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1.
Nucleic Acids Res ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619523

RESUMO

The interferon gamma-inducible protein 16 (IFI16) and its murine homologous protein p204 function in non-sequence specific dsDNA sensing; however, the exact dsDNA recognition mechanisms of IFI16/p204, which harbour two HIN domains, remain unclear. In the present study, we determined crystal structures of p204 HINa and HINb domains, which are highly similar to those of other PYHIN family proteins. Moreover, we obtained the crystal structure of p204 HINab domain in complex with dsDNA and provided insights into the dsDNA binding mode. p204 HINab binds dsDNA mainly through α2 helix of HINa and HINb, and the linker between them, revealing a similar HIN:DNA binding mode. Both HINa and HINb are vital for HINab recognition of dsDNA, as confirmed by fluorescence polarization assays. Furthermore, a HINa dimerization interface was observed in structures of p204 HINa and HINab:dsDNA complex, which is involved in binding dsDNA. The linker between HINa and HINb reveals dynamic flexibility in solution and changes its direction at ∼90° angle in comparison with crystal structure of HINab:dsDNA complex. These structural information provide insights into the mechanism of DNA recognition by different HIN domains, and shed light on the unique roles of two HIN domains in activating the IFI16/p204 signaling pathway.

2.
Chem Soc Rev ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616126

RESUMO

The coordination connection of organic linkers to the metal clusters leads to the formation of metal-organic frameworks (MOFs), where the metal clusters and ligands are spatially entangled in a periodic manner. The immense availability of tuneable ligands of different length and functionalities gives rise to robust molecular porosity ranging from several angstroms to nanometres. Among the large family of MOFs, hafnium (Hf) based MOFs have been demonstrated to be highly promising for practical applications due to their unique and outstanding characteristics such as chemical, thermal, and mechanical stability, and acidic nature. Since the report of UiO-66(Hf) and DUT-51(Hf) in 2012, less than 200 Hf-MOFs (ca. 50 types of structures) have been reported. Besides, tetravalent cerium [Ce(iv)] has been proven to be capable of forming similar topological MOF structures to Zr and Hf since its first discovery in 2015. So far, ca. 40 Ce(iv) MOFs with 60% having UiO-66-type structure have been reported. This review will offer a holistic summary of the chemistry, uniqueness, synthesis, and applications of Hf/Ce(iv)-MOFs with a focus on presenting the development in the Hf/Ce(iv)-clusters, topologies, ligand structures, synthetic strategies, and practical applications of Hf/Ce(iv)-MOFs. In the end, we will present the research outlook for the development of Hf/Ce(iv)-MOFs in the future, including fundamental design of Hf/Ce(iv)-clusters, defect engineering, and various applications including membrane development, diversified types of catalytic reactions, irradiation absorption in nuclear waste treatment, water production and wastewater treatment, etc. We will also present the emerging computational approaches coupled with machine-learning algorithms that can be applied in screening Hf and Ce(iv) based MOF structures and identifying the best-performing MOFs for tailor-made applications in future practice.

3.
J Diabetes Investig ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544958

RESUMO

AIMS/INTRODUCTION: Current literature suggested diabetic men had a lower prostate-specific antigen concentration than non-diabetic men, but the causal association remains unclear. We aimed to investigate the association between serum prostate-specific antigen concentrations and the risk of type 2 diabetes mellitus in a cohort study of a Chinese population. MATERIALS AND METHODS: We designed a cohort study that comprised 16,811 initially non-diabetic Chinese men who received annal health check-ups between 2009 and 2016. The outcome of this study was type 2 diabetes mellitus, identified by medical diagnose, self-reportage, medication use, fasting glucose, 2-h post oral glucose or glycated hemoglobin measurements. Cox proportional hazard models were performed to evaluate the association. RESULTS: During a median follow-up period of 3.8 years (interquartile range: 1.91 - 5.73 years), 1,260 participants developed incident type 2 diabetes mellitus. The multivariable model, adjusted for various potential confounders, showed that serum prostate-specific antigen concentrations was inversely related to type 2 diabetes mellitus risk (P for trend = 0.014). Compared with the lowest quartile of serum prostate-specific antigen, the hazard ratio and 95% confidence intervals of type 2 diabetes mellitus risk for quartile 2 - 4 were 0.84 (0.66 - 1.07), 0.75 (0.59 - 0.94) and 0.77 (0.62 - 0.96), respectively. Subgroup analyses suggested the inverse relationship was more prominent in overweight or obese participants (P for interaction = 0.013). CONCLUSIONS: High serum prostate-specific antigen concentrations was associated with a low risk of type 2 diabetes mellitus in Chinese men. Future studies are needed to confirm these findings and investigate underlying mechanisms.

