing new motifs for their further modifications.


Assuntos
Conotoxinas/farmacologia , Caramujo Conus , Antagonistas Nicotínicos/farmacologia , Animais , Animais não Endogâmicos , Organismos Aquáticos , Conotoxinas/química , Feminino , Concentração Inibidora 50 , Masculino , Camundongos , Antagonistas Nicotínicos/química , Oócitos/efeitos dos fármacos , Ratos , Receptores Nicotínicos/metabolismo , Relação Estrutura-Atividade , Xenopus laevis
6.
Biomacromolecules ; 21(8): 3301-3307, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32678613

RESUMO

Non-biodegradable microplastics have become a global problem. We propose a new enzyme-embedded biodegradable plastic that can be self-biodegraded anytime and anywhere. Proteinase K from Tritirachium album was embedded in poly(l-lactic acid) (PLLA). The PLLA solution-cast film with embedded proteinase K showed weight loss of 78% after 96 h incubation. In addition, PLLA extruded films embedding immobilized proteinase K encapsulated in polyacrylamide were produced at 200 °C and embedded-enzyme degradation was monitored. Immobilized proteinase K embedded in the extruded film maintained its degradation activity and degraded the PLLA film from inside to make small holes and cavities, suggesting that immobilization is a powerful technique to prepare thermoforms with embedded enzymes. The rate of embedded-enzyme degradation was accelerated by dividing the film into smaller pieces, which can be regarded as a model experiment for biodegradation of microplastics. Various biodegradable plastics with specific embedded enzymes will contribute to solve global environmental problems.


Assuntos
Plásticos Biodegradáveis , Temperatura Alta , Biodegradação Ambiental , Endopeptidase K , Hypocreales , Ácido Láctico , Poliésteres
7.
Environ Microbiol ; 16(6): 1579-91, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24148100

RESUMO

Studies focusing on seasonal dynamics of microbial communities in terrestrial and marine environments are common; however, little is known about seasonal dynamics in high-temperature environments. Thus, our objective was to document the seasonal dynamics of both the physicochemical conditions and the microbial communities inhabiting hot springs in Tengchong County, Yunnan Province, China. The PhyloChip microarray detected 4882 operational taxonomic units (OTUs) within 79 bacterial phylum-level groups and 113 OTUs within 20 archaeal phylum-level groups, which are additional 54 bacterial phyla and 11 archaeal phyla to those that were previously described using pyrosequencing. Monsoon samples (June 2011) showed increased concentrations of potassium, total organic carbon, ammonium, calcium, sodium and total nitrogen, and decreased ferrous iron relative to the dry season (January 2011). At the same time, the highly ordered microbial communities present in January gave way to poorly ordered communities in June, characterized by higher richness of Bacteria, including microbes related to mesophiles. These seasonal changes in geochemistry and community structure are likely due to high rainfall influx during the monsoon season and indicate that seasonal dynamics occurs in high-temperature environments experiencing significant changes in seasonal recharge. Thus, geothermal environments are not isolated from the surrounding environment and seasonality affects microbial ecology.


Assuntos
Archaea/genética , Bactérias/genética , Fontes Termais/microbiologia , Microbiologia da Água , China , Genes Arqueais , Genes Bacterianos , Sedimentos Geológicos/microbiologia , Microbiota/genética , Filogenia , RNA Ribossômico 16S/genética , Estações do Ano
8.
Front Med (Lausanne) ; 11: 1401700, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873215

RESUMO

Background: Adenocarcinoma is a common histological subtype of cervical cancer, accounting for 10-15% of all cases. The prognosis of cervical adenocarcinoma with distant organ metastases remains unclear. Therefore, our study aimed to investigate the patterns and prognosis of distant organ metastasis in cervical adenocarcinoma. Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2010 to 2019. Cox regression, Kaplan-Meier, and log-rank analyses were conducted. Results: We observed that adenocarcinoma (AC) of the cervix primarily metastasizes to single organs, with a rate of 73.3%. The lungs are the most common organs of metastasis, followed by the liver and bones. Patients with bone metastases have a median survival period of 12 months, which is slightly longer compared to metastasis in other organs. Distant organ metastasis, age, positive lymph nodes, higher AJCC stages, larger tumor diameter, and higher cell grades are related to poor prognosis (p < 0.001). Furthermore, we have observed that surgical intervention, radiotherapy, and chemotherapy can potentially provide benefits for patients with distant organ metastases. Conclusion: Metastasis is an independent prognostic factor for cervical adenocarcinoma patients. Surgery, radiotherapy, and chemotherapy can provide an overall survival advantage for patients with distant organ metastases.

