Generation and characterization of mature hepatocyte organoids for liver metabolic studies.

Hepatocyte organoids (HOs) generated in vitro are powerful tools for liver regeneration. However, previously reported HOs have mostly been fetal in nature with low expression levels of metabolic genes characteristic of adult liver functions, hampering their application in studies of metabolic regulation and therapeutic testing for liver disorders. Here, we report development of novel culture conditions that combine optimized levels of triiodothyronine (T3) with the removal of growth factors to enable successful generation of mature hepatocyte organoids (MHOs) of both mouse and human origin with metabolic functions characteristic of adult livers.

Temporal trends in disease burden and attributable risk factors for tracheal, bronchus, and lung cancer in Nepal, 1990-2019.

Background: Tracheal, bronchus, and lung (TBL) cancer is one of the most common cancers in Nepal. The aim of this study was to analyze the changing disease burden and risk factors for TBL cancer in Nepal from 1990 to 2019.

Methods: TBL cancer burden data were obtained from the Global Burden of Disease Study 2019.

Insect transient receptor potential vanilloid channels as potential targets of insecticides.

Chordotonal organs are miniature sensory organs present in insects. Chordotonal organs depend on transient receptor potential (TRP) channels. Transient receptor potential vanilloid (TRPV) channels are the only TRPs identified that can act as targets of insecticides.

The epidemic of acute lymphoid leukemia in China: current trends and future prediction.

Background: China has experienced one of the fastest increases in the incidence of acute lymphoid leukemia (ALL). The aim of this study was to assess the long-term trends of the incidence and mortality of ALL in mainland China between 1990 and 2019 and to project these trends through 2028.

Methods: Data on ALL were extracted from the Global Burden of Disease Study 2019; population data were extracted from World Population Prospects 2019.

Shikonin triggers GSDME-mediated pyroptosis in tumours by regulating autophagy via the ROS-MAPK14/p38α axis.

Background: Shikonin (SK), a botanical drug extracted from Lithospermum erythrorhizon, has been shown to inhibit tumour growth through apoptosis and necrosis. However, whether SK induces pyroptosis in cancer cells is still unknown.

Purpose: This study aims to investigated the mechanisms of SK-induced pyroptosis in tumour cells and mice.

Effects of tolfenpyrad exposure on development and response mechanism in the silkworm, Bombyx mori.

Tolfenpyrad is a broad spectrum of insecticide that can effectively kill different types of pests, including Lepidoptera. However, due to improper use, the adverse effects of tolfenpyrad on beneficial or economic insects have not been well studied. In this study, we systematically investigated the toxic effect of sublethal tolfenpyrad on silkworms.

The epidemic of stroke mortality attributed to high body mass index in mainland China: Current trends and future prediction.

Background: High body mass index (BMI) is an important risk factor for stroke. The aim of this study was to assess the long-term trend of high BMI-attributed stroke mortality and make projections through 2030.

Methods: Data were extracted from the Global Burden of Disease Study 2019 and World Population Prospects 2019.

Incidence and mortality trends of nasopharynx cancer from 1990 to 2019 in China: an age-period-cohort analysis.

Background: Nasopharynx cancer (NPC) is a great health burden in China. This study explored the long-term trends of NPC incidence and mortality in China.

Methods: We retrospectively analyzed data from the Global Burden of Disease Study 2019 using an age-period-cohort framework.

Lentivector cryptic splicing mediates increase in CD34+ clones expressing truncated HMGA2 in human X-linked severe combined immunodeficiency.

X-linked Severe Combined Immunodeficiency (SCID-X1) due to IL2RG mutations is potentially fatal in infancy where 'emergency' life-saving stem cell transplant may only achieve incomplete immune reconstitution following transplant. Salvage therapy SCID-X1 patients over 2 years old (NCT01306019) is a non-randomized, open-label, phase I/II clinical trial for administration of lentiviral-transduced autologous hematopoietic stem cells following busulfan (6 mg/kg total) conditioning. The primary and secondary objectives assess efficacy in restoring immunity and safety by vector insertion site analysis (VISA).

Prevalence of and Factors Associated With Nutritional Supplement Use Among Older Chinese Adults: A Nationwide Cross-Sectional Study in China.

Objective: This study identified the prevalence of nutritional supplement (NS) use among older Chinese adults and explored the factors associated with NS use in this population.

Methods: We used data from 11,089 Chinese men and women aged ≥ 65 years from the 2018 Chinese Longitudinal Healthy Longevity Survey. The chi-square test was used to examine the differences in demographics, health status and lifestyles at different levels.

Temporal Trends in the Incidence and Disability Adjusted Life Years of Schizophrenia in China Over 30 Years.

Background: Schizophrenia is an important public health problem in China. This study aims to assess the long-term trends in the incidence and disability-adjusted life years (DALYs) rate of schizophrenia in China between 1990 and 2019.

Methods: The incidence and DALYs data were drawn from the Global Burden of Disease Study 2019, and an age-period-cohort model was used in the analysis.

Molecular mechanism and potential application of bacterial infection in the silkworm, Bombyx mori.

As a representative species of Lepidoptera, Bombyx mori has been widely studied and applied. However, bacterial infection has always been an important pathogen threatening the growth of silkworms. Bombyx mori can resist various pathogenic bacteria through their own physical barrier and innate immune system.

Yap-Sox9 signaling determines hepatocyte plasticity and lineage-specific hepatocarcinogenesis.

