Target protein identification in live cells and organisms with a non-diffusive proximity tagging system.

Identifying target proteins for bioactive molecules is essential for understanding their mechanisms, developing improved derivatives, and minimizing off-target effects. Despite advances in target identification (target-ID) technologies, significant challenges remain, impeding drug development. Most target-ID methods use cell lysates, but maintaining an intact cellular context is vital for capturing specific drug-protein interactions, such as those with transient protein complexes and membrane-associated proteins.

Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.

Malaria remains a serious global health challenge, yet treatment and control programs are threatened by drug resistance. Dihydroorotate dehydrogenase (DHODH) was clinically validated as a target for treatment and prevention of malaria through human studies with DSM265, but currently no drugs against this target are in clinical use. We used structure-based computational tools including free energy perturbation (FEP+) to discover highly ligand efficient, potent, and selective pyrazole-based DHODH inhibitors through a scaffold hop from a pyrrole-based series.

Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria.

Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum (Pf) parasites revealed point mutations in the Pf_proteasome β5 active-site (Pfβ5).

Diagnostic Value of Radiomics Analysis Based on Multimodal MRI for Advanced Liver Fibrosis in Patients with Hepatitis B.

Background: The goal was to explore the value of using radiomics analysis based on multimodal MRI for evaluating the advanced fibrosis in patients with hepatitis B.

Methods: One hundred and forty-three patients with hepatitis B fibrosis were randomly divided into training and validation cohorts in a 2:1 ratio. In the training cohort, a clinical model was established with logistic regression, a radiomics signature based on multimodal MRI was established with support vector machine (SVM), and a nomogram integrated the radiomics signature and clinical factors.

The prevalence, hospitalization outcomes and risk factors of euthyroid sick syndrome in patients with diabetic ketosis/ketoacidosis.

Background: To investigate the prevalence of euthyroid sick syndrome (ESS) and to evaluate the outcomes and risk factors associated with ESS among hospitalized patients with diabetic ketosis (DK) or diabetic ketoacidosis (DKA).

Methods: Laboratory and clinical data of 396 adult hospitalized DK/DKA patients with or without ESS were collected and analyzed. Spearman linear analysis and multivariable logistic regression analyses were used to evaluate correlated factors of thyroid hormones and risk factors of ESS.

A Transparent, Tough and Self-Healable Biopolymeric Composites Hydrogel for Open Wound Management.

Modern healthcare engineering requires a wound dressing solution supported by materials with outstanding features such as high biological compatibility, strong mechanical strength, and higher transparency with effective antibacterial properties. Here, we present a unique hydrogel technology consisting of two negatively charged biopolymers and a positively charged synthetic polymer. The interaction between charged polymers through hydrogen bonds has been created, which are revealed in the simulation by density functional theory and Fourier transform infrared spectra of individual polymers and the hydrogel film.

Young Adults with Negative Body Image at Fatness Subscale Are More Restrained Than Normal Adults during a Chocolate Discounting Task.

Research has confirmed that people with obesity exhibit special responses to food stimuli when it comes to food-related decision tasks. However, it is unclear whether the phenomenon exists in people who feel mentally obese, even though they are not obese. The aim of this study was to investigate the behavioral and neural correlations of food-related decision-making between young adults with negative body image at fatness subscale and a control group, so as to explore the differences in executive functioning between them.

Disparities in Implementing COVID-19 Prevention Strategies in Public Schools, United States, 2021-22 School Year.

During the COVID-19 pandemic, US schools have been encouraged to take a layered approach to prevention, incorporating multiple strategies to curb transmission of SARS-CoV-2. Using survey data representative of US public K-12 schools (N = 437), we determined prevalence estimates of COVID-19 prevention strategies early in the 2021-22 school year and describe disparities in implementing strategies by school characteristics. Prevalence of prevention strategies ranged from 9.

Challenges experienced by U.S. K-12 public schools in serving students with special education needs or underlying health conditions during the COVID-19 pandemic and strategies for improved accessibility.

Background: Students with special education needs or underlying health conditions have been disproportionately impacted (e.g., by reduced access to services) throughout the COVID-19 pandemic.

Study on the quality characteristics of hot-dry noodles by microbial polysaccharides.

The effect of curdlan gum (CG), gellan gum (GG), and xanthan gum (XG) on the quality characteristics of hot-dry noodles (HDN) was investigated. The rheology properties were used to evaluate the quality of the dough, the textural, viscosity, cooking characteristics and water states were investigated to study the quality changes of HDN. Three microbial polysaccharides were found that it could improve the quality of wheat flour and significantly increase the starch viscosity of HDN and delay the water migration rate of HDN.

Repurposed dihydroorotate dehydrogenase inhibitors with efficacy against drug-resistant .

New antimicrobials are needed for the treatment of extensively drug-resistant . The de novo pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) is a validated drug target for malaria and human autoimmune diseases. We provide genetic evidence that DHODH (DHODH) is essential for bacterial survival in rodent infection models.

Dual-Energy Computed Tomography For Differentiation Between Osteoblastic Metastases and Bone Islands.

Objective: The objective of our study was to evaluate the utility of Rho/Z on dual-energy computed tomography (DECT) for the differentiation of osteoblastic metastases (OBMs) from bone islands (BIs).

Methods: DECT images of 110 patients with malignancies were collected. The effective atomic number (Z), electron density (Rho), dual energy index (DEI), and regular CT (rCT) values were measured by two observers.

