Malectin, an endoplasmic reticulum-resident lectin, promotes malignant behavior of human hepatocellular carcinoma.

Accumulating evidences have shown that unfolded protein response (UPR) contributes to the increased survival of tumor cells under endoplasmic reticulum (ER) stress conditions. Malectin is an ER-resident lectin that selectively traps misfolded glycoproteins in ER for degradation, and its expression is upregulated upon ER stress. However, contribution of malectin to malignant behavior of tumor has not been reported.

Promoter Polymorphism (Allelic Variation) Affects Tacrolimus Treatment Efficacy by Modulating E2F6 Binding Affinity.

Background: Tacrolimus is widely used as a first-line immunosuppressant in transplant immunology; however, its clinical application is constrained by the narrow therapeutic index and considerable interindividual variability. In this study, we identified the potential regulatory role of a novel promoter polymorphism, rs4519508 C > T, in the tacrolimus pharmacodynamic pathway.

Methods: Dual-luciferase reporter assays and bioinformatic analysis were applied to assess the impact of allelic variation.

Refining antipsychotic treatment strategies in schizophrenia: discovery of genetic biomarkers for enhanced drug response prediction.

Schizophrenia (SCZ) is a severe mental disorder affecting around 1% of individuals worldwide. The variability in response to antipsychotic drugs (APDs) among SCZ patients presents a significant challenge for clinicians in determining the most effective medication. In this study, we investigated the biological markers and established a predictive model for APD response based on a large-scale genome-wide association study using 3269 Chinese schizophrenia patients.

Targeted Discovery of a Natural -Quinone Methide Precursor and Green Generation of Its Oligomers.

-Quinone methides (-QMs) are a class of highly reactive intermediates that serve as important nonisolable building blocks (NBBs) in organic synthesis and small-molecule library construction. Because of their instability and nonisolability, most reported -QMs are generated through chemical synthesis, and only a few natural -QMs have been reported due to the lack of directed discovery strategies. Herein, a new natural -QM precursor (trichophenol A, ) was identified from the fungal strain of sp.

Biosynthesis of Enfumafungin-type Antibiotic Reveals an Unusual Enzymatic Fusion Pattern and Unprecedented C-C Bond Cleavage.

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis.

Blended Genome Exome (BGE) as a Cost Efficient Alternative to Deep Whole Genomes or Arrays.

Genomic scientists have long been promised cheaper DNA sequencing, but deep whole genomes are still costly, especially when considered for large cohorts in population-level studies. More affordable options include microarrays + imputation, whole exome sequencing (WES), or low-pass whole genome sequencing (WGS) + imputation. WES + array + imputation has recently been shown to yield 99% of association signals detected by WGS.

Association between CYP2C9 and VKORC1 genetic polymorphisms and efficacy and safety of warfarin in Chinese patients.

Objectives: Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy.

GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases.

Partial endothelial-to-mesenchymal transition (EndMT) is an intermediate phenotype observed in endothelial cells (ECs) undergoing a transition toward a mesenchymal state to support neovascularization during (patho)physiological angiogenesis. Here, we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4 (GTF2H4) as a positive regulator of this process. In addition, we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3 (ERCC3) to co-regulate partial EndMT.

Identification of differentially expressed miRNAs in plasma exosomes from patients with early-onset pre-eclampsia using next generation sequencing.

Pre-eclampsia (PE), a major cause of perinatal morbidity and mortality, accounts for up to 14 % mortality of maternal and 18 % of fetal or infant mortalities. However, the pathogenesis process of PE remains unclear. The aim of this study was to identify differentially expressed microRNAs (miRNAs) in the peripheral blood exosomes of early-onset PE patients versus healthy pregnant women using high-throughput sequencing, and to find candidate miRNAs as molecular markers.

A spectrum of altered non-rapid eye movement sleep in schizophrenia.

