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Emerging organophosphate flame retardants (eOPFRs) have attracted attention in recent times and are expected to gain extensive usage in the coming years. However, they may have adverse effects on organisms. Due to their novel nature, there are few relevant articles dealing with toxicological studies of the above eOPFRs, especially their information on the perturbation of cellular metabolism, which is, thus far, marginally understood. Our research initially assessed the cytotoxicity of eOPFRs, which include compounds like cresyl diphenyl phosphate (CDP), resorcinol bis(diphenyl phosphate) (RDP), triallyl phosphate (TAP), and pentaerythritol phosphate alcohol (PEPA). This evaluation was conducted using the methyl thiazolyl tetrazolium (MTT) assay. Subsequently, we utilized a gas chromatography/mass spectrometry (GC/MS)-based metabolomic approach to investigate the metabolic disruptions induced by these four eOPFRs in A549 cells. The MTT results showed that, at high concentrations of 1 mM, their cytotoxicity was ranked as CDP > TAP > RDP > PEPA. In addition, metabolic studies at low concentrations of 10 μM showed that the metabolic interference of CDP, TAP, and PEPA focuses on oxidative stress, amino acid metabolism, and energy metabolism, while RDP mainly affects energy metabolism—galactose metabolism and gluconeogenesis. Therefore, from the perspective of cytotoxicity and metabolic analysis, RDP may be a more promising alternative. Our experiments provide important insights into the possible metabolic effects of potential toxic substances and complement the evidence on the human health risks of eOPFRs. [ABSTRACT FROM AUTHOR]

High efficient nitrogen (N) application method and proper N management strategies can further reduce the losses and enhance N use efficiency. Field experiments were conducted in the 2015–2016 and 2016–2017 growing seasons to evaluate the effects of four fertigation frequencies treatments (FT-1: all the topdressing N was applied at the jointing stage; FT-2: 67% and 33% of the topdressing N was applied at the jointing and filling stages; FT-3: 33%, 50% and 17% of the topdressing N was applied at the regreening, jointing and filling stages; FT-4: 33%, 33%, 17% and 17% of the topdressing N were applied at the regreening, jointing, anthesis and filling stages) on wheat yield, water use efficiency (WUE), partial productivity of N fertilizer (PFPN) and N harvest index (NHI). In addition, one-time topdressing by surface broadcasting at the jointing stage was set up as a control (BC-1). The results showed that FT-3 and FT-4 supplied sufficient NO3−-N in the 0–40 cm soil layer, which reduced the risk of soil NO3−-N leaching to the deeper layers. FT-4 had the highest grain yield, WUE, PFPN and NHI, with average values of 9153.4 kg ha−1, 2.1 kg m−3, 0.74 kg kg−1 and 31.3 kg kg−1, respectively, followed by these values corresponding to the FT-3 in two years. These findings suggest that topdressing N split with 3–4 times, that is to say applying approximately 16.7% of topdressing N in anthesis and filling stages, respectively by the center pivot fertigation method can significantly improve yield, WUE, PFPN and NHI. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), the most common type of arthritis, is an age-associated disease, characterized by the progressive degradation of articular cartilage, synovial inflammation, and degeneration of subchondral bone. Chondrocyte proliferation is regulated by the Indian hedgehog (IHH in humans, Ihh in animals) signaling molecule, which regulates hypertrophy and endochondral ossification in the development of the skeletal system. microRNAs (miRNAs, miRs) are a family of about 22-nucleotide endogenous non-coding RNAs, which negatively regulate gene expression. In this study, the expression level of IHH was upregulated in the damaged articular cartilage tissues among OA patients and OA cell cultures, while that of miR-199a-5p was the opposite. Further investigations demonstrated that miR-199a-5p could directly regulate IHH expression and reduce chondrocyte hypertrophy and matrix degradation via the IHH signal pathway in the primary human chondrocytes. The intra-articular injection of synthetic miR-199a-5p agomir attenuated