An in-depth understanding of the role and mechanisms of T cells in immune organ aging and age-related diseases.

T cells play a critical and irreplaceable role in maintaining overall health. However, their functions undergo alterations as individuals age. It is of utmost importance to comprehend the specific characteristics of T-cell aging, as this knowledge is crucial for gaining deeper insights into the pathogenesis of aging-related diseases and developing effective therapeutic strategies.

Global analysis of HLA-A2 restricted MAGE-A3 tumor antigen epitopes and corresponding TCRs in non-small cell lung cancer.

Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis. Adoptive cell therapy using engineered T-cell receptors (TCRs) targeting cancer-testis antigens, such as Melanoma-associated antigen 3 (MAGE-A3), is a potential approach for the treatment of NSCLC. However, systematic analysis of T cell immune responses to MAGE-A3 antigen and corresponding antigen-specific TCR is still lacking.

Insufficient epitope-specific T cell clones are responsible for impaired cellular immunity to inactivated SARS-CoV-2 vaccine in older adults.

Aging is a critical risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy. The immune responses to inactivated vaccine for older adults, and the underlying mechanisms of potential differences to young adults, are still unclear. Here we show that neutralizing antibody production by older adults took a longer time to reach similar levels in young adults after inactivated SARS-CoV-2 vaccination.

Multidimensional single-cell analysis of human peripheral blood reveals characteristic features of the immune system landscape in aging and frailty.

Frailty is an intermediate status of the human aging process, associated with decompensated homeostasis and death. The immune phenotype of frailty and its underlying cellular and molecular processes remain poorly understood. We profiled 114,467 immune cells from cord blood, young adults and healthy and frail old adults using single-cell RNA and TCR sequencing.

The Abnormal Proliferation of Hepatocytes is Associated with MC-LR and C-Terminal Truncated HBX Synergistic Disturbance of the Redox Balance.

Background: Microcystin-LR (MC-LR) and hepatitis B virus (HBV) are associated with hepatocellular carcinoma (HCC). However, the concentrations of MC-LR in drinking water and the synergistic effect of MC-LR and HBV on hepatocellular carcinogenesis through their disturbance of redox balance have not been fully elucidated.

Methods: We measured the MC-LR concentrations in 168 drinking water samples of areas with a high incidence of HCC.

Immunological risk factors for sepsis-associated delirium and mortality in ICU patients.

Background: A major challenge in intervention of critical patients, especially sepsis-associated delirium (SAD) intervention, is the lack of predictive risk factors. As sepsis and SAD are heavily entangled with inflammatory and immunological processes, to identify the risk factors of SAD and mortality in the intensive care unit (ICU) and determine the underlying molecular mechanisms, the peripheral immune profiles of patients in the ICU were characterized.

Methods: This study contains a cohort of 52 critical patients who were admitted to the ICU of the First Affiliated Hospital of Jinan University.

Effectiveness of Booster Doses of the SARS-CoV-2 Inactivated Vaccine KCONVAC against the Mutant Strains.

As the COVID-19 epidemic progresses with the emergence of different SARS-CoV-2 variants, it is important to know the effectiveness of inactivated SARS-CoV-2 vaccines against the variants. To maximize efficiency, a third boost injection of the high-dose SARS-CoV-2 inactivated vaccine KCONVAC was selected for investigation. In addition to the ancestral strain, KCONVAC boost vaccination induced neutralizing antibodies and antigen-specific CD8 T cells to recognize several variants, including B.

Phase separation in epigenetics and cancer stem cells.

Accumulating evidence indicates that liquid-liquid phase separation (LLPS) is the basis of the formation of membrane-less compartments in cells. This biomolecular condensate represented by phase separation may influence epigenetics in cancer stem cells (CSCs), a small subpopulation of cancer cells responding to the initiation, maintenance, metastasis, and therapy resistance of cancer. Understanding the underlying biophysical principles and the specific characteristics of biocondensates would provide insights into the precise blocking of potential tumor targets, thereby fundamentally curbing tumor occurrence, recurrence and metastasis.

Accurate Prediction of Metachronous Liver Metastasis in Stage I-III Colorectal Cancer Patients Using Deep Learning With Digital Pathological Images.

Objectives: Metachronous liver metastasis (LM) significantly impacts the prognosis of stage I-III colorectal cancer (CRC) patients. An effective biomarker to predict LM after surgery is urgently needed. We aimed to develop deep learning-based models to assist in predicting LM in stage I-III CRC patients using digital pathological images.

Production and purification of infectious diseases-associated tetramer for staining of CD8 T cells from PBMCs.

Major histocompatibility complex (MHC) tetramers can work as diagnostic tools to identify antigen-specific T cells in immunological research and monitoring. Here, we provide a general protocol for the production of MHC tetramer. We obtain highly pure N-terminal His-tagged HLA-A2 α chain and β2-microglobulin (βm) to fold a monomer with a photocleavable peptide, which can exchange with an HLA-A2 presented peptide derived from influenza A virus.

SARS-CoV-2 variant B.1.1.7 caused HLA-A2 CD8 T cell epitope mutations for impaired cellular immune response.

Here, we evaluated the immune properties of the HLA-A2 restricted CD8 T cell epitopes containing mutations from B.1.1.

CD8 T-Cell Epitope Variations Suggest a Potential Antigen HLA-A2 Binding Deficiency for Spike Protein of SARS-CoV-2.

We identified SARS-CoV-2 specific antigen epitopes by HLA-A2 binding affinity analysis and characterized their ability to activate T cells. As the pandemic continues, variations in SARS-CoV-2 virus strains have been found in many countries. In this study, we directly assess the immune response to SARS-CoV-2 epitope variants.

