Efficacy and safety of hetrombopag in the treatment of recombinant human thrombopoietin-resistant thrombocytopenia after allogeneic hematopoietic stem cell transplantation.

Background: Thrombocytopenia after allogeneic hematopoietic cell transplantation is a challenging clinical problem. Recombinant human thrombopoietin (rhTPO) and thrombopoietin receptor agonists are increasingly used in posttransplant thrombocytopenia. However, the use of hetrombopag in patients with posttransplant thrombocytopenia, especially in patients with resistance to rhTPO, has not yet been reported.

Myofibroblast-derived extracellular vesicles facilitate cancer stemness of hepatocellular carcinoma via transferring ITGA5 to tumor cells.

Background: Myofibroblasts constitute a significant component of the tumor microenvironment (TME) and play a pivotal role in the progression of hepatocellular carcinoma (HCC). Integrin α5 (ITGA5) is a crucial regulator in myofibroblasts of malignant tumors. Therefore, the potential of ITGA5 as a novel target for the therapeutic strategy of HCC should be investigated.

Applications of different forms of nitrogen fertilizers affect soil bacterial community but not core ARGs profile.

The objective of this study was to investigate the impact of various chemical nitrogen fertilizers on the profile of antibiotic resistance genes (ARGs) in soil. A microcosm experiment was conducted with four treatments, including CK (control with no nitrogen), AN (ammonium nitrogen), NN (nitrate nitrogen), and ON (urea nitrogen), and the abundance of ARGs was assessed over a 30-day period using a metagenomic sequencing approach. The levels of core ARGs varied between 0.

Normalization of WISP1 circulating level and tissue expression following metabolic and bariatric surgery using rat model.

Wingless-type inducible signaling pathway protein-1 (WISP1) is a newly recognized adipokine, associated with obesity and type 2 diabetes (T2DM). This study aimed to investigate the effect of metabolic and bariatric surgery (MBS) on WISP1 circulating (serum) levels and tissue expression using rat models. We initially investigated whether WISP1 circulating levels were altered between the T2DM and normal rats.

Yap methylation-induced FGL1 expression suppresses anti-tumor immunity and promotes tumor progression in KRAS-driven lung adenocarcinoma.

Background: Despite significant strides in lung cancer immunotherapy, the response rates for Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven lung adenocarcinoma (LUAD) patients remain limited. Fibrinogen-like protein 1 (FGL1) is a newly identified immune checkpoint target, and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients. This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in KRAS-mutated cancer.

Discovery of novel, orally bioavailable phenylacetamide derivatives as multikinase inhibitors and in vivo efficacy study in hepatocellular carcinoma animal models.

Hepatocellular carcinoma (HCC) is considered as one of the leading causes of death in liver disease patients. Several signal transduction pathways are involved in HCC pathogenesis. Multikinase inhibitors (MKIs) show beneficial effects for HCC and the FDA approved a few MKIs including sorafenib, lenvatinib for HCC treatments.

Next-generation EGFR tyrosine kinase inhibitors to overcome C797S mutation in non-small cell lung cancer (2019-2024).

Lung cancer is a leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for the major portion (80-85%) of all lung cancer cases. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are commonly used as the targeted therapy for -mutated NSCLC.

Immune isolation-enabled nanoencapsulation of donor T cells: a promising strategy for mitigating GVHD and treating AML in preclinical models.

Background: In allogeneic-hematopoietic stem cell transplantation for acute myeloid leukemia (AML), donor T cells combat leukemia through the graft-versus-leukemia (GVL) effect, while they also pose a risk of triggering life-threatening graft-versus-host disease (GVHD) by interacting with recipient cells. The onset of GVHD hinges on the interplay between donor T cells and recipient antigen-presenting cells (APCs), sparking T-cell activation. However, effective methods to balance GVHD and GVL are lacking.

A new mechanism of respiratory syncytial virus entry inhibition by small-molecule to overcome K394R-associated resistance.

Unlabelled: Infection with respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract disease in young children and older people. Despite intensive efforts over the past few decades, no direct-acting small-molecule agents against RSV are available. Most small-molecule candidates targeting the RSV fusion (F) protein pose a considerable risk of inducing drug-resistant mutations.

SHR-A1811 (antibody-drug conjugate) in advanced HER2-mutant non-small cell lung cancer: a multicenter, open-label, phase 1/2 study.

A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion.

Topological Transformation of Hydrogen-Terminated Germanium to Germanium Nanosheets for Fast Lithium Storage.

Germanium has been recognized as a promising anode material for lithium-ion batteries (LIBs) due to its high theoretical capacity and excellent lithium-ion diffusivity. Nonetheless, it is challenging to enhance both the high-rate performance and long-term cycling stability simultaneously. This study introduces a novel heterostructure composed of germanium nanosheets integrated with graphene (Ge NSs@Gr).

