A 1,2,3-Triazole Derivative of Quinazoline Exhibits Antitumor Activity by Tethering RNF168 to SQSTM1/P62.

Quinazoline and its derivatives have drawn much attention in the development of potential antitumor agents. Here, we synthesized a series of 1,2,3-triazole derivatives of quinazoline at the C6 position and evaluated for their cytotoxic activity in various human cancer cell lines. We found that compound was the most cytotoxic to HCT-116 cells (IC, 0.

Inhibition of macrophage migration inhibitory factor (MIF) suppresses apoptosis signal-regulating kinase 1 to protect against liver ischemia/reperfusion injury.

Hepatic ischemia-reperfusion (I/R) injury is a major complication leading to surgical failures in liver resection, transplantation, and hemorrhagic shock. The role of cytokine macrophage migration inhibitory factor (MIF) in hepatic I/R injury is unclear. We examined changes of MIF expression in mice after hepatic I/R surgery and hepatocytes challenged with hypoxia-reoxygenation (H/R) insult.

Interaction analysis of FADS2 gene variants with chronic hepatitis B infection in Chinese patients.

The risk of chronic hepatitis B (CHB) infection is often affected by polyunsaturated fatty acids (PUFAs) metabolism which is strongly influenced by single nucleotide polymorphisms (SNPs) within the PUFA metabolic pathway. Given this, we designed this study to determine the relationship between specific polymorphisms within fatty acid desaturase 2 (FADS2), a key enzyme in PUFA metabolism, and CHB infection. We completed this evaluation using a case-control study comprising 230 CHB patients and 234 unrelated healthy controls in which the genetic relationships between three previously identified SNPs, isolated via mass spectrometry, and CHB infection.

Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney.

Brain death (BD) induces an organ-level inflammatory response. However, the underlying mechanisms have not been fully elucidated. Here, we investigated the role of caspase-1-mediated pyroptosis in BD-induced kidney injury in rats.

E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination.

Background And Aims: Hepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear.

Approach And Results: RNF5 expression was significantly down-regulated during HIR in mice and hepatocytes.

Dopamine and dopamine receptor D1 as a novel favourable biomarker for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) remains one of the most common malignant tumours worldwide. Therefore, the identification and development of sensitivity- genes as novel diagnostic markers and effective therapeutic targets is urgently needed. Dopamine and dopamine receptor D1 (DRD1) are reported to be involved in the progression of various cancers.

High expression of DHX9 promotes the growth and metastasis of hepatocellular carcinoma.

Background: DHX9, an NTP-dependent RNA helicase, is closely associated with the proliferation and metastasis of some tumor cells and the prognosis of patients, but its role in hepatocellular carcinoma (HCC) is not well-known. This study was performed to explore the expression and role of DHX9 in HCC.

Methods: The expression of DHX9 in HCC tissues and cell lines was detected by TCGA database, qPCR, western blotting, and immunohistochemistry.

Multi-species hydrocarbon measurement using TDLAS with a wide scanning range DFG laser.

Tunable diode laser absorption spectroscopy (TDLAS) is a widely used diagnostic technique due to its high sensitivity, fast response, low cost, and other merits. Hydrocarbon detection is a field of great interest in the application of tunable diode lasers as hydrocarbons are fundamental molecules in many industrial processes. Many tunable diode lasers are only suitable for single species detection due to the short scanning range and in real situations.

Pharmacological Activating Transcription Factor 6 Activation Is Beneficial for Liver Retrieval With Normothermic Mechanical Perfusion From Cardiac Dead Donor Rats.

Normothermic machine perfusion (NMP) could be beneficial for organ retrieval from donors after cardiac death (DCD). Activating transcription factor 6 (ATF6) was recently shown to mitigate liver ischemia/reperfusion injury and confer protection. The aims of this study were to assess the implication of ATF6 in liver retrieval from DCD rat livers with NMP and explore the effect of pharmacologic ATF-6 activation on liver retrieval.

