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1.
Diabetes Metab ; : 101278, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520837

RESUMO

OBJECTIVES: This study aimed to estimate the association between overweight and type 2 diabetes mellitus (T2DMM) in twins, and further to explore whether genetic and early-life environmental factors account for this association. METHODS: This study included 31,197 twin individuals from the Chinese National Twin Registry (CNTR). Generalised estimating equation (GEE) models were applied for unmatched case-control analysis. Conditional logistic regressions were used in co-twin matched case-control analysis. Logistic regressions were fitted to examine the differences in odds ratios (ORs) from the GEE models and conditional logistic regressions. Bivariate genetic model was used to explore the genetic and environmental correlation between body mass index (BMI) and T2DM. RESULTS: In the GEE model, overweight was associated with a higher T2DM risk (OR=2.71, 95% confidence interval (CI): 1.96∼3.73), compared with participants with normal BMI. In the multi-adjusted conditional logistic regression, the association was still significant (OR=2.60, 95% CI: 1.15∼5.87). The ORs from the unmatched and matched analyses were different (P = 0.042). Particularly, overweight could increase T2DM risk in monozygotic (MZ) twins, and the difference in ORs between the unmatched and matched designs was significant (P = 0.014). After controlling for age and sex, the positive BMI-T2DM association was partly due to a significant genetic correlation (rA= 0.31, 95% CI: 0.20∼0.41). CONCLUSIONS: Our findings suggest that genetics and early-life environments might account for the observed overweight-T2DM association. Genetic correlation between BMI and T2DM further provides evidence for the influence of overlap genes on their association.

2.
Liver Int ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521152

RESUMO

BACKGROUND AND AIMS: Hyperinsulinemia and insulin resistance play a central role in the progression of hepatic steatosis and fibrosis, and diet can modulate insulin response. We thus hypothesized that diet with higher insulinemic potential is associated with increased risk of these conditions. METHODS: Two empirically dietary indices for hyperinsulinemia (EDIH) and insulin resistance (EDIR) were derived to identify food groups most predictive of fasting concentrations of C-peptide and insulin and homeostatic model assessment for insulin resistance, respectively. Hepatic steatosis and fibrosis were defined by controlled attenuation parameter and liver stiffness measurement using transient elastography (TE). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. RESULTS: Of the 4,171 participants with TE examination, 1,436 (age-standardized prevalence, 33.8%) were diagnosed with steatosis, 255 (5.6%) with advanced fibrosis, and 101 (2.2%) with cirrhosis. The multivariable-adjusted ORs for participants comparing the highest to the lowest EDIH tertile were 1.17 (95% CI: 0.99-1.39, Ptrend = 0.005) for steatosis, 1.74 (95% CI: 1.24-2.44, Ptrend = 0.001) for advanced fibrosis, and 2.05 (95% CI: 1.21-3.46, Ptrend = 0.004) for cirrhosis. Similar associations were observed for EDIR with ORs of 1.32 (95% CI: 1.11-1.55, Ptrend < 0.001) for steatosis and 1.43 (95% CI: 1.03-1.99, Ptrend = 0.006) for advance fibrosis. These positive associations remained among never drinkers and individuals who were free of hepatitis B and/or C. CONCLUSIONS: Our findings suggest that hyperinsulinemia and insulin resistance may partially underlie the influence of diet on hepatic steatosis and fibrosis, and highlight the importance of reducing or avoiding insulinemic dietary pattern.

3.
Methods Mol Biol ; 2388: 79-85, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34524663

RESUMO

Natural killer T cells (NKT) are abundant in the hepatic sinuses and account for about 20-50% of rat liver lymphocytes. Type I or invariant NKT cells (iNKT) exert a powerful pro-inflammatory effect when activated, while type II NKT cells are more heterogeneous and mainly play an immunomodulatory role. Here we mainly introduced the isolation and characterization methods of human invariant NKT cells. Through immunomagnetic beads and flow cytometry, iNKT cells can be isolated specifically, and that explains functional analysis can be further established.

