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1.
Artigo em Inglês | MEDLINE | ID: mdl-32356177

RESUMO

PURPOSE: As a type of cancer with the highest morbidity and mortality, lung squamous cell carcinoma (LUSC) has a very poor prognosis. Long-non-coding RNA (lncRNA) has recently attracted attentions because it can play the role of competing endogenous RNA (ceRNA) to inhibit microRNA (miRNA) functions. In this study, we aimed to find prognosis-related lncRNAs, miRNAs and mRNAs and construct a prognosis-related ceRNA network. METHODS: The original LUSC RNA-sequencing data and miRNA profiles data were downloaded from the cancer genome atlas (TCGA) database. Differentially expressed lncRNAs, miRNAs and mRNAs were then identified between patients with lymph node metastasis and no lymph node metastasis. Univariate Cox regression analysis was performed to find the survival-associated lncRNAs, miRNAs and mRNAs. Subsequently, prognostic-related ceRNA network was established. By multivariate Cox regression analysis, three lncRNA signatures and three mRNA signatures were developed and used for predicting LUSC patients' survival. RESULTS: A total of 224 lncRNAs, 160 miRNAs, 913 mRNAs were identified between samples with lymph node metastasis and no lymph node metastasis. Univariate Cox regression analysis showed that, among them, 28 lncRNAs, 8 miRNAs, 105 mRNAs were significantly associated with patients' overall survival time. Further pathway and enrichment analysis suggested that these mRNAs were associated with the regulation of transmembrane transport, regulation of blood circulation, plasma lipoprotein particle organization. Then we constructed a survival-related ceRNA network including 9 lncRNAs, 8 miRNAs and 23 mRNAs. Additionally, a multivariate Cox regression analysis demonstrated that three lncRNAs (AL161431.1, LINC02389, APCDD1L.DT) and three mRNAs (KLK6, SLITRK5, CCDC177) had a significant prognostic value. Risk score indicated that lncRNA signature and mRNA signature could independently predict overall survival in LUSC patients. CONCLUSION: The current study provided a better understanding of the ceRNA network in the progression of LUSC and laid a theoretical foundation for LUSC prognosis.

2.
Clin Infect Dis ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32271374

RESUMO

The 2019 novel coronavirus was detected in the self-collected throat washings. Positive testing rate of throat washing was much higher than that of Nasopharyngeal swabs. Throat washing is a promising candidate for 2019-nCoV screening and monitoring due to its noninvasive and reliability.

3.
J Phys Chem Lett ; : 2902-2909, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32212731

RESUMO

Zero-dimensional (0D) hybrid metal halides have emerged as a new generation of luminescent phosphors owing to their high radiative recombination rates, which, akin to their three-dimensional cousins, commonly demonstrate thermal quenching of luminescence. Here, we report on the finding of antithermal quenching of luminescence in 0D hybrid metal halides. Using (C9NH20)2SnBr4 single crystals as an example system, we show that 0D metal halides can demonstrate antithermal quenching of luminescence. A combination of experimental characterizations and first-principles calculations suggests that antithermal quenching of luminescence is associated with trap states introduced by structural defects in (C9NH20)2SnBr4. Importantly, we find that antithermal quenching of luminescence is not only limited to (C9NH20)2SnBr4 but also exists in other 0D metal halides. Our work highlights the important role of defects in impacting photophysical properties of hybrid metal halides and may stimulate new efforts to explore metal halides exhibiting antithermal quenching of luminescence at higher temperatures.

4.
Br J Nutr ; : 1-9, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32122412

RESUMO

N-Carbamylglutamate (NCG) has been shown to enhance arginine synthesis and improve growth performance in animals. However, the effect of NCG on body fat deposition remains unknown. This study examined the effects of NCG on body fat deposition and evaluated the potential mechanisms involved. Rex rabbits (3 months old) were assigned to one of four dietary groups and supplemented with NCG at the following different concentrations in a feeding trial that lasted 67 d: 0 (control), 0·04, 0·08, and 0·12 %. NCG supplementation increased serum concentrations of arginine and proline by activating intestinal carbamoylphosphate synthase-І at the posttranscriptional level. Final body weights and growth performance were not affected by dietary NCG levels. However, NCG-treated rabbits had lower perirenal and subcutaneous fat percentages, serum TAG content, and hepatic fatty acid synthase (FAS) activity and increased NO synthase activity and serum levels of NO, growth hormone (GH), and insulin-like growth factor 1 (IGF-1). There were significant positive correlations between TAG content and perirenal fat percentage, as well as FAS activity and perirenal fat percentage, but significant negative correlations between TAG and NO levels, and FAS activity and IGF-1 level in rabbits after NCG treatment. NCG supplementation did not affect hepatic health indicators, except for serum ammonia concentrations, which were decreased in NCG-treated rabbits. Our results suggest that NCG can serve as a dietary supplement to reduce unfavourable fat deposition through inhibiting hepatic lipogenesis in animals since it appears to have no negative effects on growth performance or hepatic health.

