Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high ...bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.
Measuring multiple omics profiles from the same single cell opens up the opportunity to decode molecular regulation that underlies intercellular heterogeneity in development and disease. Here, we ...present co-sequencing of microRNAs and mRNAs in the same single cell using a half-cell genomics approach. This method demonstrates good robustness (~95% success rate) and reproducibility (R
= 0.93 for both microRNAs and mRNAs), yielding paired half-cell microRNA and mRNA profiles, which we can independently validate. By linking the level of microRNAs to the expression of predicted target mRNAs across 19 single cells that are phenotypically identical, we observe that the predicted targets are significantly anti-correlated with the variation of abundantly expressed microRNAs. This suggests that microRNA expression variability alone may lead to non-genetic cell-to-cell heterogeneity. Genome-scale analysis of paired microRNA-mRNA co-profiles further allows us to derive and validate regulatory relationships of cellular pathways controlling microRNA expression and intercellular variability.
The best of three worlds: Gold nanorods coated with poly(styrene‐alt‐maleic acid) (see picture; pink), the photosensitizer indocyanine green (black), and antibodies (green “Y”) serve not only as ...photodynamic therapy and hyperthermia agents to destroy malignant cells, but they also act as optical contrast agents to simultaneously to monitor cells by imaging in the near‐IR region.
The present research examined the effectiveness of digital storytelling (DST) on foreign language learners' English speaking and creative thinking. In this study, DST was realized in the form of an ...interdisciplinary project integrated in a partnership between an English course and a computer course, with the class time of the former devoted to the content design and that of the latter to the multimedia design of learner-generated digital stories. The participants were required to work in small groups to create their digital stories in the target language, English, under an eight-week interdisciplinary curriculum. A two-group quasi-experiment with a pretest and posttest design was then conducted to compare the participants' learning outcomes. The findings reveal the authentic and meaningful learning opportunities that DST has to offer for effectively fostering the students' development of becoming proficient English speakers and creative thinkers. Future implementations on interdisciplinary DST projects are thus recommended for educators.
Impaired growth factor production, angiogenic response, macrophage function, and collagen accumulation have been shown to delay wound healing. Delayed wound healing is a debilitating complication of ...diabetes that leads to significant morbidity. In this study, curcumin and Lithospermi radix (LR) extract, which are used in traditional Chinese herbal medicine, were added within nanofibrous membranes to improve wound healing in a streptozotocin (STZ)-induced diabetic rat model. Gelatin-based nanofibers, which were constructed with curcumin and LR extract at a flow rate of 0.1 mL/hour and an applied voltage of 20 kV, were electrospun onto chitosan scaffolds to produce bilayer nanofibrous scaffolds (GC/L/C). The wounds treated with GC/L/C exhibited a higher recovery rate and transforming growth factor-beta (TGF-
) expression in Western blot assays. The decreased levels of pro-inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor-
(TNF-
), provided evidence for the anti-inflammatory effects of GC/L/C treatment. Chronic wounds treated with GC/L/C achieved better performance with a 58 ± 7% increase in recovery rate on the seventh day. Based on its anti-inflammatory and wound-healing effects, the GC/L/C bilayer nanofibrous scaffolds can be potential materials for chronic wound treatment.
The international and national HIV treatment guidelines in 2016 have focused on scaling up access to combination antiretroviral therapy (cART). We aimed to assess the trends and treatment outcomes of ...late cART initiation in Taiwan.
Between June 2012 and May 2016, we retrospectively included antiretroviral-naive HIV-positive adults who initiated cART. Late initiation was defined as when cART was initiated in patients with a CD4 count <200 cells/mm3 or having experienced AIDS-defining illnesses. The treatment outcomes were assessed up to 6 months after starting cART.
We included 3655 HIV-positive patients, and the majority of the patients were male (95.4%) with a median age of 31 years and initiated non-nucleoside reverse-transcriptase inhibitor-containing regimens (87.0%). The median CD4 count at cART initiation increased from 207 cells/mm3 in 2012 to 298 cells/mm3 in 2016, and the overall proportion of late cART initiation decreased from 49.1% in 2012 to 29.0% in 2016 (P for trend <0.001). Late cART initiation mainly resulted from late presentation for HIV care and was associated with older age (per 1-year increase, adjusted odds ratio AOR, 1.05; 95% CI, 1.04-1.06), HBsAg seropositivity (AOR, 1.31; 95% CI, 1.04-1.64), HIV care in central and southern Taiwan, initiating cART in earlier year, non-intravenous drug users (AOR, 1.96; 95% CI, 1.33-2.86), and negative hepatitis C serostatus (AOR, 1.47; 95% CI, 1.04-2.08). Compared with non-late initiators, late initiators had a higher rate of all-cause mortality (1.7% vs. 0.3%) and regimen modification due to virological failure (7.1% vs. 2.6%). The predicting factors of all-cause mortality were late cART initiation (adjusted hazard ratio AHR, 5.40; 95% CI, 2.14-13.65) and older age (AHR, 1.06; 95% CI, 1.03-1.10).
