Intratumor heterogeneity of EGFR expression mediates targeted therapy resistance and formation of drug tolerant microenvironment.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used to treat non-small cell lung cancers with EGFR mutations, but drug resistance often emerges. Intratumor heterogeneity is a known cause of targeted therapy resistance and is considered a major factor in treatment failure. This study identifies clones of EGFR-mutant non-small cell lung tumors expressing low levels of both wild-type and mutant EGFR protein.

One-pot isothermal CRISPR/Dx system for specific and sensitive detection of microRNA.

MicroRNA (miRNA) is a promising biomarker for the early diagnosis of pancreatic cancer. To enable sensitive and reliable miRNA detection, we have developed a one-pot isothermal CRISPR/Dx detection system by combining rolling circle amplification (RCA) and CRISPR/Cas12a. RCA and CRISPR/Cas12a reactions are carried out in a single closed tube, bypassing the transferring step.

Risk Factors and Incidence for In-Stent Restenosis with Drug-Eluting Stent: A Systematic Review and Meta-Analysis.

Background: Despite significant reductions in in-stent restenosis (ISR) incidence with the adoption of drug-eluting stents (DES) over bare metal stents (BMS), ISR remains an unresolved issue in the DES era. The risk factors associated with DES-ISR have not been thoroughly analyzed. This meta-analysis aims to identify the key factors and quantify their impact on DES-ISR.

Generation of Multiple-Depth 3D Computer-Generated Holograms from 2D-Image-Datasets Trained CNN.

Generating computer-generated holograms (CGHs) for 3D scenes by learning-based methods can reconstruct arbitrary 3D scenes with higher quality and faster speed. However, the homogenization and difficulty of obtaining 3D high-resolution datasets seriously limit the generalization ability of the model. A novel approach is proposed to train 3D encoding models based on convolutional neural networks (CNNs) using 2D image datasets.

Haplotype-Resolved Genotyping and Association Analysis of 1,020 β-Thalassemia Patients by Targeted Long-Read Sequencing.

Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci.

LEF3 phosphorylation attenuates the replication of Bombyx mori nucleopolyhedrovirus by suppressing its interaction with alkaline nuclease.

Late expression factor 3 (LEF3), a multifunctional single-stranded DNA binding protein encoded by baculoviruses, is indispensable for viral DNA replication and plays a pivotal role in viral infection. Our previous quantitative analysis of phosphorylomics revealed that the phosphorylation levels of two serine residues (S8 and S25) located in LEF3 nuclear localization sequence were significantly up-regulated after Bombyx mori nucleopolyhedrovirus (BmNPV) infection, but the underlying mechanism remained unknown. To investigate the impact of phosphorylation on BmNPV infection, site-direct mutagenesis was performed on LEF3 to obtain phosphorylated mimic (S/D) or dephosphorylated mimic (S/A) mutants.

Arginine depletion-induced autophagy and metabolic dysregulation are involved in the disease severity of hand, foot, and mouth disease.

Amino acid metabolism provides significant insight into the development and prevention of many viral diseases. Therefore, the present study aimed to compare the amino acid profiles of hand, foot, and mouth disease (HFMD) patients with those of healthy individuals and to further reveal the molecular mechanisms of HFMD severity. Using UPLC-MS/MS, we determined the plasma amino acid expression profiles of pediatric patients with HFMD (mild,  = 42; severe, = 43) and healthy controls ( = 25).

Freehand Placement of a Transiliac-Transsacral Screw for Fixation of Posterior Pelvic Ring Injuries.

Objective: There are many advantages to stabilize the posterior pelvic ring injuries with a transiliac-transsacral (TITS) screw percutaneously. To identify the correct entry point and insert a guidewire accurately for a TITS screw, we propose a method of specifying the optimal entry point, and introduce a technique of enabling freehand placement of a guidewire with fluoroscopic guidance.

Methods: In this retrospective study, 116 patients who underwent pelvic CT scans and pelvic lateral radiographs at our institution from January 2020 to April 2022 were enrolled.

Identification of Potential Drug Targets for the Treatment of Severe Burn Wounds from a Multi-Omics Perspective.

Purpose: Severe burns result in significant skin damage, impairing its primary role as an infection barrier and presenting substantial treatment challenges. Despite improvements in the treatment of burn patients due to advancements in materials and techniques, there remains a need for novel therapeutic approaches to enhance burn prognosis further.

Patients And Methods: Several types of genomic methods are used in this study, such as differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), machine learning, and Mendelian randomization (MR), to find genes that are linked to severe burns and create a diagnostic nomogram to see how well these genes can predict severe burns.

The metabolomics provides insights into the Pacific abalone () response to low temperature stress.

The low temperatures in winter, particularly the cold spells in recent years, have posed significant threats to China's abalone aquaculture industry. The low temperature tolerance of cultured abalone has drawn plenty of attention, but the metabolic response of abalone to low-temperature stress remains unclear. In this study, we investigated the metabolomic analysis of Pacific abalone () during low-temperature stress.

Improved topical delivery of curcumin by hydrogels formed by composite carriers integrated with cyclodextrin metal-organic frameworks and cyclodextrin nanosponges.

Curcumin (CUR) is highly promising for topical therapeutic applications, but water-insolubility is one of the major challenges plaguing its drugability, while conventional lipid nanocarriers are limited by low drug-carrying capacity, many additives, and complex processes. In the current work, we constructed a composite carrier integrated with cyclodextrin metal-organic framework (γ-CD-MOF) and cyclodextrin nanosponge (β-CDNS), in which the γ-CD-MOF had 13.9 % drug loading and 267.

