Discovery of HPG1860, a Structurally Novel Nonbile Acid FXR Agonist Currently in Clinical Development for the Treatment of Nonalcoholic Steatohepatitis.

The farnesoid X receptor (FXR) is a ligand-activated nuclear receptor. Activation of FXR significantly impacts the expressions of the pivotal genes involved in bile acid metabolism, inflammation, fibrosis, and homeostasis of lipid and glucose, leading to considerable interests in developing FXR agonists for the treatment of nonalcoholic steatohepatitis (NASH) or other FXR-relevant diseases. Herein, we describe the design, optimization, and characterization of a series of -methylene-piperazinyl derivatives as the nonbile acid FXR agonists.

Characterizing dry mass and volume changes in human multiple myeloma cells upon treatment with proteotoxic and genotoxic drugs.

Multiple myeloma (MM) is a cancer of terminally differentiated plasma cells. MM remains incurable, but overall survival of patients has progressively increased over the past two decades largely due to novel agents such as proteasome inhibitors (PI) and the immunomodulatory agents. While these therapies are highly effective, MM patients can be de novo resistant and acquired resistance with prolonged treatment is inevitable.

A modular strategy for distributed, embodied control of electronics-free soft robots.

Robots typically interact with their environments via feedback loops consisting of electronic sensors, microcontrollers, and actuators, which can be bulky and complex. Researchers have sought new strategies for achieving autonomous sensing and control in next-generation soft robots. We describe here an electronics-free approach for autonomous control of soft robots, whose compositional and structural features embody the sensing, control, and actuation feedback loop of their soft bodies.

Premature aging of skeletal stem/progenitor cells rather than osteoblasts causes bone loss with decreased mechanosensation.

A distinct population of skeletal stem/progenitor cells (SSPCs) has been identified that is indispensable for the maintenance and remodeling of the adult skeleton. However, the cell types that are responsible for age-related bone loss and the characteristic changes in these cells during aging remain to be determined. Here, we established models of premature aging by conditional depletion of Zmpste24 (Z24) in mice and found that Prx1-dependent Z24 deletion, but not Osx-dependent Z24 deletion, caused significant bone loss.

Research hotspots and trends on acupuncture therapy on vomiting from 1990 to 2022: A bibliometric analysis.

Objectives: Acupuncture treatment (AT) is commonly utilized for vomiting; however, limited bibliometric analyses exist in this area. Employing a bibliometric approach, we conducted a comprehensive review spanning three decades to assess the research landscape, advancements, and emerging trends in AT for vomiting.

Methods: We collected the related literature data from the Web of Science Core Collection (WOSCC) from 1990 to 2022.

CRISPR/Cas9-Mediated Gene Correction in Osteopetrosis Patient-Derived iPSCs.

Background: Osteopetrosis represents a rare genetic disease with a wide range of clinical and genetic heterogeneity, which results from osteoclast failure. Although up to 10 genes have been identified to be related with osteopetrosis, the pathogenesis of osteopetrosis remains foggy. Disease-specific induced pluripotent stem cells (iPSCs) and gene-corrected disease specific iPSCs provide a platform to generate attractive disease cell models and isogenic control cellular models respectively.

Post-Ripening and Key Glycosyltransferase Catalysis to Promote Sweet Mogrosides Accumulation of Fruits.

Sweet mogrosides are not only the primary bioactive ingredient in fruits that exhibit anti-tussive properties and expectorate phlegm, but they are also responsible for the fruit's sweetness. Increasing the content or proportion of sweet mogrosides in fruits is significant for improving their quality and industrial production. Post-ripening is an essential step in the post-harvest processing of fruits, but the underlying mechanism and condition of post-ripening on quality improvement need to be studied systematically.

Substrate-enzyme interactions and catalytic mechanism in a novel family VI esterase with dibutyl phthalate-hydrolyzing activity.

