Dysregulated epigenetic programs that restrict differentiation, reactivate fetal genes, and confer phenotypic plasticity are critical to colorectal cancer (CRC) development. By screening a small molecule library targeting epigenetic regulators using our dual reporter system, we found that inhibiting histone deacetylase (HDAC) 1/2 promotes CRC differentiation and anti-tumor activity. Comprehensive biochemical, chemical, and genetic experiments revealed that on-target blockade of the HDAC1/2 catalytic domain mediated the differentiated phenotype.
View Article and Find Full Text PDFLeaf senescence, the final stage of leaf development, is crucial for plant fitness as it enhances nutrient reutilization, supporting reproductive success and overall plant adaptation. Understanding its molecular and genetic regulation is essential to improve crop resilience and productivity, particularly in the face of global climate change. This review explores the significant contributions of natural genetic diversity to our understanding of leaf senescence, focusing on insights from model plants and major crops.
View Article and Find Full Text PDFBackground: Breast screening recommendation based on individual risk assessment is emerging as an alternative approach to improve compliance and efficiency to detect breast cancer (BC) early. In Vietnam, prior knowledge to stratify risk based on genetic factors is currently lacking.
Methods: This study recruited 892 BC patients and 735 healthy Vietnamese women from 2016 to 2021.
Leaf senescence is a crucial process throughout evolution, vital for plant fitness as it facilitates the gradual shift of energy allocation between photosynthesis and catabolism overtime. This onset is influenced by a complex interplay of genetic and environmental factors, making senescence a key adaptation mechanism for plants in their natural habitats. Our study investigated the genetic mechanism underlying age-induced leaf senescence in Arabidopsis natural populations.
View Article and Find Full Text PDFNewcastle Disease Virus (NDV) genotype VII (GVII) is becoming the predominant strain of NDV in the poultry industry. It causes high mortality even in vaccinated chickens with a common NDV genotype II vaccine (GII-vacc). To overcome this, the killed GVII vaccine has been used to prevent NDV outbreaks.
View Article and Find Full Text PDFObjectives: To prospectively compare systemic anti-tumour immune responses induced by irreversible electroporation (IRE) and robot-assisted radical prostatectomy (RARP) in patients with localised intermediate-risk prostate cancer (PCa).
Patients And Methods: Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2-3, clinical cancer stage ≤T2c, prostate-specific antigen level <20 ng/mL).
Small-cell neuroendocrine cervical carcinoma (NECC) is a rare histology, and diagnosis and treatment of this condition are challenging because of its rarity, non-specific abdominopelvic symptoms, and less favorable prognosis compared to other cervical cancers. Here, we present a case of a 20-year-old patient diagnosed with small-cell NECC, defined within a cervical polyp, initially mimicking a benign lesion. Because of the difficulty in diagnosis, the patient underwent thorough diagnostics and interventions, including imaging, histopathology, and immunohistochemistry.
View Article and Find Full Text PDFProstate cancer exhibits high prevalence and accounts for a high number of cancer-related deaths. The discovery and characterization of molecular determinants of aggressive prostate cancer represents an active area of research. The Immediate Early Response (IER) family of genes, which regulate Protein Phosphatase 2A (PP2A) activity, has emerged among the factors that influence cancer biology.
View Article and Find Full Text PDFThe iron-molybdenum cofactor of nitrogenase (FeMoco) catalyzes fixation of N via Fe hydride intermediates. Our understanding of these species has relied heavily on the characterization of well-defined 3d metal hydride complexes, which serve as putative spectroscopic models. Although the Fe ions in FeMoco, a weak-field cluster, are expected to adopt locally high-spin Fe configurations, synthetically accessible hydride complexes featuring d or d electron counts are almost exclusively low-spin.
View Article and Find Full Text PDFResident memory T cells (Ts) help control local immune homeostasis and contribute to tissue-protective immune responses. The local cues that guide their differentiation and localization are poorly defined. We demonstrate that mucosal vascular addressin cell adhesion molecule 1, a ligand for the gut-homing receptor αβ integrin, in the presence of retinoic acid and transforming growth factor-β (TGF-β) provides a co-stimulatory signal that induces blood cluster of differentiation (CD8 T cells to adopt a T-like phenotype.
View Article and Find Full Text PDFThe MbnBC enzyme complex converts cysteine residues in a peptide substrate, MbnA, to oxazolone/thioamide groups during the biosynthesis of copper chelator methanobactin (Mbn). MbnBC belongs to the mixed-valent diiron oxygenase (MVDO) family, of which members use an Fe(II)Fe(III) cofactor to react with dioxygen for substrate modification. Several crystal structures of the inactive Fe(III)Fe(III) form of MbnBC alone and in complex with MbnA have been reported, but a mechanistic understanding requires determination of the oxidation states of the crystallographically observed Fe ions in the catalytically active Fe(II)Fe(III) state, along with the site of MbnA binding.
