Distinct functions of EHMT1 and EHMT2 in cancer chemotherapy and immunotherapy.

EHTM1 (GLP) and EHMT2 (G9a) are closely related protein lysine methyltransferases often thought to function together as a heterodimer to methylate histone H3 and non-histone substrates in diverse cellular processes including transcriptional regulation, genome methylation, and DNA repair. Here we show that EHMT1/2 inhibitors cause ATM-mediated slowdown of replication fork progression, accumulation of single-stranded replication gaps, emergence of cytosolic DNA, and increased expression of STING. EHMT1/2 inhibition strongly potentiates the efficacy of alkylating chemotherapy and anti-PD-1 immunotherapy in mouse models of tripe negative breast cancer.

Biomarkers for chemotherapy and drug resistance in the mismatch repair pathway.

Drugs targeting DNA repair have developed rapidly in cancer therapy, and numerous inhibitors have already been utilized in preclinical and clinical stages. To optimize the selection of patients for treatment, it is essential to discover biomarkers to anticipate chemotherapy response. The DNA mismatch repair (MMR) pathway is closely correlated with cancer susceptibility and plays an important role in the occurrence and development of cancers.

A rapid multiplex assay of human malaria parasites by digital PCR.

Background: Blood smear examination through traditional optical microscopy is the gold standard for malaria diagnosis. However, it imposes strict requirements for operational staff and its sensitivity cannot perfectly satisfy the needs of clinical requirements. More sensitive and accurate modern technologies should be applied to this field.

Rare germline variants in PALB2 and BRCA2 in familial and sporadic chordoma.

Chordoma is a rare bone tumor with genetic risk factors largely unknown. We conducted a whole-exome sequencing (WES) analysis of germline DNA from 19 familial chordoma cases in five pedigrees and 137 sporadic chordoma patients and identified 17 rare germline variants in PALB2 and BRCA2, whose products play essential roles in homologous recombination (HR) and tumor suppression. One PALB2 variant showed disease cosegregation in a family with four affected people or obligate gene carrier.

Disrupted BRCA1-PALB2 interaction induces tumor immunosuppression and T-lymphocyte infiltration in HCC through cGAS-STING pathway.

Background And Aims: BRCA1 (BRCA1 DNA repair associated) and PALB2 (partner and localizer of BRCA2) interact with each other to promote homologous recombination and DNA double-strand breaks repair. The disruption of this interaction has been reported to play a role in tumorigenesis. However, its precise function in HCC remains poorly understood.

The mycorrhizal fungi of promote the growth of by increasing environmental stress tolerance.

is a medicinal herbal plant with important health care value and high demand. Due to its slow growth and scarcity in nature, its yield depends on intensified cultivation while biotic and abiotic stresses were important factors that causes production loss. Orchidaceae can form association with rhizoctonias collectively, and studies have found that some orchids showed a high level of strain-species specificity to orchid mycorrhizal fungi (OMF), yet the specificity of OMF on needs to explored.

Detection of 2 Gene Methylation in Extramammary Paget's Disease by Methylation-Sensitive High-Resolution Melting Analysis.

Background: Extramammary Paget's disease (EMPD) is a rare skin tumor. Hypermethylation in the 2 promoter resulting in the downregulation of its protein expression shows a high detection rate in EMPD tumor tissue, which indicates that the methylation of 2 may play an important role in the pathogenesis of EMPD.

Objective: This study aims to establish a rapid analysis strategy based on the methylation-sensitive high-resolution melting curve (MS-HRM) to detect the methylation level of the 2 promoter.

BRCA2 associates with MCM10 to suppress PRIMPOL-mediated repriming and single-stranded gap formation after DNA damage.

The BRCA2 tumor suppressor protects genome integrity by promoting homologous recombination-based repair of DNA breaks, stability of stalled DNA replication forks and DNA damage-induced cell cycle checkpoints. BRCA2 deficient cells display the radio-resistant DNA synthesis (RDS) phenotype, however the mechanism has remained elusive. Here we show that cells without BRCA2 are unable to sufficiently restrain DNA replication fork progression after DNA damage, and the underrestrained fork progression is due primarily to Primase-Polymerase (PRIMPOL)-mediated repriming of DNA synthesis downstream of lesions, leaving behind single-stranded DNA gaps.

