Integrated analyses of multi-omic data derived from paired primary lung cancer and brain metastasis reveal the metabolic vulnerability as a novel therapeutic target.

Background: Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs.

Methods: Here, we performed integrated analyses of genomic, transcriptomic, proteomic, metabolomic, and single-cell RNA sequencing data which were derived from a total number of 154 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels.

Effect of the mRNA decapping enzyme scavenger (DCPS) inhibitor RG3039 on glioblastoma.

Background: Patients with glioblastoma (GBM) have a poor prognosis and limited treatment options. The mRNA decapping enzyme scavenger (DCPS) is a cap-hydrolyzing enzyme. The DCPS inhibitor RG3039 exhibited excellent central nervous system bioavailability in vivo and was safe and well tolerated in healthy volunteers in a phase 1 clinical trial.

Trophoblast fusion in fetal growth restriction is inhibited by CTGF in a cell-cycle-dependent manner.

Fetal growth restriction (FGR) is a relatively common complication of pregnancy, and insufficient syncytialization in the placenta may play an important role in the pathogenesis of FGR. However, the mechanism of impaired formation of the syncytiotrophoblast layer in FGR patients requires further exploration. In the present study, we demonstrated that the level of syncytialization was decreased in FGR patient placentas, while the expression of connective tissue growth factor (CTGF) was significantly upregulated.

N6-methyladenosine dynamics in placental development and trophoblast functions, and its potential role in placental diseases.

N6-methyladenosine (m6A) is the most abundant modification controlling RNA metabolism and cellular functions, but its roles in placental development are still poorly understood. Here, we characterized the synchronization of m6A modifications and placental functions by mapping the m6A methylome in human placentas (n = 3, each trimester), revealing that the dynamic patterns of m6A were associated with gene expression homeostasis and different biological pathways in placental development. Then, we generated trophoblast-specific knockout mice of Wtap, a critical component of methyltransferase complex, and demonstrated that Wtap was essential for trophoblast proliferation, placentation and perinatal growth.

Extra villous trophoblast-derived PDL1 can ameliorate macrophage inflammation and promote immune adaptation associated with preeclampsia.

Introduction: Severe preeclampsia (sPE) is a systemic syndrome that may originate from chronic inflammation. Maintaining maternal-fetal hemostasis by the co-inhibitory molecule programmed death ligand 1 (PDL1) can be favorable for ameliorating inflammation from immune cells. Apart from programmed death 1 (PD1) expression, decidual macrophages (dMs) produce inflammatory cytokines, in response to cells which express PDL1.

Comprehensive analysis of femoral head necrosis based on machine learning and bioinformatics analysis.

Osteonecrosis of the femoral head (ONFH) is a kind of disabling disease, given that the molecular mechanism of ONFH has not been elucidated, it is of significance to use bioinformatics analysis to understand the disease mechanism of ONFH and discover biomarkers. Gene set for ONFH GSE74089 was downloaded in the Gene Expression Omnibus, and "limma" package in R software was used to identify differentially expressed genes related to oxidative stress. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyze were performed for functional analysis.

Influence of different implant designs on replacement of four teeth of the posterior free-end edentulism: Three-dimensional finite element analysis and clinic case validation.

Background: With periodontal disease having an increasing incidence, mandibular free-end edentulism caused by periodontitis is clinically more common. Finite element analysis and clinical case reports were used to evaluate the influence of different designs on the load distribution of implant prosthesis in mandibular posterior free-end edentulism.

Method: A finite element model of a mandible with posterior free-end edentulism was established.

N6-methyladenosine modifications in maternal-fetal crosstalk and gestational diseases.

As a medium among pregnant women, environment and fetus, placenta owns powerful and delicate epigenetic processes to regulate gene expression and maintain cellular homeostasis. N6-methyladenosine (mA) is the most prevalent modification that determines the fate of RNA, and its dynamic reversibility indicates that mA may serve as a sensitive responder to environmental stimuli. Emerging evidence suggests that mA modifications play an essential role in placental development and maternal-fetal crosstalk, and are closely related to gestational diseases.

Incidence and risk factors of postoperative nausea and vomiting in lung cancer patients following lobectomy and application of analgesic pumps.

