Exploring the molecular mechanisms of tirzepatide in alleviating metabolic dysfunction-associated fatty liver in mice through integration of metabolomics, lipidomics, and proteomics.

Clinical studies have suggested that tirzepatide may also possess hepatoprotective effects; however, the molecular mechanisms underlying this association remain unclear. In our study, we performed biochemical analyses of serum and histopathological examinations of liver tissue in mice. To preliminarily explore the molecular mechanisms of tirzepatide on metabolic dysfunction-associated fatty liver disease (MAFLD), liquid chromatography-mass spectrometry (LC-MS) was employed for comprehensive metabolomic, lipidomic, and proteomic analyses in MAFLD mice fed a high-fat diet (HFD).

Cross-species metabolomic profiling reveals phosphocholine-mediated liver protection from cold and ischemia/reperfusion.

Cold and ischemia/reperfusion (IR)-associated injuries are seemingly inevitable during liver transplantation and hepatectomy. Because Syrian hamsters demonstrate intrinsic tolerance to transplantation-like stimuli, cross-species comparative metabolomic analyses were conducted with hamster, rat, and donor liver samples to seek hepatic cold and IR-adaptive mechanisms. Lower hepatic phosphocholine contents were found in recipients with early graft-dysfunction and with virus-caused cirrhosis or high model for end-stage liver disease scores (≥30).

FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC.

Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI.

Pseudouridine synthase 1 promotes hepatocellular carcinoma through mRNA pseudouridylation to enhance the translation of oncogenic mRNAs.

Background And Aims: Pseudouridine is a prevalent RNA modification and is highly present in the serum and urine of patients with HCC. However, the role of pseudouridylation and its modifiers in HCC remains unknown. We investigated the function and underlying mechanism of pseudouridine synthase 1 (PUS1) in HCC.

Effect Of Urinary Kidney Injury Molecule-1 Levels On Short-Term Prognosis Of Chronic Heart Failure.

Objectives: To explore the influential elements of urinary kidney injury molecule-1 levels in chronic heart failure, and to judge its ability to predict 90-day rehospitalisation.

Methods: The cross-sectional case-control study was conducted from November 2020 to April 2021, at Hanzhong Central Hospital, China, and comprised adult patients having chronic heart failure with normal renal function in group A and healthy subjects in control group B. Patients in group A received anti-heart failure therapy for 1 week in hospital and were followed up for 90 days after discharge.

5-aminolevulinate and CHIL3/CHI3L1 treatment amid ischemia aids liver metabolism and reduces ischemia-reperfusion injury.

Liver resection and transplantation surgeries are accompanied by hepatic ischemia-reperfusion (HIR) injury that hampers the subsequent liver recovery. Given that the liver is the main organ for metabolism and detoxification, ischemia-reperfusion in essence bestows metabolic stress upon the liver and disrupts local metabolic and immune homeostasis. Most of the recent and current research works concerning HIR have been focusing on addressing HIR-induced hepatic injury and inflammation, instead of dealing with the metabolic reprogramming and restoration of redox homeostasis.

Single-cell immune profiling of mouse liver aging reveals Cxcl2+ macrophages recruit neutrophils to aggravate liver injury.

Background And Aims: Immune cells play a crucial role in liver aging. However, the impact of dynamic changes in the local immune microenvironment on age-related liver injury remains poorly understood. We aimed to characterize intrahepatic immune cells at different ages to investigate key mechanisms associated with liver aging.

Combined inhibition of surface CD51 and γ-secretase-mediated CD51 cleavage improves therapeutic efficacy in experimental metastatic hepatocellular carcinoma.

Background & Aims: Integrin αv (ITGAV, CD51) is regarded as a key component in multiple stages of tumor progression. However, the clinical failure of cilengitide, a specific inhibitor targeting surface CD51, suggests the importance of yet-unknown mechanisms by which CD51 promotes tumor progression.

Methods: In this study, we used several hepatocellular carcinoma (HCC) cell lines and murine hepatoma cell lines.

Synergy of 5-aminolevulinate supplement and CX3CR1 suppression promotes liver regeneration via elevated IGF-1 signaling.

Inadequate remnant volume and regenerative ability of the liver pose life-threatening risks to patients after partial liver transplantation (PLT) or partial hepatectomy (PHx), while few clinical treatments focus on safely accelerating regeneration. Recently, we discovered that supplementing 5-aminolevulinate (5-ALA) improves liver cold adaptation and functional recovery, leading us to uncover a correlation between 5-ALA metabolic activities and post-PLT recovery. In a mouse 2/3 PHx model, 5-ALA supplements enhanced liver regeneration, promoting infiltration and polarization of anti-inflammatory macrophages via P53 signaling.

The Conserved LncRNA DIO3OS Restricts Hepatocellular Carcinoma Stemness by Interfering with NONO-Mediated Nuclear Export of ZEB1 mRNA.

Hepatocellular carcinoma (HCC) is an aggressive and fatal disease caused by a subset of cancer stem cells (CSCs). It is estimated that there are approximately 100 000 long noncoding RNAs (lncRNAs) in humans. However, the mechanisms by which lncRNAs affect tumor stemness remain poorly understood.

Development of pseudo-targeted profiling of isotopic metabolomics using combined platform of high resolution mass spectrometry and triple quadrupole mass spectrometry with application of C-glucose tracing in HepG2 cells.

Isotope tracing assisted metabolic analysis is becoming a unique tool to understand metabolic regulation in cell biology and biomedical research. Targeted mass spectrometry analysis based on selected reaction monitoring (SRM) has been widely applied in isotope tracing experiment with the advantages of high sensitivity and broad linearity. However, its application for new pathway discovery is largely restrained by molecular coverage.