Optimization of antigen-specific CD8 T cell activation conditions for infectious diseases including COVID-19.

Here, we describe the use of the artificial antigen-presenting cell (aAPC) system for the verification of T-cell epitopes. We purify and activate CD8 T cells from blood samples from HLA-A2 that are negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CD8 T cells are combined with peptide-loaded T2-A2 cells, which are then stained with a SARS-CoV-2-specific MHC-1 tetramer to identify specific HLA-A2-restricted T-cell epitopes.

C-terminal-truncated hepatitis B virus X protein promotes hepatocarcinogenesis by activating the MAPK pathway.

Purpose: C-terminally truncated hepatitis B virus X (ctHBx) is frequently detected in hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) integrated into their genomes, but the molecular mechanisms of ctHBx-related oncogenic signaling remain unclear. In this study, the effects of ctHBx on HepG2 cells were investigated by measuring ctHBx-induced changes in the cell cycle-related target proteins cell division cycle 25C (cdc25C) and p53 downstream of the mitogen-activated protein kinase (MAPK) pathway.

Materials And Methods: ctHBx lentiviruses were constructed and transfected into HepG2 cells.

Capsaicin Inhibits Proliferation and Induces Apoptosis in Breast Cancer by Down-Regulating FBI-1-Mediated NF-κB Pathway.

Background: As a natural compound extracted from a variety of hot peppers, capsaicin has drawn increasing attention to its anti-cancer effects against multiple human cancers including breast cancer. FBI-1 is a major proto-oncogene negatively regulating the transcription of many tumor suppressor genes, and plays a vital role in tumorigenesis and progression. However, whether FBI-1 is involved in capsaicin-induced breast cancer suppression has yet to be ascertained.

Synergistic Effect of MC-LR and C-Terminal Truncated HBx on HepG2 Cells and Their Effects on PP2A Mediated Downstream Target of MAPK Signaling Pathway.

C-terminally truncated hepatitis B virus (HBV) X (ctHBx) infection and exposure to microcystins-LR (MC-LR) can lead to human hepatitis and liver cancer, but the mechanism associated with their synergistically effects not been fully elucidated. The ctHBx (HBxΔ4 and HBxΔ32) lentivirus were constructed and transfected into the HepG2 cells. Then we investigated the function of MC-LR and ctHBx using the molecular biology approaches, including enzyme-linked immunosorbent assay, clone formation assay, scratch wound testing, transwell assays, carried out flow cytometry respectively to examine cell cycle and apoptosis in each group, and detected the related proteins of HBx, MEK/ERK/JNK/p38 in mitogen-activated protein kinase (MAPK) pathway and the downstream proteins such as cdc2, cdc25C, and p53 by western blotting.

Sodium Butyrate Combined with Docetaxel for the Treatment of Lung Adenocarcinoma A549 Cells by Targeting Gli1.

Purpose: This study is aimed to investigate the combined treating efficacy of sodium butyrate and docetaxel on proliferation and apoptosis of the lung adenocarcinoma A549 cell line based on Gli1 regulation in vitro and in vivo.

Materials And Methods: RNA interference method was used to overexpress Gli1 in A549 cells. Cells were treated with varying concentrations of sodium butyrate, docetaxel or both in combination.

Novel nomogram with microvascular density in the surgical margins can accurately predict the risk for anastomotic leakage after anterior resection for rectal cancer.

Background: Anastomotic leakage (AL) is a serious complication after anterior resection. The purpose of this study was to determine the role of microvascular density (MVD) in AL and to develop a nomogram to accurately predict AL.

Methods: This study retrospectively enrolled 477 consecutive patients who underwent anterior resection for rectal cancer from January 2011 to January 2019.

Triptolide Suppresses Growth of Breast Cancer by Targeting HMGB1 in Vitro and in Vivo.

Triptolide has been indicated potent anti-cancer effect involving multiple molecular targets and signaling pathways. High-mobility group box 1 (HMGB1) is a highly conserved DNA-binding protein taking part in breast cancer development. The therapeutic effect of triptolide on HMGB1 has not been reported.

Analysis of HBV X gene quasispecies characteristics by next-generation sequencing and cloning-based sequencing and its association with hepatocellular carcinoma progression.

Objectives: This study aimed to describe the differences between next-generation sequencing (NGS) and cloning-based sequencing (CBS) in HBX quasispecies research and primitively investigate the relationship between the dominant HBX quasispecies and hepatocellular carcinoma (HCC).

Methods: A total of 12 serum samples were collected. Serum hepatitis B virus (HBV) DNA was extracted, and the HBV X-region (HBX) was amplified by nested polymerase chain reaction (PCR).

Influencing factors and health risk assessment of microcystins in the Yongjiang river (China) by Monte Carlo simulation.

The Yongjiang river is a large, shallow, hyper-trophic, freshwater river in Guangxi, China. To investigate the presence of microcystin-RR, microcystin-LR, and microcystin-YR (MC-RR, MC-LR, and MC-YR) in the Yongjiang river and describe their correlation with environmental factors, as well as, assess health risk using Monte Carlo simulation, 90 water samples were collected at three sample points from March to December 2017. Results showed that during the monitoring period, total concentrations of MC-RR (TMC-RR), MC-YR (TMC-YR), and MC-LR (TMC-LR) varied from 0.

Associations between serum HBX quasispecies and their integration in hepatocellular carcinoma.

HBV quasispecies are closely related to the course and outcome of liver disease. However, whether the complexity and diversity of HBX quasispecies affects its integration in the liver cell and thereby enhances the resultant carcinogenesis is still not clear. 15 HCC patients were recruited; genomic DNA and HBV DNA were extracted from liver cancer tissue and serum respectively.