BPTF Drives Gastric Cancer Resistance to EGFR Inhibitor by Epigenetically Regulating the C-MYC/PLCG1/Perk Axis.

Erlotinib, an EGFR tyrosine kinase inhibitor, is used for treating patients with cancer exhibiting EGFR overexpression or mutation. However, the response rate of erlotinib is low among patients with gastric cancer (GC). The findings of this study illustrated that the overexpression of bromodomain PHD finger transcription factor (BPTF) is partially responsible for erlotinib resistance in GC, and the combination of the BPTF inhibitor AU-1 with erlotinib synergistically inhibited tumor growth both in vivo and in vitro.

High-resolution metabolomic biomarkers for lung cancer diagnosis and prognosis.

Lung cancer is the leading cause of human cancer mortality due to the lack of early diagnosis technology. The low-dose computed tomography scan (LDCT) is one of the main techniques to screen cancers. However, LDCT still has a risk of radiation exposure and it is not suitable for the general public.

Genomic features of rapid versus late relapse in triple negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease and we have previously shown that rapid relapse of TNBC is associated with distinct sociodemographic features. We hypothesized that rapid versus late relapse in TNBC is also defined by distinct clinical and genomic features of primary tumors.

Methods: Using three publicly-available datasets, we identified 453 patients diagnosed with primary TNBC with adequate follow-up to be characterized as 'rapid relapse' (rrTNBC; distant relapse or death ≤2 years of diagnosis), 'late relapse' (lrTNBC; > 2 years) or 'no relapse' (nrTNBC: > 5 years no relapse/death).

Fecal Multidimensional Assay for Non-Invasive Detection of Colorectal Cancer: Fecal Immunochemical Test, Stool DNA Mutation, Methylation, and Intestinal Bacteria Analysis.

Background: Fecal immunochemical test (FIT), DNA mutation, DNA methylation, and microbial dysbiosis all showed promising in colorectal cancer (CRC) non-invasive detection. We assessed CRC detection with an assay combining all these strategies and investigated the effect of clinical features on the performance of this comprehensive test.

Methods: We performed a multidimensional analysis study using stool samples collected from 108 patients with CRC, 18 patients with colorectal adenoma, and 36 individuals with no evidence of colorectal disease.

Transparent and Hard Siloxane Based Hybrid UV-Curable Coating Materials with Amphiphobic Properties.

In this study, highly transparent siloxane-based hybrid UV-curable coating materials were prepared using (acryloxypropyl)methylsiloxane monomer (APMS), a thiol-ene monomer, with benzoin ethyl ether. For the thiol-ene monomer, either pentaerythritol tetrakis(3-mercaptopropionate) (PETTMP) or trimethylolpropane tris(3-mercaptopropionate) (TMPTMP) was used. The siloxane-based hybrid coating materials were highly transparent and hard (pencil hardness of 6-7H).

A predictor of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer patients with the DNA repair genes.

Background: We conducted this study to investigate the prevalence of potential chemo-response-related gene mutations in triple-negative breast cancer (TNBC) patients and to evaluate the potential relationship between these gene mutations and neoadjuvant chemotherapy response in TNBC patients.

Methods: One hundred sixty-two TNBC patients in Fudan University Shanghai Cancer Center who received NAC with 4 cycles of paclitaxel and carboplatin were enrolled in this study. Fifty-six pathological complete response (pCR) patients and 56 non-pCR patients were enrolled in this retrospective study for the training set.

A Biomimetic Glue Protein Modulates Hepatic Gene Expression.

Glue protein as secretion from fruit fly larva plays a significant role in metamorphosis as cementing material for pupation sites. However, the biochemical composition of this macromolecule remains obscure. This study takes the advantage of high-resolution proteomic analysis to unveil the protein compositions.

Multiple cancer susceptible genes sequencing in BRCA-negative breast cancer with high hereditary risk.

Background: Hereditary factors contributed to breast cancer susceptibility. Low mutation prevalence was demonstrated in previous mutation screening in Chinese breast cancer patients. Multiple-gene sequencing may assist in discovering detrimental germline mutation in.

Associations of maternal soy product consumption and urinary isoflavone concentrations with neonatal anthropometry: A prospective cohort study.

Isoflavones (ISOs) are naturally occurring endocrine-disrupting compounds. Few human studies have evaluated the effects of ISO exposure on neonatal anthropometry. This study aimed to examine the associations of maternal soy product consumption and urinary ISO concentrations, including genistein, daidzein, glycitein, and equol, with neonatal anthropometry, based on a Chinese cohort study.

The Polygenic and Monogenic Basis of Blood Traits and Diseases.

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics.

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro.

Gene dysregulation analysis builds a mechanistic signature for prognosis and therapeutic benefit in colorectal cancer.

