PTGES3 proteolysis using the liposomal peptide-PROTAC approach.

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, and the lack of effective biomarkers for early detection leads to poor therapeutic outcomes. Prostaglandin E Synthase 3 (PTGES3) is a putative prognostic marker in many solid tumors; however, its expression and biological functions in HCC have not been determined. The proteolysis-targeting chimera (PROTAC) is an established technology for targeted protein degradation.

Roles of CDK12 mutations in PCa development and treatment.

Prostate cancer (PCa) is one of the most common cancers in men, and cyclin-dependent kinase 12 (CDK12) is emerging as a novel star player in the PCa tumorigenesis and progression to castration-resistant prostate cancer (CRPC). In PCa, CDK12 alterations are mostly loss-of-function mutations featuring intronic polyadenylation (IPA), focal tandem duplications (FTDs), and R-loops formation and transcription-replication conflicts (TRCs). The occurrence of IPA can result in homologous recombination deficiency (HRD) and androgen receptor (AR) variation.

Cell Type Differentiation Using Network Clustering Algorithms.

Single cell RNA-seq (scRNA-seq) technologies provide unprecedented resolution representing transcriptomics at the level of single cell. One of the biggest challenges in scRNA-seq data analysis is the cell type annotation, which is usually inferred by cell separation approaches. In-silico algorithms that accurately identify individual cell types in ongoing single-cell sequencing studies are crucial for unlocking cellular heterogeneity and understanding the biological basis of diseases.

Kupffer cells, the limelight in the liver regeneration.

Kupffer cells are pivotal in initiating hepatocyte proliferation and establishing connections between different cell types during liver regeneration following partial hepatectomy. As resident macrophages within the liver, Kupffer cells collaborate with hepatocytes and non-parenchymal cells to release various inflammatory mediators that promote hepatocyte proliferation through induction signals like STAT3 phosphorylation. Additionally, the regeneration and replenishment of Kupffer cells themselves are integral components of liver regeneration.

Radiolabelled anti-PD-L1 peptide PET/CT in predicting the efficacy of neoadjuvant immunotherapy combined with chemotherapy in resectable non-small cell lung cancer.

Background: This study aimed to evaluate the predictive value of baseline PD-L1 targeted peptide Ga-NOTA-WL12 PET/CT in neoadjuvant immunotherapy combined with chemotherapy of resectable NSCLC.

Methods: Patients with resectable NSCLC (n = 20) enrolled in this prospective study received baseline paired Ga-NOTA-WL12 PET/CT and F-FDG PET/CT. After 2-4 cycles of toripalimab plus nab-paclitaxel and cisplatin, surgery was performed if R0 resection was available.

Insights Into the Role of π-Electrons of Aromatic Aldehydes in Passivating Perovskite Defects.

Carbonyl-containing aromatic ketones or aldehydes have been demonstrated to be effective defect passivators for perovskite films to improve performances of perovskite solar cells (PSCs). It has been claimed that both π-electrons within aromatic units and carbonyl groups can, separately, interact with ionic defects, which, however, causes troubles in understanding the passivation mechanism of those aromatic ketone/aldehyde molecules. Herein, we clarify the effect of both moieties in one molecule on the defect passivation by investigating three aromatic aldehydes with varied conjugation planes, namely, biphenyl-4-carbaldehyde (BPCA), naphthalene-2-carbaldehyde (NACA) and pyrene-1-carbaldehyde (PyCA).

IKBKE regulates renal cell carcinoma progression and sunitinib resistance through the RRM2-AKT pathway.

Tyrosine kinase inhibitors (TKIs), such as sunitinib, have emerged as promising agents in renal cell carcinoma (RCC) treatment, particularly in patients at advanced/metastatic clinical stages. However, acquired resistance to sunitinib is common following prolonged clinical treatment in RCC. Increasing evidence has demonstrated a strong correlation between inhibitor of nuclear factor kappa B kinase subunit epsilon (IKBKE) and cancer progression as well as drug resistance.

Spatial Conformation Engineering of Aromatic Ketones for Highly Efficient and Stable Perovskite Solar Cells.

Carbonyl-containing materials employed in state-of-the-art hybrid lead halide perovskite solar cells (PSCs) exhibit a strong structure-dependent electron donor effect that predominates in defect passivation. However, the impact of the molecular spatial conformation on the efficacy of carbonyl-containing passivators remains ambiguous, hindering the advancement of molecular design for passivating materials. Herein, we show that altering the spatial torsion angle of aromatic ketones from twisted to planar configurations, as seen in benzophenone (BP, 27.

Mechanism and nanotechnological-based therapeutics for tolerance and resistance of bacterial biofilms.