9.
J Cancer ; 14(10): 1763-1772, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37476184

RESUMO

Background: This study aimed to construct a preoperative model predicting lymph node metastasis (LNM) in IB1-IIA2 stage cervical squamous cell cancer (CSCC) based on hematological indexes. Merhods: Between February 2011 and February 2022, 463 patients with IB1-IIA2 stage CSCC underwent radical resection. Patients were allocated to either a model-development cohort (n=337) or a validation cohort (n=126). The final model was determined by comparing different methods of variable selection, and then its discrimination and calibration metrics were evaluated. A predicted probability of LNM < 5% was defined as low risk. ROC curves were used to define high risk. Results: Age, lactate dehydrogenase level, FIGO stage, squamous cell carcinoma antigen, cancer antigen 125, and cancer antigen 199 were identified as critical factors for the construction of the model. The model demonstrated good discrimination and calibration (concordance index, 0.761; 95% confidence interval, 0.666-0.884). In the validation cohort the discrimination accuracy was 0.821 (95% confidence interval, 0.714 - 0.927). In the model-development cohort, 11.9% were classified as low risk with a negative predictive value of 95.0%, and 24.9% were classified as high risk with a positive predictive value of 39.3%. Conclusion: A predictive model was developed and validated for LNM in IB1-IIA2 stage CSCC. The model will assist physicians in appraising the risk of LNM in preoperative patients and could aid in patient counseling and individualized clinical decision-making.

10.
Front Oncol ; 13: 1059539, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124485

RESUMO

Background: The study aimed to develop a nomogram model to predict overall survival (OS) and construct a risk stratification system of upper thoracic esophageal squamous cell carcinoma (ESCC). Methods: Newly diagnosed 568 patients with upper ESCC at Fujian Medical University Cancer Hospital were taken as a training cohort, and additional 155 patients with upper ESCC from Sichuan Cancer Hospital Institute were used as a validation cohort. A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS. The predictive power of nomogram model was evaluated by using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). Results: In this study, multivariate analysis revealed that gender, clinical T stage, clinical N stage and primary gross tumor volume were independent prognostic factors for OS in the training cohort. The nomogram based on these factors presented favorable prognostic efficacy in the both training and validation cohorts, with concordance statistics (C-index) of 0.622, 0.713, and area under the curve (AUC) value of 0.709, 0.739, respectively, which appeared superior to those of the American Joint Committee on Cancer (AJCC) staging system. Additionally, net reclassification index (NRI) and integrated discrimination improvement (IDI) of the nomogram presented better discrimination ability to predict survival than those of AJCC staging. Furthermore, decision curve analysis (DCA) of the nomogram exhibited greater clinical performance than that of AJCC staging. Finally, the nomogram fairly distinguished the OS rates among low, moderate, and high risk groups, whereas the OS curves of clinical stage could not be well separated among clinical AJCC stage. Conclusion: We built an effective nomogram model for predicting OS of upper ESCC, which may improve clinicians' abilities to predict individualized survival and facilitate to further stratify the management of patients at risk.

11.
Oncol Lett ; 26(5): 482, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37818132

RESUMO

The aim of the present study was to evaluate the association between serum lactate dehydrogenase (LDH) and the risk of lymph node metastasis (LNM) in the International Federation of Gynecology and Obstetrics (FIGO) 2009 cervical cancer (CC) stages IB1-IIA2. All patient medical records with FIGO 2009 stage IB1-IIA2 CC between January 2012 and January 2022 were analyzed retrospectively. The association between serum LDH and LNM was assessed using uni- and multivariate logistic regression analyses, subgroup analyses and P-splines. The present study included 586 patients, 91 (15.5%) of whom had LNM. Patients with an elevated LDH level were more likely to have a deep stromal invasion, lymph-vascular space invasion, LNM and to be of an older age. Multivariate logistic regression revealed a significant association between LNM and LDH levels. After adjusting for age, FIGO stage, tumor markers and risk factors according to the Sedlis criteria, patients in the highest LDH quartile had an increased risk of LNM compared with those in the lowest LDH quartile (odds ratio, 3.5; 95% CI, 1.57-7.81). Furthermore, P-spline regression revealed a dependence of LNM on LDH. The predictive value of LDH level remained significant in the subgroup analysis. The present study suggested that a higher LDH level was independently associated with CC and LNM, and that LDH level may serve as a potential tumor marker and treatment-related indicator.

