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1.
Chemistry ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034923

RESUMO

Continuous-flow multi-step synthesis takes the advantages of microchannel flow chemistry and may transform the conventional multi-step organic synthesis by using integrated synthetic systems. To realize the goal, however, innovative chemical methods and techniques are urgently required to meet the significant remaining challenges. In the past years, by using green reactions, telescoped chemical design and/or novel in-line separation techniques, major and rapid advancement has been made in this direction. This minireview summarize the most recent reports (2017-) on continuous-flow synthesis of functional molecules. Particularly, several complex active pharmaceutical ingredients (APIs) have been prepared by the continuous-flow approach. Key technologies to the successes and remaining challenges are discussed. These results exemplified the feasibility of using modern continuous-flow chemistry for complex synthetic targets, and bode well for the future development of integrated, automated artificial synthetic systems.

2.
IEEE Trans Cybern ; PP2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001812

RESUMO

The scheduling and control of wireless cloud control systems involving multiple independent control systems and a centralized cloud computing platform are investigated. For such systems, the scheduling of the data transmission as well as some particular design of the controller can be equally important. From this observation, we propose a dual channel-aware scheduling strategy under the packet-based model predictive control framework, which integrates a decentralized channel-aware access strategy for each sensor, a centralized access strategy for the controllers, and a packet-based predictive controller to stabilize each control system. First, the decentralized scheduling strategy for each sensor is set in a noncooperative game framework and is then designed with asymptotical convergence. Then, the central scheduler for the controllers takes advantage of a prioritized threshold strategy, which outperforms a random one neglecting the information of the channel gains. Finally, we prove the stability for each system by constructing a new Lyapunov function, and further reveal the dependence of the control system stability on the prediction horizon and successful access probabilities of each sensor and controller. These theoretical results are successfully verified by numerical simulation.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33037153

RESUMO

Blue light using flavin (BLUF) photoreceptor proteins are critical for many light-activated biological processes and are promising candidates for optogenetics because of their modular nature and long-range signaling capabilities. Although the photocycle of the Slr1694 BLUF domain has been characterized experimentally, the identity of the light-adapted state following photoexcitation of the bound flavin remains elusive. Herein hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations of this photocycle provide a nonequilibrium dynamical picture of a possible mechanism for the formation of the light-adapted state. Photoexcitation of the flavin induces a forward proton-coupled electron transfer (PCET) process that leads to the formation of an imidic acid tautomer of Gln50. The calculations herein show that the subsequent rotation of Gln50 allows a reverse PCET process that retains this tautomeric form. In the resulting purported light-adapted state, the glutamine tautomer forms a hydrogen bond with the flavin carbonyl group. Additional ensemble-averaged QM/MM calculations of the dark-adapted and purported light-adapted states demonstrate that the light-adapted state with the imidic acid glutamine tautomer reproduces the experimentally observed spectroscopic signatures. Specifically, the calculations reproduce the red shifts in the flavin electronic absorption and carbonyl stretch infrared spectra in the light-adapted state. Further hydrogen-bonding analyses suggest the formation of hydrogen-bonding interactions between the flavin and Arg65 in the light-adapted state, providing a plausible explanation for the experimental observation of faster photoinduced PCET in this state. These characteristics of the light-adapted state may also be essential for the long-range signaling capabilities of this photoreceptor protein.

4.
Cell Mol Biol (Noisy-le-grand) ; 66(5): 36-40, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33040810

RESUMO

This experiment was carried out to observe and analyze the effect of floium ginkgo extract and tertram ethypyrazine sodium chloride injection in patients with cerebral infarction. A total of 200 patients diagnosed with cerebral infarction were enrolled in the study. They were randomly divided into a research group and control group, each containing 100 patients. The control group was given routine treatment measures while the research group was given floium ginkgo extract and tertram ethypyrazine sodium chloride injection on the basis of routine treatment. The therapeutic effects of the two groups were observed and compared. After implementing different treatment schemes, the levels of MMP-9, SOD, CBV and CBF in the research group were significantly higher than those in the control group, p<0.05. The research group was lower in hs-CRP, MDA, MTT, TTP and TNF-α as compared with the control group, p<0.05. In terms of the quality of life of the two groups after six months of treatment, the scores of various indicators in the research group were all significantly superior, p<0.05. Conclusion: The treatment of cerebral infarction patients with floium ginkgo extract and tertram ethypyrazine sodium chloride injection can significantly improve the therapeutic effect, which is a relatively ideal treatment.