4.
Int Dent J ; 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33531146

RESUMO

OBJECTIVE: There is a need to develop easy-to-use tools to screen for periodontal conditions in daily practice. This study aimed to evaluate the FDI World Dental Federation "Chairside Guide" (FDI-CG) developed by the Task Team of the FDI Global Periodontal Health Project (GPHP) as a potential tool for screening. METHODS: Databases from 3 centres in Germany, Hong Kong, and Spain (n = 519) were used to evaluate the association of the FDI-CG and its individual items with the periodontitis case definitions proposed by the Centers for Disease Control and Prevention (CDC) and the American Academy of Periodontology (AAP) for population-based surveillance of periodontitis. RESULTS: Statistically significant differences were observed among the databases for the prevalence of periodontitis and the items included in the FDI-CG. The FDI-CG score and its individual components were significantly associated with the periodontal status in the individual databases and the total sample, with bleeding on probing showing the strongest association with severe periodontitis (odds ratio [OR] = 12.9, 95% CI [5.9; 28.0], P < .001, for those presenting bleeding on probing >50%), followed by age (OR = 4.8, 95% CI [1.7; 4.2], P = .004, for those older than 65 years of age). Those subjects with a FDI-CG score >10 had an OR of 54.0 (95% CI [23.5; 124.2], P < .001) and presented with severe periodontitis. A significant correlation was found between the different FDI-CG scoring categories (mild, moderate, and severe) and the categories for mild, moderate, and severe periodontitis using the Centers for Disease Control and Prevention and the American Academy of Periodontology criteria (r = 0.57, Spearman rank correlation test, P < .001). CONCLUSION: The FDI Chairside Guide may represent a suitable tool for screening the periodontal condition by general practitioners in daily dental practice.

5.
Microb Pathog ; 153: 104788, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33571624

RESUMO

Acinetobacter baumannii (A. baumannii), one of the major pathogens that causes severe nosocomial infections, is characterised by a high prevalence of drug resistance. It has been reported that A. baumannii triggers the NOD-like receptor 3 (NLRP3) inflammasome, but the role of its virulence-related outer membrane protein A (ompA) remains unclear. Therefore, this study aimed to explore the effects of ompA on the NLRP3 inflammasome and its underlying molecular mechanisms. Results showed that ompA enhanced inflammatory damage, which was reduced as a result of knockout of the ompA gene. Additionally, ompA-stimulated expression of NLRP3 inflammasome was significantly blocked by silencing caspase-1, but activation of NLRP3 inflammasome was not altered after silencing ASC; this indicated that ompA was dependent on the caspase-1 pathway to activate the inflammatory response. Simultaneously, the wild-type (WT) strains triggered NLRP3 inflammasome after inhibition of caspase-1 degradation by proteasome inhibitor MG-132, aggravating tissue damage. These findings indicated that ompA may be dependent on the caspase-1 pathway to enhance inflammation and exacerbate tissue damage. Taken together, these results confirmed a novel capsase-1-modulated mechanism underpinning ompA activity, which further reveals the NLRP3 inflammasome pathway as a potential immunomodulatory target against A. baumannii infections.

