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1.
BMC Plant Biol ; 21(1): 123, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648456

RESUMO

BACKGROUND: The CIPKs are a group of plant-specific Ser/Thr protein kinases acting in response to calcium signaling, which plays an important role in the physiological and developmental adaptation of plants to adverse environments. However, the functions of halophyte-derived CIPKs are still poorly understood, that limits a potential application of CIPKs from halophytes for improving the tolerance of glycophytes to abiotic stresses. RESULTS: In this study, we characterized the NtCIPK11 gene from the halophyte Nitraria tangutorum and subsequently analyzed its role in salt and drought stress tolerance, using Arabidopsis as a transgenic model system. NtCIPK11 expression was upregulated in N. tangutorum root, stem and blade tissues after salt or drought treatment. Overexpressing NtCIPK11 in Arabidopsis improved seed germination on medium containing different levels of NaCl. Moreover, the transgenic plants grew more vigorously under salt stress and developed longer roots under salt or drought conditions than the WT plants. Furthermore, NtCIPK11 overexpression altered the transcription of genes encoding key enzymes involved in proline metabolism in Arabidopsis exposed to salinity, however, which genes showed a relatively weak expression in the transgenic Arabidopsis undergoing mannitol treatment, a situation that mimics drought stress. Besides, the proline significantly accumulated in NtCIPK11-overexpressing plants compared with WT under NaCl treatment, but that was not observed in the transgenic plants under drought stress caused by mannitol application. CONCLUSIONS: We conclude that NtCIPK11 promotes plant growth and mitigates damage associated with salt stress by regulating the expression of genes controlling proline accumulation. These results extend our understanding on the function of halophyte-derived CIPK genes and suggest that NtCIPK11 can serve as a candidate gene for improving the salt and drought tolerance of glycophytes through genetic engineering.

2.
Medicine (Baltimore) ; 100(7): e24382, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607772

RESUMO

INTRODUCTION: Subchromosomal deletions and duplications could currently be detected by noninvasive preliminary screening (NIPS). However, NIPS is a screening test that requires further diagnosis. Here we report a fetus with an autosomal abnormality revealed by NIPS and conventional karyotype combined with copy number variations sequencing (CNV-seq) confirmed the fetus with an unbalanced translocation. PATIENT CONCERN: This was the fourth pregnancy of a 30-year-old woman who underwent 2 spontaneous abortions and gave birth to a child with a normal phenotype. The woman and her husband were healthy and nonconsanguineous. NIPS indicated a repeat of about 19-Mb fragment at the region of 16q22.1-q22.4 at 17-week gestation. DIAGNOSES: The combination of traditional karyotype and CNV-seq could better locate the abnormal chromosomal region and further identify the source of fetal chromosomal abnormalities. Simultaneously, we evaluated the fetal morphology by ultrasound examination. The karyotype of the fetus was 46,XX,der(7)t(7;16)(p22;q23) and CNV-seq results showed an approximately 20.96-Mb duplication in 16q22.1-q24.3 (69200001-90160000) and an approximately 3.86-Mb deletion in 7p22.3-p22.2 (40001-3900000). Prenatal ultrasound revealed the fetal micrognathia. The paternal karyotype was 46,XY, t (7;16) (p22;q23), while the maternal was normal. The fetus inherited an abnormal chromosome 7 from its father. INTERVENTIONS: No treatment for the fetus. OUTCOMES: Pregnancy was terminated. CONCLUSIONS: To our knowledge, the occurrence of de novo partial trisomy 16q (16q22.1-qter) and partial monosomy 7p (7p22.2-pter) has not previously been reported up to now. Here, we present the perinatal findings of such a case and a review of the literatures. CNV-seq combined with karyotype is a useful tool for chromosomal abnormalities indicated by NIPS.