4.
Ecotoxicol Environ Saf ; 225: 112761, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509161

RESUMO

Salt stress, as an abiotic stress, limits crops production worldwide. Autophagy and programmed cell death (PCD) have been functionally linked to plant adaptation to abiotic stress. However, the relation of autophagy and PCD is still under debate and the mechanism behind remains not fully understood. In this study, salt-tolerant wheat cultivar Jimai22 was used as the experimental material, and 150 mM NaCl was added to the hydroponic culture to test the effect of salt treatment. The results showed that NaCl stress enhances autophagic activity and induced occurrence of PCD in roots and leaves of wheat seedlings. Then, the barley stripe mosaic virus-induced silencing (BSMV-VIGS) method was used to inhibit autophagy by silencing the expression of ATG2 or ATG7. The results showed that silencing of ATG2 or ATG7 significantly inhibited autophagy and impaired the tolerance of wheat to NaCl stress. Moreover, silencing of ATG2 or ATG7 disrupted the absorption of Na, Cl, K and Ca elements and led to subsequent disequilibrium of Na+, Cl-, K+ and Ca2+, induced generation of excess reactive oxygen species (ROS), decreased the antioxidant activity, damaged photosynthesis apparatus, increased the level of PCD and led to differential expression of the genes, two metacaspase genes, cysteine-rich receptor-like kinase (CRK) 10, and CRK26 in leaves of wheat seedlings under NaCl stress. The effect of the inhibitor 3-methyladenine (3-MA) on roots and leaves of wheat seedlings was in accordance with that of ATG2 and ATG7 silencing. Our results suggest that autophagy negatively regulates salt-induced PCD, or limits the scale of salt-induced PCD to avoid severe tissue death in wheat seedlings.

5.
BMC Musculoskelet Disord ; 22(1): 787, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517870

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication after arthroplasty. Numerous prophylactic strategies and studies to reduce VTEs have focused on the duration of the hospital stay and on few extramural hospitals. This study aimed to investigate extramural hospital management of VTE after total hip/knee arthroplasty (THA/TKA) in China with a novel survey tool. METHODS: A total of 180 patients undergoing arthroplasty, including 68 THA patients and 112 TKA patients, were enrolled in this study. All patients received anticoagulant treatment management. A survey querying VTE management and adherence, such as therapy information, understanding of anticoagulation, satisfaction with the ability of medical staff, and satisfaction with health care costs, was administered by a questionnaire (TKA/THA Patients' Experience with Anticoagulation in the Post-discharge Period) for quality improvement. RESULTS: The average age of the patients was 65.27 ± 13.62 years. All patients knew their follow-up times. 85 % of them were suggested that re-examine at the next 14 days, and the others at the next 28 days. All patients continued to visit the orthopaedic clinic after discharge without choosing other types of outpatient services, such as an anticoagulant clinic or home visit with a nurse/pharmacist or remote evaluation by telephone. A total of 96.6 % of all patients used new oral anticoagulants, and the most common treatment duration was 2-4 weeks (93.3 %). 48 % informed their physicians that they were taking anticoagulation medications when they visited ophthalmology, dentistry, dermatology, and other departments. The overall rate of satisfaction with anticoagulation management was 81.67 %, and 6.67 % of patients were not unsatisfied with their medical expenses. Patient compliance decreased with increasing follow-up time. Continuous follow-ups after discharge significantly improved patient compliance. CONCLUSIONS: These results elucidate how we can improve the quality of anticoagulation. Continuous follow-up appointments for 30 days after discharge, especially for individuals over 65 years old, significantly improved patient satisfaction and reduced the incidence of VTE and medical costs.

6.
Hepatology ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510484

RESUMO

OBJECTIVES: Aging exacerbates liver neutrophil infiltration and alcohol-associated liver disease (ALD) in mice and humans, but the underlying mechanisms remain obscure. This study aimed to examine the effect of aging and alcohol consumption on neutrophilic Sirtuin 1 (SIRT1) and microRNA-223 (miR-223), and their contribution to ALD pathogeneses. DESIGN: Young and aged mice, myeloid-specific Sirt1 knockout mice were subjected to chronic-plus-binge ethanol feeding. Blood samples from healthy controls and patients with chronic alcohol drinking presented with acute intoxication were analyzed. RESULTS: Neutrophilic Sirt1 and miR-223 expression were downregulated in aged mice compared to young mice. Deletion of the Sirt1 gene in myeloid cells including neutrophils exacerbated chronic-plus-binge ethanol-induced liver injury and inflammation and downregulated neutrophilic miR-223 expression. Immunoprecipitation experiments revealed that SIRT1 promoted C/EBPα deacetylation by directly interacting with C/EBPα, a key transcription factor that controls miR-223 biogenesis, and subsequently elevated miR-223 expression in neutrophils. Importantly, downregulation of SIRT1 and miR-223 expression was also observed in circulating neutrophils from middle-aged and elderly subjects compared to those from young individuals. Chronic alcohol users with acute intoxication had a reduction in neutrophilic SIRT1 expression in young and middle-aged patients, with a greater reduction in the latter group. The neutrophilic SIRT1 expression correlated with neutrophilic miR-223 and serum alanine transaminase levels in those patients. CONCLUSIONS: Aging increases the susceptibility of alcohol-induced liver injury in mice and humans via the downregulation of the neutrophilic SIRT1-C/EBPα-miR-223 axis, which could be a novel therapeutic target for the prevention and/or treatment of ALD.

