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1.
J Orthop Surg Res ; 16(1): 422, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215290

RESUMO

BACKGROUND: When symptomatic spondylolysis fail to respond to nonoperative treatment, surgical management may be required. A number of techniques have been described for repair by intrasegmental fixation with good results; however, there are still some problems. We reported a repair technique with temporary intersegmental pedicle screw fixation and autogenous iliac crest graft. The aim of present study is to assess the clinical outcomes of L5 symptomatic spondylolysis with this technique. METHODS: A retrospective analysis of 128 patients with L5 spondylolysis treated with this method was performed. According to CT scan, the spondylolysis were classified into 3 categories: line, intermediate, and sclerosis type. The diagnostic block test of L5 bilateral pars defect was done in all patients preoperatively. The sagittal and axial CT images were used to determine the bone union. The healing time, complications, number of spina bifida occulta, Japanese Orthopedic Association (JOA) score, and VAS for back pain were recorded. After fixation removal, the rate of ROM preservation at L5S1 was calculated. RESULTS: There were 97 patients (194 pars) followed with mean follow-up of 23 months (range, 12-36 months). The union rate of pars was 82.0% at 12 months and 94.3% at 24 months postoperatively. Low back pain VAS significantly (P < 0.05) improved from preoperative mean value of 7.2 to 1.3 at the final follow-up postoperatively (P < 0.05). JOA score increased significantly postoperatively (P < 0.05) with average improvement rate of 79.3%. The rates of L5S1 ROM preservation were 79.8% and 64.0% after fixation removal at 1 and 2 years postoperatively. There were 3 patients of delayed incision healing without other complications. CONCLUSIONS: Although sacrificing L5S1 segment motion temporarily, more stability was obtained with intersegmental fixation. This technique is reliable for spondylolysis repair which has satisfactory symptom relief, high healing rate, low incidence of complications, and preserve a large part of ROM for fixed segment.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34236508

RESUMO

PURPOSE: Although professional societies agreed that CT screening inconsistent with recommendation leads to radiation-related cancer and unexpected cost, many patients still undergo unnecessary Chest CT before treatment. The goal of this study was to assess the overuse of Chest CT in different type of patients. METHODS: Data on 1853 patients who underwent pulmonary resection from May 2019 to May 2020 were retrospectively analyzed. Data collected include age, sex, follow-up period, density and size of nodules and frequency of undergoing Chest CT. Pearson χ2 test and logistic regression were conducted to compare the receipt of CT screening. RESULTS: Among 1853 patients in the study, 689 (37.2%) overused Chest CT during follow-up of the pulmonary nodules. This rate was 16.2% among patients with solid nodules, 57.5% among patients with pure ground glass opacity (pGGO), and 41.4% among patients with mixed ground glass opacity (mGGO) (P < 0.001). 50.7% in the "age ≤ 40" group, 39.8% in the "41 ≤ age ≤ 50" group, 38.7% in the "51 ≤ age ≤ 60" group, 32.3% in the "61 ≤ age ≤ 70" group, 27.8% in the " > 70" group underwent unnecessary CT (P < 0.001). Female got more unnecessary CT than male (40.6% vs 32.8%, P < 0.001). Factors associated with a greater likelihood of overusing Chest CT was the density of nodules [odds ratios (ORs) of 0.53 for mGGO; 0.15 for solid nodule, P < 0.0001, vs patients with pGGO]. CONCLUSION: Roughly 37% patients with pulmonary nodules received Chest CT too frequently despite national recommendations against the practice. Closer adherence to clinical guidelines is likely to result in more cost-effective care.

3.
New Phytol ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255862

RESUMO

Soluble sugars, organic acids and volatiles are important components that determine unique fruit flavor and consumer preferences. However, the metabolic dynamics and underlying regulatory networks that modulate overall flavor formation during fruit development and ripening remain largely unknown for most fruit species. In this study, by integrating flavor-associated metabolism and transcriptome data from 12 fruit developmental and ripening stages of Actinidia chinensis cv. Hongyang, we generated a global map of changes in the flavor-related metabolites throughout development and ripening of kiwifruit. Using this dataset, we constructed complex regulatory networks allowing to identify key structural genes and transcription factors that regulate the metabolism of soluble sugars, organic acids and important volatiles in kiwifruit. Moreover, our study revealed the regulatory mechanism involving key transcription factors regulating flavor metabolism. The modulation of flavor metabolism by the identified key transcription factors was confirmed in different kiwifruit species providing the proof of concept that our dataset provides a suitable tool for clarification of the regulatory factors controlling flavor biosynthetic pathways that have not been previously illuminated. Overall, in addition to providing new insight into the metabolic regulation of flavor during fruit development and ripening, the outcome of our study establishes a foundation for flavor improvement in kiwifruit.

