The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.

Objective: To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis.

Design: Multicentre, double blinded, placebo controlled phase 3 trial.

Setting: 22 centres in China, September 2016 to December 2020.

Multi-stain deep learning prediction model of treatment response in lupus nephritis based on renal histopathology.

The response of the kidney after induction treatment is one of the determinants of prognosis in lupus nephritis, but effective predictive tools are lacking. Here, we sought to apply deep learning approaches on kidney biopsies for treatment response prediction in lupus nephritis. Patients who received cyclophosphamide or mycophenolate mofetil as induction treatment were included and the primary outcome was 12-month treatment response, complete response defined as 24h urinary protein under 0.

A histopathology-based artificial intelligence system assisting the screening of genetic alteration in intrahepatic cholangiocarcinoma.

Background: Targeted therapy for intrahepatic cholangiocarcinoma (ICC) shows superior survival outcomes but patients with certain targetable alterations are no more than 20%. Genetic alteration screening for all ICC patients is of high cost and not routinely performed. This study intends to develop a histopathology-based artificial intelligence (AI)-assisted system for predicting genetic alteration of ICC.

Generation of terahertz beam with longitudinally varied polarization state via coherent superposition based on metasurface.

Polarization is an important dimension in the research and applications of light waves. However, traditional polarization optics often only focus on the polarization characteristics in the transverse plane. Here, we demonstrate a new scheme for the generation of longitudinally varied polarization state in terahertz beam using all-silicon metasurface.

The neurotransmitter calcitonin gene-related peptide shapes an immunosuppressive microenvironment in medullary thyroid cancer.

Neurotransmitters are key modulators in neuro-immune circuits and have been linked to tumor progression. Medullary thyroid cancer (MTC), an aggressive neuroendocrine tumor, expresses neurotransmitter calcitonin gene-related peptide (CGRP), is insensitive to chemo- and radiotherapies, and the effectiveness of immunotherapies remains unknown. Thus, a comprehensive analysis of the tumor microenvironment would facilitate effective therapies and provide evidence on CGRP's function outside the nervous system.

FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma.

Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer and is highly lethal. Clonorchis sinensis (C. sinensis) infection is an important risk factor for iCCA.

A Subpopulation of Luminal Progenitors Secretes Pleiotrophin to Promote Angiogenesis and Metastasis in Inflammatory Breast Cancer.

Unlabelled: Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in patients with IBC, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors.

Th17 Cells Secrete TWEAK to Trigger Epithelial-Mesenchymal Transition and Promote Colorectal Cancer Liver Metastasis.

Unlabelled: Liver metastasis is the leading cause of mortality in patients with colorectal cancer. Given the significance of both epithelial-mesenchymal transition (EMT) of tumor cells and the immune microenvironment in colorectal cancer liver metastasis (CRLM), the interplay between them could hold the key for developing improved treatment options. We employed multiomics analysis of 130 samples from 18 patients with synchronous CRLM integrated with external datasets to comprehensively evaluate the interaction between immune cells and EMT of tumor cells in liver metastasis.

Single-cell profiling reveals kidney CD163 dendritic cell participation in human lupus nephritis.

Objectives: The current work aimed to provide a comprehensive single-cell landscape of lupus nephritis (LN) kidneys, including immune and non-immune cells, identify disease-associated cell populations and unravel their participation within the kidney microenvironment.

Methods: Single-cell RNA and T cell receptor sequencing were performed on renal biopsy tissues from 40 patients with LN and 6 healthy donors as controls. Matched peripheral blood samples from seven LN patients were also sequenced.

Predicting 5-year recurrence risk in colorectal cancer: development and validation of a histology-based deep learning approach.

Background: Accurate estimation of the long-term risk of recurrence in patients with non-metastatic colorectal cancer (CRC) is crucial for clinical management. Histology-based deep learning is expected to provide more abundant information for risk stratification.

Methods: We developed and validated a weakly supervised deep-learning model for predicting 5-year relapse-free survival (RFS) to stratify patients with different risks based on histological images from three hospitals of 614 cases with non-metastatic CRC.

N6-Methyladenosine Reader YTHDF1 Promotes Stemness and Therapeutic Resistance in Hepatocellular Carcinoma by Enhancing NOTCH1 Expression.

Unlabelled: N6-methyladenosine (m6A) RNA modification is the most common and conserved epigenetic modification in mRNA and has been shown to play important roles in cancer biology. As the m6A reader YTHDF1 has been reported to promote progression of hepatocellular carcinoma (HCC), it represents a potential therapeutic target. In this study, we evaluated the clinical significance of YTHDF1 using human HCC samples and found that YTHDF1 was significantly upregulated in HCCs with high stemness scores and was positively associated with recurrence and poor prognosis.

Predicting T Cell-Inflamed Gene Expression Profile in Hepatocellular Carcinoma Based on Dynamic Contrast-Enhanced Ultrasound Radiomics.

Purpose: The T cell-inflamed gene expression profile (GEP) quantifies 18 genes' expression indicative of a T-cell immune tumor microenvironment, playing a crucial role in the immunotherapy of hepatocellular carcinoma (HCC). Our study aims to develop a radiomics-based machine learning model using contrast-enhanced ultrasound (CEUS) for predicting T cell-inflamed GEP in HCC.

Methods: The primary cohort of HCC patients with preoperative CEUS and RNA sequencing data of tumor tissues at the single center was used to construct the model.