5.
Bioresour Technol ; 317: 124052, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32877845

RESUMO

In this study, ten spent edible fungus (SEF) with different compositional features were used for the maximum methanogenic potential (P0) evaluation, and the prediction models including regression and kinetics based on this were developed separately. The results showed that the regression model with more chemical components had a good correlation with the P0, and at least three chemical compositions could reach the threshold of sensitivity. The Cone model showed the best fitting effect on P0 in all kinetic models, which had higher R-square (>0.994) and lower error (1.004-5.672%). Meanwhile, the minimum digestive testing time (14 days) was determined by the evaluation of sensitivity via statistical indicators. It is concluded that the determination of the prediction model of P0 should be evaluated with the combination of statistical indicators and specific requirements.


Assuntos
Fungos , Metano , Anaerobiose , Reatores Biológicos , Cinética
6.
J Immunol ; 205(8): 2207-2221, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32917788

RESUMO

Foot-and-mouth disease is a highly contagious disease of pigs, sheep, goats, bovine, and various wild cloven-hoofed animals caused by foot-and-mouth disease virus (FMDV) that has given rise to significant economic loss to global livestock industry. FMDV 3B protein is an important determinant of virulence of the virus. Modifications in 3B protein of FMDV considerably decrease virus yield. In the current study, we demonstrated the significant role of 3B protein in suppression of type I IFN production and host antiviral response in both human embryonic kidney HEK293T cells and porcine kidney PK-15 cells. We found that 3B protein interacted with the viral RNA sensor RIG-I to block RIG-I-mediated immune signaling. 3B protein did not affect the expression of RIG-I but interacted with RIG-I to block the interaction between RIG-I and the E3 ubiquitin ligase TRIM25, which prevented the TRIM25-mediated, Lys63-linked ubiquitination and activation of RIG-I. This inhibition of RIG-I-mediated immune signaling by 3B protein decreased IFN-ß, IFN-stimulated genes, and proinflammatory cytokines expression, which in turn promoted FMDV replication. All of the three nonidentical copies of 3B could inhibit type I IFN production, and the aa 17A in each copy of 3B was involved in suppression of IFN-related antiviral response during FMDV infection in porcine cells. Together, our results indicate the role of 3B in suppression of host innate immune response and reveal a novel antagonistic mechanism of FMDV that is mediated by 3B protein.

8.
Medicine (Baltimore) ; 99(38): e22210, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957355

RESUMO

BACKGROUND: Total hip arthroplasty (THA) is a safe and mature surgical method for the treatment of post-traumatic arthritis and end-stage degenerative osteoarthritis. The cohort study regarding the outcomes of THA following acetabulum fracture is sparse. Therefore, we carried out this present retrospective paired cohort study to study the long-term outcomes of patients receiving THA after the acetabular fracture versus patients receiving THA for the primary osteoarthritis. METHODS: Patients with posttraumatic arthritis who received the initial THA after open reduction and internal fixation of acetabular fractures or patients with end-stage degenerative osteoarthritis were included in our study. A retrospective review of patients who receiving the primary total hip arthroplasty in the same institution from 2008 to 2015 was conducted. This present retrospective cohort research was authorized via our hospital institutional review committee. The patients in cohort group were matched 2:1 with the patients in study group according to following criteria: body mass index (±3 points), and age at THA time (±3 years), sex, as well as the score of American Society of Anesthesiologists (±1 point). The measure of primary outcome was the improved Harris Hip Score. Secondary outcomes included surgery time, hip range of motion, revision, complications (infection, loosening, polyethylene wear, dislocation, wound complications, deep vein thrombosis, or pulmonary embolism). RESULTS: It was assumed that there is a remarkable difference in postoperative outcomes between the 2 groups. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5921).