7.
Dig Dis Sci ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515875

RESUMO

BACKGROUND: Circular RNA (circRNA) tubulin gamma complex associated protein 3 (circTUBGCP3) has been reported to play an oncogenic role in colorectal cancer and osteosarcoma. AIMS: We further assessed the role and working mechanism of circTUBGCP3 in rectal cancer progression. METHODS: Colony formation assay and transwell assays were performed to analyze cell colony formation ability and motility. Flow cytometry was utilized to assess cell cycle progression and cell apoptosis. The production of lactate and the consumption of glucose were evaluated by fluorescence-based glucose/lactate assay kit to analyze cell glycolysis. The intermolecular interaction was verified by dual-luciferase reporter assay. In vivo experiments were carried out to analyze the role of circTUBGCP3 in tumor growth using xenograft tumor model. RESULTS: CircTUBGCP3 was significantly up-regulated in rectal cancer tissues and cell lines. CircTUBGCP3 interference inhibited the colony formation ability, migration, invasion, cell cycle progression, and glycolysis and promoted the apoptosis in rectal cancer cells. CircTUBGCP3 negative regulated microRNA-375 (miR-375) expression through interacting with it and circTUBGCP3 silencing-mediated effects in rectal cancer cells were largely based on the up-regulation of miR-375. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) was a target of miR-375, and ROCK1 was regulated by circTUBGCP3/miR-375 axis in rectal cancer cells. MiR-375 overexpression suppressed the malignant behaviors of rectal cancer cells partly through down-regulating ROCK1. CircTUBGCP3 interference restrained rectal cancer progression in vivo. CONCLUSION: CircTUBGCP3 acted as an oncogene to promote the malignant phenotypes of rectal cancer cells by modulating miR-375/ROCK1 axis.

8.
Exp Brain Res ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476536

RESUMO

To investigate the association of miR-106b-5p with neuroinflammation and microglial activation in a status epilepticus (SE) mouse model. We examined changes in the expression of microRNA-106b-5p (miRNA-106b-5p), repulsive guidance molecule A (RGMa), triggering receptor expressed on myeloid cells 2 (TREM2), and the microglia-related markers interleukin (IL)-1ß, IL-4, IL-6, IL-10, inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1) in the mouse hippocampus of the lithium-pilocarpine-induced SE mouse model. Eighty-four female C57BL/6 mice were randomly divided into a normal control group (n = 12), and six SE groups (n = 12/group), which were monitored at 6 h and at 1, 3, 7, 14, and 21 days (d) post-SE induction. Unlike in the dentate gyrus, immunohistochemical staining revealed prominent neuronal swelling at 6 h, significant neuronal loss and apoptosis on day 3, and recovery by day 14 in the hippocampal cornu ammonis (CA)1 and CA3 pyramidal cells in SE mice. We noted elevated levels of miRNA-106b-5p and all microglia-related markers, which peaked at 3 days post-SE, except IL-4, which peaked at 7 days post-SE, indicating inflammation and microglial activation. RGMa and TREM2 levels decreased at 6 h post-SE. All markers but miRNA-106b-5p, RGMa, and TREM2 returned to baseline levels at 21 days post-SE. Dual luciferase reporter gene assay showed that microRNA-106b-5p can interact with RGMa. We observed that miR-106b-5p level increased while both RGMa and TREM2 levels decreased post-SE and showed associations with microglial activation and inflammation in the mouse hippocampus, suggesting their potential as SE therapeutic targets.

9.
Front Immunol ; 12: 722027, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489971

RESUMO

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals who mounted a detectable antibody response with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients did. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections.