5.
Genes Dev ; 34(7-8): 580-597, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32115408

RESUMO

Dysregulation of early neurodevelopment is implicated in macrocephaly/autism disorders. However, the mechanism underlying this dysregulation, particularly in human cells, remains poorly understood. Mutations in the small GTPase gene RAB39b are associated with X-linked macrocephaly, autism spectrum disorder (ASD), and intellectual disability. The in vivo roles of RAB39b in the brain remain unknown. We generated Rab39b knockout (KO) mice and found that they exhibited cortical neurogenesis impairment, macrocephaly, and hallmark ASD behaviors, which resembled patient phenotypes. We also produced mutant human cerebral organoids that were substantially enlarged due to the overproliferation and impaired differentiation of neural progenitor cells (NPCs), which resemble neurodevelopmental deficits in KO mice. Mechanistic studies reveal that RAB39b interacts with PI3K components and its deletion promotes PI3K-AKT-mTOR signaling in NPCs of mouse cortex and cerebral organoids. The mTOR activity is robustly enhanced in mutant outer radial glia cells (oRGs), a subtype of NPCs barely detectable in rodents but abundant in human brains. Inhibition of AKT signaling rescued enlarged organoid sizes and NPC overproliferation caused by RAB39b mutations. Therefore, RAB39b mutation promotes PI3K-AKT-mTOR activity and alters cortical neurogenesis, leading to macrocephaly and autistic-like behaviors. Our studies provide new insights into neurodevelopmental dysregulation and common pathways associated with ASD across species.

7.
J Cell Biochem ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32056305

RESUMO

Kinesin family member 2C (KIF2C), a substantial mitotic regulator, has been verified to exert a malignant function in several cancers. However, its function in hepatocellular carcinoma (HCC) remains unclear. In this study, the expression profile of KIF2C in HCC was characterized through the dataset from the TCGA and clinical tissue microarrays containing 220 pairs of resected HCC tissues and adjacent nontumor tissues in our hospital. The results indicated that KIF2C was substantially higher expression in tumor tissues than adjacent nontumor tissues. High expression of KIF2C significantly correlated with large tumor (>5.0 cm) (P = .001) and implied a dismal postoperative overall survival (OS) (hazard ratio [HR] = 1.729; P = .002) in our cohort of patients. Gain and loss of function assays displayed that KIF2C promoted HCC cell proliferation, accelerated cell cycle progression, and impeded apoptosis. By bioinformatic tools and mechanistic investigation, we found that KIF2C interacted with various cell-cycle-related proteins and was significantly involved in growth-promoting pathways. KIF2C upregulated PCNA and CDC20 expression. Subsequently, we investigated the regulation of KIF2C by competing endogenous RNA and elucidated that has-miR-6715a-3p was directly bond to the 3'-untranslated region of KIF2C through dual luciferase assays, thereby inhibiting KIF2C expression. Furthermore, the long noncoding RNA GS1-358P8.4 was found to be a candidate of KIF2C for has-miR-6715a-3p binding. HCC patients with high lncRNA-GS1-358P8.4 expression had shorter OS and relapse-free survival compared to those with low expression, which was accordance with the KIF2C. Taken together, KIC2C aggravated HCC progression, it could serve as a prognostic indicator and confer a novel target for clinical treatment.

8.
Carbohydr Polym ; 233: 115677, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32059916

RESUMO

The OH induced cellulose degradation was examined by analyzing the reaction products of Fenton's regents with cellobiose. Many degradation products including C2-C5 compounds such as oxaldehyde, malonaldehyde and 2-hydroxysuccinaldehyde were detected by GCMS analysis. Four reaction pathways for the formation of some degradation products were obtained from ReaxFF kinetics simulation and validated by the DFT quantum chemistry calculation at B3LYP/6-31+g(d,p) level. It was found that the H-abstraction from OH of the glucose unit by OH can cause saccharide ring open and breakage of the glycosidic bond. Pathways 1-4 showed that the glucose unit can react with OH consecutively to produce small molecular products with carbon atoms less than 6. This study indicated that ReaxFF reaction kinetics is a powerful tool for the exploration of the degradation mechanism of cellulose induced by OH at room temperature, which correlated well with the experimental results and was validated by DFT calculation.