Assuntos
Cromossomos Humanos Par 7/genética , Monossomia/diagnóstico , Trissomia/genética , Aborto Eugênico , Adulto , Amniocentese , Cromossomos Humanos Par 16/genética , Feminino , Humanos , Gravidez , Translocação Genética/genética , Trissomia/diagnóstico , Sequenciamento Completo do Genoma
3.
Bioorg Med Chem ; 29: 115890, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33285407

RESUMO

As abnormal PI3K signaling is a feature of many types of cancer, the development of orally active PI3K inhibitors is of great significance for targeted cancer therapy. Through integrating strategies of reducing aromatic character/increasing the fraction of sp3 carbons together with scaffold hopping, we designed and synthesized two new series of thieno[2,3-d]pyrimidine and thiazolo[5,4-d]pyrimidine derivatives for use as PI3K inhibitors. Our structure-activity relationship studies led to the identification of thieno[2,3-d]pyrimidine 6a and thiazolo[5,4-d]pyrimidine 7a, which exhibited remarkable nanomolar PI3K potency, good antiproliferative activity, favorable pharmacokinetic properties and significant in vivo anti-cancer efficacy. Notably, thiazolo[5,4-d]pyrimidine 7a had better anti-cancer activity than thieno[2,3-d]pyrimidine 6a and is worthy of further pre-clinical evaluation for its use in cancer treatment.

4.
Int J Mol Sci ; 21(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255277

RESUMO

Relevant, predictive normal, or disease model systems are of vital importance for drug development. The difference between nonhuman models and humans could contribute to clinical trial failures despite ideal nonhuman results. As a potential substitute for animal models, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) provide a powerful tool for drug toxicity screening, modeling cardiovascular diseases, and drug discovery. Here, we review recent hiPSC-CM disease models and discuss the features of hiPSC-CMs, including subtype and maturation and the tissue engineering technologies for drug assessment. Updates from the international multisite collaborators/administrations for development of novel drug discovery paradigms are also summarized.

5.
Zhongguo Gu Shang ; 33(11): 1068-71, 2020 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-33269860

RESUMO

OBJECTIVE: To investigate the effect of intra-articular injection of tranexamic acid on blood loss and blood transfusion rate after minimally invasive unicompartmental knee arthroplasty. METHODS: From January 2015 to September 2017, 90 patients underwent minimally invasive unicompartmental knee arthroplasty were divided into tranexamic acid group and control group, 45 cases in each group. In the tranexamic acid group, there were 22 males and 23 females, aged 62 to 69 (66.1±2.4) years;in the control group, 20 males and 25 females, aged 63 to 71(68.5±5.2) years. The amount of bleeding in the drainage ball at 48 hours after operation was recorded, and the blood transfusion rate and hematocrit level duringthe perioperative period were recorded. The factors influencing perioperative blood loss included gender, age and body mass index (BMI). RESULTS: All patients were followed up for 12.5 to 28.3 (22.8±7.9) months. During the follow-up, the wounds of the two groups healed well, and no deep vein thrombosis and pulmonary embolism occurred. There was no significant difference in postoperative blood loss between the tranexamic acid group and the control group. The postoperative bleeding volume in the tranexamic acid group was (110.0±52.1) ml, and that in the control group was (123.0±64.5) ml (P=0.39). There was no blood transfusion in the two groups. CONCLUSION: Intra articular injection of tranexamic acid can not significantly reduce the postoperative blood loss in patients with minimally invasive unicompartment.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33160629

RESUMO

Semi-transparent TiO2/graphene photoanodes are prepared at room temperature via an electrophoretic deposition method followed by compression and applied in dye-sensitized solar cells (DSSCs). Compression enhances the power conversion efficiency (PCE) of a DSSC, which constitutes up 18.4 times improvement compared to the uncompressed device. Incorporating graphene into the compressed film further improves the PCE by 28.8%. Simultaneously, compressing and graphene incorporating can greatly increase the film's transmittance at long wavelengths, benefiting to the use of DSSCs as front unit in tandem solar cells. Scanning electron microscopy, porosity measurements, electrochemical impedance spectroscopy and open circuit voltage decay are performed to investigate the mechanisms. It is demonstrated that compressing a film can reduce the porosity and improve the inter-particle connections, which accounts for the increased light transmittance and enhanced PCE. The incorporated graphene can provide extra charge carrier pathway due to its excellent charge transport properties, as well as protect TiO2 nanostructure by preventing film cracking upon pressing due to its good flexibility, thus increases PCE to 6.75%, which, to our best knowledge, is the highest value among DSSCs with room-temperature prepared photoanodes.