OA symptoms in rats, including the alleviation of articular cartilage destruction, subchondral bone degradation, and synovial inflammation. The miR-199a-5p agomir could also inhibit the Ihh signaling pathway in vivo. This study might help in understanding the role of miR-199a-5p in the pathophysiology and molecular mechanisms of OA and indicate a potential novel therapeutic strategy for OA patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Talpidae animals are commonly used in ecological studies due to their diverse ecotypes. In this study, by comparing the mitochondrial genomes of 14 species belonging to the family Talpidae, it is found that the variation of repeats in the control region is the main reason for the difference in the length of Talpidae mitochondrial genomes. By using the mitochondrial genome Cyt b genes of 48 species in family Talpidae as biomarkers, the phylogenetic tree of Talpidae was reconstructed. By combining the divergence time of Talpidae animals with the changes in the geological history period, it is found that the divergence of Talpidae is closely related to historically global climate changes. These results provide useful experimental data for systematic evolution of Talpidae, and also provide the basis for the study of ecological adaptability of Talpidae. Talpidae is a model group for evolutionary studies due to their highly specialized morphologies and diverse lifestyles. Mitochondrial genomes are molecular markers commonly used in species evolution and phylogenetic studies. In this study, the complete mitochondrial genome sequence of Scaptochirus moschatus was obtained by Illumina NovaSeq sequencing. The complete mitochondrial genomes of 14 Talpidae species (including Scaptochirus moschatus obtained in the present study) and the cytochrome b (Cyt b) gene sequences of 48 Talpidae species were downloaded from the NCBI database for comparison and phylogenetic studies to analyze the phylogenetic relationships and to find the possible reasons of the niche differentiation and ecotype specialization of Talpidae animals. The results showed that the mitochondrial genome sequences of 14 species belonging to the family Talpidae were 16,528 to 16,962 bp, all containing 13 protein-coding genes, 22 tRNA, two rRNA, and a non-coding region (control region). The difference in the number of repetitive repeats in the control region is responsible for the difference in the length of Talpidae mitochondrial genome sequences. Combining the divergence time of Talpidae animals with the geological history, it is found that the niche differentiation and ecotype divergence of Talpidae is closely related to historically global climate changes. Semi-aquatic groups diverged in the early Oligocene (about 31.22 MYA), probably in response to the global climate transition from warm to cool. During the early Miocene (about 19.54 MYA), some species of Talpidae moved to underground habitats and formed fossorial groups that were adept at digging due to the effects of the glaciation. In the middle Miocene (about 16.23 MYA), some Talpidae animals returned to the ground and formed semi-fossorial shrew moles as global climate warming again. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic biomarkers, or therapeutic targets. However, the exact mechanisms of lncRNAs in the regulation of OA progression remain unclear. In the present study, the lncRNA WDR11 divergent transcript (lncRNA WDR11-AS1) was shown to be downregulated in osteoarthritic cartilage tissues from patients, and to promote extracellular matrix (ECM) synthesis in osteoarthritic chondrocytes with knockdown and overexpression experiments. This function of lncRNA WDR11-AS1 was linked to its ability to interact with the polyadenylate-binding protein cytoplasmic 1 (PABPC1), which was screened by RNA pulldown and mass spectrometry analyses. PABPC1 was discovered to bind ECM-related mRNAs such as SOX9, and the inhibition of PABPC1 improved the mRNA stability of SOX9 to mitigate OA progression. Our results suggest that lncRNA WDR11-AS1 has a promising inhibitory effect on inflammation-induced ECM degradation in OA by directly binding PABPC1, thereby establishing lncRNA WDR11-AS1 and PABPC1 as potential therapeutic targets in the treatment of OA. [ABSTRACT FROM AUTHOR]