9.
Br J Neurosurg ; : 1-3, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31994911

RESUMO

Objective: The use of tranexamic acid (TXA) has become popular in spinal surgery, the purpose of this study is to investigate the effectiveness and safety of intraoperative TXA used to reduce surgical bleeding and transfusion requirements in spinal canal tumor resection.Methods: The data for patients with spinal canal tumors treated in our hospital from June 2014 to June 2017 were collected. The patients (≥18 years of age) were divided into a TXA group (group A, n = 30) and a non-TXA group (group B, n = 30). The TXA dose regimen in group A comprised a loading dose of 10 mg/kg 30 minutes before the operation, followed by a maintenance dose of 1 mg/kg per hour during the operation. Group B was not given TXA. The operation time, intraoperative blood loss, postoperative drainage, postoperative complications, coagulation function such as plasma thrombin time(PT), prothrombin time(TT), activated thromboplastin time(APTT), fibrinogen (Fib) were statistically analyzed.Results: The intraoperative blood loss and postoperative drainage volume were significant lower in group A than in group B (p<.05). There were no significant differences in the operation time, plasma thrombin time, prothrombin time, activated thromboplastin time, or fibrinogen between the two groups before and after the operation (p>.05), and no thrombotic complications occurred.Conclusion: TXA used during spinal tumor surgery can reduce the amount of intraoperative blood loss and postoperative drainage without increasing the risk of deep vein thrombosis and related complications.

10.
Sci Rep ; 10(1): 150, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924830

RESUMO

We provide a unified and exact framework for the variance-based uncertainty relations. This unified framework not only recovers some well-known previous uncertainty relations, but also fixes the deficiencies of them. Utilizing the unified framework, we can construct the new uncertainty relations in both product and sum form for two and more incompatible observables with any tightness we require. Moreover, one can even construct uncertainty equalities to exactly express the uncertainty relation by the unified framework, and the framework is therefore exact in describing the uncertainty relation. Some applications have been provided to illustrate the importance of this unified and exact framework. Also, we show that the contradiction between uncertainty relation and non-Hermitian operator, i.e., most of uncertainty relations will be violated when applied to non-Hermitian operators, can be fixed by this unified and exact framework.

11.
Biophys J ; 118(5): 1009-1018, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31995738

RESUMO

Replica exchange molecular dynamics (REMD) simulation is a popular enhanced sampling method that is widely used for exploring the atomic mechanism of protein conformational change. However, the requirement of huge computational resources for REMD, especially with the explicit solvent model, largely limits its application. In this study, the availability and efficiency of a variant of velocity-scaling REMD (vsREMD) was assessed with adenylate kinase as an example. Although vsREMD achieved results consistent with those from conventional REMD and experimental studies, the number of replicas required for vsREMD (30) was much less than that for conventional REMD (80) to achieve a similar acceptance rate (∼0.2), demonstrating high efficiency of vsREMD to characterize the protein conformational change and associated free-energy profile. Thus, vsREMD is a highly efficient approach for studying the large-scale conformational change of protein systems.

12.
Cancer Res Treat ; 52(1): 10-23, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31048666

RESUMO

PURPOSE: Although cathepsin C (CTSC) has been reported to maintain malignant biological properties in various cancers, its functions in hepatocellular carcinoma (HCC) remain obscure. We aimed to investigate the potential role of CTSC in HCC. Materials and Methods: HCC tissue microarrays (n=122) were employed to analyze the correlation between CTSC expression and clinicopathological characteristics through immunohistochemistry staining. Quantitative real-time polymerase chain reaction, western blot assay, Cell Counting Kit-8 assay, colony formation, cell migration, and invasion assays, xenograft mice model were adopted to validate what had been indicated by the bioinformatic web tools. RESULTS: By bioinformatic tools and tissue microarrays, CTSC was found upregulated in HCC compared with normal liver tissues, and its higher expression was correlated with poor prognosis of HCC patients (hazard ratio, 2.402; 95% confidence interval, 1.493 to 3.865; p < 0.001). By gain/loss-of-function assays, we implicated that CTSC functioned as an oncogene to promote the proliferation and metastasis of HCC cells. Mechanistically, we revealed that CTSC was involved in several cancer-related signaling pathways by Gene Set Enrichment Analysis, among which tumor necrosis factor α (TNF-α)/p38 pathway was verified to be activated by CTSC. Furthermore, we found that TNF-α could activate CTSC expression in a concentration- dependent manner. Ralimetinib, an oral p38 mitogen-activated protein kinase (MAPK) inhibitor could inhibit CTSC expression. These indicated a potential positive feedback loop between CTSC and TNF-α/MAPK (p38) signaling. CONCLUSION: Taken together, CTSC plays an important role in the growth and metastasis of HCC and may be a promising therapeutic target upon HCC.