6.
Sci Rep ; 11(1): 4024, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597656

RESUMO

Plant-specific WRKY transcription factors play important roles in regulating the expression of defense-responsive genes against pathogen attack. A multiple stress-responsive WRKY gene, ZmWRKY65, was identified in maize by screening salicylic acid (SA)-induced de novo transcriptomic sequences. The ZmWRKY65 protein was localized in the nucleus of mesophyll protoplasts. The analysis of the ZmWRKY65 promoter sequence indicated that it contains several stress-related transcriptional regulatory elements. Many environmental factors affecting the transcription of ZmWRKY65 gene, such as drought, salinity, high temperature and low temperature stress. Moreover, the transcription of ZmWRKY65 gene was also affected by the induction of defense related plant hormones such as SA and exogenous ABA. The results of seed germination and stomatal aperture assays indicated that transgenic Arabidopsis plants exhibit enhanced sensitivity to ABA and high concentrations of SA. Overexpression of ZmWRKY65 improved tolerance to both pathogen attack and abiotic stress in transgenic Arabidopsis plants and activated several stress-related genes such as RD29A, ERD10, and STZ as well as pathogenesis-related (PR) genes such as PR1, PR2 and PR5; these genes are involved in resistance to abiotic and biotic stresses in Arabidopsis. Together, this evidence implies that the ZmWRKY65 gene is involved in multiple stress signal transduction pathways.

7.
Org Lett ; 23(4): 1285-1290, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33529040

RESUMO

An efficient copper(I)-catalyzed enyne oxidation/cyclopropanation for the modular synthesis of cyclopropane derivatives is described, which represents the first non-noble metal-catalyzed enynes oxidation/cyclopropanation by the in situ generated α-oxo copper carbenes. This protocol allows the assembly of valuable cyclopropane-γ-lactams in generally good to excellent yields with excellent diastereoselectivity. More significantly, the enantioselective version of enyne oxidation/cyclopropanation has been disclosed with chiral copper catalysts.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33599088

RESUMO

The realization of regulating permeance and selectivity in membrane systems may allow effective relief of conventional energy-intensive separations. Here, pressure-responsive ultrathin membranes (~100 nm) fabricated by compositing flexible two-dimensional metal-organic framework nanosheets (MONs) with graphene oxide nanosheets for CO2 separation are reported. By controlling the gas permeation direction to leverage the pressure-responsive phase transition of the MONs, CO2-induced gate opening and closing behaviors are observed in the resultant membranes, which are accompanied with the sharp increase of CO2 permeance (from 173.8 to 1144 gas permeation units) as well as CO2/N2 and CO2/CH4 selectivities (from 4.1 to 22.8 and from 4 to 19.6, respectively). The flexible behaviors and separation mechanism are further elucidated by molecular dynamics simulations. This work establishes the relevance of structural transformation-based framework dynamics chemistry in smart membrane systems.

9.
BMC Psychiatry ; 21(1): 78, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549084

RESUMO

BACKGROUND: Previous studies have revealed that single physical chronic condition was associated with suicidal ideation/plans, but few studies have examined the relationship between multimorbidity and suicidal ideation/plans, and no studies have explored the underlying potential mechanism on this relationship in China. This study aimed to explore association between physical multimorbidity and suicidal ideation as well as plans, and further examine the mediating role of psychological distress (PD) on this relationship. METHODS: This study was based on the data from a survey about the health service of rural elderly household in Shandong, China. A total of 3242 adults aged 60 years and older were included in this study. PD was measured by Kessler Psychological Distress Scale (K10). Ordinal and binary logistic regression analyses were employed to explore the association between physical multimorbidity, PD and suicide ideation/plans. Bootstrapping analysis was further used to examine the mediation effect of PD on the association of multimorbidity and suicidal ideations/plans. RESULTS: The prevalence of multimorbidity, lifetime suicidal ideation, and suicidal plan in rural older adults was 35.2, 10.6 and 2.2%, respectively. Older adults living in rural areas with two or more chronic physical conditions experienced significantly higher risk of suicidal ideation and suicidal plans. The association between multimorbidity and suicidal ideations/plans was partially mediated by PD, of which, the mediating effect of PD accounted for 31.7 and 25.5% of the total effect, respectively. CONCLUSION: This study demonstrated the associations between physical multimorbidity and suicidal ideation/plans, and the mediating role of PD on this relationship among Chinese rural elderly. Healthcare providers in rural community should provide regular surveillance for the mental health status among the rural elderly with multimorbidity, and carry out various effective intervention measures to improve the mental health status, so as to reduce the risk of suicide.