Objective: To investigate the occurrence rate and risk factors of postoperative nausea and vomiting (PONV) in lung cancer patients following lobectomy and application of analgesic pumps.

Methods: This retrospective study reviewed clinical data from patients that had undergone lobectomy for lung cancer under general anaesthesia. The risk factors of PONV were analysed using binary logistic regression models.

Environmental Enrichment Protects Offspring of a Rat Model of Preeclampsia from Cognitive Decline.

Preeclampsia affects 5-7% of all pregnancies and contributes to adverse pregnancy and birth outcomes. In addition to the short-term effects of preeclampsia, preeclampsia can exert long-term adverse effects on offspring. Numerous studies have demonstrated that offspring of preeclamptic women exhibit cognitive deficits from childhood to old age.

Trophoblast-derived interleukin 9 mediates immune cell conversion and contributes to maternal-fetal tolerance.

In the maternal-fetal crosstalk, fetal derived trophoblast cells can secret several molecules to regulate immune tolerance such as cytokines and chemokines, besides human leukocyte antigens (HLA) providing. However, the mechanism of these factors in pregnancy is still unknown. Our previous study showed that IL9 could be secreted by trophoblasts and exerted a positive effect on trophoblasts themselves through autocrine signaling.

Differentially expressed circular RNAs and the competing endogenous RNA network associated with preeclampsia.

Introduction: Circular RNAs (circRNAs) are non-coding RNAs that are implicated in preeclampsia (PE) pathogenesis; however, their expression and functions in PE remain unclear. In this study, we aimed to investigate the expression of circRNAs in PE and construct a competing endogenous RNA (ceRNA) network, and analyze the associated pathways in PE pathogenesis.

Methods: We performed circRNA sequencing to identify the differential expression profile of circRNAs in PE as compared to normal pregnancy.

The Inhibition of Protein Kinase C β Contributes to the Pathogenesis of Preeclampsia by Activating Autophagy.

Background: Preeclampsia is a devastating hypertensive disorder of pregnancy with unknown mechanism. Recent studies have considered abnormal autophagy as a new cellular mechanism for this disorder, while little is known about how autophagy is specifically involved and what factors are implicated. Here, we report a previously unrecognized preeclampsia-associated autophagic regulator, PKCβ, that is involved in placental angiogenesis.

Optimized cutoff maternal age for adverse obstetrical outcomes: a multicenter retrospective cohort study in Urban China during 2011 to 2012.

Background: China's two-child policy has led to a trend of aging in pregnancy which was associated with adverse outcomes. This study aimed to identify the clinically cutoff maternal age for adverse obstetric outcomes in China.

Methods: This secondary analysis of a multicenter retrospective cohort study included data of childbearing women from 39 hospitals collected in urban China during 2011 to 2012.

Evolution and Expression Characteristics of Receptor-Like Cytoplasmic Protein Kinases in , and .

Receptor-like cytoplasmic protein kinases (RLCKs) are involved in various activities in plant growth and development. We have totally identified 162, 160, and 402 genes in maize, rice, and Arabidopsis genomes, respectively. Phylogenetic analyses divided 724 genes into 15 subfamilies and similar structural patterns of kinase activity sites and functional sites were observed within the subfamilies.

A gender-specific association of the polymorphism Ile197Met in the kininogen 1 gene with plasma irbesartan concentrations in Chinese patients with essential hypertension.

This study was conducted to explore interactions in the association of the kininogen (KNG1) Ile197Met polymorphism and gender with plasma concentrations of irbesartan in Chinese patients with essential hypertension. A total of 1100 subjects with essential hypertension received a daily oral dose of 150 mg irbesartan for twenty-eight consecutive days. High-performance liquid chromatography-fluorescence (HPLC) was used to detect plasma irbesartan concentrations on day 28.

Elevation in Total Homocysteine Levels in Chinese Patients With Essential Hypertension Treated With Antihypertensive Benazepril.

Objective: To investigate the effect of benazepril on plasma homocysteine (Hcy) levels and to analyze the correlation between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and changes in Hcy levels in response to benazepril.

Methods: A total of 231 patients with mild to moderate essential hypertension were enrolled, and benazepril was orally administered at a dose of 10 mg/d for 2 weeks. Plasma Hcy levels were measured by high-performance liquid chromatography at baseline and after 2 weeks of treatment.