13.
World Neurosurg ; 134: 58-61, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629926

RESUMO

BACKGROUND: Posttraumatic internal carotid aneurysms are rare. Two posttraumatic aneurysms occurring at the same time are even more rare. Two pseudoaneurysms located in different segments of the ipsilateral internal carotid artery have not been found in the literature. We provide the results of angiographic images of traumatic aneurysms over time. CASE DESCRIPTION: We report a young man aged 17 years with multiple aneurysms of the internal carotid artery following head injury. Head computed tomography examination was performed in our hospital showing a small amount of subarachnoid hemorrhage, nodular high-density shadow on the left side of the sellar region, casting a high-density shadow on the suprasellar cistern and left sulcus approximately 1 x 1 cm in size, and subarachnoid hemorrhage. Digital subtraction angiography was performed on the sixth day of admission: the C5 and C6 segments of the left internal carotid artery had 2 x 4 mm mound processes and 7 x 7 mm saccular processes, respectively. Interventional surgery was performed immediately. Due to aneurysm enlargement, intravascular surgery was performed for coiling of the corresponding aneurysms. The left internal carotid artery occlusion test showed that the right internal carotid artery was well compensated by the left side via the anterior communicating artery. The ophthalmic artery aneurysm of the left internal carotid artery and the clinoid segment pseudoaneurysms were embolized. Follow-up for 1 year showed no obvious sequelae and a good recovery. CONCLUSIONS: This case suggests that patients with posttraumatic subarachnoid hemorrhage should be considered for the possibility of traumatic aneurysms. If this occurs, an aggressive operation would achieve a good outcome.

14.
Sensors (Basel) ; 19(23)2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31816997

RESUMO

Biometric systems allow recognition and verification of an individual through his or her physiological or behavioral characteristics. It is a growing field of research due to the increasing demand for secure and trustworthy authentication systems. Compressed sensing is a data compression acquisition method that has been proposed in recent years. The sampling and compression of data is completed synchronously, avoiding waste of resources and meeting the requirements of small size and limited power consumption of wearable portable devices. In this work, a compression reconstruction method based on compression sensing was studied using bioelectric signals, which aimed to increase the limited resources of portable remote bioelectric signal recognition equipment. Using electrocardiograms (ECGs) and photoplethysmograms (PPGs) of heart signals as research data, an improved segmented weak orthogonal matching pursuit (OMP) algorithm was developed to compress and reconstruct the signals. Finally, feature values were extracted from the reconstructed signals for identification and analysis. The accuracy of the proposed method and the practicability of compression sensing in cardiac signal identification were verified. Experiments showed that the reconstructed ECG and PPG signal recognition rates were 95.65% and 91.31%, respectively, and that the residual value was less than 0.05 mV, which indicates that the proposed method can be effectively used for two bioelectric signal compression reconstructions.