10.
Mikrochim Acta ; 188(3): 74, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558967

RESUMO

The architecture of PO43- modified 2D TiO2 nanosheets was constructed by ionic liquids (ILs)-assisted hydrothermal method. The nanosheet structure can be regulated by the addition of different amount of ionic liquid. Using the composite nanosheets  a chemoresistive gas sensor was prepared for trimethylamine (TMA) detection. Most reported TMA sensors need to be operated at a relatively high operating temperature, but in this paper, the as-synthesized PO43--modified 2D TiO2/Ti2O(PO4)2 nanosheet sensor has high response (S = 87.46), short response time (14.6 s), and good reproducibility to 100 ppm TMA gas, when the temperature is 170 °C. In contrast to the single-phase TiO2 sensor, the gas-sensing property of the composite one is obviously enhanced. Moreover, its response shows excellent linear relationship with TMA concentration from 0.2 to 500 ppm, and a detection limit of 0.2 ppm. The TMA detection mechanism was investigated by analyzing the changes of the surface adsorption oxygen content by XPS and gaseous products using gas chromatography after the sensor was in contact with TMA.

11.
Proc Natl Acad Sci U S A ; 118(6)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33526657

RESUMO

RNA polymerase II (Pol II) generally pauses at certain positions along gene bodies, thereby interrupting the transcription elongation process, which is often coupled with various important biological functions, such as precursor mRNA splicing and gene expression regulation. Characterizing the transcriptional elongation dynamics can thus help us understand many essential biological processes in eukaryotic cells. However, experimentally measuring Pol II elongation rates is generally time and resource consuming. We developed PEPMAN (polymerase II elongation pausing modeling through attention-based deep neural network), a deep learning-based model that accurately predicts Pol II pausing sites based on the native elongating transcript sequencing (NET-seq) data. Through fully taking advantage of the attention mechanism, PEPMAN is able to decipher important sequence features underlying Pol II pausing. More importantly, we demonstrated that the analyses of the PEPMAN-predicted results around various types of alternative splicing sites can provide useful clues into understanding the cotranscriptional splicing events. In addition, associating the PEPMAN prediction results with different epigenetic features can help reveal important factors related to the transcription elongation process. All these results demonstrated that PEPMAN can provide a useful and effective tool for modeling transcription elongation and understanding the related biological factors from available high-throughput sequencing data.

12.
Pediatr Res ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504964

RESUMO

BACKGROUND: Intrauterine growth restriction (IUGR) leads to cardiac dysfunction and adverse remodeling of the fetal heart, as well as a higher risk of postnatal cardiovascular diseases. The rat model of IUGR, via uterine artery ligation, is a popular model but its cardiac sequelae is not well investigated. Here, we performed an echocardiographic evaluation of its cardiac function to determine how well it can represent the disease in humans. METHODS: Unilateral uterine artery ligation was performed at embryonic day 17 (E17) and echocardiography was performed at E19 and E20. RESULTS: Growth-restricted fetuses were significantly smaller and lighter, and had an higher placenta-to-fetus weight ratio. Growth-restricted fetal hearts had reduced wall thickness-to-diameter ratio, indicating left ventricular (LV) dilatation, and they had elevated trans-mitral and trans-tricuspid E/A ratios and reduced left and right ventricular fractional shortening (FS), suggesting systolic and diastolic dysfunction. These were similar to human IUGR fetuses. However, growth-restricted rat fetuses did not demonstrate head-sparing effect, displayed a lower LV myocardial performance index, and ventricular outflow velocities were not significantly reduced, which were dissimilar to human IUGR fetuses. CONCLUSIONS: Despite the differences, our results suggest that this IUGR model has significant cardiac dysfunction, and could be a suitable model for studying IUGR cardiovascular physiology. IMPACT: Animal models of IUGR are useful, but their fetal cardiac function is not well studied, and it is unclear if they can represent human IUGR fetuses. We performed an echocardiographic assessment of the heart function of a fetal rat model of IUGR, created via maternal uterine artery ligation. Similar to humans, the model displayed LV dilatation, elevated E/A ratios, and reduced FS. Different from humans, the model displayed reduced MPI, and no significant outflow velocity reduction. Despite differences with humans, this rat model still displayed cardiac dysfunction and is suitable for studying IUGR cardiovascular physiology.