4.
Pathol Oncol Res ; 27: 594931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257545

RESUMO

Introduction: Secretogranin III (SCG3) physiologically participates in neurotransmitter storage/transport and is widely expressed in neuroendocrine tumors. However, there is no report on SCG3 protein expression in gliomas. Methods: The method of immunohistochemical staining on a glioma tissue microarray was utilized to detect SCG3 protein expression and investigate the correlations of its expression with clinicopathological and genetic features in gliomas. The RNA-seq data of SCG3 in The Cancer Genome Atlas database was exploited to explore these correlations at the transcriptional level. Results: There were 57.5% (130/226) glioma cases having SCG3 cytoplasmic staining in the tissue microarray. SCG3 expression inversely correlated with malignancy grade at both transcriptional and protein levels. The highest level was observed in oligodendroglial tumors, especially in oligodendrogliomas (ODs) with IDH-mutation/1p19q-codeletion. The lowest SCG3 expression was observed in glioblastomas (GBMs), especially in the mesenchymal subtype. Nearly a half of GBM cases (44.4%, 64/144) had any discernible SCG3 staining, and were defined as SCG3-positive by the microarray study. SCG3-positive GBM cases exhibited improved overall survival as compared with the SCG3-negative cases (29.3 vs. 14.5 months; Hazard ratio, 0.364; 95% CI, 0.216-0.612; p < 0.001). A multivariate Cox regression analysis also revealed SCG3 positivity as an independent favorable prognosticator in GBM patients. Conclusion: SCG3 protein expression inversely correlates with glioma malignancy and predicts favorable outcomes in GBM patients.

5.
Adv Sci (Weinh) ; 8(13): 2004670, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34258156

RESUMO

The low delivery efficiency of nanoparticles to solid tumors greatly reduces the therapeutic efficacy and safety which is closely related to low permeability and poor distribution at tumor sites. In this work, an "intrinsic plus extrinsic superiority" administration strategy is proposed to dramatically enhance the mean delivery efficiency of nanoparticles in prostate cancer to 6.84% of injected dose, compared to 1.42% as the maximum in prostate cancer in the previously reported study. Specifically, the intrinsic superiority refers to the virus-mimic surface topology of the nanoparticles for enhanced nano-bio interactions. Meanwhile, the extrinsic stimuli of microbubble-assisted low-frequency ultrasound is to enhance permeability of biological barriers and improve intratumor distribution. The enhanced intratumor enrichment can be verified by photoacoustic resonance imaging, fluorescence imaging, and magnetic resonance imaging in this multifunctional nanoplatform, which also facilitates excellent anticancer effect of photothermal treatment, photodynamic treatment, and sonodynamic treatment via combined laser and ultrasound irradiation. This study confirms the significant advance in nanoparticle accumulation in multiple tumor models, which provides an innovative delivery paradigm to improve intratumor accumulation of nanotherapeutics.