10.
J Hazard Mater ; 416: 126112, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492909

RESUMO

Nano-bio interface is of great importance in dictating the interaction between the nanomaterials and biological system and thus the toxicity to aquatic organisms. Herein, two specific faceted TiO2 nanocrystals, {101} and {001} facet, were exposed to Daphnia magna to explore facet-dependent toxicological responses in aquatic environment. Due to the different influences on oxidative stress process, the half-maximal effective concentration (EC50) value of {001} TiO2 (1.27 g L-1) to D. magna was less than that of {101} TiO2 (1.68 g L-1). Suwannee river humic acid (SRHA) could significantly reduce the oxidative stress responses of TiO2 nanocrystals and thus alleviate their toxicities to D. magna in aquatic environment. The protective effect of SRHA against TiO2 toxicity exhibited a facet-dependent manner. Compared to {101} TiO2, a more obvious detoxification effect was observed for {001} TiO2. The high SRHA concentration could endow both faceted TiO2 nanocrystals with a similar toxicity due to the formation of SRHA-corona on TiO2 surface. This facet-affected toxicity of nanomaterials in aquatic environment would provide us new insights in predicting the exposure risk of nanomaterials in nature waters.

11.
Chem Commun (Camb) ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494065

RESUMO

The direct 3,3'-dimerization of BODIPYs lacking substituent groups in the 1,2,6, and 7 positions was developed by oxidative coupling with FeCl3. This regioselective dimerization was achieved for BODIPYs substituted only in the 5-position with Cl or aryl groups. Further functionalization of the 5,5'-dichloride dimer gave the corresponding pyrrole or 4-(2-aminoethyl)morpholine disubstituted dimers 2f and 2g, respectively. While dimer 2f exhibited intense NIR absorption/emission maxima at 773/827 nm in toluene, dimer 2g showed favorable lysosome-targeting NIR fluorescence in living cells.

12.
Eur J Histochem ; 65(3)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34494412

RESUMO

Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long noncoding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury.

13.
BMC Musculoskelet Disord ; 22(1): 760, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488703

RESUMO

BACKGROUND: Acromial anatomy has been found to be correlated with degenerative full-thickness rotator cuff tears in current studies. However, research on the relationship between acromial anatomy and articular-sided partial thickness of rotator cuff tears (PTRCTs) is still lacking. The purpose of this study was to evaluate whether these imaging graphic parameters exhibit any association between acromial anatomy and degenerative articular-sided PTRCTs. METHODS: Between January 2016 and December 2018, a total of 91 patients without a history of trauma underwent arthroscopy as an articular-sided PTRCT group. In the control group, with age- and sex-matched patients, we selected 91 consecutive outpatient patients who underwent shoulder magnetic resonance imaging (MRI) because of shoulder pain and an MRI diagnosis of only synovial hyperplasia and effusion. MRI was used to measure the acromial type, acromiohumeral distance (AHD), lateral acromial angle (LAA), acromion index (AI), and critical shoulder angle (CSA) by 2 independent observers. RESULTS: The acromion type, AHD and LAA showed no difference between degenerative articular-sided PTRCTs and controls (P = 0.532, 0.277, and 0.108, respectively). AI and CSA were significantly higher in degenerative articular-sided PTRCTs (P = 0.002 and 0.003, respectively). A good correlation was found between AI and CSA to measurement(Pearson correlation coefficient = 0.631). CONCLUSIONS: Our study revealed that higher AI and CSA were found in degenerative articular-sided PTRCTs. Acromial anatomy with a large acromial extension was associated with the occurrence of degenerative articular-sided PTRCTs.


Assuntos
Lesões do Manguito Rotador , Articulação do Ombro , Acrômio/diagnóstico por imagem , Artroscopia , Humanos , Imageamento por Ressonância Magnética , Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Articulação do Ombro/diagnóstico por imagem
14.
Pharmacol Res ; : 105873, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34500060

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease targeting the synovium. Previous studies have found that IgD may be a potential target for the treatment of RA. We designed a new type of fusion protein, hIgDFc-Ig (DG), to block the binding of IgD to IgD receptor (IgDR). In this study, we found that DG has a significant therapeutic effect in mice with collagen-induced arthritis (CIA). DG improved the claw of irritation symptoms in these mice, inhibited the pathological changes in spleen and joint tissues, and had a moderating effect on B cell subsets at different inflammatory stages. Moreover, DG could also decrease the levels of IgA, IgD, IgM and IgG subtypes of immunoglobulin in the serum of mice with CIA. In vitro, B cell antigen receptor (BCR) knockout Ramos cells were established using the CRISPR/Cas9 technology to further study the activation of BCR signalling by IgD and the effect of DG. We found that the therapeutic effect of DG in mice with CIA may be achieved by inhibiting the activation of BCR signalling by IgD, which may be related to the activation of Igß. In summary, DG may be a potential biological agent for the treatment of RA and it has broad application prospects in the future.

