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Our results showed that SMRT has great advantages in detection of α-globin gene triplications, rare deletions and determination of a cis or trans configuration. SMRT is a comprehensive and one-step method for thalassemia screening and diagnosis, especially for detection of rare thalassemia mutations.Acute kidney injury (AKI) is a sudden loss of kidney function that causes a rise in serum creatinine and a decrease in urine output, which leads to high morbidity and mortality. However, effective therapeutic drugs have not yet been developed due to the poor understanding of the cellular and molecular mechanisms of AKI. Recent studies have revealed that AKI leads to renal disorders, including inflammation, cell apoptosis, oxidative stress, mitochondrial dysfunction and autophagy, and multiple signaling pathways are involved in these disorders during the pathogenesis of AKI, which suggests that drugs specifically targeting these signaling pathways may be effective in preventing and treating AKI. In addition, a great number of small molecules show a therapeutic effect on AKI by targeting these signaling pathways and may be promising therapeutic drugs in the treatment of AKI. Moreover, an in-depth analysis of failed clinical trials is carried out to find out an effective strategy for AKI therapy. Taken together, this review focuses on the cellular and molecular mechanisms of AKI and the small molecules that alleviate AKI, which will provide new insight into AKI therapy.Although screening tools are available for alcohol use disorders (AUD), such as the Alcohol Use Disorders Identification Test (AUDIT), these tools do not directly characterize individual drinking behavior for patients with AUD. Therefore, the aim of this study was to develop a new self-report questionnaire to identify the characteristics of drinking behavior patterns in patients with AUD.The study team developed a self-administered 20-item questionnaire for drinking behavior pattern (DBP-20) based on semi-structured interviews of patients with AUD. The DBP-20 and AUDIT were administered to 232 patients with AUD and 222 normal drinkers (1 ≤ AUDIT less then 20) as controls. Exploratory factor analysis of the DBP-20 was conducted for patients with AUD, followed by comparisons of its item and subscale scores between patients with AUD and controls. Correlations of AUDIT with total and subscale scores of the DBP-20 were also analyzed. Receiver operating characteristic (ROC) analyses for the DBP-20 and its subscales were performed to distinguish patients with AUD from controls.Exploratory factor analysis revealed a multidimensional 4-factor model of the DBP-20 coping with negative affect, automaticity, enhancement, and social use. Significant differences in DBP-20 total and subscale scores were observed for patients with AUD versus controls for all factors, except the social use subscale. Both the coping with negative affect and automaticity subscale scores as well as total DBP-20 scores were highly correlated with AUDIT scores. Total DBP-20 scores showed the greatest sensitivity, negative predictive value, and area under the ROC curve to distinguish patients with AUD from normal drinkers.Drinking as a means of coping with negative affect and automaticity may be specific for patients with AUD. DBP-20 may help patients with AUD to be aware of their own targeted problematic drinking behaviors and to seek their personalized behavioral approaches in a collaborative relationship with therapists.People living with HIV (PLWH) are at increased risk for noncommunicable diseases such as lung disease in part due to opportunistic infections including pneumonia. HIV infection is associated with increased prevalence of impaired lung function and abnormal gas exchange. Alcohol use disorder (AUD) is exceedingly common in PLWH and is associated with higher risk of pneumonia in PLWH. Alcohol use may lead to lung damage through several mechanisms. Data on the long-term effect of AUD on pulmonary function in PLWH are sparse and conflicting. selleck chemicals llc To evaluate this relationship, we conducted a cross-sectional analysis of adult PLWH in care in Louisiana. We hypothesized that chronic alcohol use would be associated with subsequent pulmonary dysfunction in a dose-dependent fashion. All participants performed standardized spirometry on study entry. In total, 350 participants with acceptable spirometry were included in this analysis. Thirty-one percent of participants were female. Women reported less lifetime alcohol use and less smoking; however, they reported more chronic respiratory symptoms. In adjusted models, total lifetime alcohol use was not associated with spirometry measures of pulmonary function. HIV-related variables (CD4 count and viral load) were also not associated with measures of pulmonary function. We then conducted sex-stratified analyses to eliminate residual confounding of sex and similarly found no association of total lifetime alcohol use and pulmonary function. We found no association of AUDIT score or early life alcohol use and pulmonary function. In latent class factor analysis, current heavy alcohol use was associated with lower measures of pulmonary function as compared to former heavy alcohol use. In summary, in this cohort of New Orleanian men and women living with HIV with robust measures of alcohol use, though total lifetime alcohol use and early life alcohol use were not associated with pulmonary function, current heavy alcohol use was associated with impaired pulmonary function.Multiple myeloma is a plasma cell malignancy, accounting for approximately 