6.
Cancer Med ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34258887

RESUMO

BACKGROUND: Even though immunotherapy has been an effective treatment for solid tumors, its efficacy in osteosarcoma remains sub-optimal. It is therefore imperative to understand the complex tumor microenvironment (TME) of osteosarcoma to facilitate the development of immunotherapies against this cancer. METHODS: The mRNA expression profiles of osteosarcoma tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Next, the ssGSEA, MCP-counter, CIBERSORT, and Xcell algorithm analyses were performed to characterize the tumor microenvironment of osteosarcoma tissues. The tumor tissues were divided into inflammatory and non-inflammatory. A comprehensive assessment of immune cell infiltration in osteosarcoma tissues was then performed. Sub-group analysis of immune cell infiltration between men and women patients with osteosarcoma was also carried out. RESULTS: The results revealed that the infiltration of immune cells including activated B cell, activated CD8 T cell, CD56dim natural killer cell, and cytotoxic lymphocytes cells, in osteosarcoma tissues was higher in male than in female patients. Based on the infiltration profile of different immune cells, the osteosarcoma tissues were grouped into four clusters. The four clusters were further divided into hot and cold tumors. The differently expressed genes (DEGs) between cold and hot tumors were mainly associated with the activation and regulation of immune response. Additionally, a neuronal pentraxin (NPTX2) expression which was upregulated in cold tumors was found to be negatively correlated with the expression of CD8a Molecule (CD8A), Granzyme B (GZMB), and Interferon Gamma (IFNG). NPTX2 decreased CCL4 secretion. Knockdown of NPTX2 in osteosarcoma cells inhibited tumor growth and increased tumor cell apoptosis. Moreover, a prognosis prediction model of osteosarcoma was constructed and validated in patients receiving immunotherapy using external data. CONCLUSIONS: To the best of our knowledge, this is the first study to characterize the infiltration of immune cells in osteosarcoma tissues from patients receiving immune infiltration therapy.

7.
Front Immunol ; 12: 647894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262560

RESUMO

Acute graft-versus-host disease (aGVHD) is a lethal complication after allogeneic hematopoietic stem cell transplantation. The mechanism involves the recognition of host antigens by donor-derived T cells which induces augmented response of alloreactive T cells. In this study, we characterized the role of a previously identified novel classical secretory protein with antitumor function-LYG1 (Lysozyme G-like 1), in aGVHD. LYG1 deficiency reduced the activation of CD4+ T cells and Th1 ratio, but increased Treg ratio in vitro by MLR assay. By using major MHC mismatched aGVHD model, LYG1 deficiency in donor T cells or CD4+ T cells attenuated aGVHD severity, inhibited CD4+ T cells activation and IFN-γ expression, promoted FoxP3 expression, suppressed CXCL9 and CXCL10 expression, restrained allogeneic CD4+ T cells infiltrating in target organs. The function of LYG1 in aGVHD was also confirmed using haploidentical transplant model. Furthermore, administration of recombinant human LYG1 protein intraperitoneally aggravated aGVHD by promoting IFN-γ production and inhibiting FoxP3 expression. The effect of rhLYG1 could partially be abrogated with the absence of IFN-γ. Furthermore, LYG1 deficiency in donor T cells preserved graft-versus-tumor response. In summary, our results indicate LYG1 regulates aGVHD by the alloreactivity of CD4+ T cells and the balance of Th1 and Treg differentiation of allogeneic CD4+ T cells, targeting LYG1 maybe a novel therapeutic strategy for preventing aGVHD.

8.
Mol Phylogenet Evol ; : 107257, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34252547

RESUMO

Despite numerous phylogenetic studies on the family Drosophilidae, relationships among some important lineages are still poorly resolved. An example is the equivocal position of the Zygothrica genus group that is mostly comprised of the mycophagous genera Hirtodrosophila, Mycodrosophila, Paramycodrosophila, and Zygothrica. To fill this gap, we conducted a phylogenetic analysis by assembling a dataset of 24 genes from 92 species, including 42 species of the Zygothrica genus group mainly from the Palearctic and Oriental regions. The resulting tree shows that the Zygothrica genus group is monophyletic and places as the sister to the genus Dichaetophora, and the clade Zygothrica genus group + Dichaetophora is sister to the Siphlodora + Idiomyia/Scaptomyza clade. Within the Zygothrica genus group, the genera Mycodrosophila and Paramycodrosophila are both recognized as monophyletic, while neither the genus Zygothrica nor Hirtodrosophila is monophyletic. We also used this phylogenetic tree to investigate the evolution of mycophagy by reconstructing ancestral food habit in the Drosophilidae. We found that fungus-feeding habit has been gained independently in two lineages. The most recent common ancestor (MRCA) of the subgenus Drosophila was estimated to have acquired mycophagy by expanding its ancestral feeding niche on fermenting fruits to decayed fungi, while the MRCA of the Zygothrica genus group shifted its niche from fruits to fungi as a specialist probably preferring fresh fruiting bodies.