Small-world effects in a modified epidemiological model with mutation and permanent immune mechanism.

Pandemic with mutation and permanent immune spreading in a small-world network described is studied by a modified SIR model, with consideration of mutation-immune mechanism. First, a novel mutation-immune model is proposed to modify the classical SIR model to simulate the transmission of mutable viruses that can be permanently immunized in small-world networks. Then, the influences of the size, coordination number and disorder parameter of the small-world network on the spread of the epidemic are analyzed in detail.

Interaction analysis of gene variants related to one-carbon metabolism with chronic hepatitis B infection in Chinese patients.

Background: The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one-carbon metabolism genes. In the present study, we investigated the relationship between polymorphisms belonging to the one-carbon metabolic pathway and CHB infection.

Methods: A case-control study using 230 CHB patients and 234 unrelated healthy controls was carried out to assess the genetic association of 24 single nucleotide polymorphisins (SNPs) determined by mass spectrometry.

Alpinetin protects against hepatic ischemia/reperfusion injury in mice by inhibiting the NF-κB/MAPK signaling pathways.

Liver damage induced by ischemia/reperfusion (I/R) remains a primary issue in liver transplantation and resection. Alpinetin, a novel plant flavonoid derived from Alpinia katsumadai Hayata, is widely used to treat various inflammatory diseases. However, the effects of alpinetin on hepatic I/R injury remain unclear.

Single nucleotide polymorphisms in interleukin-6 attenuates hepatocytes injury in hypoxia/re-oxygenation via STAT3 signal pathway mediated autophagy.

Ischemia-reperfusion injury (IRI) is inevitable during liver surgery, and it is an important factor affecting the prognosis of patients. IL-6 rs1800796 single nucleotide polymorphisms (SNPs) can promote synthesis and secretion of IL-6 and protect hepatocytes from IRI. In this study, we investigated the mechanisms by which IL-6 alleviates hepatic IRI.

The Impact of Social Value Orientation, Game Context and Trust on Cooperative Behavior After Cooperative Video Game Play.

This study explores the effects of the cooperative video game context, social value orientation (SVO) and trust on cooperative behavior. The main finding is that collaborative game play significantly increases cooperative behavior, especially in prosocial individuals. In addition, a mediation model is established in which trust partially mediates the association between the game mode and cooperative behavior.

[Study on the epidemic development of COVID-19 in Hubei province by a modified SEIR model].

Objective: To establish a SEIR epidemic dynamics model that can be used to evaluate the COVID-19 epidemic, and to predict and evaluate the COVID-19 epidemic in Hubei province using the proposed model.

Methods: COVID-19 SEIR transmission dynamics model was established, which took transmission ability in latent period and tracking quarantine interventions into consideration. Based on the epidemic data of Hubei province from January 23, 2020 to February 24, 2020, the parameters of the newly established modified SEIR model were fitted.

Donor Brain Death Leads to a Worse Ischemia-Reperfusion Injury and Biliary Injury After Liver Transplantation in Rats.

Background: Brain-dead (BD) donor is the main source for liver transplantation (LT). We aim to investigate the effect of brain death on donor liver inflammatory activity and its association with ischemia-reperfusion (I/R) injury and biliary tract injury after LT.

Material And Method: A brain death model using male Lewis rats was established, in both BD and non-BD groups; livers were harvested for transplantation using a 2-cuff technique.

Microarray Analysis For Expression Profiles of lncRNAs and circRNAs in Rat Liver after Brain-Dead Donor Liver Transplantation.

The mechanisms underlying severe liver injury after brain-dead (BD) donor liver transplantation (BDDLT) remain unclear. In this study, we aimed to explore the roles of lncRNAs and circRNAs in liver injury after BDDLT. Rat liver injury was detected in the sham, BD, control, and BDDLT groups.