Assuntos
Acetábulo/lesões , Artroplastia de Quadril , Fraturas Ósseas , Osteoartrite do Quadril/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
10.
J Chem Theory Comput ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-32975951

RESUMO

Calculations of the free energy profile, also known as potential of mean force (PMF), along a chosen collective variable (CV) are now routinely applied in the studies of chemical processes, such as enzymatic reactions and chemical reactions in condensed phases. However, if the ab initio quantum mechanical/molecular mechanics (QM/MM) level of accuracy is required for the PMF, it can be formidably demanding even with the most advanced enhanced sampling methods, such as umbrella sampling. To ameliorate this difficulty, we developed a novel method for the computation of the free energy profile based on the reference-potential method recently, in which a low-level reference Hamiltonian is employed for phase space sampling and the free energy profile can be corrected to the level of interest (the target Hamiltonian) by energy reweighting in a nonparametric way. However, when the reference Hamiltonian is very different from the target Hamiltonian, the calculated ensemble averages, including the PMF, often suffer from numerical instability, which mainly comes from the overestimation of the density-of-states (DoS) in the low-energy region. Stochastic samplings of these low-energy configurations are rare events, and some low-energy conformations may get oversampled in simulations of a finite length. In this work, an assumption of Gaussian distribution is applied to the DoS in each CV bin, and the weight of each configuration is rescaled according to the accumulated DoS. The results show that this smoothing process can remarkably reduce the ruggedness of the PMF and increase the reliability of the reference-potential method.

11.
Org Lett ; 22(19): 7475-7479, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-32903007

RESUMO

The rhodium(III)-catalyzed coupling of C-H substrates with iodonium ylides has been realized for the efficient synthesis of diverse cyclic skeletons, where the iodonium ylides have been identified as efficient and outstanding carbene precursors. The reaction systems are applicable to both sp2 and sp3 C-H substrates under mild and redox-neutral conditions. The catalyst loading can be as low as 0.5 mol % in a gram-scale reaction. Representative products exhibit cytotoxicity toward human cancer cells at nanomolar levels.

12.
Medicine (Baltimore) ; 99(36): e21802, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899008

RESUMO

Bone is a frequent site for the occurrence of metastasis of thyroid cancer (TC). TC with bone metastasis (TCBM) is associated with skeletal-related events (SREs), with poor prognosis and low overall survival (OS). Therefore, it is necessary to develop a predictive nomogram for prognostic evaluation. This study aimed to construct an effective nomogram for predicting the OS and cancer-specific survival (CSS) of TC patients with BM. Those TC patients with newly diagnosed BM were retrospectively examined over a period of 6 years from 2010 to 2016 using data from the Surveillance, Epidemiology and End Results (SEER) database. Demographics and clinicopathological data were collected for further analysis. Patients were randomly allocated into training and validation cohorts with a ratio of ∼7:3. OS and CSS were retrieved as research endpoints. Univariate and multivariate Cox regression analyses were performed for identifying independent predictors. Overall, 242 patients were enrolled in this study. Age, histologic grade, histological subtype, tumor size, radiotherapy, liver metastatic status, and lung metastatic status were determined as the independent prognostic factors for predicting the OS and CSS in TCBM patients. Based on the results, visual nomograms were separately developed and validated for predicting 1-, 2-, and 3-year OS and CSS in TCBM patients on the ground of above results. The calibration, receiver operating characteristic (ROC) curve and decision curve analysis (DCA) also demonstrated the reliability and accuracy of the clinical prediction model. Our predictive model is expected to be a personalized and easily applicable tool for evaluating the prognosis of TCBM patients, and may contribute toward making an accurate judgment in clinical practice.


Assuntos
Neoplasias Ósseas/secundário , Nomogramas , Neoplasias da Glândula Tireoide/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Estudos Retrospectivos , Programa de SEER/estatística & dados numéricos , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
14.
Eur J Surg Oncol ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32980212

RESUMO

OBJECTIVE: To assess the impact of neoadjuvant chemotherapy on postoperative pathology for stage IB2 and IIA2 cervical squamous cell carcinoma. METHODS: Postoperative pathology was compared between patients who received neoadjuvant chemotherapy followed by radical hysterectomy (NACT group) and patients who received upfront radical hysterectomy (URH group). Then, patients in the NACT group were divided into a chemotherapy-sensitive group and a chemotherapy-insensitive group according to their response to chemotherapy. RESULTS: After 1:1 propensity score matching (PSM), the positive rates of lymphovascular space invasion (LVSI) (7.9% vs 17.7%, P = 0.001) and cervical deep stromal invasion (60.4% vs 76.2%, P < 0.001) in the NACT group were significantly lower than those in the URH group, while the positive rates of parametrial invasion, lymph node metastasis, and vaginal margin invasion were not significantly different between the two groups. The rate of positive lymph node metastasis in the chemotherapy-sensitive group was significantly lower than that in the URH group (18.1% vs 26.5%, P = 0.037). CONCLUSION: Among patients with stage IB2 and IIA2 cervical squamous cell carcinomas, NACT can reduce the positive rate of intermediate-risk factors, such as deep cervical stromal invasion and LVSI, but cannot reduce the positive rate of high-risk factors. For patients who are chemotherapy sensitive, NACT can reduce the positive rate of lymph node metastasis.