Extracellular vesicles derived from mesenchymal stromal cells as nanotherapeutics for liver ischaemia-reperfusion injury by transferring mitochondria to modulate the formation of neutrophil extracellular traps.

As nanotherapeutics, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are considered a potent alternative for whole-cell therapy and are gradually entering the clinical field of liver diseases. In this study, neutrophil extracellular traps (NETs) formation in liver tissue was verified as a critical factor for liver ischaemia-reperfusion injury (IRI) in both clinical samples and animal models. Human umbilical cord-derived MSC-EVs (hUC-MSC-EVs) might function to reduce the NETs formation and subsequently improve liver IRI.

5-Aminolevulinate improves metabolic recovery and cell survival of the liver following cold preservation.

Hibernating thirteen-lined ground squirrels (GS; ) are naturally adapted to prolonged periods of ultraprofound hypothermia (body temperature < 5 ºC) during torpor, and drastic oscillations of body temperature and ischemia/reperfusion-like stress during their short euthermic interbout arousals. Thus, their superior adaptability may hold tremendous promise for the advancement of donor organ cold preservation and subsequent organ transplantation. However, bridging hibernation research and translational medicine has been impeded by a dearth of research tools, till the recent establishment of the GS induced pluripotent stem cells (iPSCs).

CCR2-overexpressing mesenchymal stem cells targeting damaged liver enhance recovery of acute liver failure.

Background: Mesenchymal stem cell (MSC) transplantation is emerging as a promising cell therapeutic strategy in acute liver failure (ALF) clinical research. The potency of MSCs to migrate and engraft into targeted lesions could largely determine their clinical efficacy, in which chemokine/receptor axes play a crucial role. Unfortunately, the downregulation of chemokine receptors expression after in vitro expansion results in a poor homing capacity of MSCs.

Demonstration of Controlled Hydrogen Release Using Rh@GQDs during Hydrolysis of NHBH.

Achieving the controlled release of H through an effective approach still faces many challenges. Herein, high-quality graphene quantum dots (GQDs) are synthesized from a new precursor, 1,2,4-trihydroxy benzene, and a multifunctional platform of Rh@GQDs is further developed for the controlled H evolution upon the hydrolysis of NHBH (AB). More importantly, the designing concepts of multistep and stepless speed controls have been introduced in the domains of both H evolution for the first time.

Ammonia removal in selective catalytic oxidation: Influence of catalyst structure on the nitrogen selectivity.

Selective catalytic oxidation is regarded as an effective and favored method for the removal of hazardous ammonia. A number of M-Pt/USY (M=Mn, Fe, Ce and Pr) catalysts were prepared and the resulting materials were characterized using N adsorption/desorption, XRD, TEM, NH-TPD, XPS and H-TPR. It was found that the addition of non-stoichiometric metal oxides to Pt/USY leads to the generation of additional acid sites for ammonia chemisorption and that N selectivity improved with increased strong acidity of the bi-functional catalysts.

Targeting Nestin hepatic stellate cells ameliorates liver fibrosis by facilitating TβRI degradation.

Background & Aims: Liver fibrosis is a wound healing response that arises from various aetiologies. The intermediate filament protein Nestin has been reported to participate in maintaining tissue homeostasis during wound healing responses. However, little is known about the role Nestin plays in liver fibrosis.

Onset of adrenal ganglioneuroblastoma in an adult after delivery.

A case of adrenal ganglioneuroblastoma is presented here. This adrenal ganglioneuroblastoma was found in a 27-year-old female 7 months after delivery. CT clarified that the tumor originated retroperitoneally and was large in size (11.

[In vitro toxicity of naturally occurring silica nanoparticles in C1 coal in bronchial epithelial cells].

Background And Objective: China's Xuan Wei County in Yunnan Province have the world's highest incidence of lung cancer in nonsmoking women-20 times higher than the rest of China. Previous studies showed, this high lung cancer incidence may be associated with the silica particles embedded in the production combustion from the C1 coal. The aim of this study is to separate the silica particles from production combustion from the C1 bituminous coal in Xuan Wei County of Yunnan Province, and study in vitro toxicity of naturally occurring silica particles on BEAS-2B.

catena-Poly[[iodidocopper(I)]-μ-4,4',6,6'-tetra-methyl-2,2'-(ethyl-enedithio)dipyrimidine-κN:N'].

In the title coordination polymer, [CuI(C(14)H(18)N(4)S(2))](n), the Cu(I) center is trigonally coordinated by two pyrimidine N-atom donors from two distinct dithio-ether ligands and one iodide anion. The Cu and I atoms are located on a twofold axis, whereas the midpoint of the central C-C bond of the dithio-ether ligand is located on an inversion center. Each organic ligand, acting in a bidentate mode, bridges two Cu(I )ions, resulting in the formation of polymeric zigzag chains.

Abundance and diversity of aerobic anoxygenic phototrophic bacteria in saline lakes on the Tibetan plateau.

Aerobic anoxygenic phototrophic (AAP) bacteria are heterotrophic prokaryotes that are capable of utilizing light as an energy source but are not capable of producing molecular oxygen. Recently, multiple studies have found that AAP bacteria are widely distributed in oceans and estuaries and may play an important role in carbon cycling. However, AAP bacteria in inland lake ecosystems have not been investigated in depth.

Chlorido[6-phenyl-4-(p-tol-yl)-2,2'-bipyridyl-κN,N']platinum(II).

The asymmetric unit of the title compound, [Pt(C(23)H(17)N(2))Cl], contains two independent mol-ecules with distinct dihedral angles between the central pyridyl and methylbenzene rings [7.77 (2) and 24.07 (2)°].