Bacterial biofilms are one of the most relevant drivers of chronic and recurrent infections and a significant healthcare problem. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure and low drug permeability, leading to tolerance and resistance of biofilms to antibiotics and to host responses.

Tau pathway-based gene analysis on PET identifies CLU and FYN in a Korean cohort.

Introduction: The influence of genetic variation on tau protein aggregation, a key factor in Alzheimer's disease (AD), remains not fully understood. We aimed to identify novel genes associated with brain tau deposition using pathway-based candidate gene association analysis in a Korean cohort.

Methods: We analyzed data for 146 older adults from the well-established Korean AD continuum cohort (Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease; KBASE).

Unfavorable Prognostic Impact of HER2 2+/FISH-Negativity in Older Patients with HER2-Negative and High-Risk Breast Cancer.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer, consisted of carcinomas with HER2 protein 1+ or 2+ without gene amplification, has been considered a biologically heterogeneous disease. Limited research separately investigated the prognostic significance of HER2 2+ without gene amplification, and no evidence can be identified in older patients. In this dedicated cohort of older patients with HER2-negative and high-risk breast cancer, we analyzed the real-world prognosis after standard adjuvant chemotherapy, and investigated the associations of survival with HER2 2+ without gene amplification.

Assessing alcohol industry penetration and government safeguards: the International Alcohol Control Study.

Background: The alcohol industry uses many of the tobacco industry's strategies to influence policy-making, yet unlike the Framework Convention on Tobacco Control, there is no intergovernmental guidance on protecting policies from alcohol industry influence. Systematic assessment of alcohol industry penetration and government safeguards is also lacking. Here, we aimed to identify the nature and extent of industry penetration in a cross-section of jurisdictions.

Controlled Sensor Derived from COF Materials for the Effective Detection of -Methylpyrrolidone.

-methylpyrrolidone (NMP) is an excellent advanced solvent that can be easily absorbed by the human body and has the characteristics of flammability and explosion. To reduce the risk, the environmental concentrations of NMP need to be measured. A series of covalent organic frameworks (COF) connected by an imine bond have been successfully prepared at room temperature by changing the synthesis time catalyzed by scandium(III) trifluoromethanesulfonate (Sc(OTf)).

A novel multiple plant-based milk alternative containing various preprocessed grains achieves better performance in protein digestibility and free amino acid profile via in vitro gastrointestinal digestion analysis.

Plant-based milk alternatives are sustainable, hypoallergenic, and nutrient-rich, but challenges related to their lower bioavailability compared with animal-based milk still exist. In this study, we developed a multiple plant-based milk alternative using germinated soybeans and fermented cereals, and compared the protein digestible behaviors with commercial soy and bovine milk via in vitro gastrointestinal digestion. The multiple plant-based milk alternative possessed a higher level of essential amino acids and amino acid scores than the soy milk and a smaller percentage of low-molecular-weight peptides than the bovine milk.

Differences in axillary response and treatment implications in HER2 positive node positive breast cancer during neoadjuvant HER2 targeted dual therapy.

Explore whether the axillary outcomes differ among HER2 positive subgroups receiving standard dual-targeted therapy, aiming to identify subgroups exhibiting enhanced sensitivity to NAT among HER2-positive/node-positive breast cancer patients. HER2 positive female patients with biopsy-proven node-positive disease from April 2020 to May 2023 were included. All patients underwent standard Neoadjuvant HER2-targeted dual therapy and axillary lymph node dissection (ALND) at Breast Surgery Center of Sichuan Cancer Hospital.

Pathway enrichment in genome-wide analysis of longitudinal Alzheimer's disease biomarker endophenotypes.

Introduction: The genetic pathways that influence longitudinal heterogeneous changes in Alzheimer's disease (AD) may provide insight into disease mechanisms and potential therapeutic targets.

Methods: Longitudinal endophenotypes from the Alzheimer's Disease Neuroimaging Initiative (ADNI) representing amyloid, tau, neurodegeneration (A/T/N), and cognition were selected. Genome-wide association analysis was performed using a linear mixed model (LMM) approach, followed by gene and pathway enrichment with significant and functionally relevant SNPs.

The association between the triglyceride-glucose index and vitamin D status: a systematic review and meta-analysis.

Objective: This study aims to explore the association between the triglyceride-glucose (TyG) index and vitamin D status to enhance our understanding of how vitamin D status relates to metabolic health and to provide evidence for the early diagnosis of vitamin D deficiency (VDD) using the TyG index.

Methods: We conducted a comprehensive search in various databases, including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc, China Science and Technology Journal Database, and Wanfang Data to gather articles published from the inception of these databases until February 19, 2024. We assessed the quality of included studies using the Newcastle-Ottawa Scale (NOS) for case-control studies and the Agency for Healthcare Research and Quality (AHRQ) methodology checklist for cross-sectional studies.