Development of a bacteria-nanosapper for the active delivery of ZIF-8 particles containing therapeutic genes for cancer immune therapy.

Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment (TME). Some bacteria exhibit spontaneous chemotaxis toward the anaerobic and immune-suppressive TME, which makes them ideal natural vehicles for cancer gene therapy. Here, we conjugated ZIF-8 metal-organic frameworks encapsulating eukaryotic murine interleukin 2 () expression plasmid onto the surface of VNP20009, an attenuated strain with well-documented anti-cancer activity, and constructed a TME-targeted delivery system named /ZIF-8@.

Comparison of Jinzhen oral liquid and ambroxol hydrochloride and clenbuterol hydrochloride oral solution in the treatment of acute bronchitis in children: A multicenter, non-inferiority, prospective, randomized controlled trial.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days.

Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity.

Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.

Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

Fluoride binding-modulated supramolecular chirality of urea-containing triarylamine and its photo-manifestation.

In recent years, the regulation of anion-mediated chiral assemblies has gained significant interest. This study investigated the modulation of supramolecular chiroptical signals and chiral assembled structures in a triarylamine system containing a urea moiety through fluoride ion-urea bond interactions, aiming to understand the chiral sense amplification in supramolecular assemblies. Chiral triarylamine derivatives containing urea or amide units were synthesized and the self-assemblies were examined in the absence and presence of fluoride ions.

Enhanced upconversion and photoconductive nanocomposites of lanthanide-doped nanoparticles functionalized with low-vibrational-energy inorganic ligands.

Upconverting nanoparticles (UCNPs) convert near-infrared (IR) light into higher-energy visible light, allowing them to be used in applications such as biological imaging, nano-thermometry, and photodetection. It is well known that the upconversion luminescent efficiency of UCNPs can be enhanced by using a host material with low phonon energies, but the use of low-vibrational-energy inorganic ligands and non-epitaxial shells has been relatively underexplored. Here, we investigate the functionalization of lanthanide-doped NaYF UCNPs with low-vibrational-energy SnS ligands.

κ/β-GaO Type-II Phase Heterojunction.

Ultrawide-bandgap gallium oxide (GaO) holds immense potential for crucial applications such as solar-blind photonics and high-power electronics. Although several GaO polymorphs, i.e.

Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Pretreatment plasma vitamin D and response to neoadjuvant chemotherapy in breast cancer: evidence from pooled analysis of cohort studies.

Background: Biological evidence has revealed antitumor effect of vitamin D, but whether it could predict the response to neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients remains inconclusive. The aim was to investigate the association between pretreatment vitamin D level and response to NAC and subsequent survival outcomes in BC patients.

Materials And Methods: The authors systematically searched the Medline, Embase, Cochrane Library, and Web of Science databases and clinical trial registries to identify relevant articles from inception to 8 October 2024.

Epidemiology of New Psychoactive Substances in Relation to Traditional Drugs of Abuse in Clinical Oral Fluid Samples.

New psychoactive substances (NPS) are health-hazardous through unpredictable toxicity and effects and largely unknown epidemiology, motivating studies of the latter. Up to 138 NPS were retrospectively identified using liquid chromatography-high resolution mass spectrometry data from all 34 183 oral fluid drug samples collected in one Swedish health care region 2019-2020 representing 9468 psychiatric and addiction care patients. In total, 618 findings representing 58 NPS were detected in 481 samples from 201 patients.

Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: a comparative neuroimaging analysis.

Background: Psychostimulants and nonstimulants have partially overlapping pharmacological targets on attention-deficit/hyperactivity disorder (ADHD), but whether their neuroimaging underpinnings differ is elusive. We aimed to identify overlapping and medication-specific brain functional mechanisms of psychostimulants and nonstimulants on ADHD.