15.
Glia ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498776

RESUMO

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized primarily by impaired social communication and rigid, repetitive, and stereotyped behaviors. Many studies implicate abnormal synapse development and the resultant abnormalities in synaptic excitatory-inhibitory (E/I) balance may underlie many features of the disease, suggesting aberrant neuronal connections and networks are prone to occur in the developing autistic brain. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function during a critical developmental period may also contribute to the pathogenesis of ASD. Here, we report that increasing hippocampal astrogenesis during development induces autistic-like behavior in mice and a concurrent decreased E/I ratio in the hippocampus that results from enhanced GABAergic transmission in CA1 pyramidal neurons. Suppressing the aberrantly elevated GABAergic synaptic transmission in hippocampal CA1 area rescues autistic-like behavior and restores the E/I balance. Thus, we provide direct evidence for a developmental role of astrocytes in driving the behavioral phenotypes of ASD, and our results support that targeting the altered GABAergic neurotransmission may represent a promising therapeutic strategy for ASD.

16.
BMJ Open ; 11(8): e053617, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452972

RESUMO

INTRODUCTION: Chromosomal abnormalities and monogenic disorders account for ~15%-25% of recognisable birth defects. With limited treatment options, preconception and prenatal screening were developed to reduce the incidence of such disorders. Currently, non-invasive prenatal screening (NIPS) for common aneuploidies is implemented worldwide with superiority over conventional serum or sonographic screening approaches. However, the clinical validity for the screening of frequent chromosome segmental copy number variations and monogenic disorders still awaits to be proved. METHODS AND ANALYSIS: This study is a multicentre, prospective study. The participants were recruited from three tertiary hospitals in China starting from 10 April 2021. The study is expected to conclude before 10 October 2022. Pregnant women with abnormal prenatal screening results indicated for invasive prenatal diagnosis or those who decide to terminate their pregnancies due to abnormal ultrasound findings will be evaluated for enrolment. Cell-free DNA extracted from the maternal plasma will be used for an analytically validated comprehensive NIPS test developed by Beijing BioBiggen Technology Co. (Beijing, China). The diagnostic results from prenatal or postnatal specimens as well as the pregnancy outcome data will be collected to examine the clinical sensitivity, specificity, positive and negative predictive values of the test. ETHICS AND DISSEMINATION: This study was approved by the Obstetrics and Gynecology Hospital of Fudan University (2020-178). Results of this study will be disseminated to public through scientific conferences and a peer-reviewed journal. Written informed consents will be obtained from participants. TRIAL REGISTRATION NUMBER: ChiCTR2100045739.


Assuntos
Transtornos Cromossômicos , Variações do Número de Cópias de DNA , Aneuploidia , Feminino , Humanos , Estudos Multicêntricos como Assunto , Gravidez , Resultado da Gravidez , Diagnóstico Pré-Natal , Estudos Prospectivos
17.
PLoS One ; 16(8): e0255610, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34379642

RESUMO

13 Reasons Why is a Netflix original series adapted from Jay Asher's 2007 young adult novel with the same title. Season 1 premiered on March 31, 2017 and featured the sensitive issue of teen suicide along with bullying, substance use, depression, and sexual assault. Unlike the typical teen dramas on popular streaming platforms, this show was created not only for entertainment, but also to stimulate conversations about taboo topics that people often shy away from. However, it also caused significant controversy, especially criticism around the main character Hannah's suicide scene. More than three years into the initial controversy and at least two dozen scholarly publications later, this study is the first to examine the entertainment narrative content of 13 Reasons Why Season 1 to better understand how these health and social issues were portrayed in the show, what specific examples we could identify as potential behavioral modeling, and to what degree it complied with the 2017 WHO guidelines for media professionals. We used the framing theory and social cognitive theory in communication research and media studies as our guiding conceptual frameworks and a narrative analysis approach to investigate a total of 660 cut scenes in all 13 episodes. Our findings provided empirical evidence, along with contextual information and detailed examples, to demonstrate that a popular entertainment program like the Netflix series 13 Reasons Why serves as a double-edged sword. The production team's good will and due diligence are commendable. Yet, additional steps can be taken in the future to effectively promote professional resources and reduce viewers' risks, especially the most vulnerable groups.