The Ameliorative Effect of COST on Diet-Induced Lipid Metabolism Disorders by Regulating Intestinal Microbiota.

Background: Chitosan oligosaccharides, with an average molecular weight ≤ 1000 Da (COST), is a natural marine product that has the potential to improve intestinal microflora and resist lipid metabolism disorders.

Methods: First, by establishing a mice model of lipid metabolism disorder induced by a high fat and high sugar diet, it is proven that COST can reduce lipid metabolism disorder, which may play a role in regulating intestinal microorganisms. Then, the key role of COST in the treatment of intestinal microorganisms is further confirmed through the method of COST-treated feces and fecal bacteria transplantation.

[Preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and influencing factors for follow-up compliance: a multicenter investigation].

Objectives: To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance.

Methods: A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance.

Organocatalytic enantioselective S1-type dehydrative nucleophilic substitution: access to bis(indolyl)methanes bearing quaternary carbon stereocenters.

A highly general and straightforward approach to access chiral bis(indolyl)methanes (BIMs) bearing quaternary stereocenters has been realized enantioconvergent dehydrative nucleophilic substitution. A broad range of 3,3'-, 3,2'- and 3,1'-BIMs were obtained under mild conditions with excellent efficiency and enantioselectivity (80 examples, up to 98% yield and >99 : 1 ). By utilizing racemic 3-indolyl tertiary alcohols as precursors of alkyl electrophiles and indoles as C-H nucleophiles, this organocatalytic strategy avoids pre-activation of substrates and produces water as the only by-product.

Diagnostic Performance of Diffusion Kurtosis Imaging for Benign and Malignant Breast Lesions: A Systematic Review and Meta-Analysis.

Purpose: Magnetic resonance imaging (MRI) has a high sensitivity for differentiating between malignant and non-malignant breast lesions but is sometimes limited due to its low specificity. Here, we performed a meta-analysis to evaluate the diagnostic performance of mean kurtosis (MK) and mean diffusivity (MD) values in magnetic resonance diffusion kurtosis imaging (DKI) for benign and malignant breast lesions.

Methods: Original articles on relevant topics, published from 2010 to 2019, in PubMed, EMBASE, and WanFang databases were systematically reviewed.

Ventilation Improvement Strategies Among K-12 Public Schools - The National School COVID-19 Prevention Study, United States, February 14-March 27, 2022.

Effective COVID-19 prevention in kindergarten through grade 12 (K-12) schools requires multicomponent prevention strategies in school buildings and school-based transportation, including improving ventilation (1). Improved ventilation can reduce the concentration of infectious aerosols and duration of potential exposures (2,3), is linked to lower COVID-19 incidence (4), and can offer other health-related benefits (e.g.

lncRNA-mRNA Expression Patterns in Invasive Pituitary Adenomas: A Microarray Analysis.

Background: Long noncoding RNAs (lncRNAs) play important roles in the tumorigenesis and progression of various cancer types; however, their roles in the development of invasive pituitary adenomas (PAs) remain to be investigated.

Methods: lncRNA microarray analysis was performed for three invasive and three noninvasive PAs. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed, and coexpression networks between lncRNA and mRNA were constructed.

Use of Tobacco Products, Alcohol, and Other Substances Among High School Students During the COVID-19 Pandemic - Adolescent Behaviors and Experiences Survey, United States, January-June 2021.

The COVID-19 pandemic has been associated with established risk factors for adolescent substance use, including social isolation, boredom, grief, trauma, and stress. However, little is known about adolescent substance use patterns during the pandemic. CDC analyzed data from the Adolescent Behaviors and Experiences Survey, an online survey of a probability-based, nationally representative sample of public- and private-school students in grades 9-12 (N = 7,705), to examine the prevalence of current use of tobacco products, alcohol, and other substances among U.

Disruptions to School and Home Life Among High School Students During the COVID-19 Pandemic - Adolescent Behaviors and Experiences Survey, United States, January-June 2021.

Youths have experienced disruptions to school and home life since the COVID-19 pandemic began in March 2020. During January-June 2021, CDC conducted the Adolescent Behaviors and Experiences Survey (ABES), an online survey of a probability-based, nationally representative sample of U.S.

Downregulation of Kcnq1ot1 attenuates β-cell proliferation and insulin secretion via the miR-15b-5p/Ccnd1 and Ccnd2 axis.

Aim: To examine the effect of lncRNA Kcnq1ot1 on pancreatic β cells in the development of diabetes.

Methods: The expression levels of Kcnq1ot1 were detected in the islets of diabetes mouse models and the serum of patients with type 2 diabetes by qRT-PCR. CCK8, Ki67 staining, immunohistochemical analyses, glucose-stimulated insulin secretion and intraperitoneal glucose tolerance test were performed to detect the effect of Kcnq1ot1 on β-cell proliferation and insulin secretion in vitro and in vivo.

Evaluation of the Thyroid Characteristics and Correlated Factors in Hospitalized Patients with Newly Diagnosed Type 2 Diabetes.

Background: Diabetes mellitus (DM) and thyroid dysfunction (TD) are two closely associated disorders. The objective of the present study was to investigate the thyroid status and the relationships between thyroid hormones, diabetic complications and metabolic parameters in hospitalized patients with newly diagnosed type 2 DM (T2DM).

Methods: This was an observational cross-sectional study, conducting on 340 patients with newly diagnosed T2DM who were admitted to ward of endocrinology department and 120 matched individuals without diabetes.