9.
Molecules ; 26(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: covidwho-1273485

RESUMO

The human testis and epididymis play critical roles in male fertility, including the spermatogenesis process, sperm storage, and maturation. However, the unique functions of the two organs had not been systematically studied. Herein, we provide a systematic and comprehensive multi-omics study between testis and epididymis. RNA-Seq profiling detected and quantified 19,653 in the testis and 18,407 in the epididymis. Proteomic profiling resulted in the identification of a total of 11,024 and 10,386 proteins in the testis and epididymis, respectively, including 110 proteins that previously have been classified as MPs (missing proteins). Furthermore, Five MPs expressed in testis were validated by the MRM method. Subsequently, multi-omcis between testis and epididymis were performed, including biological functions and pathways of DEGs (Differentially Expressed Genes) in each group, revealing that those differences were related to spermatogenesis, male gamete generation, as well as reproduction. In conclusion, this study can help us find the expression regularity of missing protein and help related scientists understand the physiological functions of testis and epididymis more deeply.

10.
Biochem Biophys Res Commun ; 569: 93-99, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34237433

RESUMO

Salinity is one of the major environmental stresses that limit crop growth and productivity. In this study, the FvMYB24 gene that encodes an R2R3-type MYB transcription factor was cloned and characterized. An expression analysis showed that FvMYB24 had a tissue- and stage-specific profile and was induced by salt treatment. Arabidopsis plants that overexpressed transgenic FvMYB24 exhibited a higher germination rate, fresh weight, chlorophyll content, and longer root length than the wild type (WT) under salt stress. The transgenic plants had higher activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) and the accumulation of proline, while these plants accumulated lower amounts of malondialdehyde (MDA) compared with the WT. Furthermore, our results also revealed that the overexpression of FvMYB24 up-regulated the expression of several stress-related genes (AtSOS1, AtSOS2, AtSOS3, AtSOD, AtPOD, AtCAT1, AtNHX1, and AtLEA3) in response to salt stress, thus, enhancing the tolerance of transgenic Arabidopsis. An analysis of the cis-acting elements in the SOS1, SOS2, and SOS3 promoters revealed MYB-binding sites. However, FvMYB24 could only bind to the SOS1 promoter to mediate salt tolerance but not to the SOS2 and SOS3 promoters. These findings suggest that FvMYB24 could potentially be used as a positive regulator in transgenic plant breeding to improve the tolerance of strawberry plants to salt.

11.
Comp Biochem Physiol C Toxicol Pharmacol ; 249: 109130, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34246796

RESUMO

Avermectin (AVM), is widely applied in the fields of agriculture, possess activities against mites and insects. AVM is generally thought to keep the GABA-related chloride channels open in insect cells. However, AVM induces cytotoxicity in non-neural cells still ambiguous. Here we evaluate the cytotoxicity and other mode of action of AVM in Spodoptera frugiperda (Sf9) cells. Our results showed that AVM suppressed the activity of Sf9 cells and induced programmed cell death. DNA damage of Sf9 cells was detected by alkaline comet assay and PARP. The cleavage of poly ADP-ribose polymerase (PARP) and DNA double-strand breaks demonstrated AVM induced DNA damage in Sf9 cells. In addition, a series of established cytotoxicity tests were conducted to explore the mechanism of AVM toxicity in Sf9 cells. Typical apoptosis changes were occurred including increasing the expression of Bax/Bcl-2 and the activation of caspase-9/-3. Subsequently, Western blotting was used to detected autophagy related proteins including LC3, Beclin1 and p62. We found that AVM upregulated LC3, Beclin1 expression and downregulated p62 expressions. Moreover, we found that AVM induced autophagy may through AMPK/mTOR-mediated autophagy pathway. These results showed that AVM-induced DNA damage and programmed cell death in Sf9 cells.