View Article and Find Full Text PDFDuring a 2023 outbreak of Mycoplasma pneumoniae-associated community-acquired pneumonia among children in northern Vietnam, we analyzed M. pneumoniae isolated from nasopharyngeal samples. In almost half (6 of 13) of samples tested, we found known A2063G mutations (macrolide resistance) and a novel C2353T variant on the 23S rRNA gene.
View Article and Find Full Text PDFAberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators of these key cellular programs, we engineer a dual endogenous reporter system by genome-editing the SOX9 and KRT20 loci of human CRC cell lines to express fluorescent reporters, broadcasting aberrant stem cell-like and differentiation activity, respectively. By applying a CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs to this platform, we identify factors that contribute to stem cell-like activity and differentiation in CRC.
View Article and Find Full Text PDFObjectives: Quality of surgery has recently become an essential topic in the prognosis of colon cancer. Complete mesocolic excision for colon cancer has recently gained popularity with high-quality surgery. Patient specimens after complete mesocolic excision with central vessel ligation procedures have an integrity of the mesocolon and the yield of three fields of lymph node harvest.
View Article and Find Full Text PDFBackground: A rounded lateral first metatarsal head shape is associated with higher rates of hallux abducto valgus recurrence following corrective surgery; however, the effect of the lateral first metatarsal head shape on the hallux abduction angle (HAA) has not yet been explored in a nonpathologic, pre-pointe ballet dancer population. The primary purpose of this study was to investigate the effect of the lateral first metatarsal head shape on the HAA when pre-pointe female dancers force their turnout.
Methods: Seventeen female, pre-pointe ballet students (mean age, 10.
Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators that regulate these key cellular programs in CRC, we developed an endogenous reporter system by genome-editing human CRC cell lines with knock-in fluorescent reporters at the SOX9 and KRT20 locus to report aberrant stem cell-like activity and differentiation, respectively, and then performed pooled genetic perturbation screens. Constructing a dual reporter system that simultaneously monitored aberrant stem cell-like and differentiation activity in the same CRC cell line improved our signal to noise discrimination.
View Article and Find Full Text PDFVibrio cholerae (V. cholerae), the etiological agent of cholera, uses cholera toxin (CT) to cause severe diarrheal disease. Cholera is still a significant cause of mortality worldwide with about half of all cholera cases and deaths occurring in children under five.
View Article and Find Full Text PDFBackground: In active surveillance there is significant interest in whether imaging modalities such as multiparametric magnetic resonance imaging (mpMRI) or Gallium prostate-specific membrane antigen positron emission tomography/computerized tomography (Ga-PSMA-PET/CT) can improve the detection of progression to clinically significant prostate cancer (csPCa) and thus reduce the frequency of prostate biopsies and associated morbidity. Recent studies have demonstrated the value of mpMRI in active surveillance; however, mpMRI does miss a proportion of disease progression and thus alone cannot replace biopsy. To date, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown additive value to mpMRI in its ability to detect prostate cancer (PCa) in the primary diagnostic setting.
View Article and Find Full Text PDFBackground: Under the pressure of Human Adenovirus (HAdV)-associated acute respiratory infection (ARI) outbreak in children in Northern Vietnam in the end of 2022, this study was initiated to identify the HAdV subtype(s) and examine the associated clinical features and risk factors of more severe cases.
Methods: This study evaluated pediatric patients with ARI which had tested positive for HAdV between October and November 2022 using a multiplex real-time PCR panel. Nasopharyngeal aspirates or nasal swab samples were used for sequencing to identify HAdV subtypes.
Objective: To evaluate the additional value of prostate-specific membrane antigen positron emission tomography (PSMA-PET) to conventional diagnostic tools to select patients for hemi-ablative focal therapy (FT).
Patients And Methods: We performed a retrospective analysis on a multicentre cohort (private and institutional) of 138 patients who underwent multiparametric magnetic resonance imaging (mpMRI), PSMA-PET, and systematic biopsies prior to radical prostatectomy between January 2011 and July 2021. Patients were eligible when they met the consensus criteria for FT: PSA <15 ng/mL, clinical/radiological T stage ≤T2b, and International Society of Urological Pathology (ISUP) grade 2-3.
Over 60% of single-gene diseases in newborns are autosomal dominant variants. Noninvasive prenatal testing for monogenic conditions (NIPT-SGG) is cost-effective and timesaving, but not widely applied. This study introduces and validates NIPT-SGG in detecting 25 monogenic conditions.
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