15.
Autophagy ; : 1-16, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31847700

RESUMO

How lysosome and MTORC1 signaling interact remains elusive in terminally differentiated cells. A G4C2 repeat expansion in C9orf72 is the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS-FTD). We previously identified a C9orf72-SMCR8-containing complex. Here we found that c9orf72 and smcr8 double-knockout (dKO) mice exhibit similar but more severe immune defects than the individual knockouts. In c9orf72 or smcr8 mutant macrophages, lysosomal degradation and exocytosis were impaired due to the disruption of autolysosome acidification. As a result of impaired lysosomal degradation, MTOR protein was aberrantly increased, resulting in MTORC1 signaling overactivation. Inhibition of hyperactive MTORC1 partially rescued macrophage dysfunction, splenomegaly and lymphadenopathy in c9orf72 or smcr8 mutant mice. Pharmacological inhibition of lysosomal degradation upregulated MTOR protein and MTORC1 signaling in differentiated wild-type macrophages, which resemble phenotypes in KO mice. In contrast, C9orf72 or Smcr8 depletion in proliferating macrophages decreased MTORC1 signaling. Our studies causatively link C9orf72-SMCR8's cellular functions in lysosomal degradation, exocytosis, and MTORC1 signaling with their organism-level immune regulation, suggesting cell state (proliferation vs. differentiation)-dependent regulation of MTOR signaling via lysosomes.Abbreviations: ALS: amyotrophic lateral sclerosis; ATG13: autophagy related 13; BMDMs: bone marrow-derived macrophages; BafA1: bafilomycin A1; C9orf72: C9orf72, member of C9orf72-SMCR8 complex; CD68: CD68 antigen; ConA: concanamycin A; dKO: double knockout; DENN: differentially expressed in normal and neoplastic cells; FTD: frontotemporal dementia; GEF: guanine nucleotide exchange factor; IFNB1: interferon beta 1, fibroblast; IFNG: interferon gamma; IL1B/IL-1ß: interleukin 1 beta; IL6: interleukin 6; iPSCs: induced pluripotent stem cells; LAMP1: lysosomal-associated membrane protein 1; LPOs: LAMP1-positive organelles; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; LPS: lipopolysaccharide; MTORC1: mechanistic target of rapamycin kinase complex 1; MEFs: mouse embryonic fibroblasts; MNs: motor neurons; NOS2/iNOS: nitric oxide synthase 2, inducible; RAN: repeat-associated non-AUG; RB1CC1/FIP200: RB1-inducible coiled-coil 1; RPS6/S6: ribosomal protein S6; RPS6KB1/S6K1: ribosomal protein S6 kinase, polypeptide 1; SMCR8: Smith-Magenis syndrome chromosome region, candidate 8; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TNF: tumor necrosis factor; TSC1: TSC complex subunit 1; ULK1: unc-51 like kinase 1; v-ATPase: vacuolar-type H⁺-translocating ATPase.

16.
Med Sci Monit ; 25: 8562-8570, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721757

RESUMO

BACKGROUND This study aimed to compare femoral obturator nerve block (FONB) with fascia iliaca compartment block (FICB) in the management of acute preoperative pain in elderly patients with hip fracture. MATERIAL AND METHODS Patients ≥65 years (n=154) diagnosed with hip fracture who had surgery within 48 hours of hospital admission included two groups who received ultrasound-guided nerve block, the FONB group (n=77), and the FICB group (n=77). The visual analog scale (VAS) score for pain, requirement for analgesic drugs, nursing care requirements after hospitalization, post-operative complications, and rehabilitation were compared between the FONB and FICB patient groups. RESULTS The VAS scores after both nerve block procedures were significantly reduced compared with those before both nerve block procedures (P<0.05), but there were no differences on the second day after nerve block. The VAS scores at rest and on exercise in the FONB group were significantly lower than those in the FICB group at 30 min and one day after nerve block (P<0.05). The requirement for postoperative analgesic drugs in the FONB group was significantly lower than that in the FICB group (P=0.048). The incidence of nausea and vertigo in the FICB group were significantly higher than in the FONB group (P=0.031 and P=0.034, respectively). Patients in the FONB group experienced significantly improved quality of postoperative function (P=0.029). CONCLUSIONS Both FONB and FICB provided pain control for elderly patients with hip fracture. However, compared with FICB, FONB resulted in significantly improved analgesia with a reduced requirement for analgesic drugs.

17.
Hum Mol Genet ; 28(23): 3940-3953, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625563

RESUMO

G4C2 repeat expansions in an intron of C9ORF72 cause the most common familial amyotrophic lateral sclerosis and frontotemporal dementia (collectively, C9ALS/FTD). Mechanisms and mediators of C9ALS/FTD pathogenesis remain poorly understood. C9orf72 and Smcr8 form a protein complex. Here, we show that expression of Smcr8, like C9orf72, is reduced in C9ALS/FTD mouse models and patient tissues. Since Smcr8 is highly conserved between human and mouse, we evaluated the effects of Smcr8 downregulation in mice. Smcr8 knockout (KO) mice exhibited motor behavior deficits, which resemble those of C9ALS/FTD mouse models, and displayed axonal swellings in their spinal cords and neuromuscular junctions. These deficits are caused by impaired autophagy-lysosomal functions due to disrupted axonal transport in mutant motor neurons. Consistent with its interaction with C9orf72 and their downregulation in patient tissues, Smcr8 deficiency exacerbated autophagy-lysosomal impairment in C9orf72 KO mice. The disease relevance of Smcr8 downregulation was reflected by exacerbated axonal swellings and gain of toxicity pathology arising from Smcr8 haploinsufficiency in a mouse model of C9ALS/FTD. Thus, our in vivo studies suggested that Smcr8 deficiency impairs axonal transport dependent autophagy-lysosomal function and exacerbates axonal degeneration and gain of toxicity in C9ALS/FTD mouse models.

