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Background Continual expression of PD-L1 in tumor cells is critical for tumor immune escape and host T cell exhaustion, however, knowledge on its clinical benefits through inhibition is limited in breast cancer. N 6 -methyladenosine (m 6 A) plays a crucial role in multiple biological activities. Our study aimed to investigate the regulatory role of the m 6 A modification in PD-L1 expression and immune surveillance in breast cancer. Methods MeRIP-seq and epitranscriptomic microarray identified that PD-L1 is the downstream target of METTL3. MeRIP-qPCR, absolute quantification of m 6 A modification assay, and RIP-qPCR were used to examine the molecular mechanism underlying METTL3/m 6 A/IGF2BP3 signaling axis in PD-L1 expression. B-NDG and BALB/c mice were used to construct xenograft tumor models to verify the phenotypes upon METTL3 and IGF2BP3 silencing. In addition, breast cancer tissue microarray was used to analyze the correlation between PD-L1 and METTL3 or IGF2BP3 expression. Results We identified that PD-L1 was a downstream target of METTL3-mediated m 6 A modification in breast cancer cells. METTL3 knockdown significantly abolished m 6 A modification and reduced stabilization of PD-L1 mRNA. Additionally, METTL3-mediated PD-L1 mRNA activation was m 6 A-IGF2BP3-dependent. Moreover, inhibition of METTL3 or IGF2BP3 enhanced anti-tumor immunity through PD-L1-mediated T cell activation, exhaustion, and infiltration both in vitro and in vivo. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues. Conclusion Our study suggested that METTL3 could post-transcriptionally upregulate PD-L1 expression in an m 6 A-IGF2BP3-dependent manner to further promote stabilization of PD-L1 mRNA, which may have important implications for new and efficient therapeutic strategies in the tumor immunotherapy.

Ferroptosis is a newly defined programmed cell death process with the hallmark of the accumulation of iron‐dependent lipid peroxides. The term was first coined in 2012 by the Stockwell Lab, who described a unique type of cell death induced by the small molecules erastin or RSL3. Ferroptosis is distinct from other already established programmed cell death and has unique morphological and bioenergetic features. The physiological role of ferroptosis during development has not been well characterized. However, ferroptosis shows great potentials during the cancer therapy. Great progress has been made in exploring the mechanisms of ferroptosis. In this review, we focus on the molecular mechanisms of ferroptosis, the small molecules functioning in ferroptosis initiation and ferroptosis sensitivity in different cancers. We are also concerned with the new arising questions in this particular research area that remains unanswered.

Immune checkpoints play important roles in immune regulation, and blocking immune checkpoints on the cell membrane is a promising strategy in the treatment of cancer. Based on this, monoclonal antibodies are having much rapid development, such as those against CTLA-4 (cytotoxic T lymphocyte antigen 4) and PD-1 (programmed cell death protein 1).But the cost of preparation of monoclonal antibodies is too high and the therapeutic effect is still under restrictions. Recently, a series of soluble immune checkpoints have been found such as sCTLA-4 (soluble CTLA-4) and sPD-1 (soluble PD-1). They are functional parts of membrane immune checkpoints produced in different ways and can be secreted by immune cells. Moreover, these soluble checkpoints can diffuse in the serum. Much evidence has demonstrated that these soluble checkpoints are involved in positive or negative immune regulation and that changes in their plasma levels affect the development, prognosis and treatment of cancer. Since they are endogenous molecules, they will not induce immunological rejection in human beings, which might make up for the deficiencies of monoclonal antibodies and enhance the utility value of these molecules. Therefore, there is an increasing need for investigating novel soluble checkpoints and their functions, and it is promising to develop relevant therapies in the future. In this review, we describe the production mechanisms and functions of various soluble immune checkpoint receptors and ligands and discuss their biological significance in regard to biomarkers, potential candidate drugs, therapeutic targets, and other topics.