12.
Biomarkers ; : 1-8, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34266319

RESUMO

BACKGROUND: Patients with colorectal cancer usually have a poor prognosis because of the absence of suitable biomarkers for diagnosing asymptomatic patients. Here we determined the ability of MIC-1 to detect precancerous lesions and CRC in an asymptomatic cohort from CRC Screening Program. METHODS: We screened 2759 subjects with risk factors. Endoscopic and histopathological analyses revealed that 19 and 47 subjects had CRC or precancerous lesions. We randomly selected 24 subjects with normal colonoscopies as healthy controls. We used receiver operating characteristic curve analysis to evaluate the diagnostic efficacy of MIC-1 for CRC and precancerous lesions. RESULTS: The optimal thresholds of MIC-1 levels with precancerous lesions or CRC were 314.12 pg/mL (sensitivity, 91.50%; specificity, 54.20%) and 357.64 pg/mL (sensitivity, 82.40%; specificity, 70.80%). Moreover, MIC-1 levels distinguished precancerous lesions better than CEA, CA19-9, or CA24-2 (AUC: 0.760 vs. 0.529, 0.624, and 0.585) or CRC (AUCs: 0.821 vs. 0.743, 0.657, and 0.688) from the healthy controls. The combination of MIC-1, CEA, CA19-9, and CA24-2 showed the highest in sensitivity and specificity for CRC diagnosis (sensitivity, 94.10%; specificity, 87.50%). CONCLUSIONS: Serum MIC-1 levels increased the sensitivity of detection of precancerous colorectal lesions and CRC and can be used to improve screening.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34287680

RESUMO

OBJECTIVES: Reports about the radiologic features of minute pulmonary meningothelial-like nodules are sparse. This study aims to investigate the radiologic features of minute pulmonary meningothelial-like nodules. METHOD: From January 2016 to April 2019, 7589 patients underwent pulmonary resections at Fudan University Shanghai Cancer Center. Postoperative pathology records were reviewed retrospectively. Fifty-nine patients with minute pulmonary meningothelial-like nodule were included. The identification of minute pulmonary meningothelial-like nodules in pathology specimen included pathologically confirmed in resected nodules, and discovery in the peripheral tissue of other resected nodules incidentally. We went back and checked all the pre-operative scans of patients to analyze surgical decision and observe any change of visible minute pulmonary meningothelial-like nodule over time. Clinic, radiologic and pathological features were collected. RESULT: Fifty-nine patients included 10 men and 49 women, with a mean age of 57.7. Five patients had history, while 54 patients were non-smokers. 79 min pulmonary meningothelial-like nodules was found. Of them, 36 nodules were not visible on computed tomography scan. 43 nodules were visible on computed tomography scan, with an average size of 5.3 mm in 29 patients. Computed tomography appearance included pure ground-glass opacity in 36, mixed in 2, and solid nodules in 5. Nearly half of patients had a pre-operative follow-up more than 6 months (13/29, 44.8%). The median pre-operative radiologic follow-up was 4.9 months. Approximately 90% of patients underwent pulmonary surgery because of other malignant nodule on chest computed tomography scan (52/59, 88.1%). CONCLUSION: Most minute pulmonary meningothelial-like nodules tend to present as ground-glass opacity, especially pure ground-glass opacity. Continuous computed tomography monitoring revealed no radiologic change over time. Continuous computed tomography monitoring was necessary part of management of minute pulmonary meningothelial-like nodule.

15.
Molecules ; 26(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199411

RESUMO

The human testis and epididymis play critical roles in male fertility, including the spermatogenesis process, sperm storage, and maturation. However, the unique functions of the two organs had not been systematically studied. Herein, we provide a systematic and comprehensive multi-omics study between testis and epididymis. RNA-Seq profiling detected and quantified 19,653 in the testis and 18,407 in the epididymis. Proteomic profiling resulted in the identification of a total of 11,024 and 10,386 proteins in the testis and epididymis, respectively, including 110 proteins that previously have been classified as MPs (missing proteins). Furthermore, Five MPs expressed in testis were validated by the MRM method. Subsequently, multi-omcis between testis and epididymis were performed, including biological functions and pathways of DEGs (Differentially Expressed Genes) in each group, revealing that those differences were related to spermatogenesis, male gamete generation, as well as reproduction. In conclusion, this study can help us find the expression regularity of missing protein and help related scientists understand the physiological functions of testis and epididymis more deeply.