Background & Aims: Primary liver tumors comprise distinct subtypes. A subset of intrahepatic cholangiocarcinoma (iCCA) can arise from cell fate reprogramming of mature hepatocytes in mouse models. However, the underpinning of cell fate plasticity during hepatocarcinogenesis is still poorly understood, hampering therapeutic development for primary liver cancer.

Insertional activation of and by HIV-1 proviruses in T cell lymphomas.

Retroviruses cause cancers in animals by integrating in or near oncogenes. Although HIV-1 infection increases the risk of cancer, most of the risk is associated with immunodeficiency and coinfection by oncogenic virus (Epstein-Barr virus, Kaposi sarcoma herpesvirus, and human papillomavirus). HIV-1 proviruses integrated in some oncogenes cause clonal expansion of infected T cells in vivo; however, the infected cells are not transformed, and it is generally believed that HIV-1 does not cause cancer directly.

NLRP3 Inhibition Ameliorates Severe Cutaneous Autoimmune Manifestations in a Mouse Model of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy-Like Disease.

Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy show diverse endocrine and nonendocrine manifestations initiated by self-reactive T cells because of AIRE mutation-induced defective central tolerance. A large number of American patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy suffer from early-onset cutaneous inflammatory lesions accompanied by an infiltration of T cells and myeloid cells. The role of myeloid cells in this setting remains to be fully investigated.

Characteristics of Breast Ducts in Normal-Risk and High-risk Women and Their Relationship to Ductal Cytologic Atypia.

Breast ductal cytologic atypia is an important risk factor for sporadic breast cancer. Characterization of the associated normal breast tissue is needed to develop additional methods of risk assessment and new targets for breast cancer prevention. We conducted a prospective clinical trial evaluating women at normal-risk or at high-risk for sporadic breast cancer.

Spindle-like and telophase-like self-assemblies mediated by complementary nucleobase molecular recognition.

Inspired by nature, supramolecular nanoparticles based on complementary nucleobase interactions have aroused wide interest. In our study, two kinds of fluorophores were conjugated at the end of nucleobase containing homopolymers, which can be used to confirm the binding state and calculate the binding constants among different nucleobase pairs. Furthermore, we describe a facile synthesis of nucleobase-functionalized amphiphilic polymers with rigid and flexible backbones using RAFT polymerization.

IKKα inactivation promotes Kras-initiated lung adenocarcinoma development through disrupting major redox regulatory pathways.

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct and predominant types of human lung cancer. IκB kinase α (IKKα) has been shown to suppress lung SCC development, but its role in ADC is unknown. We found inactivating mutations and homologous or hemizygous deletions in the locus, which encodes IKKα, in human lung ADCs.

Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis.

Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell-driven autoimmune disease caused by impaired central tolerance, are susceptible to chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop APECED-like phenotypes, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers.

Gene expression analysis upon lncRNA DDSR1 knockdown in human fibroblasts.

Long non-coding RNAs (lncRNAs) play important roles in regulating diverse biological processes including DNA damage and repair. We have recently reported that the DNA damage inducible lncRNA DNA damage-sensitive RNA1 (DDSR1) regulates DNA repair by homologous recombination (HR). Since lncRNAs also modulate gene expression, we identified gene expression changes upon DDSR1 knockdown in human fibroblast cells.

The pivotal role of IKKα in the development of spontaneous lung squamous cell carcinomas.

Here, we report that kinase-dead IKKα knockin mice develop spontaneous lung squamous cell carcinomas (SCCs) associated with IKKα downregulation and marked pulmonary inflammation. IKKα reduction upregulated the expression of p63, Trim29, and keratin 5 (K5), which serve as diagnostic markers for human lung SCCs. IKKα(low)K5(+)p63(hi) cell expansion and SCC formation were accompanied by inflammation-associated deregulation of oncogenes, tumor suppressors, and stem cell regulators.

Protective effect of Cox-2 allelic variants on risk of colorectal adenoma development in African Americans.

Background: Recent evidence indicates that single nucleotide polymorphisms (SNPs) in the Cox-2 gene may modulate the risk of colorectal adenoma development.

Patients And Methods: We explored possible associations between Cox-2 polymorphisms and risk of adenoma development in an African American case-control study comprising 72 cases of advanced adenomas and 146 polyp-free controls. An exhaustive approach of genotyping 13 haplotype-tagging SNPs (ht SNPs) distributed over the entire COX-2 gene was used.

Real-time PCR analysis of candidate imprinted genes on mouse chromosome 11 shows balanced expression from the maternal and paternal chromosomes and strain-specific variation in expression levels.

Imprinted genes are monoallelically expressed from either the maternal or paternal genome. Because cancer develops through genetic and epigenetic alterations, imprinted genes affect tumorigenesis depending on which parental allele undergoes alteration. We have shown previously in a mouse model of neurofibromatosis type 1 (NF1) that inheriting mutant alleles of Nf1 and Trp53 on chromosome 11 from the mother or father dramatically changes the tumor spectrum of mutant progeny, likely due to alteration in an imprinted gene(s) linked to Nf1 and Trp53.

An imprinted locus epistatically influences Nstr1 and Nstr2 to control resistance to nerve sheath tumors in a neurofibromatosis type 1 mouse model.

Cancer is a complex disease in which cells acquire many genetic and epigenetic alterations. We have examined how three types of alterations, mutations in tumor suppressor genes, changes in an imprinted locus, and polymorphic loci, interact to affect tumor susceptibility in a mouse model of neurofibromatosis type 1 (NF1). Mutations in tumor suppressor genes such as TP53 and in oncogenes such as KRAS have major effects on tumorigenesis due to the central roles of these genes in cell proliferation and cell survival.