This study contributes to the field of sustainability by analyzing changes in firms following the adoption of new environmental protection laws to meet community sustainability needs. Focusing on the Chinese context, it examined the relationship between firms' environmental protection measures (i.e., corporate green behavior) and profitability (i.e., corporate tax avoidance). The moderating roles of environmental uncertainty and digital technology application in this relationship were also investigated. The findings offer insights into the complex dynamics linking firms’ environmental initiatives to their business outcomes and financial decisions within the framework of a sustainable community. Ultimately, this study highlights the importance and implications of sustainable practices for both the environment and corporate financial performance. Firms’ environmental behaviors are enablers of sustainable communities by deploying natural resources and creating a more resilient economy through active community participation in green production models.

FOXO3a is a member of the FOXO subfamily of forkhead transcription factors that mediate a variety of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage and tumorigenesis. It also responds to several cellular stresses such as UV irradiation and oxidative stress. The function of FOXO3a is regulated by a complex network of processes, including post-transcriptional suppression by microRNAs (miRNAs), post-translational modifications (PTMs) and protein–protein interactions. FOXO3a is widely implicated in a variety of diseases, particularly in malignancy of breast, liver, colon, prostate, bladder, and nasopharyngeal cancers. Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. In experimental studies, overexpression of FOXO3a inhibits the proliferation, tumorigenic potential, and invasiveness of cancer cells, while silencing of FOXO3a results in marked attenuation in protection against tumorigenesis. The role of FOXO3a in both normal physiology as well as in cancer development have presented a great challenge to formulating an effective therapeutic strategy for cancer. In this review, we summarize the recent findings and overview of the current understanding of the influence of FOXO3a in cancer development and progression.

Transcription factor 21 (TCF21) is a member of the basic helix-loop-helix (bHLH) transcription factors that mediate cell fate and differentiation by orchestrating temporal and spatial gene expression during the development of various organs. It plays a crucial role in a wide spectrum of biological processes, including organogenesis, epithelial-mesenchymal transition (EMT), cell cycle, autophagy, proliferation, differentiation, specification, maturation, and survival of cells, as well as invasion and metastasis of cancer cells. Controlled expression and activity of TCF21 provide a balanced transcriptional program that guarantees appropriate growth and maturation during embryogenesis and organ development. Its dysregulation is closely correlated with a variety of diseases, including cancer. Its function is mainly regulated by non-coding RNAs (ncRNAs), post-translational modifications (PTMs), and protein–protein interactions. However, the exact mechanisms of TCF21 dysregulation in disease progression are still elusive. This review summarizes the regulatory mechanisms of TCF21 expression and activity and highlights its critical role in health and disease. This information may contribute to the development of better diagnostics and treatments for cancer and other developmental diseases.

Global warming is one of the greatest threats to the social development of human beings. It is a typical example of global climate change, and has profoundly affected human production and life in various aspects. As the foundation of human existence, agricultural production is particularly vulnerable to climate change, which has altered environmental factors such as temperature, precipitation, and wind speed, and affected crop growth cycles, the frequency of extreme weather events, and the occurrence patterns of pests and diseases directly or indirectly, ultimately influencing crop yield and quality. This article reviews the latest research progress in this field, summarizes the impact of global climate change on agricultural production as well as the feedback mechanisms of agricultural activities on climate change, and proposes strategies for agricultural production to cope with global climate change. This paper aims to provide a scientific basis and suggestions for ensuring the sustainable development of agricultural production.

Cancer is a leading disease-related cause of death worldwide. Despite advances in therapeutic interventions, cancer remains a major global public health problem. Cancer pathogenesis is extremely intricate and largely unknown. Fas-associated protein with death domain (FADD) was initially identified as an adaptor protein for death receptor-mediated extrinsic apoptosis. Recent evidence suggests that FADD plays a vital role in non-apoptotic cellular processes, such as proliferation, autophagy, and necroptosis. FADD expression and activity of are modulated by a complicated network of processes, such as DNA methylation, non-coding RNA, and post-translational modification. FADD dysregulation has been shown to be closely associated with the pathogenesis of numerous types of cancer. However, the detailed mechanisms of FADD dysregulation involved in cancer progression are still not fully understood. This review mainly summarizes recent findings on the structure, functions, and regulatory mechanisms of FADD and focuses on its role in cancer progression. The clinical implications of FADD as a biomarker and therapeutic target for cancer patients are also discussed. The information reviewed herein may expand researchers’ understanding of FADD and contribute to the development of FADD-based therapeutic strategies for cancer patients.