Assuntos
Epididimo/química , Perfilação da Expressão Gênica/métodos , Mapas de Interação de Proteínas , Proteômica/métodos , Testículo/química , Cromatografia Líquida , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , Especificidade de Órgãos , Análise de Sequência de RNA , Espermatogênese , Espectrometria de Massas em Tandem
16.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209110

RESUMO

Positively charged groups that mimic arginine or lysine in a natural substrate of trypsin are necessary for drugs to inhibit the trypsin-like serine protease TMPRSS2 that is involved in the viral entry and spread of coronaviruses, including SARS-CoV-2. Based on this assumption, we identified a set of 13 approved or clinically investigational drugs with positively charged guanidinobenzoyl and/or aminidinobenzoyl groups, including the experimentally verified TMPRSS2 inhibitors Camostat and Nafamostat. Molecular docking using the C-I-TASSER-predicted TMPRSS2 catalytic domain model suggested that the guanidinobenzoyl or aminidinobenzoyl group in all the drugs could form putative salt bridge interactions with the side-chain carboxyl group of Asp435 located in the S1 pocket of TMPRSS2. Molecular dynamics simulations further revealed the high stability of the putative salt bridge interactions over long-time (100 ns) simulations. The molecular mechanics/generalized Born surface area-binding free energy assessment and per-residue energy decomposition analysis also supported the strong binding interactions between TMPRSS2 and the proposed drugs. These results suggest that the proposed compounds, in addition to Camostat and Nafamostat, could be effective TMPRSS2 inhibitors for COVID-19 treatment by occupying the S1 pocket with the hallmark positively charged groups.


Assuntos
Antivirais/química , Serina Endopeptidases/metabolismo , Inibidores de Serino Proteinase/química , Antivirais/metabolismo , Antivirais/uso terapêutico , Benzamidinas/química , Benzamidinas/metabolismo , Sítios de Ligação , COVID-19/tratamento farmacológico , COVID-19/patologia , COVID-19/virologia , Domínio Catalítico , Ésteres/química , Ésteres/metabolismo , Guanidinas/química , Guanidinas/metabolismo , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Serina Endopeptidases/química , Inibidores de Serino Proteinase/metabolismo , Inibidores de Serino Proteinase/uso terapêutico , Termodinâmica
17.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: covidwho-1288905

RESUMO

Positively charged groups that mimic arginine or lysine in a natural substrate of trypsin are necessary for drugs to inhibit the trypsin-like serine protease TMPRSS2 that is involved in the viral entry and spread of coronaviruses, including SARS-CoV-2. Based on this assumption, we identified a set of 13 approved or clinically investigational drugs with positively charged guanidinobenzoyl and/or aminidinobenzoyl groups, including the experimentally verified TMPRSS2 inhibitors Camostat and Nafamostat. Molecular docking using the C-I-TASSER-predicted TMPRSS2 catalytic domain model suggested that the guanidinobenzoyl or aminidinobenzoyl group in all the drugs could form putative salt bridge interactions with the side-chain carboxyl group of Asp435 located in the S1 pocket of TMPRSS2. Molecular dynamics simulations further revealed the high stability of the putative salt bridge interactions over long-time (100 ns) simulations. The molecular mechanics/generalized Born surface area-binding free energy assessment and per-residue energy decomposition analysis also supported the strong binding interactions between TMPRSS2 and the proposed drugs. These results suggest that the proposed compounds, in addition to Camostat and Nafamostat, could be effective TMPRSS2 inhibitors for COVID-19 treatment by occupying the S1 pocket with the hallmark positively charged groups.


Assuntos
Antivirais/química , Serina Endopeptidases/metabolismo , Inibidores de Serino Proteinase/química , Antivirais/metabolismo , Antivirais/uso terapêutico , Benzamidinas/química , Benzamidinas/metabolismo , Sítios de Ligação , COVID-19/tratamento farmacológico , COVID-19/patologia , COVID-19/virologia , Domínio Catalítico , Ésteres/química , Ésteres/metabolismo , Guanidinas/química , Guanidinas/metabolismo , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Serina Endopeptidases/química , Inibidores de Serino Proteinase/metabolismo , Inibidores de Serino Proteinase/uso terapêutico , Termodinâmica
18.
Ann Palliat Med ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34263622