Metoprolol adverse events and literature analyses: case/non-case analyses using the FDA Adverse Event Reporting System (FAERS).

Background: In recent years, β-blockers such as metoprolol have been upgraded to first-line antihypertensive drugs. However, metoprolol demonstrates poor prognosis effects on diseases such as stroke. Further clinical application may expand the possibility of its related adverse reactions.

Association of dietary patterns with chronic respiratory health among U.S. adults.

Background: Respiratory health is closely related to immune system function, and diet can also influence immune homeostasis. Diet, an important part of a healthy lifestyle, is also linked to respiratory health. We aimed to explore the relationship between different dietary patterns and the risk of chronic respiratory diseases (CRDs), including chronic bronchitis (CB), emphysema, and asthma.

The Impact of Non-Pharmacological Sleep Interventions on Delirium Prevention and Sleep Improvement in Postoperative ICU Patients: A Systematic Review and Network Meta-Analysis.

Objectives: Analyze the effectiveness of different non-pharmacological sleep interventions in preventing delirium among postoperative ICU patients.

Research Methodology: We conducted a comprehensive search on PubMed, Cochrane Library, Web of Science, Embase, CINAHL, OpenGrey and reference lists up to May 2024.

Setting: We systematically searched all randomized controlled trials related to non-pharmacological sleep interventions for the prevention of delirium.

Clinical and functional characterization of a novel STUB1 mutation in a Chinese spinocerebellar ataxia 48 pedigree.

Background: Spinocerebellar ataxias (SCAs) encompass a wide spectrum of inherited neurodegenerative diseases, primarily characterized by pathological changes in the cerebellum, spinal cord, and brainstem degeneration. Autosomal dominant spinocerebellar ataxia type 48 (SCA48) is a newly identified subtype of SCA, marked by early-onset ataxia and cognitive impairment, and is associated with mutations in the STIP1 homology and U-box-containing protein 1 (STUB1) gene. The STUB1 gene encodes the protein CHIP (C-terminus of HSC70-interacting protein) which functions as E3 ubiquitin ligase and is crucial to the development of neural systems.

Deciphering genetic characteristics of South China and North China indigenous pigs through selection signatures.

Background: Indigenous pig breeds in China have accumulated significant genetic diversity due to regional selection pressures. Investigating the selection signatures of these populations helps to understand their adaptive evolution and contributes to genetic improvement programs.

Results: We collected whole-genome sequencing data from 133 individuals, including South China and North China indigenous pigs and Asian wild boars.

An integrated approach using proximity labelling and chemical crosslinking to probe host-virus protein-protein interactions.

Host-virus interactions are critically important for various stages of the viral replication cycle. The reliance of viruses on the host factors for their entry, replication, and maturation processes can be exploited for the development of antiviral therapeutics. Thus, the identification and characterization of such viral-host dependency factors has been an attractive area of research to provide novel antiviral targets.

Mediated by H3K27me3 Inhibits Porcine Follicular Development by Regulating the Transcription of .

It is well known that the function of granulosa cells (GCs) is closely related to follicular development, and and histone methylation have been implicated in follicular development. However, the specific mechanisms by which and histone methylation regulate follicular development are still largely unknown. To explore the specific mechanism of in regulating follicular development, in this study, we showed that the expression of in immature ovaries and small follicles was significantly higher than in mature ovaries and large follicles of sows, respectively.

Evaluation of the Breed Composition of Pork via Population Structure Analysis in Pigs.

The quality of pork meat directly influences the price and consumption. The genetic improvement of pigs has mainly focused on high productive efficiency, which has resulted in poor meat quality. Crossbreeds containing commercial and indigenous breeds could improve the meat quality, but identifying breed composition was difficult because of the lack of an ancestry reference panel.

Neoadjuvant immunology therapy in patients with non-small cell lung cancer and chronic obstructive pulmonary disease.

Background: For patients with early non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD), the efficacy and safety of immunotherapy are still unclear. This study was designed to investigate the effect and safety of neoadjuvant immunotherapy for patients with resectable NSCLC including those with coexisting COPD and the effect on patients' lung function.

Methods: Data of patients with resectable NSCLC who received neoadjuvant immunotherapy at the Shanghai Chest Hospital were retrospectively analyzed.

Utility of cardiac implantable electronic device algorithm for detecting severe sleep-disordered breathing in cardiomyopathy.

Background: Half of patients with heart failure are estimated to have sleep-disordered breathing (SDB). However, many are undiagnosed as they do not report typical symptoms. This study aims to evaluate the implantable cardiac defibrillator (ICD) sleep-disordered breathing algorithm in a cohort of multi-racial Asian patients for detection of SDB against polysomnography (PSG).

S32, a Novel 3-Acetylaminocoumarin Compound, Exerts Neuroprotective Effects through the Inhibition of Neuroinflammation and Oxidative Stress and .

Neuroinflammation and oxidative stress are key factors leading to neuronal injury. In this study, we investigated the role of S32, a novel 3-acetylaminocoumarin compound, in ameliorating neuronal injury induced by neuroinflammation and oxidative stress and . First, we found that S32 reduced the expression levels of p-P65 and p-P38, inhibited the nuclear translocation of P65, and lowered the levels of pro-inflammatory factors in LPS-induced BV2 cells, which indicated that S32 had an antineuroinflammatory effect.

Establishment of an Early Prediction Model for Severe Fever With Thrombocytopenia Syndrome-Associated Encephalitis.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease primarily transmitted by ticks. The development of encephalitis in SFTS patients significantly increases the risk of adverse outcomes. However, the understanding of SFTS-associated encephalitis (SFTSAE) is still limited.