Microbial degradation has been confirmed as effective and environmentally friendly approach to remediate phthalates from the environment, and hydrolase is an effective element for contaminant degradation. In the present study, a novel dibutyl phthalate (DBP)-hydrolyzing carboxylesterase (named PS06828) from Pseudomonas sp. PS1 was heterogeneously expressed in E.

Association of length of service and job category with occupational health literacy of port employees in Shenzhen, China.

Background: Health literacy (HL) is associated with health outcomes, but little is known about the occupational HL (OHL) for port employees and its link to the length of service and job category.

Method: A cross-sectional survey was conducted on 3492 port employees from the Occupational Health Survey for Port Employees project, and a special questionnaire was utilized to measure the OHL status. Binary and ordinal logistic regressions were used to estimate the association.

A synthetic light-inducible photorespiratory bypass enhances photosynthesis to improve rice growth and grain yield.

Bioengineering of photorespiratory bypasses is an effective strategy for improving plant productivity by modulating photosynthesis. In previous work, two photorespiratory bypasses, the GOC and GCGT bypasses, increased photosynthetic rates but decreased seed-setting rate in rice (Oryza sativa), probably owing to excess photosynthate accumulation in the stem. To solve this bottleneck, we successfully developed a new synthetic photorespiratory bypass (called the GMA bypass) in rice chloroplasts by introducing Oryza sativa glycolate oxidase 1 (OsGLO1), Cucurbita maxima malate synthase (CmMS), and Oryza sativa ascorbate peroxidase7 (OsAPX7) into the rice genome using a high-efficiency transgene stacking system.

Postbiotics as potential new therapeutic agents for sepsis.

Sepsis is the main cause of death in critically ill patients and gut microbiota dysbiosis plays a crucial role in sepsis. On the one hand, sepsis leads to the destruction of gut microbiota and induces and aggravates terminal organ dysfunction. On the other hand, the activation of pathogenic gut flora and the reduction in beneficial microbial products increase the susceptibility of the host to sepsis.

Deciphering the causal relationship between blood pressure and regional white matter integrity: A two-sample Mendelian randomization study.

Elevated arterial blood pressure (BP) is a common risk factor for cerebrovascular and cardiovascular diseases, but no causal relationship has been established between BP and cerebral white matter (WM) integrity. In this study, we performed a two-sample Mendelian randomization (MR) analysis with individual-level data by defining two nonoverlapping sets of European ancestry individuals (genetics-exposure set: N = 203,111; mean age = 56.71 years, genetics-outcome set: N = 16,156; mean age = 54.

Nanoengineering Natural Leather for Dynamic Thermal Management and Electromagnetic Interference Shielding.

Unpredictable and extreme weather conditions, along with increasing electromagnetic pollution, have resulted in a significant threat to human health and productivity, causing irreversible damage to society's well-being and economy. However, existing personal temperature management and electromagnetic protection materials lack adaptability to dynamic environmental changes. To address this, a unique asymmetric bilayer leather/a-MWCNTs/CA fabric is developed by vacuum-infiltrating interconnected a-MWCNTs networks into natural leather's microfiber backbone and spraying porous acetic acid (CA) on the reverse side.

The relationship between women's body mass index and breast cancer outcomes was U-shaped.

Background: Several studies have analyzed the relationship between body mass index (BMI) and the prognosis of breast cancer (BC). However, whether their relationship is linear or curvilinear remains unclear. This cohort study examined the specific relationship between BMI and BC outcomes.

The correlation of molecule weight of chitosan oligomers with the corresponding viscosity and antibacterial activity.

In order to explore the correlation between the viscosity of chitosan oligomers-acetic solution and its viscosity average molecular weight (M), and determine the M range with a strong bactericidal effect. A series of chitosan oligomers were obtained by degraded chitosan (728.5 kDa) with dilute acid and chitosan oligomer (101.

Identification of conserved linear epitopes in the SARS-CoV-2 receptor-binding region using monoclonal antibodies.

