The cellular and molecular mechanisms mediating the protective effects of sodium-glucose linked transporter 2 inhibitors against metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a common, highly heterogeneous condition that affects about a quarter of the world's population, with no approved drug therapy. Current evidence from preclinical research and a number of small clinical trials indicates that SGLT2 inhibitors could also be effective for MAFLD. MAFLD is associated with a higher risk of chronic liver disease and multiple extrahepatic events, especially cardiovascular disease (CVD) and chronic kidney disease (CKD).

TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors.

Chimeric antigen receptor (CAR)-T cell therapy shows impressive efficacy treating hematologic malignancies but requires further optimization in solid tumors. Here, we developed a TMIGD2 optimized potent/persistent (TOP) CAR that incorporated the costimulatory domain of TMIGD2, a T and NK cell costimulator, and monoclonal antibodies targeting the IgV domain of B7-H3, an immune checkpoint expressed on solid tumors and tumor vasculature. Comparing second- and third-generation B7-H3 CARs containing TMIGD2, CD28, and/or 4-1BB costimulatory domains revealed superior antitumor responses in B7-H3.

Laws Governing Nitrogen Loss and Its Numerical Simulation in the Sloping Farmland of the Miyun Reservoir.

Surface flow (SF) and subsurface flow (SSF) are important hydrological processes occurring on slopes, and are driven by two main factors: rainfall intensity and slope gradient. To explore nitrogen (N) migration and loss from sloping farmland in the Miyun Reservoir, the characteristics of total nitrogen (TN) migration and loss via SF and SSF under different rainfall intensities (30, 40, 50, 60, 70, and 80 mm/h) and slope gradients (5°, 10°, and 15°) were studied using indoor stimulated rainfall tests and mathematical models. Nitrogen loss via SF and SSF was found to increase exponentially and linearly with time, respectively, with SSF showing 14-78 times higher loss than SF.

Effects of the Rainfall Intensity and Slope Gradient on Soil Erosion and Nitrogen Loss on the Sloping Fields of Miyun Reservoir.

Environmental loss is primarily caused by soil, water, and nutrient loss, and runoff is associated with nutrient transport and sediment loss. Most existing studies have focused on one influencing factor, namely slope gradient or rainfall intensity, for slope erosion and nutrient loss, but the joint effects of the two factors have rarely been researched. In this context, the impact of slope gradients (0°, 5°, 10°, and 15°) and rainfall intensities (30, 40, 50, 60, 70, and 80 mm/h) on soil erosion and nutrient loss on the sloping fields of Miyun Reservoir were explored using the indoor artificial rainfall simulation testing system.

Changes in fungal community during different phases in conventional and bioreactor composting systems according to metatranscriptomics analysis.

We determined the changes that occurred in fungal community structures and their functions in conventional and bioreactor composting systems. The Illumina MiSeq platform was employed to sequence cDNA by reverse transcription to conduct metatranscriptomics analysis of RNA, and the FUNGuild tool was applied. The α-diversity of fungi in the bioreactor composter increased throughout composting, especially in the initial three phases, but decreased in the conventional composting system.

Positive Effects of Organic Substitution in Reduced-Fertilizer Regimes on Bacterial Diversity and N-Cycling Functionality in Greenhouse Ecosystem.

Conventional fertilization in the greenhouses of North China used excessive amounts of chemical and organic fertilizer, resulting in soil degradation and severe agricultural non-point source pollution. A nine-year study was conducted on a loamy clay soil in Shijiazhuang, Hebei province, to investigate the effects of reduced-fertilizer input regimes on soil property, bacterial diversity, nitrogen (N) cycling and their interactions. There were four treatments, including high organic + chemical fertilizer application rate and three reduced-fertilizer treatments with swine manure, maize straw or no substitution of 50% chemical N.

mediates stomatal movement in response to drought stress by repressing expression.

Drought stress limits plant development and reproduction. Multiple mechanisms in plants are activated to respond to stress. The MYC2 transcription factor is a core regulator of the jasmonate (JA) pathway and plays a vital role in the crosstalk between abscisic acid (ABA) and JA.

Ginsenoside Rb1 prevents osteoporosis via the AHR/PRELP/NF-κB signaling axis.

Background: Accumulating clinical and experimental evidence shows multiple biological effects of ginsenoside Rb1 (GRb1) in the treatment of aging related diseases such as osteoporosis (OP). Recently, GRb1 has attracted extensive attention as an anti-osteoporosis agent. Here, we sought to identify the mechanism by which GRb1 improves OP.