Fine Particulate Matter (PM) upregulates expression of Inflammasome NLRP1 ROS/NF-κB signaling in HaCaT Cells.

Skin, as the major organ of a human body, is constantly exposed to PM stimulation, which may exert specific toxic influences on the physiology of skin. This study aims to investigate the effect of PM on the formation of inflammasomes in skin cells and to explore the potential mechanism linking PM and skin inflammation. Changes in mRNA and protein levels of inflammasome-related genes were detected by real-time PCR and western blot in human immortalized epidermal cells (HaCaT) treated with PM at multiple concentrations for 24 hours.

Bordetella pertussis Infection in Infants and Young Children in Shanghai, China, 2016-2017: Clinical Features, Genotype Variations of Antigenic Genes and Macrolides Resistance.

Background: The global resurgence of pertussis in countries with high vaccination coverage has been a concern of public health.

Methods: Nasopharyngeal swabs were collected for Bordetella pertussis culture from children with suspected pertussis. Clinical and vaccination information were reviewed through electronic medical chart and immunization record.

Detection of BRAF V600E mutation in fine-needle aspiration fluid of papillary thyroid carcinoma by droplet digital PCR.

Objectives: Papillary thyroid carcinoma (PTC) accounts for 85% of thyroid carcinoma, which is the most common endocrine tumor. For the diagnosis of PTC, ultrasound-guided fine needle aspiration (FNA) with pathological evaluation is the standard test and BRAF V600E mutation is the most common molecular marker associated with the occurrence, progression and poor clinicopathological characteristics of PTC. However, because of the small amount of the tumor cells obtained by FNA for pathological evaluation or BRAF V600E mutation detection, more sensitive and accurate methods are required.

Comprehensive Validation of Snapback Primer-Based Melting Curve Analysis to Detect Nucleotide Variation in the Codon 12 and 13 of KRAS Gene.

Background: KRAS genotyping in tumor samples is a decisive clinical test for the anti-EGFR therapy management. However, the complexity of KRAS mutation landscape across different cancer types and the mosaic effect caused by cancer cellularity and heterogeneity make the choice of KRAS genotyping method a challenging topic in the clinical practice.

Methods: We depicted the landscape of somatic KRAS mutation in 7,844 primary tumors and 10,336 metastatic tumors across over 30 types of cancer using the Cancer Genome Atlas (TCGA) and Integrated Mutation Profiling of Actionable Cancer Targets (MSKCC-IMPACT) databases, respectively.

A triplex probe-based TaqMan qPCR assay for Calreticulin type I and II mutation detection.

Background: Calreticulin (CALR) exon 9 frameshift mutations have recently been identified in 30-40% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) without JAK2 or MPL mutations. We aimed to develop a qPCR assay to screen type I and II mutations of CALR.

Methods: Three different fluorescent-labeled hydrolysis probes and one pair of primers in a closed-tube system were developed to detect CALR type I and II mutations and distinguish them from wild-type.

Rapid detection of CALR type 1 and type 2 mutations using PNA-LNA clamping loop-mediated isothermal amplification on a CD-like microfluidic chip.

Bleeding and thrombosis represent common complications in myeloproliferative neoplasms (MPN) and significantly contribute to morbidity and mortality. Molecular markers, including CALR mutations, were considered not only as diagnostic markers, but also as risk factors for bleeding and thrombosis associated with MPN, especially for patients in remote primary hospitals. We sought to develop an easy-to-use assay for the rapid detection of CALR type 1 (CALR-1) and type 2 (CALR-2) mutations in Philadelphia chromosome-negative MPN patients.

Ligand-dependent EphA7 signaling inhibits prostate tumor growth and progression.