18.
J Phys Chem B ; 123(38): 7974-7983, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31478672

RESUMO

Understanding the protein-ligand binding is of fundamental biological interest and is essential for structure-based drug design. The difficulty in capturing the dynamic process, however, poses a great challenge for current experimental and theoretical simulation techniques. A selective integrated-tempering-sampling molecular dynamics (SITSMD) method offering an option for selectively enhanced sampling of the ligand in a protein-ligand complex was utilized to quantitatively illuminate the binding of benzamidine to the wild-type trypsin protease and its two mutants (S214E and S214K). The SITSMD simulations could produce consistent results as the extensive conventional MD simulation and gave additional insights into the binding pathway for the test protein-ligand complex system using significantly saved computational resource and time, indicating the potential of such a method in investigating protein-ligand binding. Additionally, the simulations identified the different roles of trypsin-benzamidine van der Waals (vdW) and electrostatic interactions in the binding: the former interaction works as the driving force for dragging the benzamidine close to the native binding pocket, and the latter interaction mainly contributes to stabilizing the benzamidine inside the pocket. The S214E mutation introduces more favorable electrostatic interactions, and as a result, both vdW and electrostatic interactions drive the benzamidine binding, lowering the binding and unbinding free energy barrier. In contrast, the S214K mutation prohibits the binding of the benzamidine to the native ligand binding pocket by introducing disliked charge-charge interactions. In summary, these findings suggest that the change in specific residues could modify the protein druggability, including the binding kinetics and thermodynamics.

19.
Am J Crit Care ; 28(5): 370-376, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474607

RESUMO

BACKGROUND: High-flow oxygen therapy has been widely adopted, but its use for weaning patients from mechanical ventilation has not been reported. OBJECTIVE: To evaluate whether high-flow oxygen therapy improves the efficiency of weaning patients from mechanical ventilation. METHODS: In a single-center, prospective study, patients receiving mechanical ventilation were randomly assigned to 1 of 3 groups (T-tube, pressure support ventilation, or high-flow oxygen) during 2-hour spontaneous breathing trials in a 14-day study. Participants were followed up until hospital discharge or death. RESULTS: Of 268 patients included, 90 were assigned to the T-tube group, 96 to the pressure support ventilation group, and 82 to the high-flow oxygen group. The first-day 2-hour spontaneous breathing trial passing rates were higher in the pressure support ventilation and high-flow oxygen groups than in the T-tube group (P < .05). The time needed to pass the spontaneous breathing trial was less in the pressure support ventilation and high-flow oxygen groups than in the T-tube group (P < .05). The reintubation rate was lower and the successful weaning rate on the first day was higher in the high-flow oxygen group than in the T-tube and pressure support ventilation groups (P < .05). During the 14-day study period, the weaning time was less in the high-flow oxygen group than in the T-tube and pressure support ventilation groups (P < .05). CONCLUSION: High-flow oxygen therapy can reduce the time needed to wean patients from mechanical ventilation by shortening the time needed to pass a spontaneous breathing trial and by decreasing the reintubation rate.

20.
J Chem Phys ; 151(7): 070902, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438687

RESUMO

Although molecular dynamics simulations have become a useful tool in essentially all fields of chemistry, condensed matter physics, materials science, and biology, there is still a large gap between the time scale which can be reached in molecular dynamics simulations and that observed in experiments. To address the problem, many enhanced sampling methods were introduced, which effectively extend the time scale being approached in simulations. In this perspective, we review a variety of enhanced sampling methods. We first discuss collective-variables-based methods including metadynamics and variationally enhanced sampling. Then, collective variable free methods such as parallel tempering and integrated tempering methods are presented. At last, we conclude with a brief introduction of some newly developed combinatory methods. We summarize in this perspective not only the theoretical background and numerical implementation of these methods but also the new challenges and prospects in the field of the enhanced sampling.

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