12.
J Cancer ; 14(6): 1039-1048, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37151386

RESUMO

Background: This retrospective review of patients with upper thoracic esophageal squamous cell carcinoma (ESCC) analyzed the prognostic value of age, as a continuous variable, and offered insight into treatment options. Methods: 568 upper ESCC patients underwent radical therapy between 2004 and 2016. Age as a continuous variable was entered into the Cox regression model with penalized spline (P-spline) analysis to investigate a correlation between age and survival outcomes. Results: Before adjustment, P-spline regression revealed U-shaped survival curves. Sixty years was the optimal cut-off age for differences in overall and progression-free survival (OS, PFS). The cohort was divided into age groups ≤ 50, 51-69, and ≥ 70 years. Multivariate analyses showed no significant differences in either PFS or OS for patients aged ≤ 50 and 51-69 years. After adjusting for covariates, P-spline regression showed that the risk of mortality and disease progression increased with age, and ≥ 70 years was an unfavorable independent prognostic factor. For age ≥ 70 years, the OS and PFS associated with non-surgery was comparable to that of surgery. For patients younger, the OS and PFS of patients given surgery was significantly better than that of patients given non-surgery. Conclusion: Age was an independent prognostic factor for upper ESCC. Patients ≥ 70 years achieved no significant survival benefit from surgery, but for those younger than 70 years surgery was the preferred treatment option.

13.
Microbiol Spectr ; 10(6): e0319122, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36301115

RESUMO

Dimethylsulfoniopropionate (DMSP) is an abundant organic compound in marine surface water and source of dimethyl sulfide (DMS), the largest natural sulfur source to the upper atmosphere. Marine bacteria either mineralize DMSP through the demethylation pathway or transform it to DMS through the cleavage pathway. Factors that regulate which pathway is utilized are not fully understood. In chemostat experiments, the marine Roseobacter Ruegeria pomeroyi DSS-3 was exposed to oxidative stress either during growth with H2O2 or by mutation of the gene encoding catalase. Oxidative stress reduced expression of the genes in the demethylation pathway and increased expression of those encoding the cleavage pathway. These results are contrary to the sulfur demand hypothesis, which theorizes that DMSP metabolism is driven by sulfur requirements of bacterial cells. Instead, we find strong evidence consistent with oxidative stress control over the switch in DMSP metabolism from demethylation to DMS production in an ecologically relevant marine bacterium. IMPORTANCE Dimethylsulfoniopropionate (DMSP) is the most abundant low-molecular-weight organic compound in marine surface water and source of dimethyl sulfide (DMS), a climatically active gas that connects the marine and terrestrial sulfur cycles. Marine bacteria are the major DMSP consumers, either generating DMS or consuming DMSP as a source of reduced carbon and sulfur. However, the factors regulating the DMSP catabolism in bacteria are not well understood. Marine bacteria are also exposed to oxidative stress. RNA sequencing (RNA-seq) experiments showed that oxidative stress induced in the laboratory reduced expression of the genes encoding the consumption of DMSP via the demethylation pathway and increased the expression of genes encoding DMS production via the cleavage pathway in the marine bacterium Ruegeria pomeroyi. These results support a model where DMS production in the ocean is regulated in part by oxidative stress.


Assuntos
Peróxido de Hidrogênio , Rhodobacteraceae , Peróxido de Hidrogênio/metabolismo , Rhodobacteraceae/genética , Rhodobacteraceae/metabolismo , Água/metabolismo , Estresse Oxidativo , Enxofre/metabolismo
14.
Toxicon ; 208: 53-61, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35104533

RESUMO

α-conotoxin (α-CTX) MI is a small peptide toxin with 14 amino acids and two disulfide bonds. It potently inhibits muscle-type nicotinic acetylcholine receptors (nAChRs), and poses a threat as a toxin to tropical fishermen. However, there are currently no effective drugs for the treatment of MI envenomation due to the toxin's low immunogenicity. In this report, we generated neutralizing antiserum and F(ab')2 to MI by synthesizing a new MI antigen through the coupling of alkynyl-modified MI and azide-modified bovine serum albumin (BSA), followed by immunization into mouse and horse. The new MI-BSA antigen generated high titers of mouse and horse antiserum (1:204,800 and 1:51,200, respectively), and both the antiserum as well as the horse F(ab')2 displayed highly potent neutralization and detoxification efficacy. 12.5 µL of mouse or horse antiserum preincubated with MI could completely neutralize a lethal dose of the MI (0.4 µg, 1.7 × LD50), while 6.25 µL (mouse) or 10.41 µL (horse) of the antiserum could exert complete detoxification of mice injected with 1.7 × LD50 of MI. Moreover, the mouse and horse antiserum exhibited medium cross-reactivity for highly toxic α-CTX GI. These results demonstrate that the integrity of MI's antigen epitope and carrier effect of BSA can improve MI's immunogenicity, and provides an effective detoxification treatment for highly toxic α-conotoxins as well as an effective method for the preparation of antiserum of small peptide toxins.