13.
Cancer Res ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446575

RESUMO

Ethnicity is considered to be one of the major risk factors in certain subtypes of breast cancer. However, the mechanism of this racial disparity remains poorly understood. Here we demonstrate that SOS1, a key regulator of Ras pathway, is highly expressed in African American (AA) breast cancer patients compared to Caucasian American (CA) patients. Because of the higher obesity rate in AA women, increased levels of SOS1 facilitated signal transduction of the c-Met pathway which was highly activated in AA breast cancer patients via HGF secreted from adipocytes. Elevated expression of SOS1 also enhanced cancer stemness through upregulation of PTTG1 and promoted M2 polarization of macrophages by CCL2 in metastatic sites. SOS1 was epigenetically regulated by a super-enhancer identified by H3K27ac in AA patients. Knockout of the super-enhancer by CRISPR in AA cell lines significantly reduced SOS1 expression. Furthermore, SOS1 was post-transcriptionally regulated by miR-483 whose expression is reduced in AA patients through histone tri-methylation (H3K27me3) on its promoter. The natural compound taxifolin suppressed signaling transduction of SOS1 by blocking the interaction between SOS1 and Grb2, suggesting a potential utility of this compound as a therapeutic agent for AA breast cancer patients.

14.
Theranostics ; 11(6): 2634-2654, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33456564

RESUMO

Background and purpose: Activation of liver X receptor (LXR) by its ligand T0901317 (T317) enhances interferon-γ (IFNγ) production to inhibit tumor growth. However, induction of severe hypertriglyceridemia and fatty liver by T317 limits its application. The naphthylacetic acid modified D-enantiomeric-glycine-phenylalanine-phenylalanine-tyrosine (D-Nap-GFFY) can form a nanofiber hydrogel which is selectively taken up by antigen-presenting cells (APCs). In this study, we determined if D-Nap-GFFY-encapsulated T317 (D-Nap-GFFY-T317) can potently inhibit tumor growth while having no adverse lipogenic effects on the liver. Methods: We prepared D-Nap-GFFY-T317 nanofiber hydrogel and subcutaneously injected it into IFNγ deficient (IFNγ-/-) and wild-type (WT) mice with lung carcinoma, either inoculated LLC1 cells or urethane-induced carcinoma. Mice received oral T317 administration were used for comparison. Effects of treatment on tumor growth, lipogenesis and involved mechanisms were investigated. Results: Compared with T317 oral administration, injection of D-Nap-GFFY-T317 more potently inhibited LLC1 tumor growth in mice. The inhibition was dependent on LXR-activated IFNγ expression in APCs. D-Nap-GFFY-T317 increased M1 while reducing M2 type macrophages in tumors. Associated with activation of IFNγ expression, D-Nap-GFFY-T317 enhanced dendritic cell maturation and infiltration into tumors, increased CD3+/CD8+ cells in tumors, and inhibited tumor angiogenesis. Similarly, D-Nap-GFFY-T317 more potently inhibited growth of urethane-induced lung carcinomas than T317 oral administration. In these two tumor models, T317 oral administration, but not D-Nap-GFFY-T317 injection, activated hepatic lipogenesis and induced fatty liver. Conclusion: Our study demonstrates that D-Nap-GFFY-T317 inhibits lung tumor growth without adverse effects on the liver, indicating the hydrogel-encapsulated LXR ligand might be a novel therapy for tumor treatment.