Urine-derived stem cells-extracellular vesicles ameliorate diabetic osteoporosis through HDAC4/HIF-1α/VEGFA axis by delivering microRNA-26a-5p.

Critical roles of stem cell-extracellular vesicles (EVs) in the management of osteoporosis have been documented. Here, this study was designed to enlarge the research of the specific effects and underlying mechanism of urine-derived stem cells-EVs (USCs-EVs) on osteoporosis in diabetes rats. Firstly, miR-26a-5p and histone deacetylase 4 (HDAC4) expression in USCs of rats after diabetic osteoporosis (DOP) modeling induced by streptozotocin injection was determined, followed by study of their interaction.

Decarboxylated osteocalcin, a possible drug for type 2 diabetes, triggers glucose uptake in MG63 cells.

Background: Uncarboxylated osteocalcin (GluOC) has been reported to improve glucose metabolism, prevent type 2 diabetes, and decrease the severity of obesity in mice with type 2 diabetes. GluOC can increase glucose uptake in a variety of cells. Glucose metabolism is the main source of energy for osteoblast proliferation and differentiation.

Effects of applying inorganic fertilizer and organic manure for 35 years on the structure and diversity of ammonia-oxidizing archaea communities in a Chinese Mollisols field.

In this study, we investigated the physicochemical properties of soil, and the diversity and structure of the soil ammonia-oxidizing archaea (AOA) community, when subjected to fertilizer treatments for over 35 years. We collected soil samples from a black soil fertilization trial in northeast China. Four treatments were tested: no fertilization (CK); manure (M); nitrogen (N), phosphorus (P), and potassium (K) chemical fertilizer (NPK); and N, P, and K plus M (MNPK).

The Anti-proliferative Activity of GnRH Through Downregulation of the Akt/ERK Pathways in Pancreatic Cancer.

Gonadotropin-releasing hormone (GnRH) has been demonstrated to exert anti-proliferative functions on various tumor cells in endometrial, ovarian, bladder, or prostate cancer as a part of the autocrine system. In addition, the expression levels of GnRH and its receptor had been identified in breast cancer or non-reproductive cancers, such as glioblastoma and pancreatic cancer. Previous studies have reported abnormal GnRH expression in several malignant tumors, suggesting that GnRH and its receptor might be essential for tumourigenesis.

Orexin-A Stimulates Insulin Secretion Through the Activation of the OX1 Receptor and Mammalian Target of Rapamycin in Rat Insulinoma Cells.

Objectives: The study aimed to investigate the involvement of the mammalian target of rapamycin (mTOR) signaling pathway in orexin-A/OX1 receptor-induced insulin secretion in rat insulinoma INS-1 cells.

Methods: Rat insulinoma INS-1 cells were grown and treated with various concentrations of orexin-A, with or without OX1 receptor-selective antagonist SB674042 or the phosphatidylinositol 3-kinase/mTOR antagonist PF-04691502. Insulin release experiments, Western blot analysis, and statistical analysis were conducted using INS-1 cells.

The Orexin-A-Regulated Akt/mTOR Pathway Promotes Cell Proliferation Through Inhibiting Apoptosis in Pancreatic Cancer Cells.

The orexin-A and its receptors are associated with many physiological processes in peripheral organs and the central nervous system and play important roles in a series of human diseases, including narcolepsy, obesity, and drug addiction. Increasing evidence has indicated high expression of orexin-A and OX1 receptor (OX1R) in malignant tumors, suggesting that the stimulation of OX1R might be essential for tumorigenesis. Here, we attempted to clarify the correlation between orexin-A expression and malignancy in pancreatic cancer.

Gender differences in associations of serum ferritin and diabetes, metabolic syndrome, and obesity in the China Health and Nutrition Survey.

Scope: This study examines gender differences in associations of serum ferritin and diabetes, metabolic syndrome (MetS), and obesity in Chinese.

Methods And Results: Based on a nationwide, population-based China Health and Nutrition survey this study included 8564 men and women aged 18 years or older. Anthropometric and fasting blood glucose, insulin, lipids, ferritin, and transferrin data were collected.

Effect of pretreatment on biomass residue structure and the application of pyrolysed and composted biomass residues in soilless culture.

The changes in the structural characteristics of biomass residues during pyrolysis and composting were investigated. The biomass residues particles were prepared by pyrolysing at temperatures ranging from 350 to 400. For soilless production of the ornamental plant Anthurium andraeanum, pure sphagnum peat moss (P) has traditionally been used as the growing medium.