Assuntos
Conotoxinas , Receptores Nicotínicos , Animais , Conotoxinas/toxicidade , Cavalos , Soros Imunes , Antagonistas Nicotínicos , Peptídeos
15.
ACS Chem Biol ; 17(9): 2483-2494, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36048451

RESUMO

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels widely distributed in the central peripheral nervous system and muscles which participate in rapid synaptic transmission. The α9α10 nAChR is an acetylcholine receptor subtype and is involved in chronic pain. In the present study, a new A-superfamily conotoxin Bt14.12 cloned from Conus betulinus was found to selectively inhibit α9α10 nAChRs with an IC50 of 62.3 nM. Unlike α-conotoxins and other A-superfamily conotoxins, Bt14.12 contains a four Cys (C-C-C-C) framework with a unique disulfide bond connection "C1-C4, C2-C3". The structure-activity studies of Bt14.12 demonstrate that all amino acid residues contribute to its potency. Interestingly, mutation experiments show that the deletion of Asp2 or the addition of three Arg residues at the N-terminus of Bt14.12 significantly enhances its inhibitory activity (IC50 is 21.9 nM or 12.7 nM, respectively) by 2- or 4-fold compared to the wild-type Bt14.12. The NMR structure of Bt14.12 shows that it contains α-helix- and ß-turn-like elements, and further computational modelings of the interaction between Bt14.12 and the α9α10 nAChR demonstrate that Bt14.12 possesses a distinctive mode of action and displays a different structure-activity relationship from known α9α10 nAChR targeting α-conotoxins. Our findings provide a novel conotoxin that potently targets α9α10 nAChRs and a new motif for designing potent inhibitors against α9α10 nAChRs.


Assuntos
Conotoxinas , Caramujo Conus , Receptores Nicotínicos , Sequência de Aminoácidos , Aminoácidos , Animais , Conotoxinas/química , Conotoxinas/farmacologia , Caramujo Conus/química , Caramujo Conus/metabolismo , Dissulfetos/metabolismo , Antagonistas Nicotínicos/química , Antagonistas Nicotínicos/farmacologia , Receptores Nicotínicos/metabolismo
16.
Extremophiles ; 15(5): 549-63, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21695489

RESUMO

The diversity of archaea and bacteria was investigated in ten hot springs (elevation >4600 m above sea level) in Central and Central-Eastern Tibet using 16S rRNA gene phylogenetic analysis. The temperature and pH of these hot springs were 26-81°C and close to neutral, respectively. A total of 959 (415 and 544 for bacteria and archaea, respectively) clone sequences were obtained. Phylogenetic analysis showed that bacteria were more diverse than archaea and that these clone sequences were classified into 82 bacterial and 41 archaeal operational taxonomic units (OTUs), respectively. The retrieved bacterial clones were mainly affiliated with four known groups (i.e., Firmicutes, Proteobacteria, Cyanobacteria, Chloroflexi), which were similar to those in other neutral-pH hot springs at low elevations. In contrast, most of the archaeal clones from the Tibetan hot springs were affiliated with Thaumarchaeota, a newly proposed archaeal phylum. The dominance of Thaumarchaeota in the archaeal community of the Tibetan hot springs appears to be unique, although the exact reasons are not yet known. Statistical analysis showed that diversity indices of both archaea and bacteria were not statistically correlated with temperature, which is consistent with previous studies.


Assuntos
Archaea/crescimento & desenvolvimento , Bactérias/crescimento & desenvolvimento , Biodiversidade , Fontes Termais/microbiologia , Microbiologia da Água , Temperatura Alta , Tibet
17.
IEEE Trans Pattern Anal Mach Intell ; 43(12): 4205-4216, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-32054568

RESUMO

Vision-language navigation (VLN) is the task of navigating an embodied agent to carry out natural language instructions inside real 3D environments. In this paper, we study how to address three critical challenges for this task: the cross-modal grounding, the ill-posed feedback, and the generalization problems. First, we propose a novel Reinforced Cross-Modal Matching (RCM) approach that enforces cross-modal grounding both locally and globally via reinforcement learning (RL). Particularly, a matching critic is used to provide an intrinsic reward to encourage global matching between instructions and trajectories, and a reasoning navigator is employed to perform cross-modal grounding in the local visual scene. Evaluation on a VLN benchmark dataset shows that our RCM model significantly outperforms baseline methods by 10 percent on Success Rate weighted by Path Length (SPL) and achieves the state-of-the-art performance. To improve the generalizability of the learned policy, we further introduce a Self-Supervised Imitation Learning (SIL) method to explore and adapt to unseen environments by imitating its own past, good decisions. We demonstrate that SIL can approximate a better and more efficient policy, which tremendously minimizes the success rate performance gap between seen and unseen environments (from 30.7 to 11.7 percent).