7.
Biomed Pharmacother ; 131: 110764, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152927

RESUMO

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is thought to be a risk factor for endometrial hyperplasia, but potential links between the two diseases are unknown. This study aims to evaluate the role of T2DM in the progression of endometrial hyperplasia. METHODS: Female Sprague-Dawley rats were randomly divided into normal (N) group, endometrial hyperplasia (NH) group, T2DM (T) group, and endometrial hyperplasia with T2DM (TH) group. Proteomics analysis was performed to determine the protein profile of endometrial tissues. Proliferation, migration, and invasion of cells with/without GLANT2-knockdown were assessed. Immunohistochemical staining and ELISA were used to examine the expression of GALNT2 in endometrial tissues and serum of clinical samples. RESULTS: The highest uterus index and endometrial thickness were observed in TH group, with the expression of proliferation marker PCNA increased significantly, indicating that T2DM facilitates the progress of endometrial hyperplasia. Proteomics analysis showed that there were significant differences in protein profiles among groups and differential proteins were mainly enriched in metabolic pathways. Further verification by molecular biology analysis indicated that GALNT2 is the key target for T2DM facilitating endometrial hyperplasia. The expression of GALNT2 was significantly decreased in high glucose environment. T2DM could synergize the proliferative function of GALNT2 aberration by activating EGFR/AKT/ERK pathway. The decreased expressions of GALNT2 in clinical samples were associated with worse subtypes of endometrial hyperplasia. CONCLUSION: T2DM promoted the progression of endometrial hyperplasia by regulating the GALNT2-mediated phosphorylation of EGFR and enhancing cell proliferation. GALNT2 has the potential to be a novel biomarker in the treatment of endometrial hyperplasia.

8.
Curr Pharm Des ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183190

RESUMO

Protein palmitoylation is a fundamental and reversible post-translational lipid modification that involves a series of biological processes. Although a large number of experimental studies have explored the molecular mechanism behind the palmitoylation process, the computational methods has attracted much attention for its good performance in predicting palmitoylation sites compared with expensive and time-consuming biochemical experiments. The prediction of protein palmitoylation sites is helpful to reveal its biological mechanism. Therefore, the research on the application of machine learning methods to predict palmitoylation sites has become a hot topic in bioinformatics and promoted the development in related fields. In this review, we briefly introduced the recent development in predicting protein palmitoylation sites by using machine learning-based methods and discussed their benefits and drawbacks. The perspective of machine learning-based methods in predicting palmitoylation sites was also provided. We hope the review could provide a guide in related fields.

9.
Molecules ; 25(20)2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33053730

RESUMO

A series of novel 2-pyridyl, 4-morpholinyl substituted thiazolo[5,4-b]pyridine analogues have been designed and synthesized in this paper. These thiazolo[5,4-b]pyridines were efficiently prepared in seven steps from commercially available substances in moderate to good yields. All of these N-heterocyclic compounds were characterized by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) analysis and tested for phosphoinositide 3-kinase (PI3K) enzymatic assay. The results indicated that these N-heterocyclic compounds showed potent PI3K inhibitory activity, and the IC50 of a representative compound (19a) could reach to 3.6 nm. The structure-activity relationships (SAR) study showed that sulfonamide functionality was important for PI3Kα inhibitory activity, and 2-chloro-4-florophenyl sulfonamide (19b), or 5-chlorothiophene-2-sulfonamide (19c) showed potent inhibitory activity with a nanomolar IC50 value. The pyridyl attached to thiazolo[5,4-b]pyridine was another key structural unit for PI3Kα inhibitory potency, and replacement by phenyl lead to a significant decrease in activity. Enzymatic Inhibition results showed that compound 19a inhibited PI3Kα, PI3Kγ, or PI3Kδ with a nanomolar IC50 value, but its inhibitory activity on PI3Kß was approximately 10-fold reduced. Further docking analysis revealed that the N-heterocyclic core of compound 19a was directly involved in the binding to the kinase through the key hydrogen bonds interaction.