The implementation of cancer precision medicine requires biomarkers or signatures for predicting prognosis and therapeutic benefits. Most of current efforts in this field are paying much more attention to predictive accuracy than to molecular mechanistic interpretability. Mechanism-driven strategy has recently emerged, aiming to build signatures with both predictive power and explanatory power.

DysRegSig: an R package for identifying gene dysregulations and building mechanistic signatures in cancer.

Summary: Dysfunctional regulations of gene expression programs relevant to fundamental cell processes can drive carcinogenesis. Therefore, systematically identifying dysregulation events is an effective path for understanding carcinogenesis and provides insightful clues to build predictive signatures with mechanistic interpretability for cancer precision medicine. Here, we implemented a machine learning-based gene dysregulation analysis framework in an R package, DysRegSig, which is capable of exploring gene dysregulations from high-dimensional data and building mechanistic signature based on gene dysregulations.

Disturbances in Metabolic Pathways and the Identification of a Potential Biomarker Panel for Early Cartilage Degeneration in a Rabbit Anterior Cruciate Ligament Transection Model.

Objective: This study aimed to assess the association between synovial fluid (SF) metabolites and magnetic resonance imaging (MRI) measurements of cartilage biochemical composition to identify potential SF biomarkers for detecting the early onset of cartilage degeneration in a rabbit model.

Methods: Both knees of 12 New Zealand White rabbits were used. The anterior cruciate ligament transection (ACLT) model was performed on right knees, and the sham surgery on left knees.

CDKL3 promotes osteosarcoma progression by activating Akt/PKB.

Osteosarcoma (OS) is a primary malignant bone neoplasm with high frequencies of tumor metastasis and recurrence. Although the Akt/PKB signaling pathway is known to play key roles in tumorigenesis, the roles of cyclin-dependent kinase-like 3 (CDKL3) in OS progression remain largely elusive. We have demonstrated the high expression levels of CDKL3 in OS human specimens and comprehensively investigated the role of CDKL3 in promoting OS progression both in vitro and in vivo.

The Metabolic Changes of Artesunate and Ursolic Acid on Syrian Golden Hamsters Fed with the High-Fat Diet.

Artesunate was well known as an antimalarial drug. Our previous research found that it has hypolipidemia effects in rabbits fed with a high-fat diet, especially combined with ursolic acid. In this study, we reconfirmed the lipid-lowering effect of artesunate and ursolic acid in hamsters and analyzed the metabolic changes using gas chromatography time-of-flight mass spectrometry (GC/TOF MS).

Systematical Analysis of the Cancer Genome Atlas Database Reveals / Combination as a Prognostic Signature for Gastric Cancer.

Digestive cancers-including gastric cancer (GC), colorectal cancer, hepatocellular carcinoma, esophageal cancer, and pancreatic cancer-accounted for 26% of cancer cases and 35% of cancer deaths worldwide in 2018. It is crucial and urgent to develop biomarkers for the diagnosis, prognosis, and therapeutic benefits of digestive cancers, especially for GC, since the incidence of GC is lower only than lung cancer in China, is hard to detect at an early stage, and is associated with poor prognosis. Mucins, glycoproteins encoded by MUC family genes, act as a part of a physical barrier in the digestive tract and participate in various signaling pathways.

Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer.

Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in tumor initiation and progression. The antisense lncRNA LDLRAD4-AS1 is the longest lncRNA of LDLRAD4, and its expression levels, cellular localization, precise function, and mechanism in colorectal cancer (CRC) remain unknown. In this study, we observed that lncRNA LDLRAD4-AS1 was located in the nucleus of CRC cells and that lncRNA LDLRAD4-AS1 was upregulated in most CRC specimens and cell lines.

Chromosome-level assembly of wild Bactrian camel genome reveals organization of immune gene loci.

Camelids are characterized by their unique adaptive immune system that exhibits the generation of homodimeric heavy-chain immunoglobulins, somatic hypermutation of T-cell receptors, and low genetic diversity of major histocompatibility complex (MHC) genes. However, short-read assemblies are typically highly fragmented in these gene loci owing to their repetitive and polymorphic nature. Here, we constructed a chromosome-level assembly of wild Bactrian camel genome based on high-coverage long-read sequencing and chromatin interaction mapping.

A Cuboid Spider Silk: Structure-Function Relationship and Polypeptide Signature.

A unique cuboid spider silk from the outer egg sac of Nephila pilipes, with an unusual square cross-section, is disclosed. The structure-function relationships within this silk are first studied through structural characterization, mechanical measurement, protein conformation, and polypeptide signature of silk proteins. This silk maintains the higher stiffness property of egg sac silks, and also shows a species difference.

Whole-genome sequencing of 128 camels across Asia reveals origin and migration of domestic Bactrian camels.

The domestic Bactrian camels were treated as one of the principal means of locomotion between the eastern and western cultures in history. However, whether they originated from East Asia or Central Asia remains elusive. To address this question, we perform whole-genome sequencing of 128 camels across Asia.