While the proportion of late cART initiation decreased over time in Taiwan, late initiation remained in a substantial proportion of HIV-positive patients. The late initiators had higher risk for poor outcomes. The need for strategies to earlier detection of HIV infection and expediting cART initiation should be highlighted, especially among the older population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mutations in genes involved in the production, migration, or differentiation of cortical neurons often lead to malformations of cortical development (MCDs). However, many genetic mutations involved ...in MCD pathogenesis remain unidentified. Here we developed a genetic screening paradigm based on transposon-mediated somatic mutagenesis by in utero electroporation and the inability of mutant neuronal precursors to migrate to the cortex and identified 33 candidate MCD genes. Consistent with the screen, several genes have already been implicated in neural development and disorders. Functional disruption of the candidate genes by RNAi or CRISPR/Cas9 causes altered neuronal distributions that resemble human cortical dysplasia. To verify potential clinical relevance of these candidate genes, we analyzed somatic mutations in brain tissue from patients with focal cortical dysplasia and found that mutations are enriched in these candidate genes. These results demonstrate that this approach is able to identify potential mouse genes involved in cortical development and MCD pathogenesis.
The study aimed to describe the evolution of the seroprevalence of hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-positive patients included in two cohorts in Taiwan.
We ...retrospectively collected the information on demographic and clinical characteristics of 4,025 and 3,856 HIV-positive Taiwanese, who were aged 18 years or older at designated hospitals around Taiwan in 2004-2007, when an outbreak of HIV infection was occurring, and 2012-2016, when the outbreak was controlled with the implementation of harm reduction program, respectively. Comparisons of HCV seropositivity were made among different age and risk groups for HIV transmission between these two cohorts.
The overall HCV seroprevalence of the 2004-2007 cohort and 2012-2016 cohort was 43.4% (1,288/2,974) and 18.6% (707/3,793), respectively (P<0.001). The HCV seroprevalence among injecting drug users (IDUs), though decreasing, was constantly high across the two cohorts, 96.4% and 94.0% (P = 0.02), respectively, and all age groups. In contrast, the corresponding figures among men who have sex with men (MSM) and heterosexuals in the two cohorts were 5.9% vs. 3.5% (P = 0.002) and 9.4% vs. 10.9% (P = 0.59), respectively. Among sexually transmitted HIV-positive patients, HCV seropositivity was significantly correlated with age (adjusted odds ratio aOR, per 1-year increase, 1.03; 95% confidence interval CI, 1.02-1.05) and a rapid plasma reagin (RPR) titer ≥1:8 (aOR, 1.58; 95% CI, 1.03-2.43) in a multivariate analysis including age, gender, route for HIV transmission, baseline CD4 count and plasma HIV RNA load, the presence of hepatitis B surface antigen, and an RPR titer ≥1:8. Compared with heterosexuals, the aOR for HCV seropositivity among MSM was 0.47 (95% CI, 0.31-0.72).
HCV seroprevalence among HIV-positive patients in Taiwan decreased with time, probably related to the inclusion of younger adults and more non-IDUs, and remained high among IDUs. HCV seropositivity was associated with age and an RPR titer ≥1:8 among patients who acquired HIV through sexual contact.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This work reports the synthesis of nitrogen and sulfur co-doped carbon dots (NS-CDs) via a one-step facile microwave-assisted pyrolysis using citric acid and thiourea as the carbon precursor and ...dopant, respectively. The resultant NS-CDs were found to be uniform in size and can be dispersed in aqueous solution. With an average size of 4.73 ± 0.65 nm, the NS-CDs exhibit excitation-dependent and pH-dependent photoluminescence properties in the visible range. Moreover, the NS-CDs also possessed a relatively high photoluminescence quantum yield of 28.9% and strong photostability in a high ionic strength environment. The NS-CDs were highly selective for Fe 3+ detection in a water sample, achieving a limit of detection (LOD) of 0.16 μM. On top of this, the NS-CDs also demonstrated high detection sensitivity with a LOD of 0.17 μM and improved selectivity to Fe 3+ in an acidic environment (pH 2). Specifically, the interference effect from Cu 2+ , Co 2+ , and Ag + was lowered by 15%, 18%, and 64% respectively, highlighting an additional merit for the as-synthesized NS-CDs. This concept of pH tuning can be implemented to exploit the detection capability in both neutral and acidic environments to create specific analytical responses correlating to a specific targeted metal ion. Finally, we also demonstrated the versatility of the NS-CDs by employing them as a low-toxicity fluorescent label and for semi-quantitative Fe 3+ sensing in cancer cells.
Social media allows any individual to disseminate information without third-party restrictions, making it difficult to verify the authenticity of a source. The proliferation of fake news has severely ...affected people's intentions and behaviors in trusting online sources. Applying AI approaches for fake news detection on social media is the focus of recent research, most of which, however, focuses on enhancing AI performance. This study proposes XFlag, an innovative explainable AI (XAI) framework which uses long short-term memory (LSTM) model to identify fake news articles, layer-wise relevance propagation (LRP) algorithm to explain the fake news detection model based on LSTM, and situation awareness-based agent transparency (SAT) model to increase transparency in human-AI interaction. The developed XFlag framework has been empirically validated. The findings suggest the use of XFlag supports users in understanding system goals (perception), justifying system decisions (comprehension), and predicting system uncertainty (projection), with little cost of perceived cognitive workload.
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