The downregulation of receptor tyrosine kinase EphA7 is frequent in epithelial cancers and linked to tumor progression. However, the detailed mechanism of EphA7-mediated prostate tumor progression remains elusive. To test the role of EphA7 receptor in prostate cancer (PCa) progression directly, we generated EphA7 receptor variants that were either lacking the cytoplasmic domain or carrying a point mutation that inhibits its phosphorylation by site-directed mutagenesis.

A portable microfluidic platform for rapid molecular diagnostic testing of patients with myeloproliferative neoplasms.

The ability to simultaneously detect JAK2 V617F and MPL W515K/L mutations would substantially improve the early diagnosis of myeloproliferative neoplasms (MPNs) and decrease the risk of arterial thrombosis. The goal of this study is to achieve a point of care testing platform for simultaneous analysis of major genetic alterations in MPN. Here, we report a microfluidic platform including a glass capillary containing polypropylene matrix that extracts genomic DNA from a drop of whole blood, a microchip for simultaneous multi-gene mutation screening, and a handheld battery-powered heating device.

Effects of Ambient Fine Particles PM on Human HaCaT Cells.

The current study was conducted to observe the effects of fine particulate matter (PM) on human keratinocyte cell line (HaCaT) cells. The potential mechanism linking PM and skin was explored. HaCaT cells were cultured and then accessed in plate with PM.

Genetic Analysis of Mismatch Repair Genes Alterations in Extramammary Paget Disease.

Extramammary Paget disease (EMPD) is a rare cutaneous malignant neoplasm. The familial occurrence of EMPD and the high risk of concomitant secondary tumors in EMPD patients have gained much attention. These findings highlight the importance of genetic alterations in the tumorigenesis of this skin cancer.

Clinical and pathological characteristics of extramammary Paget's disease: report of 246 Chinese male patients.

Extramammary Paget's disease (EMPD) is a rare cutaneous neoplasm. The aim of this study was to elaborate the clinical and pathological features of Chinese EMPD male patients. The study comprised 246 patients with EMPD at our institute from January 1993 to December 2012.

Diagnostic and prognostic value of tissue and circulating levels of Ephrin-A2 in prostate cancer.

Ephrin-A2, a member of the Eph/ephrin family, is associated with tumorigenesis and tumor progression. This study aimed to assess the diagnostic and prognostic value of both serum and tissue levels of Ephrin-A2 in prostate cancer (PCa) management. One hundred and forty-five frozen prostate tissues, 55 paraffin-embedded prostate tissues, 88 serum samples, and seven prostate cell lines (RWPE-1, LNCaP, LNCaP-LN3, PC-3, PC-3M, PC-3M-LN4, and DU145) were examined via quantitative reverse transcription-PCR (qRT-PCR), immunohistochemistry, enzyme-linked immunosorbent assay, and western blotting.

Performance analysis of compressive ghost imaging based on different signal reconstruction techniques.

We present different signal reconstruction techniques for implementation of compressive ghost imaging (CGI). The different techniques are validated on the data collected from ghost imaging with the pseudothermal light experimental system. Experiment results show that the technique based on total variance minimization gives high-quality reconstruction of the imaging object with less time consumption.

Toward point-of-care testing for JAK2 V617F mutation on a microchip.

Molecular genetics now plays a crucial role in diagnosis, the identification of prognostic markers, and monitoring of hematological malignancies. Demonstration of acquired changes such as the JAK2 V617F mutation within myeloproliferative neoplasms (MPN) has quickly moved from a research setting to the diagnostic laboratory. Microfluidics-based assays can reduce the assay time and sample/reagent consumption and enhance the reaction efficiency; however, no current assay has integrated isothermal amplification for point-of-care MPN JAK2 V617F mutation testing with a microchip.

Correlation of KIF3A and OVOL1, but not ACTL9, with atopic dermatitis in Chinese pediatric patients.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in Chinese pediatric patients. To date, the genetic susceptibility to AD in this population has not been fully clarified. Three single nucleotide polymorphisms have previously been associated with AD in Europeans, rs2897442 (KIF3A), rs479844 (OVOL1) and rs2164983 (ACTL9).