Methods: After a systematic literature search and database construction, the imputed maps of separate and pooled neuropharmacological mechanisms were meta-analyzed by Seed-based Mapping toolbox, followed by large-scale network analysis to uncover potential coactivation patterns and meta-regression analysis to examine the modulatory effects of age and sex.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Identification and validation of the important role of KIF11 in the development and progression of endometrial cancer.

Background: Human kinesin family member 11 (KIF11) plays a vital role in regulating the cell cycle and is implicated in the tumorigenesis and progression of various cancers, but its role in endometrial cancer (EC) is still unclear. Our current research explored the prognostic value, biological function and targeting strategy of KIF11 in EC through approaches including bioinformatics, machine learning and experimental studies.

Methods: The GSE17025 dataset from the GEO database was analyzed via the limma package to identify differentially expressed genes (DEGs) in EC.

%diag_test: a generic SAS macro for evaluating diagnostic accuracy measures for multiple diagnostic tests.

Background: Measures of diagnostic test accuracy provide evidence of how well a test correctly identifies or rules-out disease. Commonly used diagnostic accuracy measures (DAMs) include sensitivity and specificity, predictive values, likelihood ratios, area under the receiver operator characteristic curve (AUROC), area under precision-recall curves (AUPRC), diagnostic effectiveness (accuracy), disease prevalence, and diagnostic odds ratio (DOR) etc. Most available analysis tools perform accuracy testing for a single diagnostic test using summarized data.

A humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity.

Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.

Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.

An exploratory analysis of differences in serum protein expression by sex in patients with systemic sclerosis associated interstitial lung disease.

Background: Systemic sclerosis (SSc) is a rare connective tissue disease, frequently affecting the skin, lungs, and pulmonary vasculature. Approximately 30-50% of SSc patients develop interstitial lung disease (SSc-ILD), with 30-35% of related deaths attributed to it. Even though men are less likely to develop systemic sclerosis, they have a higher incidence of SSc-ILD than women, and they tend to develop it at a younger age with a higher mortality rate.

Dung predicts the global distribution of herbivore grazing pressure in drylands.

Dryland grazing sustains millions of people worldwide but, when poorly managed, threatens food security. Here we combine livestock and wild herbivore dung mass data from surveys at 760 dryland sites worldwide, representing independent measurements of herbivory, to generate high-resolution maps. We show that livestock and wild herbivore grazing is globally disconnected, and identify hotspots of herbivore activity across Africa, the Eurasian grasslands, India, Australia and the United States.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Ribosomal A-site interactions with near-cognate tRNAs drive stop codon readthrough.

Transfer RNAs (tRNAs) serve as a dictionary for the ribosome translating the genetic message from mRNA into a polypeptide chain. In addition to this canonical role, tRNAs are involved in other processes such as programmed stop codon readthrough (SC-RT). There, tRNAs with near-cognate anticodons to stop codons must outcompete release factors and incorporate into the ribosomal decoding center to prevent termination and allow translation to continue.

Bronchial structural changes analyzed with three-dimensional computed tomography correlate with severe acute graft-versus-host disease after allogenic hematopoietic stem cell transplantation.

Severe acute graft-versus-host disease (GVHD) can occur during allogeneic hematopoietic stem cell transplantation (allo-HSCT), causing considerable morbidity and mortality. Although several biomarkers have been reported for predicting acute GVHD, they are often difficult to measure in routine clinical practice. Recently, three-dimensional computed tomography (3D-CT) has been used to quantify the detailed bronchial structure, which might correlate with acute GVHD.

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.

Conformational diversity in class C GPCR positive allosteric modulation.

The metabotropic glutamate receptors (mGlus) are class C G protein-coupled receptors (GPCR) that form obligate dimers activated by the major excitatory neurotransmitter L-glutamate. The architecture of mGlu receptor comprises an extracellular Venus-Fly Trap domain (VFT) connected to the transmembrane domain (7TM) through a Cysteine-Rich Domain (CRD). The binding of L-glutamate in the VFTs and subsequent conformational change results in the signal being transmitted to the 7TM inducing G protein binding and activation.