10.
Diabetes Metab Syndr Obes ; 13: 3959-3968, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122932

RESUMO

Background: Few studies have considered the interplay between commuting mode and air pollution on obesity. The aim of this study was to examine whether workplace air pollutants exposure modifying the associations between different commuting mode and obesity. Methods: A cross-sectional study of workers in Beijing was conducted in 2016. The study sample comprised 10,524 participants aged 18 to 65 years old. Outcomes were defined as overall obesity (BMI≥ 28 kg/m2) and abdominal obesity (WC ≥ 85 cm in men and WC ≥ 80 cm in women). Commuting modes were divided into walking, cycling, bus, subway, and car or taxi. Logistic regression models were used to estimate odds ratios relating commuting mode to overall and abdominal obesity and stratified by gender, controlling for covariates. Results: The association between commuting mode and obesity was more strongly in men than women. In the fully adjusted models, compared with car or taxi commuters, cycling (men: OR=0.37, 95% CI=0.20 to 0.68) or bus (men: OR=0.58, 95% CI=0.36 to 0.94) counterparts had a lower risk of overall obesity. Compared with car or taxi commuters, walking (men: OR=0.57, 95% CI=0.36 to 0.91), bus (men: OR=0.59, 95% CI=0.39 to 0.89), or subway (men: OR=0.59, 95% CI=0.39 to 0.89) counterparts had a lower risk of abdominal obesity. We observed significant interactions between exposure PM10 and cycling on overall obesity in men. After adjusting for air pollutants, the association between commuting mode and obesity was slightly strengthened. Conclusion: This study findings indicate that active (walking or cycling) or public (bus or subway) commuting modes were protected factors for overall and abdominal obesity among men. Air pollutants do not obscure the benefits of active or public commuting for obesity. These associations support the policy for increasing active or public commuting as a strategy to reduce the prevalence of obesity.

11.
Cell Mol Immunol ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963358

RESUMO

Liver X receptors (LXRs) are known as key transcription factors in lipid metabolism and have been reported to play an important role in T-cell proliferation. However, whether LXRs play a role in thymocyte development remains largely unknown. Here, we demonstrated that LXRß deficiency caused a reduction in single-positive (SP) thymocytes, whereas the transitions from the double-negative to SP stage were normal. Meanwhile, LXRß-null SP thymocytes exhibited increased apoptosis and impairment of the IL-7Rα-Bcl2 axis. In addition, the LXR agonist T0901317 promoted the survival of SP thymocytes with enhanced IL-7Rα expression in wild-type mice but not in LXRß-deficient mice. Mechanistically, LXRß positively regulated the expression of IL-7Rα via direct binding to the Il7r allele in SP thymocytes, and forced expression of IL-7Rα or Bcl2 restored the survival of LXRß-defective SP thymocytes. Thus, our results indicate that LXRß functions as an important transcription factor upstream of IL-7Rα to promote the survival of SP thymocytes.

12.
Front Plant Sci ; 11: 1112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973820

RESUMO

Calcineurin B-like protein-interacting protein kinases (CIPKs) play essential roles in plant abiotic stress response. In order to better understand salt tolerance, we cloned and analyzed the NtCIPK9 gene from the halophyte Nitraria tangutorum. Phylogenetic analysis shows that NtCIPK9 belongs to a sister clade with the Arabidopsis AtCIPK9 gene and is thought to localize to the plasma membrane. NtCIPK9 shows the highest expression level in the Nitraria tangutorum root under normal growth conditions, whereas after NaCl treatment, the highest expression was found in the blade. NtCIPK9-overexpressing Arabidopsis plants have a higher seed germination rate, longer root length, and displayed higher salt tolerance than wild type seedlings under salt stress conditions. Furthermore, NtCIPK9 overexpression might enhance the expression of genes related to K+ transportation after NaCl treatment. Thus, we conclude that NtCIPK9 increases transgenic plant salt tolerance and reduces damage associated with salt stress by promoting the expression of genes controlling ion homeostasis. Our results suggest that NtCIPK9 could serve as an ideal candidate gene to genetically engineer salt-tolerant plants.