Background: Multiple facets of sleep neurophysiology, including electroencephalography (EEG) metrics such as non-rapid eye movement (NREM) spindles and slow oscillations (SO), are altered in individuals with schizophrenia (SCZ). However, beyond group-level analyses which treat all patients as a unitary set, the extent to which NREM deficits vary among patients is unclear, as are their relationships to other sources of heterogeneity including clinical factors, illness duration and ageing, cognitive profiles and medication regimens. Using newly collected high density sleep EEG data on 103 individuals with SCZ and 68 controls, we first sought to replicate our previously reported (Kozhemiako et.

An integrated analysis identifies six molecular subtypes of pancreatic ductal adenocarcinoma revealing cellular and molecular landscape.

Pancreatic ductal adenocarcinoma (PDA) has been found to have a high mortality rate. Despite continuous efforts, current histopathological classification is insufficient to guide individualized therapies of PDA. We first define the molecular subtypes of PDA (MSOP) based on a meta-cohort of 845 samples from 11 PDA datasets.

Construction and optimization of a polygenic risk model for venous thromboembolism in the Chinese population.

Background: Venous thromboembolism (VTE) has both environmental and genetic risk factors. It is regulated by polygenes and multisites. The polygenic risk score (PRS) has been widely used because any single genetic biomarker failed to accurately predict the genetic risk of VTE.

Identification of new bisabosqual-type meroterpenoids reveals non-enzymatic conversion of bisabosquals into -bisabosquals.

Bisabosqual-type meroterpenoids are fungi-derived polyketide-terpenoid hybrids bearing a 2,3,3a,3a,9,9a-hexahydro-1-benzofuro[4,3,2-]chromene skeleton (6/6/6/5 ring system) or its -C-ring structure, and exhibit diverse bioactivities. Their unique structural architecture and impressive biological activities have led to considerable interest in discovering new analogues. However, to date, only nine analogues have been identified.

Prefrontal cortex-specific Dcc deletion induces schizophrenia-related behavioral phenotypes and fail to be rescued by olanzapine treatment.

Multiple genome studies have discovered that variation in deleted in colorectal carcinoma (Dcc) at transcription and translation level were associated with the occurrences of psychiatric disorders. Yet, little is known about the function of Dcc in schizophrenia (SCZ)-related behavioral abnormalities and the efficacy of antipsychotic drugs in vivo. Here, we used an animal model of prefrontal cortex-specific knockdown (KD) of Dcc in adult C57BL/6 mice to study the attention deficits and impaired locomotor activity.

Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer's disease.

DNA methylation plays a potential role in the pathogenesis of Alzheimer's disease (AD). However, little is known about the global changes of blood leukocyte DNA methylome profiles from Chinese patients with mild cognitive impairment (MCI) and with AD, or the specific DNA methylation-based signatures associated with MCI and AD. In this study, we sought to dissect the characteristics of blood DNA methylome profiles in MCI- and AD-affected Chinese patients with the aim of identifying novel DNA methylation biomarkers for AD.

Two new alkaloids from a strain of endophytic fungus sp.

19-Hydroxybrevianamide M (1) and 6 R-methoxybrevianamide V (2), two new alkaloids, were isolated from an extract of the endophytic fungus sp. JNU18HC0517J, together with six known analogues (). Their structures were elucidated by extensive spectroscopic analyses, NMR calculations, and ECD calculations.

HCC: RNA-Sequencing in Cirrhosis.

Hepatocellular carcinoma (HCC) ranks the most common types of cancer worldwide. As the fourth leading cause of cancer-related deaths, its prognosis remains poor. Most patients developed HCC on the basis of chronic liver disease.

Methylome-wide association study of different responses to risperidone in schizophrenia.

Accumulating evidence shows that DNA methylation plays a role in antipsychotic response. However, the mechanisms by which DNA methylation changes are associated with antipsychotic responses remain largely unknown. We performed a methylome-wide association study (MWAS) to evaluate the association between DNA methylation and the response to risperidone in schizophrenia.