15.
J Clin Endocrinol Metab ; 105(12)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32893854

RESUMO

CONTEXT: Numerous studies have shown that cardiovascular disease (CVD) represents the most important cause of mortality among people with diabetes mellitus (DM). However, no studies have evaluated the risk of CVD-related mortality among different DM subgroups. OBJECTIVE: We aimed to examine all-cause, CVD-related, and cancer-related mortality for different DM subgroups. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: We included participants (age ≥ 20 years) from the National Health and Nutrition Examination Survey III (NHANES III) data set. We evaluated the risks of all-cause and cause-specific (CVD and cancer) mortality among 5 previously defined diabetes subgroups: severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). PRIMARY OUTCOME MEASURE: The hazard ratios (HRs) for all-cause and cause-specific (CVD and cancer) mortality were measured for each of the 5 DM subgroups. We also evaluated the odds ratios (ORs) for retinopathy and nephropathy in each subgroup. RESULTS: A total of 712 adults were enrolled and the median follow-up time was 12.71 years (range, 0.25-18.08 years). The number of deaths in the 5 subgroups (SAID, SIDD, SIRD, MOD, and MARD) were 50, 75, 64, 7, and 18, respectively, and the number of CVD-related deaths in the 5 subgroups was 29, 30, 26, 2, and 11, respectively. Compared to the MOD subgroup, the adjusted HRs and 95% CIs of CVD-related mortality for the SAID, SIDD, SIRD, and MARD subgroups were 3.23 (95% CI, 0.77-13.61), 2.87 (95% CI, 0.68-12.06), 2.23 (95% CI, 0.53-9.50), and 4.75 (95% CI, 1.05-21.59), respectively (the HR for the MARD subgroup had a P value of .04). In addition, compared to the MARD subgroup, the adjusted ORs and 95% CIs for retinopathy in the SAID and SIDD groups were 2.38 (95% CI, 1.13-5.01, P = .02) and 3.34 (95% CI, 1.17-6.88, P = .001), respectively. The ORs for nephropathy were nonsignificant. CONCLUSIONS: Our study of patients from the NHANES III data set indicated that among the different DM subgroups, the MARD subgroup tended to have a higher CVD-related mortality than the MOD subgroup. The all-cause and cancer-related mortality rates were similar across the different diabetes subgroups. In addition, compared to the MARD subgroup, the SAID and SIDD subgroups had a higher retinopathy risk, but there was no difference in nephropathy among the subgroups.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32932015

RESUMO

BACKGROUND & AIMS: Cancer-associated fibroblasts (CAFs) play a key role in the cancer process, but the research progress is hampered by the paucity of preclinical models that are essential for mechanistic dissection of cancer cell-CAF interactions. Here, we aimed to establish 3-dimensional (3D) organotypic co-cultures of primary liver tumor-derived organoids with CAFs, and to understand their interactions and the response to treatment. METHODS: Liver tumor organoids and CAFs were cultured from murine and human primary liver tumors. 3D co-culture models of tumor organoids with CAFs and Transwell culture systems were established in vitro. A xenograft model was used to investigate the cell-cell interactions in vivo. Gene expression analysis of CAF markers in our hepatocellular carcinoma cohort and an online liver cancer database indicated the clinical relevance of CAFs. RESULTS: To functionally investigate the interactions of liver cancer cells with CAFs, we successfully established murine and human 3D co-culture models of liver tumor organoids with CAFs. CAFs promoted tumor organoid growth in co-culture with direct cell-cell contact and in a Transwell system via paracrine signaling. Vice versa, cancer cells secrete paracrine factors regulating CAF physiology. Co-transplantation of CAFs with liver tumor organoids of mouse or human origin promoted tumor growth in xenograft models. Moreover, tumor organoids conferred resistance to clinically used anticancer drugs including sorafenib, regorafenib, and 5-fluorouracil in the presence of CAFs, or the conditioned medium of CAFs. CONCLUSIONS: We successfully established murine and human 3D co-culture models and have shown robust effects of CAFs in liver cancer nurturing and treatment resistance.