RESUMO

BACKGROUND: Ventricular late potentials (VLPs) detected by signal-averaged electrocardiogram are considered as an indicator of electrical instability in diseased myocardium. Little information exists about the VLPs and their effects on clinical prognosis in patients with obstructive hypertrophic cardiomyopathy (OHCM) undergoing septal myectomy. METHODS: Patients with OHCM who underwent septal myectomy from January 2019 to December 2019 were prospectively enrolled. All patients underwent signal-averaged electrocardiogram. Patients were subsequently divided into two groups based on the presence or absence of VLPs. All patients were followed up after surgery to obtain information of survival status and adverse events, including all-cause mortality, congestive heart failure requiring hospitalization, new-onset stroke, and unexplained syncope. RESULTS: In total, 128 patients (47.5±12.8 years, 57.8% male) were enrolled. There were 21 (16.4%) individuals in the VLPs-positive group and 107 (83.6%) individuals in the VLPs-negative group. There were no statistically significant differences in non-sustained ventricular tachycardia and late gadolinium enhancement on cardiovascular magnetic resonance images between the two groups. Eight adverse events were reported at the 14.9±4.1 months follow-up. The rates of adverse events in groups of VLPs-positive and VLPs-negative were 23.8% (5/21) and 2.8% (3/107) of cases, respectively. These events included three patients hospitalized for heart failure, two who experienced ischemic strokes, and three with unexplained syncope, respectively. Patients in the VLPs-positive group had a higher risk of adverse events than those in the VLPs-negative group (P<0.001). The presence of positive VLPs (hazard ratio =9.095, 95% confidence intervals: 2.080-39.776, P=0.003) was a strong independent risk factor of adverse events by multivariate Cox regression analysis. Cardiac function Class III or IV, as defined by the New York Heart Association classification, was also an independent risk factor of adverse events (hazard ratio =13.756, 95% confidence intervals: 1.667-113.510, P=0.015). CONCLUSIONS: VLPs may increase the risk of adverse events in patients with OHCM after septal myectomy, which may be used as a screening test for further risk stratification.

19.
J Am Coll Health ; : 1-10, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242537

RESUMO

OBJECTIVES: Mental health first aid (MHFA) may have beneficial effects on the public's knowledge, attitude, and behavior; however, its effectiveness in increasing mental health literacy on college students remains unknown. METHODS: We systematically searched the PubMed, EMBASE, and Cochrane Library databases from inception to January 2020. We included trials that compared the effect between the MHFA program group and control group on the knowledge, stigmatizing attitudes, confidence, and intention of college students. A random-effects model was used. RESULTS: We analyzed five trials involving 1134 participants and found that the MHFA program could significantly increase the student's knowledge (SMD: 0.49, 95% CI: [0.28-0.70]) and confidence (SMD: 0.71, 95% CI: 0.24-1.19). CONCLUSIONS: Overall, the MHFA program could increase college students' knowledge regarding mental health and confidence to support people with mental health problems. However, well-designed control trials are required to investigate the program's effect on mental health literacy in college students. ABBREVIATIONS: MHFA, Mental health first aid; GPs, General Practioners; CI, confidence interval; SMD, standardized mean24difference.

20.
Bioinspir Biomim ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243174

RESUMO

This research reports the numerical results of the ground effect trend for a three-dimensional (3D) flapping insect wing at a very low Reynolds number (Re=10). It demonstrates that the ground effect trend at this Re has a "single force regime," i.e., the forces only enhance as the ground distance decreases. This phenomenon is unlike the widely expected non-monotonic trend publicized in previous studies for higher Reynolds numbers, that shows "three force regimes," i.e., the forces reduce, recover, and also enhance as the ground distance decreases. The force trend in the ground effect correlates to a similar trend in wing-wake interaction or the downwash strength on the wing's head. At very low Re (10), the very large viscosity causes diffused vortices and less advected vortex wake, while at relatively high Re, the vortices are easily separated from the wing and then advected downwards. This different development of the vortex wake caused different force trends for the flapping wing in the ground effect. Furthermore, by examining only the first stroke when there is no vortex wake, we found that the "ramming effect" enhances the forces on the wing. This effect increases the pressure of the lower wing surface due to the squeezed air between the wing and the ground. The "ramming effect", combined with the reduced downwash (or wing-wake interaction) effect, causes the force enhancement of the wing near the ground's vicinity. It is further comprehended that the trend is dependent on Re. As the Re is increased, the trend becomes non-monotonic. The effect of varying angles of attack, flapping amplitude and wing planform at very low Re does not change this trend. This ground effect might help insects by enhancing their lift while they hover above the surface. This finding might prove beneficial for developing Micro Air Vehicles.

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