Targeting METTL3 as a checkpoint to enhance T cells for tumour immunotherapy.

Background: Immunotherapy has emerged as a crucial treatment modality for solid tumours, yet tumours often evade immune surveillance. There is an imperative to uncover novel immune regulators that can boost tumour immunogenicity and increase the efficacy of immune checkpoint blockade (ICB) therapy. Epigenetic regulators play critical roles in tumour microenvironment remodelling, and N6-methyladenosine (mA) is known to be involved in tumourigenesis.

Intellectual property protection as catalyst for radical technological innovation in national research program teams through innovation milieu and group potentials.

Based on the innovation-driven theory and the ability-motivation-opportunity (AMO) perspective, we explore the role of intellectual property protection (IPP) in enhancing the radical technological innovation (RTI) of national research project teams (NRPT). Survey data from 336 national research project team members from universities and enterprises were used to analyze the theoretical model of this study, bringing in the chain-mediated effects of innovation milieu (IM) and group potential (GP) for analysis, as well as two-stage hybrid partial least squares structural equation modeling (PLS-SEM) and artificial neural network techniques (ANN) to evaluate the hypotheses. The empirical findings of this paper show that the strength of IPP has a positive relationship with RTI of NRPT, and that IPP is the most important predictor of this.

Wounding induces a peroxisomal H O decrease via glycolate oxidase-catalase switch dependent on glutamate receptor-like channel-supported Ca signaling in plants.

Sensing of environmental challenges, such as mechanical injury, by a single plant tissue results in the activation of systemic signaling, which attunes the plant's physiology and morphology for better survival and reproduction. As key signals, both calcium ions (Ca ) and hydrogen peroxide (H O ) interplay with each other to mediate plant systemic signaling. However, the mechanisms underlying Ca -H O crosstalk are not fully revealed.

Transposable elements activation triggers necroptosis in mouse embryonic stem cells.

Deficiency of the histone H3K9 methyltransferase SETDB1 induces RIPK3-dependent necroptosis in mouse embryonic stem cells (mESCs). However, how necroptosis pathway is activated in this process remains elusive. Here we report that the reactivation of transposable elements (TEs) upon SETDB1 knockout is responsible for the RIPK3 regulation through both cis and trans mechanisms.

Dynamic and fluctuating generation of hydrogen peroxide via photorespiratory metabolic channeling in plants.

The homeostasis of hydrogen peroxide (H O ), a key regulator of basic biological processes, is a result of the cooperation between its generation and scavenging. However, the mechanistic basis of this balance is not fully understood. We previously proposed that the interaction between glycolate oxidase (GLO) and catalase (CAT) may serve as a molecular switch that modulates H O levels in plants.

Inhibition of BMI-1 Induces Apoptosis through Downregulation of DUB3-Mediated Mcl-1 Stabilization.

BMI-1, a polycomb ring finger oncogene, is highly expressed in multiple cancer cells and is involved in cancer cell proliferation, invasion, and apoptosis. BMI-1 represents a cancer stemness marker that is associated with the regulation of stem cell self-renewal. In this study, pharmacological inhibition (PTC596) or knockdown (siRNA) of BMI-1 reduced cancer stem-like cells and enhanced cancer cell death.

The RNA mA reader YTHDC1 silences retrotransposons and guards ES cell identity.

The RNA modification N-methyladenosine (mA) has critical roles in many biological processes. However, the function of mA in the early phase of mammalian development remains poorly understood. Here we show that the mA reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required for the maintenance of mouse embryonic stem (ES) cells in an mA-dependent manner, and that its deletion initiates cellular reprogramming to a 2C-like state.

YTHDF2/3 Are Required for Somatic Reprogramming through Different RNA Deadenylation Pathways.

N-methyladenosine (mA), the most abundant reversible modification on eukaryote messenger RNA, is recognized by a series of readers, including the YT521-B homology domain family (YTHDF) proteins, which are coupled to perform physiological functions. Here, we report that YTHDF2 and YTHDF3, but not YTHDF1, are required for reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). Mechanistically, we found that YTHDF3 recruits the PAN2-PAN3 deadenylase complex and conduces to reprogramming by promoting mRNA clearance of somatic genes, including Tead2 and Tgfb1, which parallels the activity of the YTHDF2-CCR4-NOT deadenylase complex.