13.
Cancer Lett ; 495: 22-32, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-32931884

RESUMO

The tubulin colchicine binding site has been recognized as an attractive drug target to combat cancer, but none of the candidate drugs have been approved for medical treatment. We recently identified a structurally distinct small molecule S-40 as an oral potent tubulin destabilizing agent. Crystal structure analysis of S-40 in a complex with tubulin at a resolution of 2.4 Å indicated that S-40 occupies all 3 zones in the colchicine pocket with interactions different from known microtubule inhibitors, presenting unique effects on assembly and curvature of tubulin dimers. S-40 overcomes paclitaxel resistance and lacks neurotoxicity, which are the main obstacles limiting clinical applications of paclitaxel. Moreover, S-40 harbors the ability to inhibit growth of cancer cell lines as well as patient-derived organoids, induce mitotic arrest and cell apoptosis. Xenograft mouse models of human prostate cancer DU145, non-small cell lung cancer NCI-H1299 and paclitaxel-resistant A549 were strongly restrained without apparent side effects by S-40 oral administration once daily. These findings provide evidence for the development of S-40 as the next generation of orally effective microtubule inhibitors for cancer therapy.

14.
Cell Prolif ; 53(10): e12902, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945585

RESUMO

OBJECTIVES: Calcium oxalate (CaOx) crystals can activate inflammatory cytokines by triggering inflammasomes, which cause damage to the adhered epithelium, a dysfunctional microenvironment and even renal failure. However, a comprehensive and in-depth understanding of the mechanisms underlying the effects of these crystals on damage and cytokine function in renal tubular epithelial cells (TECs) remains limited and to be explored. MATERIALS AND METHODS: We detected the pyroptosis of TECs induced after exposure to CaOx crystals and demonstrated the significance of cytokine activation in the subsequent inflammatory processes through a proteomic study. We then conducted animal and cell experiments to verify relevant mechanisms through morphological, protein, histological and biochemical approaches. Human serum samples were further tested to help explain the pathophysiological mechanism of H3 relaxin. RESULTS: We verified that crystal-induced extracellular adenosine triphosphate (ATP) upregulation via the membrane purinergic 2X7 receptor (P2X7 R) promotes ROS generation and thereby activates NLRP3 inflammasome-mediated interleukin-1ß/18 maturation and gasdermin D cleavage. Human recombinant relaxin-3 (H3 relaxin) can act on the transmembrane receptor RXFP1 to produce cAMP and subsequently improves crystal-derived damage via ATP consumption. Additionally, endogenous relaxin-3 was found to be elevated in patients with renal calculus and can thus serve as a biomarker. CONCLUSIONS: Our results provide previously unidentified mechanistic insights into CaOx crystal-induced inflammatory pyroptotic damage and H3 relaxin-mediated anti-inflammatory protection and thus suggest a series of potential therapeutic targets and methods for but not limited to nephrocalcinosis.


Assuntos
Anti-Inflamatórios/farmacologia , Oxalato de Cálcio/farmacologia , Piroptose/efeitos dos fármacos , Relaxina/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Oxalato de Cálcio/química , Linhagem Celular , AMP Cíclico/metabolismo , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Receptores de Peptídeos/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Relaxina/sangue
15.
Atherosclerosis ; 311: 44-51, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32937242

RESUMO

BACKGROUND AND AIMS: The temporal relationship between hyperuricemia and non-alcoholic fatty liver disease (NAFLD) is debatable. This study aimed to explore whether there exists a bidirectional or temporal relationship between them. METHODS: A total of 11,585 participants were recruited from the Beijing Health Management Cohort during the period 2012-2016. We evaluated whether hyperuricemia was associated with NAFLD development (part I) and whether NAFLD was associated with hyperuricemia incidence (part II) using a logistic regression model. Further, the cross-lagged panel analysis model was used to simultaneously examine the bidirectional relationship between hepatic steatosis and serum uric acid (SUA) (part III). Subgroup and interaction analyses were also performed to assess whether other variables moderated those relationships. RESULTS: In part I, multiple logistic regression indicated that baseline hyperuricemia was associated with the development of NAFLD (OR = 1.5970, p < 0.0001). In part II, multiple logistic regression showed that baseline NAFLD was not correlated with hyperuricemia incidence (OR = 0.8600, p = 0.1976). In part III, cross-lagged panel analyses indicated that the standard regression coefficient of baseline SUA to follow-up hepatic steatosis (0.1516) was significantly greater than the coefficient from the baseline hepatic steatosis to follow-up SUA (-0.0044) with p < 0.0001 for the difference. This indicated a unidirectional relationship from baseline SUA to follow-up hepatic steatosis, suggesting hyperuricemia may precede NAFLD; and this relationship was not affected by age, sex, dyslipidemia, metabolism syndrome, diabetes but was moderated by abdominal obesity. CONCLUSIONS: This study demonstrated a unidirectional relationship from hyperuricemia to NAFLD incidence, and suggested that lowering SUA levels in hyperuricemia patients may prevent subsequent NAFLD.