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of cases of infections, leading to a global health emergency. The SARS-CoV-2 spike (S) protein plays the most important role in viral infection, and S1 subunit and its receptor-binding domain (RBD) are widely considered the most attractive vaccine targets. The RBD is highly immunogenic and its linear epitopes are important for vaccine development and therapy, but linear epitopes on the RBD have rarely been reported.

A retrospective study using machine learning to develop predictive model to identify urinary infection stones in vivo.

Preoperative diagnosis of urinary infection stones is difficult, and accurate detection of stone composition can only be performed ex vivo. To provide guidance for better perioperative management and postoperative prevention of infection stones, we developed a machine learning model for preoperative identification of infection stones in vivo. The clinical data of patients with urolithiasis who underwent surgery in our hospital from January 2011 to December 2015 and January 2017 to December 2021 were retrospectively analyzed.

A quinazoline derivative suppresses B cell hyper-activation and ameliorates the severity of systemic lupus erythematosus in mice.

Aberrant autoreactive B cell responses contribute to the pathogenesis of systemic lupus erythematosus (SLE). Currently, there is no safe and effective drug for intervention of SLE. Quinazoline derivative (N4-(4-phenoxyphenethyl)quinazoline-4,6-diamine, QNZ) is a NF-κB inhibitor and has potent anti-inflammatory activity.

Influence of minerals on the foaming properties of milk.

A comprehensive study on the effect of mineral content on milk foaming properties was conducted. Samples with increased mineral concentration were prepared by adding four different types of minerals (KHPO, KCit, CaCl and MgCl) at three different concentration levels (5, 10 and 20 mM) in both reconstituted skim milk powder and milk protein concentrate. Samples with reduced minerals were prepared by reconstituting milk protein concentrate in modified simulated milk ultrafiltrates.

Bioremediation of aniline aerofloat wastewater at extreme conditions using a novel isolate Burkholderia sp. WX-6 immobilized on biochar.

Aniline aerofloat (AAF) is a refractory organic pollutant in floatation wastewater. Little information is currently available on its biodegradation. In this study, a novel AAF-degrading strain named Burkholderia sp.

Systemic immune-inflammation index associated with contrast-induced nephropathy after elective percutaneous coronary intervention in a case-control study.

Elevated systemic immune-inflammation index (SII) has associated with coronary heart disease and poor clinical outcomes. However, the relationship between SII and contrast-induced nephropathy (CIN) in patients who underwent elective percutaneous coronary intervention (PCI) is still unclear. We aimed to investigate the association of SII with the development of CIN in elective PCI patients.

The Effect and Potential Mechanism Analysis of Growth Hormone-Secreting Pituitary Adenomas on Thyroid Function.

Objective: Current studies on the effect of high growth hormone (GH)/insulin-like growth factor (IGF)-1 on thyroid function are inconsistent. The aim was to explore the effect and potential mechanism of high GH/IGF-1 on thyroid function by analyzing the changes of thyroid function in patients with growth hormone-secreting pituitary adenoma (GHPA).

Methods: This was a retrospective cross-sectional study.

Effect of neutralization treatment on properties of chitosan/bamboo leaf flavonoids/nano-metal oxide composite films and application of films in antioxidation of rapeseed oil.

Neutralization treatment improved the slow-release antioxidant food packaging function of chitosan (CS)/bamboo leaf flavone (BLF)/nano-metal oxides composite films. The film cast from the CS composite solution neutralized by KOH solution had good thermal stability. The elongation at break of the neutralized CS/BLF film was increased by about 5 times, which provided the possibility for its packaging application.

Polydatin ameliorates inflammation and oxidative stress associated with MSU-induced gouty arthritis in mice by regulating PPAR-γ and ferritin activation.

Aims: Polygonum cuspidatum Sieb. et Zucc is one of the commonly used herbs for the treatment of gouty arthritis, and polydatin is one of its main effective components. This study evaluated the therapeutic potential of polydatin for the treatment of gout.