17.
Poult Sci ; 99(9): 4227-4234, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32867966

RESUMO

Since 2017, an infectious disease, named feather shedding syndrome (FSS), has consistently broken out in Cherry Valley ducks in East China. The sick ducks showed the new clinical symptoms of feather shedding and being plucked off with difficulty after slaughter. The high incidence rate of 20 to 70% predominantly happened in ducks of 4 to 5 wk of age, and nearly 40% mortality rate was observed in infected ducks. To explore the possible role of novel goose parvovirus-associated virus (NGPV) and duck circovirus (DuCV) in this disease, a total of 540 feather sac samples were collected from sick ducks with FSS. The infection rates of NGPV and DuCV in samples were 82.78 and 78.89%, respectively, and the coinfection rate of the 2 viruses was 70.00%. Notably, ducks of 4 to 5 wk of age usually presented obvious and severe FSS in the flocks with high codetection rate of NGPV and DuCV. Furthermore, 9 NGPV strains were isolated from feather sacs and 5 synchronous amino acid mutations were demonstrated in VP3 protein. These results indicated that coinfection of NGPV and DuCV might play an important role in duck FSS disease.

18.
J Org Chem ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32882129

RESUMO

A highly efficient strategy for the construction of CF3-substituted 1,6-dihydropyridazines has been developed by cascade oxidation/cyclization of trifluoromethylated N-acylhydrazines. The produced 1,6-dihydropyridazines could be easily transformed to 3-trifluoromethyl pyridazine derivatives. Some of the 1,6-dihydropyridazines exhibited aggregation-induced emission (AIE). DFT calculations were conducted to explain the mechanism.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32974218

RESUMO

Legionella pneumophila is an environmental bacterium that has evolved to survive predation by soil and water amoebae such as Acanthamoeba castellanii, and this has inadvertently led to the ability of L. pneumophila to survive and replicate in human cells. L. pneumophila causes Legionnaire's Disease, with human exposure occurring via the inhalation of water aerosols containing both amoebae and the bacteria. These aerosols originate from aquatic biofilms found in artifical water sources, such as air-conditioning cooling towers and humidifiers. In these man-made environments, A. castellanii supports L. pneumophila intracellular replication, thereby promoting persistence and dissemination of the bacteria and providing protection from external stress. Despite this close evolutionary relationship, very little is known about how A. castellanii responds to L. pneumophila infection. In this study, we examined the global transcriptional response of A. castellanii to L. pneumophila infection. We compared A. castellanii infected with wild type L. pneumophila to A. castellanii infected with an isogenic ΔdotA mutant strain, which is unable to replicate intracellularly. We showed that A. castellanii underwent clear morphological and transcriptional rewiring over the course of L. pneumophila infection. Through improved annotation of the A. castellanii genome, we determined that these transcriptional changes primarily involved biological processes utilizing small GTPases, including cellular transport, signaling, metabolism and replication. In addition, a number of sirtuin-encoding genes in A. castellanii were found to be conserved and upregulated during L. pneumophila infection. Silencing of sirtuin gene, sir6f (ACA1_153540) resulted in the inhibition of A. castellanii cell proliferation during infection and reduced L. pneumophila replication. Overall our findings identified several biological pathways in amoebae that may support L. pneumophila replication and A. castellanii proliferation in environmental conditions.

20.
Arch Virol ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32902666

RESUMO

To our knowledge, no mycoviruses have been reported in Fusarium cerealis. Here, we describe a novel double-stranded RNA (dsRNA) virus, Fusarium cerealis partitivirus 1 (FcPV1), isolated from F. cerealis strain HN30 from Henan Province, China. The FcPV1 genome consists of two dsRNA segments, 1732 bp (dsRNA1) and 1361 bp (dsRNA2) in length, each containing a single open reading frame potentially encoding a 61.0-kDa protein and a 42.0-kDa protein, respectively. dsRNA1 encodes a putative RNA-dependent RNA polymerase (RdRp), while the dsRNA2 product has no significant similarity to any other capsid proteins (CPs) in the GenBank databases other than limited similarity to hypothetical "capsid" proteins of a few partitiviruses. Sequence alignments and phylogenetic analysis showed that FcPV1 is related to members of the newly proposed genus "Zetapartitivirus" in the family Partitiviridae.

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