16.
Pathol Res Pract ; 216(10): 153149, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853964

RESUMO

Endometrial carcinoma (EC), an estrogen-dependent gynecological malignancy, is prevalent worldwide. Estrogen receptor α (ERα) and estrogen receptor ß (ERß) are two main estrogen receptor isoforms, which mediate estrogen-induced proliferation in EC. However, the dynamic changes of ERα and ERß subtype expression and their functions on proliferation in EC remain elusive. In this study, we aimed to investigate the expression of ERα and ERß in para-tumor eutopic endometrium, endometrial atypical hyperplasia and EC by immunohistochemistry and then analyse their clinical significance. Subsequently, Ishikawa cells with ERα or ERß knockdown by lentivirus transfection were used to explore the relationship between ERα/ERß and cell proliferation, and preliminarily evaluate whether metformin's inhibitory effect on estrogen-induced cell proliferation was mediated by ERα and ERß. We found that the expression of ERα and ERß were markedly changed in endometrial hyperplasia and EC compared with that in para-tumor eutopic endometrium and exhibited different expression trends. Through further analysis, we discovered that ERα presented higher expression in endometrial atypical hyperplasia and early stage of EC than that in para-tumor eutopic endometrium, while the expression of ERß gradually decreased from para-tumor eutopic endometrium to EC. Additionally, the cell cycle-related protein, CyclinD1 was gradually increased but p21 decreased. Furthermore, knockdown of ERα and ERß severally in Ishikawa cells either inhibited or promoted estrogen-induced cell proliferation through regulating CyclinD1 and p21 expression. Meanwhile, the inhibitory effect of metformin on estrogen-induced cell proliferation was respectively blunted or partly reversed by knockdown of ERα or ERß. Altogether, ERα and ERß have different expression patterns in the progression of EC either facilitating or suppressing cell proliferation through regulating the expression of CyclinD1 and p21 in EC cells, and may also mediate the inhibitory effect of metformin on estrogen-induced EC cells proliferation.

17.
J Clin Lab Anal ; 34(10): e23547, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32860454

RESUMO

OBJECTIVE: To investigate the clinical features and risk factors for discerning the critical and predicting the outcome of patients with COVID-19. METHODS: Patients who were admitted to the intensive care unit (ICU) department and general infection department of TaiKang Tongji (Wuhan) Hospital from February 10 to March 27, 2020, were included. Data on clinical features, complications, laboratory parameters, chest CT, nutrient requirement, and electrolyte imbalance were analyzed retrospectively. RESULTS: A total of 123 (50 critical and 73 non-critical) patients were enrolled. 65% of patients with comorbidities, hypertension (45.5%), diabetes (21.9%), 36.5% of patients had more than one comorbidity. The proportion of lymphocytes in critical patients was significantly lower than that of non-critical patients. The proportion of patients with increased NLR, PLR, IL-6, CRP levels, and chest CT score was significantly higher in the critical than that of non-critical patients. The logistic regression analysis identified low lymphocyte count, high NLR, PLR, IL-6, CRP levels, and CT score as independent factors for discerning critical cases and high NLR, PLR, IL-6, and CT score could predict poor clinical outcome. Furthermore, we identified patients who needed nutrition support (HR 16.99) and with correction of electrolyte imbalance (HR 18.24) via intravenous injection were more likely to have a poor outcome. CONCLUSIONS: The potential risk factors of lower lymphocyte count, high levels of NLR, PLR, IL-6, CRP, chest CT score, and the statue of nutrient requirement or electrolyte imbalance could assist clinicians in discerning critical cases and predict the poor outcome in patients with COVID-19.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Idoso , Betacoronavirus , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Estado Terminal , Citocinas/sangue , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Radiografia Torácica , Estudos Retrospectivos , Fatores de Risco
18.
ACS Appl Mater Interfaces ; 12(35): 39282-39292, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32805903