16.
BMC Complement Med Ther ; 21(1): 34, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446178

RESUMO

BACKGROUND: Panax notoginseng is one of the most valuable traditional Chinese medicines. Polysaccharides in P. notoginseng has been shown to significantly reduce the incidence of human diseases. However the application of fermentation technology in Panax notoginseng is not common, and the mechanism of action of P. notoginseng polysaccharides produced by fermentation is still unclear. The specific biological mechanisms of fermented P. notoginseng polysaccharides (FPNP) suppresses H2O2-induced apoptosis in human dermal fibroblast (HDF) and the underlying mechanism are not well understood. METHODS: In this study, the effects of water extracted and fermentation on concentration of polysaccharides in P. notoginseng extracts were analyzed. After the H2O2-induced HDF model of oxidative damage was established, and then discussed by the expression of cell markers, including ROS, MDA, SOD, CAT, GSH-Px and MMP-1, COL-I, ELN, which were detected by related ELISA kits. The expression of TGF-ß/Smad pathway markers were tested by qRT-PCR to determine whether FPNP exerted antioxidant activity through TGF-ß signaling in HDF cells. RESULTS: The polysaccharide content of Panax notoginseng increased after Saccharomyces cerevisiae CGMCC 17452 fermentation. In the FPNP treatment group, ROS and MDA contents were decreased, reversed the down-regulation of the antioxidant activity and expression of antioxidant enzyme (CAT, GSH-Px and SOD) induced by H2O2. Furthermore, the up-regulation in expression of TGF-ß, Smad2/3 and the down-regulation in the expression of Smad7 in FPNP treated groups revealed that FPNP can inhibit H2O2-induced collagen and elastin injury by activating TGF-ß/Smad signaling pathway. CONCLUSION: It was shown that FPNP could inhibit the damage of collagen and elastin induced by H2O2 by activating the TGF-ß/Smad signaling pathway, thereby protecting against the oxidative damage induced by hydrogen peroxide. FPNP may be an effective attenuating healing agent that protects the skin from oxidative stress and wrinkles.

17.
Contemp Clin Trials ; 102: 106265, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33418097

RESUMO

In oncology dose-finding clinical trials, the key to accurately estimating the maximum tolerated dose (MTD) is to use all data efficiently given small sample sizes. Currently, popular designs dichotomize adverse events of various types and grades that occur within the first treatment cycle into binary toxicity outcomes of dose-limiting toxicity (DLT) events. Such compression of toxicity data from multiple treatment cycles causes huge loss of information, often resulting in MTD estimation with large bias and variance. To improve this, a continuous endpoint (the total toxicity profile, TTP) was proposed to incorporate adverse event types and grades. The Bayesian Repeated Measures Design (RMD) was further developed by Yin et al. (2017) to account for the cumulative toxicity information from multiple treatment cycles. However, the existing RMD method selects the dose that minimizes the loss function based on point estimates, which may generate inconsistent results due to small sample sizes in phase I trials. To reduce the variability in dose escalation decision-making, we propose an improved repeated measures design with an interval-based decision rule that selects the dose with the highest posterior probability of falling in a pre-specified target toxicity interval. Through comprehensive simulations, we compared this proposed design with the existing RMD design, along with well-established DLT-based designs such as Continual Reassessment Method (CRM) and Bayesian Logistic Regression Model (BLRM). The results demonstrated that our proposed design outperforms all other designs in terms of accurately identifying the MTD and assigning fewer patients to sub-therapeutic or overly toxic doses.