Toll-like Receptor Agonist CBLB502 Protects Against Radiation-induced Intestinal Injury in Mice.

Background/aim: The small intestine is one of the organs most vulnerable to ionizing radiation (IR) damage. However, methods to protect against IR-induced intestinal injury are limited. CBLB502, a Toll-like receptor 5 (TLR5) agonist from Salmonella flagellin, exerts radioprotective effects on various tissues and organs.

Integration of Lipidomics and Transcriptomics Identifies the Regulation of Lipid Homeostasis as Potential Mechanisms of Konjac Glucomannan against Hepatic Steatosis.

Hepatic steatosis is characterized by substantial disruption in the liver's lipid level regulation. Konjac glucomannan (KGM) is acknowledged as a nutritious food that has the potential to prevent hyperlipidemia. This study utilized lipidomics and transcriptomics to investigate the efficacy of KGM in alleviating high-fat diet-induced hepatic steatosis by regulating lipid homeostasis.

GINS1 promotes ZEB1-mediated epithelial-mesenchymal transition and tumor metastasis via β-catenin signaling in hepatocellular carcinoma.

GINS1 regulates DNA replication in the initiation and elongation phases and plays an important role in the progression of various malignant tumors. However, the role of GINS1 in hepatocellular carcinoma (HCC) remains largely unclear. In this study, we investigated the role and underlying mechanisms of GINS1 in contributing to HCC metastasis.

Mid-Term Diabetes Remission Outcome in Patients with BMI ≤ 30 kg/m Following Sleeve Gastrectomy.

Background: Bariatric and metabolic surgery is recommended for Asian patients with type 2 diabetes mellitus (T2DM) and BMI ≥ 27.5 kg/m. However, mid to long-term ·evidence is still lacking.

Improvement of an enzymatic cascade synthesis of nicotinamide mononucleotide via protein engineering and reaction-process reinforcement.

Enzymatic synthesis of β-nicotinamide mononucleotide (NMN) from D-ribose has garnered widespread attention due to its cheap material, the use of mild reaction conditions, and the ability to produce highly pure products with the desired optical properties. However, the overall NMN yield of this method is impeded by the low activity of rate-limiting enzymes. The ribose-phosphate diphosphokinase (PRS) and nicotinamide phosphoribosyltransferase (NAMPT), that control the rate of the reaction, were engineered to improve the reaction efficacy.

Aurora B facilitates cholangiocarcinoma progression by stabilizing c-Myc.

Background: Cholangiocarcinoma (CCA), a malignancy that arises from biliary epithelial cells, has a dismal prognosis, and few targeted therapies are available. Aurora B, a key mitotic regulator, has been reported to be involved in the progression of various tumors, yet its role in CCA is still unclarified.

Methods: Human CCA tissues and murine spontaneous CCA models were used to assess Aurora B expression in CCA.

A novel sulfur supply strategy for maximizing lipid production in Tribonema minus (Xanthophyceae).

Tribonema minus, a promising filamentous oleaginous microalga, was cultured under different nutrient concentrations and different culture modes (fed-batch culture, two-step culture) to study the method of rapid regulation of its lipid metabolism. In contrast to many other oleaginous microalgae, T. minus did not show that nitrogen stress promoted lipid accumulation; however, sulfur deficiency promoted rapid lipid accumulation with a maximum lipid content of 54% of dry weight.

Comparison of three different anastomotic methods of sleeve gastrectomy with transit bipartition using an obese rodent model.

The long-term effects and safety of single-anastomosis sleeve ileal (SASI) bypass have not been confirmed. The one anastomosis procedure carries the risk of bile reflux, and Braun anastomosis has the capacity to reduce bile reflux. This study was designed to compare the influences of bile reflux and histological changes in the esogastric sections of rats.

Targeting PKM2 improves the gemcitabine sensitivity of intrahepatic cholangiocarcinoma cells via inhibiting β-catenin signaling pathway.

Gemcitabine is considered the standard first-line chemotherapeutic agent for patients with intrahepatic cholangiocarcinoma (ICC). However, its therapeutic efficacy is hampered by the development of chemoresistance. Pyruvate kinase M2 (PKM2), a crucial mediator of the final step in glycolysis, has been implicated in the origination and advancement of diverse malignancies.

A DNA/RNA heteroduplex oligonucleotide coupling asparagine depletion restricts FGFR2 fusion-driven intrahepatic cholangiocarcinoma.

Pemigatinib, a pan-FGFR inhibitor, is approved to treat intrahepatic cholangiocarcinoma (ICC) harboring FGFR2 fusion mutations. Improving its targeting of FGFR2 fusions remains an unmet clinical need due to its pan selectivity and resistance. Here, we report a cholesterol-conjugated DNA/RNA heteroduplex oligonucleotide targeting the chimeric site in (F-A Cho-HDO) that accumulates in ICC through endocytosis of low-density lipoprotein receptor (LDLR), which is highly expressed in both human and murine ICC.