Synthesis and cytotoxic activity of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group as the A-ring or B-ring.

Many natural or synthetic chalcones have potential anti-tumor activity. Here, we synthesized two series of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group and evaluated for their cytotoxic activity towards cultured human lung cancer A549 and colorectal HCT-116 cells. Among them, compound 8d was the most cytotoxic against HCT-116 cells, with an IC value of 2.

Clinical significance of aberrant DEUP1 promoter methylation in hepatocellular carcinoma.

Accumulating studies have shown that methylation of tumor suppressor genes plays an important role in tumorigenesis. Deuterosome assembly protein 1 (DEUP1) has been implicated as a suppressor gene in some tumors and promoter methylation led to silencing of its expression. However, the roles of DEUP1 promoter methylation and expression in hepatocellular carcinoma (HCC) are not clear.

Six-Transmembrane Epithelial Antigen of the Prostate 3 Deficiency in Hepatocytes Protects the Liver Against Ischemia-Reperfusion Injury by Suppressing Transforming Growth Factor-β-Activated Kinase 1.

Background And Aims: Hepatic ischemia-reperfusion (I/R) injury remains a major challenge affecting the morbidity and mortality of liver transplantation. Effective strategies to improve liver function after hepatic I/R injury are limited. Six-transmembrane epithelial antigen of the prostate 3 (Steap3), a key regulator of iron uptake, was reported to be involved in immunity and apoptotic processes in various cell types.

Synthesis and evaluation of chalcone analogues containing a 4-oxoquinazolin-2-yl group as potential anti-tumor agents.

The chalcone motif can be found in many molecules that contribute to essential biological processes, and many chalcone-containing compounds exhibit potent anti-cancer activity. Here, we synthesized two series of chalcone analogues (3a-s and 6a-s) based on substituting the chalcone B-ring or A-ring with a 4-oxoquinazolin-2-yl group, and then evaluated them for cytotoxic activity in human colorectal HCT-116 and breast cancer MCF-7 cell lines. Compounds 3a-s (in which a 4-oxoquinazolin-2-yl group functioned as the B-ring) were markedly more cytotoxic than compounds 6a-s (in which 4-oxoquinazolin-2-yl group functioned as the A-ring), based on their IC values to inhibit proliferation.

A Methylthio-Functionalized-MOF Photocatalyst with High Performance for Visible-Light-Driven H Evolution.

Recently, the emergence of photoactive metal-organic frameworks (MOFs) has given great prospects for their applications as photocatalytic materials in visible-light-driven hydrogen evolution. Herein, a highly photoactive visible-light-driven material for H evolution was prepared by introducing methylthio terephthalate into a MOF lattice via solvent-assisted ligand-exchange method. Accordingly, a first methylthio-functionalized porous MOF decorated with Pt co-catalyst for efficient photocatalytic H evolution was achieved, which exhibited a high quantum yield (8.

Synthesis, cytotoxic evaluation and target identification of thieno[2,3-d]pyrimidine derivatives with a dithiocarbamate side chain at C2 position.

Two series of thieno[2,3-d]pyrimidine derivatives bearing a dithiocarbamate side chain at the C2 position were synthesized and evaluated for cytotoxic activity in human lung cancer A549 and colon cancer HCT-116 cell lines. Compound 3n exhibited the most cytotoxic effect on A549 cells with an IC value of 4.87 μM, inducing a cell cycle arrest at G2/M phase and activating the spindle assembly checkpoint (SAC).

Kupffer cell depletion by gadolinium chloride aggravates liver injury after brain death in rats.

Brain death (BD) impairs liver function in potential donors, and is associated with hormonal and metabolic changes or molecular effects with pro‑inflammatory activation. Resident macrophages in the liver named Kupffer cells (KCs) undergo pro‑ or anti‑inflammatory pathway activation, which affects liver function. However, the role of the KCs in liver dysfunction following BD has not been fully elucidated.