18.
J Affect Disord ; 282: 348-353, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33421862

RESUMO

BACKGROUND: Few studies explored the relationship between cognitive frailty and suicidal ideation (SI), and whether geographic variable modified this relationship. This study aimed to explore the association between cognitive frailty and SI, and investigated whether parent-child geographic proximity is a moderator in this relationship among Chinese rural empty-nest older adults. METHODS: A total of 2,549 rural empty-nest older adults (60+) were included in the analysis. SI was assessed using questions from the National Comorbidity Survey. Fried frailty phenotype and Mini Mental State Examination were used to measure cognitive frailty. Moderating effect analysis was performed using logistic regression models and margins plot. RESULTS: The prevalence of SI and cognitive frailty were 10.1% and 6.2% among Chinese rural empty-nest older adults. Participants with cognitive frailty were more likely to suffer from SI (OR=1.16, 95% CI=1.03-2.86). We found that far geographic distance may aggravate this relationship (OR=4.30, 95% CI=1.02-10.24), especially for rural empty-nest older adults whose nearest adult child lived outside the same prefectural city with them. LIMITATIONS: The results cannot be interpreted as causality of the data due to cross-sectional design. CONCLUSIONS: Our findings suggested that cognitive frailty was associated with SI and parent-child geographic proximity moderated this relationship. Improving the cognitive frailty of older adults is helpful to prevent SI. Adult children living far away from rural empty-nest older adults should increase intergenerational contact and pay attention to their parents' physical and mental health.

19.
Brief Bioinform ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33479731

RESUMO

Translation elongation is a crucial phase during protein biosynthesis. In this study, we develop a novel deep reinforcement learning-based framework, named Riboexp, to model the determinants of the uneven distribution of ribosomes on mRNA transcripts during translation elongation. In particular, our model employs a policy network to perform a context-dependent feature selection in the setting of ribosome density prediction. Our extensive tests demonstrated that Riboexp can significantly outperform the state-of-the-art methods in predicting ribosome density by up to 5.9% in terms of per-gene Pearson correlation coefficient on the datasets from three species. In addition, Riboexp can indicate more informative sequence features for the prediction task than other commonly used attribution methods in deep learning. In-depth analyses also revealed the meaningful biological insights generated by the Riboexp framework. Moreover, the application of Riboexp in codon optimization resulted in an increase of protein production by around 31% over the previous state-of-the-art method that models ribosome density. These results have established Riboexp as a powerful and useful computational tool in the studies of translation dynamics and protein synthesis. Availability: The data and code of this study are available on GitHub: https://github.com/Liuxg16/Riboexp. Contact:  zengjy321@tsinghua.edu.cn; songsen@tsinghua.edu.cn.

20.
BMC Gastroenterol ; 21(1): 26, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33423668

RESUMO

BACKGROUND: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) on hepatic sinusoidal obstruction syndrome (HSOS) associated with consumption of Gynura segetum (GS). METHODS: We retrospectively reviewed 9 consecutive patients with GS-related HSOS who were refractory to supportive treatment and underwent TIPS at our institution between January 2014 and September 2019. The patients were evaluated for safety and efficacy, including TIPS complications and changes in portosystemic pressure gradient (PPG), ascites, total bilirubin, liver size and portal vein diameter. RESULTS: TIPS procedures were performed successfully in the 9 patients, and no technically-related complications due to the TIPS procedure were recorded. The PPG was improved by TIPS in all patients (mean PPG before TIPS, 30.4 ± 5.2 vs. 13.0 ± 4.1 mm Hg post-TIPS, P = 0.008). One patient who was lost to follow-up, whereas the remaining 8 patients survived with a median follow-up period of 12 months (range 5-39 months). Although the total bilirubin was significantly increased 5-7 days after TIPS compared with that before the procedure (3.57 ± 1.58 vs. 4.82 ± 2.06 mg/dl, P = 0.017), it returned to baseline levels at 1-month follow-up (3.53 ± 2.72 vs. 4.82 ± 2.06 mg/dl, P = 0.401). The patients experienced complete resolution or noticeable reduction of ascites (P < 0.001), significant reduction of liver size (16.7 ± 2.2 vs. 13.7 ± 1.7 cm, P = 0.018), and significant enlargement of the portal trunk (10.7 ± 2.5 vs. 13.4 ± 2.4 mm, P = 0.017) after TIPS compared to the pre-TIPS state. CONCLUSION: TIPS may offer a potentially useful treatment for the GS-related HSOS.

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