1% of new cancer cases. It is the second most common hematological malignancy. Novel clinical agents such as the proteasome inhibitor-bortezomib, have shown improved survival rates in recent decades. However, multiple myeloma remains incurable, as most patients eventually relapse and become refractory to current treatments. Therefore, there is an urgent need for developing new regimens to overcome the bortezomib resistance. Here, we screened a library of 2370 bioactives and found that polyphyllin VII selectively suppressed multiple myeloma cell growth in vitro and in vivo. We identified moesin, one of the critical regulators of the Wnt/β-catenin pathway, as a target of polyphyllin VII by drug affinity responsive target stability assay and cellular thermal shift assay. Polyphyllin VII binds to moesin and induces its degradation via the ubiquitin-proteasome pathway, thereby impairing the Wnt/β-catenin pathway activity and leading to a reduction in the side population cells to overcome bortezomib resistance. Our study identified polyphyllin VII as a promising compound and moesin as a potential diagnostic and therapeutic target for treating multiple myeloma.The H9N2 subtype of influenza A virus circulates frequently among poultry in Asian and North African countries causing economic loss in the poultry sector. The antigenic variations of the H9N2 virus were at the origin of its genetic evolution through the emergence of viral strains transmissible to humans and resistant to chemical antivirals, which require a strengthening of the fight means against this virus. In this study, we used a random linear hexapeptide library fused to the gene III protein of M13 filamentous bacteriophage to select new antiviral peptides that inhibit the infectivity of H9N2 virus. After three rounds of stringent selection and amplification, polyclonal phage-peptides directed against H9N2 virus were assessed by ELISA, and the optimal phage-peptides were grown individually and characterized for binding to H9N2 virus by monoclonal phage ELISA. The DNA of 27 phage-peptides clones was amplified by PCR, sequenced, and their amino acid sequences were deduced. Sixteen different phage-peptides were able to bind specifically the H9N2 virus, among them, 13 phage-peptides interacted with the hemagglutinin H9. Two selected peptides, P1 (LSRMPK) and P2 (FAPRWR) have shown antiviral activity in ovo and P1 was more protective in vivo then P2 when co-administered with the H9N2 virus. Mechanistically, these peptides prevent infection by inhibiting the attachment of the H9N2 virus to the cellular receptor. Molecular docking revealed that the peptides LSRMPK and FAPRWR bind to hemagglutinin protein H9, but interact differently with the receptor binding site (RBS). The present study demonstrated that the peptide P1 (LSRMPK) could be used as a new inhibitory molecule directed against the H9N2 virus.Colombia is one of the largest pesticide consumers in South America. These products have a variety of negative consequences on the health of rural populations, especially neurocognitive disorders in children. In this work, the prenatal and postnatal exposure to pesticides was evaluated and the association between the cognitive capacity of school-age children in rural areas of the city of Bogotá, Colombia, investigated. Separate multiple linear regression models were used to evaluate associations of pesticide exposure measures and WISC-IV scales, adjusted for child sex, maternal educational attainment, growth retardation, and effect modification explored by sex, using a cross products term of 232 children between the ages of 7 and 10. It was found that among all children, pesticide exposure at school was associated with a worse working memory index (ß = -3.40; 95%CI; -6.6; -0.2) and a worst verbal comprehension index (ß = -3.2; 95%CI; -6.5; -0.2). Among girls, pesticide use at home was associated with a worse processing speed index (ß = -5.1; 95% CI; -10.1; -0.20) but not among boys (ß = 1.73; 95% CI; -2.6; 6.9). This revealed an association between the prenatal and postnatal exposure reported and some IQ sub-indices of children aged between 7 and 10 years residing in the rural areas of Usme and Sumapaz in the city of Bogotá, Colombia.The effectiveness of menu calorie labeling in limiting the amount of calories selected has been called into question since it was mandated within the Affordable Care Act. This study examined how contexts that are known to influence motivational and information processing might limit the effectiveness of calorie labeling in order to shed some light on the mixed findings in this area. An online experiment was conducted in which calorie labels were paired or not paired with visual cues in different motivational contexts greater and lesser variety and energy density choices available. Results contribute to the general conclusion that calorie labels are not particularly effective. Specifically, the only context in which a calorie label succeeded in reducing calories selected was a high variety mix of low and high energy density foods with visual food cues present; however, this type of context elicited the greatest number of calories selected on average, even more than when only highly energy density items were present. The findings from this study add to the body of knowledge about the effectiveness of calorie labeling by defining some boundary conditions on whether and when the presence of calorie labels are likely to reduce caloric intake. This knowledge is helpful in furthering food selection and choice research, but also may help health practitioners design effective intervention strategies.