18.
PLoS Pathog ; 17(8): e1009790, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34343211

RESUMO

The interferon-regulated antiviral responses are essential for the induction of both innate and adaptive immunity in mammals. Production of virus-derived small-interfering RNAs (vsiRNAs) to restrict virus infection by RNA interference (RNAi) is a recently identified mammalian immune response to several RNA viruses, which cause important human diseases such as influenza and Zika virus. However, little is known about Dicer processing of viral double-stranded RNA replicative intermediates (dsRNA-vRIs) in mammalian somatic cells. Here we show that infected somatic cells produced more influenza vsiRNAs than cellular microRNAs when both were produced by human Dicer expressed de novo, indicating that dsRNA-vRIs are not poor Dicer substrates as previously proposed according to in vitro Dicer processing of synthetic long dsRNA. We report the first evidence both for canonical vsiRNA production during wild-type Nodamura virus infection and direct vsiRNA sequestration by its RNAi suppressor protein B2 in two strains of suckling mice. Moreover, Sindbis virus (SINV) accumulation in vivo was decreased by prior production of SINV-targeting vsiRNAs triggered by infection and increased by heterologous expression of B2 in cis from SINV genome, indicating an antiviral function for the induced RNAi response. These findings reveal that unlike artificial long dsRNA, dsRNA-vRIs made during authentic infection of mature somatic cells are efficiently processed by Dicer into vsiRNAs to direct antiviral RNAi. Interestingly, Dicer processing of dsRNA-vRIs into vsiRNAs was inhibited by LGP2 (laboratory of genetics and physiology 2), which was encoded by an interferon-stimulated gene (ISG) shown recently to inhibit Dicer processing of artificial long dsRNA in cell culture. Our work thus further suggests negative modulation of antiviral RNAi by a known ISG from the interferon response.

19.
J Org Chem ; 86(17): 11492-11501, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342463

RESUMO

Organic small-molecule fluorescent chromophores have become essential to modern chemical, biological, and materials related investigations. Herein, a straightforward synthesis and subsequent borylation were presented to form a novel family of bisBF2-anchoring acyl-pyridinylhydrazine, which we named BOAPH. The chromophore enjoys outstanding structural diversities owing to varied acyl chlorides and N-heteroarenylhydrazides. These resultant BOAPH dyes are confirmed by NMR, HRMS, and single-crystal X-ray structure analysis. Their spectroscopic properties were studied, and most of the strong absorbance and bright fluorescence with maximum wavelengths centered in the range of 400 and 650 nm. More importantly, they exhibit promising fluorescence quantum yields up to 0.79 in solution and solid states, good photostability, and large Stokes shifts. Furthermore, a respective BOAPH dye with a para-dimethylaminophenyl group exhibited the interesting ability of ultrafast staining and two-photon imaging, which can specifically label lipid droplets of living cells immediately without the need for incubation.

20.
PLoS One ; 16(8): e0256884, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34460856

RESUMO

Mesosulfuron-methyl is always applied by foliar spraying in combination with the safener mefenpyr-diethyl to avoid phytotoxicity on wheat (Triticum aestivum L.) cultivars. However, it was observed that the tolerance of Tausch's goatgrass (Aegilops tauschii Coss.) to mesosulfuron-methyl significantly increased in the presence of mefenpyr-diethyl by performing bioassay. This confirmed phenomenon may lead to overuse of mesosulfuron-methyl and weed resistance evolution in field conditions. Therefore, we tested the effect of wheat seed dressing with mefenpyr-diethyl as a possible alternative and disclosed the underlying mechanisms by herbicide dissipation study, enzymatic analysis and transcriptome profiling. The results suggest that increase of ALS activity, enhancement of metabolic processes, and other stress responses are crucial for the regulation of herbicide detoxification induced by mefenpyr-diethyl. Additionally, transcription factors such as AP2/ERF-ERF, bHLH, NAC, and MYB, and protein kinase such as RLK-Pelle_DLSV might play vital regulatory roles. The current study has important implications for mesosulfuron-methyl application in wheat field to control Tausch's goatgrass and provides a comprehensive understanding of the protective effect of mefenpyr-diethyl.

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