Organic management increases beneficial microorganisms and promotes the stability of microecological networks in tea plantation soil.

Introduction: Organic agriculture is highly regarded by people for its commitment to health, ecology, care, and fairness. The soil microbial community responds quickly to environmental changes and is a good indicator for evaluating soil microecology. Therefore, from the perspective of soil microbial communities, elucidating the impact of organic management on soil microecology in tea plantations has great significance for improving local tea plantation systems.

Dual channel transformation of scalar and vector terahertz beams along the optical path based on dielectric metasurface.

The research on terahertz wave manipulation based on metasurfaces has gradually deepened, and the number of functions or electromagnetic control dimensions in a single device is constantly increasing. For the spatial dimension of terahertz field regulation, its design degrees of freedom have been expanded from a single transverse plane to the propagation path. In this paper, we propose a novel circularly polarization multiplexed metasurface for dual channel terahertz wave transmission control.

METTL5-mediated 18S rRNA mA modification promotes oncogenic mRNA translation and intrahepatic cholangiocarcinoma progression.

Intrahepatic cholangiocarcinoma (ICC) is a deadly cancer with rapid tumor progression. While hyperactive mRNA translation caused by mis-regulated mRNA or tRNA modifications promotes ICC development, the role of rRNA modifications remains elusive. Here, we found that 18S rRNA mA modification and its methyltransferase METTL5 were aberrantly upregulated in ICC and associated with poorer survival (log rank test, p < 0.

Spatial proteomics of immune microenvironment in nonalcoholic steatohepatitis-associated hepatocellular carcinoma.

Background And Aims: NASH-HCC is inherently resistant to immune checkpoint blockade, but its tumor immune microenvironment is largely unknown.

Approach And Results: We applied the imaging mass cytometry to construct a spatially resolved single-cell atlas from the formalin-fixed and paraffin-embedded tissue sections from patients with NASH-HCC, virus-HCC (HBV-HCC and HCV-HCC), and healthy donors. Based on 35 biomarkers, over 750,000 individual cells were categorized into 13 distinct cell types, together with the expression of key immune functional markers.

Hypoxia-driven tumor stromal remodeling and immunosuppressive microenvironment in scirrhous HCC.

Background And Aims: Scirrhous HCC (SHCC) is one of the unique subtypes of HCC, characterized by abundant fibrous stroma in the tumor microenvironment. However, the molecular traits of SHCC remain unclear, which is essential to develop specialized therapeutic approaches for SHCC.

Approach And Results: We presented an integrative analysis containing single-cell RNA-sequencing, whole-exome sequencing, and bulk RNA-sequencing in SHCC and usual HCC samples from 134 patients to delineate genomic features, transcriptomic profiles, and stromal immune microenvironment of SHCC.

P-doping boosting electronic properties and ionic kinetics of MnVO for high-performance lithium-ion batteries.

Vanadate electrodes are potential candidates for lithium-ion batteries (LIBs) due to their large theoretical specific capacity. However, their practical application suffers from limitations of poor conductivity, inferior ion kinetics, and severe volume changes upon cycling. Herein, a doping strategy is realized to prepare phosphorus (P)-doped MnVO (PMVO) nanosheets to enhance the electrochemical activity and structural stability.

Mechanical confinement promotes heat resistance of hepatocellular carcinoma via SP1/IL4I1/AHR axis.

Mechanical stress can modulate the fate of cells in both physiological and extreme conditions. Recurrence of tumors after thermal ablation, a radical therapy for many cancers, indicates that some tumor cells can endure temperatures far beyond physiological ones. This unusual heat resistance with unknown mechanisms remains a key obstacle to fully realizing the clinical potential of thermal ablation.

A TGF-β-dominant chemoresistant phenotype of hepatoblastoma associated with aflatoxin exposure in children.

Background And Aims: Hepatoblastoma (HB) is the most common liver cancer in children, posing a serious threat to children's health. Chemoresistance is the leading cause of mortality in patients with HB. A more explicit definition of the features of chemotherapy resistance in HB represents a fundamental urgent need.

Identification and validation of a plasma metabolomics-based model for risk stratification of intrahepatic cholangiocarcinoma.

Background: Liver resection is the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC) while the postoperative prognosis varies greatly, with no recognized biomarker. We aimed to identify the plasma metabolomic biomarkers that could be used for preoperative risk stratification of ICC patients.

Methods: 108 eligible ICC patients who underwent radical surgical resection between August 2012 and October 2020 were enrolled.

Knowledge domain and research progress in the field of crop rotation from 2000 to 2020: a scientometric review.

As one of the most fundamental and prevalent agronomic practices, crop rotation is of great significance for the optimization of regional planting structure and sustainable agricultural development. Therefore, crop rotation has attracted continuous attention from both researchers and producers worldwide. In recent years, many review articles have been published in the field of crop rotation.

Effect of inactivated COVID-19 vaccine on the negative conversion of nucleic acid in asymptomatic or mild patients with COVID-19.

Background: Negative conversion of nucleic acid was a key factor in deciding discharge or the end of isolation of asymptomatic or mild COVID-19 patients. We aimed to explore the effect of vaccination on the time to negative conversion after Omicron infection.

Methods: This retrospective cohort study included asymptomatic or mild patients with COVID-19 admitted to Fangcang shelter Hospital from November 10, 2022 to December 2, 2022.