Tubulin/HDAC dual-target inhibitors: Insights from design strategies, SARs, and therapeutic potential.

Microtubules, one of the cytoskeletons in eukaryotic cells, maintain the proper operation of several cellular functions. Additionally, they are regulated by the acetylation of HDAC6 and SIRT2 which affects microtubule dynamics. Given the fact that tubulin and HDAC inhibitors play a synergistic effect in the treatment of many cancers, the development of tubulin/HDAC dual-target inhibitors is conducive to addressing multiple limitations including drug resistance, dose toxicity, and unpredictable pharmacokinetic properties.

The Role of Lignin Molecular Weight on Activated Carbon Pore Structure.

Over the past decade, the production of biofuels from lignocellulosic biomass has steadily increased to offset the use of fuels from petroleum. To make biofuels cost-competitive, however, it is necessary to add value to the "ligno-" components (up to 30% by mass) of the biomass. The properties of lignin, in terms of molecular weight (MW), chemical functionality, and mineral impurities often vary from biomass source and biorefinery process, resulting in a challenging precursor for product development.

Across-environment seed protein stability and genetic architecture of seed components in soybean.

The recent surge in the plant-based protein market has resulted in high demands for soybean genotypes with improved grain yield, seed protein and oil content, and essential amino acids (EAAs). Given the quantitative nature of these traits, complex interactions among seed components, as well as between seed components and environmental factors and management practices, add complexity to the development of desired genotypes. In this study, the across-environment seed protein stability of 449 genetically diverse plant introductions was assessed, revealing that genotypes may display varying sensitivities to such environmental stimuli.

Progress and breakthroughs in human kidney organoid research.

The three-dimensional (3D) kidney organoid is a breakthrough model for recapitulating renal morphology and function , which is grown from stem cells and resembles mammalian kidney organogenesis. Currently, protocols for cultivating this model from induced pluripotent stem cells (iPSCs) and patient-derived adult stem cells (ASCs) have been widely reported. In recent years, scientists have focused on combining cutting-edge bioengineering and bioinformatics technologies to improve the developmental accuracy of kidney organoids and achieve high-throughput experimentation.

Obg-like ATPase 1 exacerbated gemcitabine drug resistance of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis due to inefficient diagnosis and tenacious drug resistance. Obg-like ATPase 1 (OLA1) is overexpressed in many malignant tumors. The molecular mechanism of OLA1 underlying gemcitabine (GEM)-induced drug resistance was investigated in this study.

Insights into the genetic characteristics, clustering patterns, and phylogeographic dynamics of the JC polyomavirus, 1993 to 2023.

The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other diseases in immunosuppressed individuals, including granule cell neuronopathy, JCV-associated nephropathy, encephalitis, and meningitis in rare cases. JCV classification is still unclear, where the ICTV (International Committee on Taxonomy of Viruses) has grouped all the strains into human polyomavirus 2, with no classification on clade and subclade levels. Therefore, JCV strains were previously classified using different genomic regions, e.

Inhibition of TGF-β1/Smad3 signaling by compound 5aa: A potential treatment for idiopathic pulmonary fibrosis.

The incidence of idiopathic pulmonary fibrosis (IPF) has been steadily increasing each year, posing significant challenges in its treatment. In this study, we conducted the design and synthesis of 23 new inhibitors that specifically target the TGF-β1/Smad3 pathway. Initially, we employed a cell model of TGF-β-induced pulmonary fibrosis, using cell survival rate and HYP expression as indicators to identify the potent ingredient 5aa, which demonstrated significant anti-pulmonary fibrosis activity.

[Rac1 promotes the formation of heterotypic cell-in-cell structure].

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model.

Acetic Acid-Catalyzed (3 + 2) Cyclization of 2-Aroyl-3-aryl-1,1-dicyanocyclopropanes with Arylhydrazines: To -4-Dicyanomethyl-1,3,5-triaryl-4,5-dihydropyrazoles.

Acetic acid-catalyzed (3 + 2) cyclization reaction of substituted 2-aroyl-3-aryl-1,1-dicyanocyclopropanes with arylhydrazines was investigated for the efficient synthesis of 4-dicyanomethyl-1,3,5-triaryl-4,5-dihydropyrazoles in good yields, in which 4,5-double substituents are predominantly selective. This approach included the consecutive condensation, ring opening, and double nucleophilic cyclization reaction.

A replicative recombinant HPV16 E7 expression virus upregulates CD36 in C33A cells.

Objective: In past decades, the role of high-risk HPV (HR-HPV) infection in cancer pathogenesis has been extensively studied. The viral E7 protein expressed in pre-malignant cells has been identified as an ideal target for immunological intervention. However, the cultivation of HPV remains a significant challenge, as well as the lack of methods for expressing the HPV E7 protein and generating replication-competent recombinant viral particles, which posed a major obstacle to further exploration of the function and carcinogenic mechanisms of the E7 oncoprotein.

TMM: A comprehensive CAD system for hepatic fibrosis 5-grade METAVIR staging based on liver MRI.