The Histone Lysine-specific Demethylase 1 Inhibitor, SP2509 Exerts Cytotoxic Effects against Renal Cancer Cells through Downregulation of Bcl-2 and Mcl-1.

Lysine-specific histone demethylase 1 (LSD1), also known as KDM1A, can remove the methyl group from lysine 4 and 9 at histone H3, which regulates transcriptional suppression and activation. Recently, high expression of LSD1 in tumors has been shown to be involved in cancer cell proliferation, metastasis, and poor prognosis. We found that SP2509, a potent and reversible inhibitor of LSD1, induced apoptosis in human renal carcinoma (Caki and ACHN) and glioma (U87MG) cells.

BMP4 resets mouse epiblast stem cells to naive pluripotency through ZBTB7A/B-mediated chromatin remodelling.

BMP4 regulates a plethora of developmental processes, including the dorsal-ventral axis and neural patterning. Here, we report that BMP4 reconfigures the nuclear architecture during the primed-to-naive transition (PNT). We first established a BMP4-driven PNT and show that BMP4 orchestrates the chromatin accessibility dynamics during PNT.

SETDB1-Mediated Cell Fate Transition between 2C-Like and Pluripotent States.

Known as a histone H3K9 methyltransferase, SETDB1 is essential for embryonic development and pluripotent inner cell mass (ICM) establishment. However, its function in pluripotency regulation remains elusive. In this study, we find that under the "ground state" of pluripotency with two inhibitors (2i) of the MEK and GSK3 pathways, Setdb1-knockout fails to induce trophectoderm (TE) differentiation as in serum/LIF (SL), indicating that TE fate restriction is not the direct target of SETDB1.

Dissipation behavior, residue distribution and risk assessment of three fungicides in pears.

Background: Fungicides are often applied to pears before they are kept in storage facilities. The scientific application of pesticides can reduce unnecessary exposure, which in turn could benefit both humans and the environment.

Results: We investigated dissipation behavior and residue distribution, and conducted risk assessments for prochloraz, pyraclostrobin, and tebuconazole in pears stored under different conditions using ultra-performance liquid chromatography (UPLC).

Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq.

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs), which is a highly heterogeneous process. Here we report the cell fate continuum during somatic cell reprogramming at single-cell resolution. We first develop SOT to analyze cell fate continuum from Oct4/Sox2/Klf4- or OSK-mediated reprogramming and show that cells bifurcate into two categories, reprogramming potential (RP) or non-reprogramming (NR).

Transposable elements are regulated by context-specific patterns of chromatin marks in mouse embryonic stem cells.

The majority of mammalian genomes are devoted to transposable elements (TEs). Whilst TEs are increasingly recognized for their important biological functions, they are a potential danger to genomic stability and are carefully regulated by the epigenetic system. However, the full complexity of this regulatory system is not understood.

N-oxide reduction of quinoxaline-1,4-dioxides catalyzed by porcine aldehyde oxidase SsAOX1.

Quinoxaline-1,4-dioxides (QdNOs) are a class of quinoxaline derivatives that are widely used in humans or animals as drugs or feed additives. However, the metabolic mechanism, especially the involved enzymes, has not been reported in detail. In this study, the N-oxide reduction enzyme, porcine aldehyde oxidase SsAOX1 was identified and characterized.

Proteomic changes in chicken primary hepatocytes exposed to T-2 toxin are associated with oxidative stress and mitochondrial enhancement.

T-2 toxin is a mycotoxin that is toxic to plants, animals, and humans. However, its molecular mechanism remains unclear, especially in chickens. In this study, using 2D electrophoresis with MALDI-TOF/TOF-MS, 53 proteins were identified as up- or downregulated by T-2 toxin in chicken primary hepatocytes.