RESUMO

The Hoberman sphere is a stable and stretchable spatial structure with a unique design concept, which can be taken as the ideal prototype of the internal mechanical/conductive skeleton for the anode with large volume change. Herein, Mn3O4 nanoparticles are interlaced with a Hoberman sphere-like interconnected carbon nanotube (CNT) network via a facile self-assembly strategy in which Mn3O4 can "locally expand" in the CNT network, limit the volume expansion to the interior space, and maintain a stable outer surface of the hybrid particle. Furthermore, an ultrathin uniform ALD-coated TiO2 shell is adopted to stabilize the solid electrolyte interphase (SEI), provide high electron conductivity and lithium ion (Li+) diffusivity with lithiated LixTiO2, and enhance the reaction kinetics of the Mn3O4 by an "electron-density enhancement effect". With this design, the Mn3O4@CNT/TiO2 exhibits a high capacity of 1064 mAh g-1 at 0.1 A g-1, a stable cycling stability over 200 cycles, a superior rate capability, and a commercial-level areal capacity of 4.9 mAh cm-2. In this way, a novel electrode design strategy is achieved by the Hoberman sphere-like CNT design along with the in situ porous formation, which can not only achieve a high-performance anode for LIBs but also can be widely adapted in a variety of advanced electrode materials for alkali metal ion batteries.

19.
Int J Clin Exp Pathol ; 13(7): 1500-1505, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32782668

RESUMO

OBJECTIVE: This project investigated the inhibitory effect of Fraxetin on endometrial cancer cell proliferation, and explored the possibility of applying Fraxetin in the treatment of endometrial cancer. METHODS: Human endometrial cancer RL95-2 cell line was cultured in vitro, and the cells were administered different concentrations of Fraxetin. MTS was used to detect the inhibitory effect of Fraxetin on proliferation. Flow cytometry was applied to detect the effect of Fraxetin on RL95-2 cell cycle. Western blot was employed to determine the expression of apoptosis-related proteins, such as caspase-3, caspase-9, p-AMPK, AMPK, p-mTOR, and mTOR. JC-1 staining was used to measure the mitochondrial membrane potential changes in the cells before and after the administration. The glucose oxidase method and the lactate oxidase method were used to detect changes in glucose consumption and lactic acid production in endometrial cancer cells before and after drug intervention, respectively. RESULTS: Fraxetin inhibited cell proliferation and promoted apoptosis. The expressions of caspase-3 and caspase-9 increased significantly, p-AMPK gradually increased, and mitochondrial membrane potential weakened. Glucose consumption and lactic acid production increased significantly. CONCLUSION: Fraxetin can inhibit the proliferation of RL95-2 cells, promote apoptosis, inhibit mitochondrial oxidation of endometrial cancer cells, promote anaerobic metabolism of cells, and exert an inhibitory effect on endometrial cancer cells by inhibiting mitochondria.

20.
Curr Top Med Chem ; 20(21): 1858-1867, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32648840

RESUMO

Anticancer drug screening can accelerate drug discovery to save the lives of cancer patients, but cancer heterogeneity makes this screening challenging. The prediction of anticancer drug sensitivity is useful for anticancer drug development and the identification of biomarkers of drug sensitivity. Deep learning, as a branch of machine learning, is an important aspect of in silico research. Its outstanding computational performance means that it has been used for many biomedical purposes, such as medical image interpretation, biological sequence analysis, and drug discovery. Several studies have predicted anticancer drug sensitivity based on deep learning algorithms. The field of deep learning has made progress regarding model performance and multi-omics data integration. However, deep learning is limited by the number of studies performed and data sources available, so it is not perfect as a pre-clinical approach for use in the anticancer drug screening process. Improving the performance of deep learning models is a pressing issue for researchers. In this review, we introduce the research of anticancer drug sensitivity prediction and the use of deep learning in this research area. To provide a reference for future research, we also review some common data sources and machine learning methods. Lastly, we discuss the advantages and disadvantages of deep learning, as well as the limitations and future perspectives regarding this approach.

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