Background: Precise staging of hepatic fibrosis with MRI is necessary as it can assist precision medicine. Computer aided diagnosis (CAD) system with distinguishing radiomics features and radiologists domain knowledge is expected to obtain 5-grade meta-analysis of histological data in viral hepatitis (METAVIR) staging.

Purpose: This study aims to obtain the precise staging of hepatic fibrosis based on MRI as it predicts the risk of future liver-related morbidity and the need for treatment, monitoring and surveillance.

Formation of Epitaxial PdO(100) During the Oxidation of Pd(100).

The catalytic oxidation of CO and CH can be strongly influenced by the structures of oxide phases that form on metallic catalysts during reaction. Here, we show that an epitaxial PdO(100) structure forms at temperatures above 600 K during the oxidation of Pd(100) by gaseous O atoms as well as exposure to O-rich mixtures at millibar partial pressures. The oxidation of Pd(100) by gaseous O atoms preferentially generates an epitaxial, multilayer PdO(101) structure at 500 K, but initiating Pd(100) oxidation above 600 K causes an epitaxial PdO(100) structure to grow concurrently with PdO(101) and produces a thicker and rougher oxide.

Discrete Mononuclear Platinum(II) Complexes Realize High-Performance Red Phosphorescent OLEDs with EQEs of up to 31.8% and Superb Device Stability.

Designing mononuclear platinum(II) complexes that do not rely on intermolecular aggregation for high-performance red organic light-emitting diodes remains a formidable challenge. In this work, three robust red-emitting Pt(II) complexes are created by utilizing a rigid 4-coordination configuration, where the ligands are formed by linking electron-donor of triphenylamine (TPA) moieties with electron-acceptor of pyridine, isoquinoline, and/or δ-carboline units. The thermal stability, electrochemical, and photophysical properties of the complexes are thoroughly examined.

A novel biomimetic trabecular bone metal plate for bone repair and osseointegration.

Fracture is one of the most common traumatic diseases in clinical practice, and metal plates have always been the first choice for fracture treatment because of their high strength. However, the bone plates have high elastic modulus and do not match the biomechanics of human bone, which adversely affects callus formation and fracture healing. Moreover, the complex microenvironment in the human body can induce corrosion of metallic materials and release toxic ions, which reduces the biocompatibility of the bone plate, and may necessitate surgical removal of the implant.

Identifying Dopamine D3 Receptor Ligands through Virtual Screening and Exploring the Binding Modes of Hit Compounds.

The dopamine D3 receptor (D3R) is an important central nervous system target for treating various neurological diseases. D3R antagonists modulate the improvement of psychostimulant addiction and relapse, while D3R agonists can enhance the response to dopaminergic stimulation and have potential applications in treating Parkinson’s disease, which highlights the importance of identifying novel D3R ligands. Therefore, we performed auto dock Vina-based virtual screening and D3R-binding-affinity assays to identify human D3R ligands with diverse structures.

P-Y/G@NHs sensitizes non-small cell lung cancer cells to radiotherapy via blockage of the PI3K/AKT signaling pathway.

Radioresistance represents a common phenomenon found in cancer treatment. Herein, the current study sought to evaluate the effects of a nanodrug delivery system of YSAYPDSVPMMS (YSA) peptide-modified gold nanoparticles-dextran-based hydrogel loaded with paclitaxel-succinic anhydride (P-Y/G@NHs) on non-small cell lung cancer (NSCLC) cell radiosensitivity. Firstly, utilizing the coupling reaction and layer-by-layer assembly technique, P-Y/G@NHs was prepared.

China's Accession to the WTO as a Shock to Residents' Health-A Difference-in-Difference Approach.

The impact of regional trade shocks on population health has been a topic of interest in health economics in recent years. Unfortunately, there are few studies directly discussing the impact of regional trade shocks caused by China's WTO accession on the health of Chinese residents, which is essential to explore the connection between a country´s opening to international trade and the health of its residents. Taking China's accession to the WTO as a quasi-natural experiment, based on the micro individual samples of the China Health and Nutrition Survey (CHNS) from 1993 to 2011, this paper, for the first time, studies the impact of regional tariff uncertainty caused by China's accession to the WTO on the health of Chinese residents and its mechanisms by adopting the Difference-in-Difference (DID) model.

Bioinformatic analysis identifies HPV-related tumor microenvironment remodeling prognostic biomarkers in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinomas (HNSCCs) are highly aggressive tumors with rapid progression and poor prognosis. Human papillomavirus (HPV) infection has been identified as one of the most important carcinogens for HNSCC. As an early event in HNSCC, infection with HPV leads to altered immune profiles in the tumor microenvironment (TME).

Circulating mitochondrial DNA is associated with anemia in newly diagnosed hematologic malignancies.

Recent reports discovered that red blood cells (RBCs) could scavenge cell-free mitochondrial DNA (mtDNA), which drives the accelerated erythrophagocytosis and innate immune activation characterized by anemia and inflammatory cytokine production. However, the clinical value of the circulating mtDNA copy number alterations in hematologic malignancies is poorly understood. Our data showed that in comparison to healthy group, the patients group had significantly higher mtDNA and histone H4 levels.