To investigate the effects of nano selenium (nano-Se), curcumin (CUR), and glycyrrhiza extracts (GE) on reproductive performance, antioxidant and immune functions of primiparous sows and parity-2 sows, 54 primiparous sows (Landrace × Yorkshire) were randomly divided into three groups (18 sows per group): (1) CON group, basal diet (0.30 mg·kg −1 Se, sodium selenite); (2) CUR group, basal diet + 0.20 mg·kg −1 Se (nano-Se) + 300 mg·kg −1 CUR; (3) GE group, basal diet + 0.20 mg·kg −1 Se (nano-Se) + 500 mg·kg −1 GE. The trial lasted for approximately 180 days from day 90 of gestation of primiparous sows to parity-2 sows. There were no significant differences in reproductive performance among three groups ( p  > 0.05), but the litter weight gain of piglets from primiparous sows in the GE group was 16.49% higher than that in the CON group ( p  < 0.05). Compared with the CON group, the serum SOD and GSH-Px levels of primiparous sows in the GE group were significantly increased, and the MDA content was extremely decreased. The concentrations of serum IL-6 and IL-1β ( p  < 0.05) of primiparous sows in the GE group were significantly lower than those in the CON group, and the serum IL-10 and TNF-α concentrations ( p  < 0.05) was significantly higher. The combination of nano-Se and CUR decreased the serum IL-1β level and increased the TNF-α concentration ( p  < 0.05). In conclusion, the addition of nano-Se along with CUR or GE in the diet of primiparous sows significantly increased the antioxidant and immune levels in the serum of primiparous sows at parturition, enhanced their stress resistance, and thus improved growth performance of offspring piglets and reproductive performance of parity-2 sows.

HighlightsNoble metals (Pt, Au) decorated Sr-incorporated g-C3N4 photocatalysts are fabricated via facile calcination and photo-deposition methods.The optical absorption and charge separation properties of the photocatalysts are remarkably improved and the Pt/0.15Sr-CN photocatalyst exhibited excellent activity for CO2 conversion.A quantum efficiency of 2.92% is predicted for CO2 reduction over the Pt/0.15Sr-CN photocatalyst at 420 nm wavelength, which is accredited to the improved optical absorption and enhanced charge separation via Sr-incorporation and the surface plasmon resonance effect of noble metal nanoparticles.The photocatalytic performance of g-C3N4 for CO2 conversion is still inadequate by several shortfalls including the instability, insufficient solar light absorption and rapid charge carrier’s recombination rate. To solve these problems, herein, noble metals (Pt and Au) decorated Sr-incorporated g-C3N4 photocatalysts are fabricated via the simple calcination and photo-deposition methods. The Sr-incorporation remarkably reduced the g-C3N4 band gap from 2.7 to 2.54 eV, as evidenced by the UV–visible absorption spectra and the density functional theory results. The CO2 conversion performance of the catalysts was evaluated under visible light irradiation. The Pt/0.15Sr-CN sample produced 48.55 and 74.54 µmol h−1 g−1 of CH4 and CO, respectively. These amounts are far greater than that produced by the Au/0.15Sr-CN, 0.15Sr-CN, and CN samples. A high quantum efficiency of 2.92% is predicted for the Pt/0.15Sr-CN sample. Further, the stability of the photocatalyst is confirmed via the photocatalytic recyclable test. The improved CO2 conversion performance of the catalyst is accredited to the promoted light absorption and remarkably enhanced charge separation via the Sr-incorporated mid gap states and the localized surface plasmon resonance effect induced by noble metal nanoparticles. This work will provide a new approach for promoting the catalytic efficiency of g-C3N4 for efficient solar fuel production.