18.
Appl Environ Microbiol ; 76(13): 4538-41, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20435758

RESUMO

Using RNA-based techniques and hot spring samples collected from Yunnan Province, China, we show that the amoA gene of aerobic ammonia-oxidizing archaea can be transcribed at temperatures higher than 74 degrees C and up to 94 degrees C, suggesting that archaeal nitrification can potentially occur at near boiling temperatures.


Assuntos
Amônia/metabolismo , Archaea/enzimologia , Fontes Termais/microbiologia , Oxirredutases/metabolismo , RNA Arqueal , Archaea/genética , Archaea/isolamento & purificação , Archaea/metabolismo , Proteínas Arqueais/genética , Proteínas Arqueais/metabolismo , China , Fontes Termais/química , Temperatura Alta , Dados de Sequência Molecular , Oxirredução , Oxirredutases/genética , RNA Arqueal/análise , RNA Arqueal/genética , RNA Arqueal/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
19.
Extremophiles ; 14(4): 367-76, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20490582

RESUMO

The diversity and community structure of planktonic Actinobacteria in a freshwater river and five fresh/saline/hypersaline lakes on the Tibetan Plateau, China were investigated with a combination of geochemical and 16S rRNA gene phylogenetic analyses. A total of 387 actinobacterial 16S rRNA gene clones were sequenced, and they could be classified into Actinobacteridae, Acidimicrobidae, and unclassified Actinobacteria. The Actinobacteridae sequences were distributed into five suborders (e.g., Corynebacterineae, Frankineae, Micrococcineae, Propionibacterineae, and Streptosporangineae) and unclassified Actinobacteridae. Some actinobacterial members (specifically Micrococcineae) were present in a wide range of salinities (from freshwater to NaCl saturation). Statistical analysis showed that salinity and salinity-related environmental variables (such as ions and total nitrogen) significantly (r > 0.5; P < 0.05) influenced the distribution of planktonic actinobacterial community in the investigated aquatic biotopes. Our data have implications for a better understanding of the distribution of Actinobacteria in high-elevation lakes.


Assuntos
Actinobacteria/classificação , Actinobacteria/genética , Sequência de Bases , Biodiversidade , Primers do DNA , Água Doce , Filogenia , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Cloreto de Sódio , Tibet
20.
Wei Sheng Wu Xue Bao ; 50(1): 132-6, 2010 Jan.
Artigo em Zh | MEDLINE | ID: mdl-20344952

RESUMO

OBJECTIVE: Investigation of ammonia-oxidizing microorganisms (AOMs) in hot springs is of significant importance to understand global nitrogen cycling. However, we still know little about the abundance of AOMs in hot springs. In this research, the abundance of AOMs in thirteen hot springs located in Yunnan Province, China, and the effects of environmental variables (e. g. temperature, pH and ammonia concentration, and certain ions) on the AOM abundance were studied. METHODS: Microbial abundance in collected hot spring samples was determined by using an integrated approach including reverse-transcription quantitative polymerase chain reaction and catalyzed reporter deposition-fluorescence in situ hybridisation. RESULTS: Total biomass in the collected hot spring samples was 10(8) - 10(9) cells/g, among which ammonia-oxidizing archaea (AOA) occupied 0.02%-1.32%, whereas no ammonia-oxidizing bacteria were detected. Statistical analysis indicated that AOA abundance was significantly (P < 0.05) correlated with concentrations of NH3, NO2-, NO3-, pH and temperature, but not related (P > 0.05) to salinity and concentrations of Fe2+ and salinity. CONCLUSION: AOA were the major component of AOM in the studied hot springs, and play an important role in ammonia oxidation in hot springs. Multiple environmental variables (e. g. NH3, NO2-, NO3-, pH and temperature) were together controlling the AOA distribution among hot springs of different conditions, and some environmental variables, such as Fe2+ and salinity may not be the key factors for AOA in hot springs.


Assuntos
Amônia/metabolismo , Archaea/isolamento & purificação , Fontes Termais/microbiologia , Biomassa , Meio Ambiente , Oxirredução
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