Autophagy is a complex process of degradation of senescent or dysfunctional organelles in cells. Dysfunctional autophagy is associated with many diseases such as cancers, immune dysfunction, and aging. Hydrogen sulfide (H2S) is considered to be the third gas signal molecule after nitrous oxide and carbon monoxide. In recent years, H2S has been found to have a variety of important biological functions, and plays an important role in a variety of physiological and pathological processes. In this review, we review the recent role and mechanism of H2S in regulating autophagy in liver disorders, in order to provide a basis for further research in the future. [ABSTRACT FROM AUTHOR]

Flubendazole, belonging to benzimidazole, is a broad-spectrum insect repellent and has been repurposed as a promising anticancer drug. In recent years, many studies have shown that flubendazole plays an anti-tumor role in different types of cancers, including breast cancer, melanoma, prostate cancer, colorectal cancer, and lung cancer. Although the anti-tumor mechanism of flubendazole has been studied, it has not been fully understood. In this review, we summarized the recent studies regarding the anti-tumor effects of flubendazole in different types of cancers and analyzed the related mechanisms, in order to provide the theoretical reference for further studies in the future. [ABSTRACT FROM AUTHOR]

Since the discovery of protein arginine methyltransferase 5 (PRMT5) and the resolution of its structure, an increasing number of papers have investigated and delineated the structural and functional role of PRMT5 in diseased conditions. PRMT5 is a type II arginine methyltransferase that catalyzes symmetric dimethylation marks on histones and non-histone proteins. From gene regulation to human development, PRMT5 is involved in many vital biological functions in humans. The role of PRMT5 in various cancers is particularly well-documented, and investigations into the development of better PRMT5 inhibitors to promote tumor regression are ongoing. Notably, emerging studies have demonstrated the pathological contribution of PRMT5 in the progression of inflammatory diseases, such as diabetes, cardiovascular diseases, and neurodegenerative disorders. However, more research in this direction is needed. Herein, we critically review the position of PRMT5 in current literature, including its structure, mechanism of action, regulation, physiological and pathological relevance, and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Over the last several decades, colorectal cancer (CRC) has been one of the most prevalent cancers. While significant progress has been made in both diagnostic screening and therapeutic approaches, a large knowledge gap still remains regarding the early identification and treatment of CRC. Specifically, identification of CRC biomarkers that can help with the creation of targeted therapies as well as increasing the ability for clinicians to predict the biological response of a patient to therapeutics, is of particular importance. This review provides an overview of CRC and its progression stages, as well as the basic types of CRC biomarkers. We then lay out the synopsis of signaling pathways related to CRC, and further highlight the pivotal and multifaceted role of nuclear factor (NF) κB signaling in CRC. Particularly, we bring forth knowledge regarding the tumor microenvironment (TME) in CRC, and its complex interaction with cancer cells. We also provide examples of NF-κB signaling-related CRC biomarkers, and ongoing efforts made at targeting NF-κB signaling in CRC treatment. We conclude and anticipate that with more emerging novel regulators of the NF-κB pathway being discovered, together with their in-depth characterization and the integration of large groups of genomic, transcriptomic and proteomic data, the day of successful development of more ideal NF-κB inhibitors is fast approaching. [ABSTRACT FROM AUTHOR]

The nuclear factor kappa B (NF-κB) is a ubiquitous transcription factor central to inflammation and various malignant diseases in humans. The regulation of NF-κB can be influenced by a myriad of post-translational modifications (PTMs), including phosphorylation, one of the most popular PTM formats in NF-κB signaling. The regulation by phosphorylation modification is not limited to NF-κB subunits, but it also encompasses the diverse regulators of NF-κB signaling. The differential site-specific phosphorylation of NF-κB itself or some NF-κB regulators can result in dysregulated NF-κB signaling, often culminating in events that induce cancer progression and other hyper NF-κB related diseases, such as inflammation, cardiovascular diseases, diabetes, as well as neurodegenerative diseases, etc. In this review, we discuss the regulatory role of phosphorylation in NF-κB signaling and the mechanisms through which they aid cancer progression. Additionally, we highlight some of the known and novel NF-κB regulators that are frequently subjected to phosphorylation. Finally, we provide some future perspectives in terms of drug development to target kinases that regulate NF-κB signaling for cancer therapeutic purposes. [ABSTRACT FROM AUTHOR]

Scarce water resources limit protected vegetable production in North China. Implementing efficient water-saving techniques is crucial for maintaining protected vegetable production and sustainability. A two-growing season field experiment was conducted in a glass greenhouse to explore the effects of water-saving techniques with irrigation scheduling based on soil water content on the growth and quality of pakchoi and the fate of irrigation water. Three water-saving techniques were investigated: micro-irrigation (M-0), furrow irrigation with plastic mulch (F-P), and micro-irrigation with plastic mulch (M-P) compared to furrow irrigation (F-0). F-P and M-P treatments enhanced pakchoi growth and primarily increased the total root length of the root system (0–0.2 m) compared to F-0. The two treatments further induced an improvement of pakchoi quality. Compared to M-0, F-P and M-P treatments showed better performance in reducing evaporation by 57–70% and proportion of evaporation in evapotranspiration, and consequently exhibited more pronounced effects on water saving. Irrigation water use efficiency (IWUE) was improved in F-P by 50% in both seasons and was improved in M-P by 84 and 95% in spring season and autumn season, respectively. Combining irrigation scheduling based on soil water content with plastic mulch is a feasible way to improve IWUE in protected vegetable production by reducing water consumption and enhancing crop growth. [ABSTRACT FROM AUTHOR]

The overexpression of PRMT5 is highly correlated to poor clinical outcomes for colorectal cancer (CRC) patients. Importantly, our previous work demonstrated that PRMT5 overexpression could substantially augment activation of the nuclear factor kappa B (NF-κB) via methylation of arginine 30 (R30) on its p65 subunit, while knockdown of PRMT5 showed the opposite effect. However, the precise mechanisms governing this PRMT5/NF-κB axis are still largely unknown. Here, we report a novel finding that PRMT5 is phosphorylated on serine 15 (S15) in response to interleukin-1β (IL-1β) stimulation. Interestingly, we identified for the first time that the oncogenic kinase, PKCι could catalyze this phosphorylation event. Overexpression of the serine-to-alanine mutant of PRMT5 (S15A), in either HEK293 cells or CRC cells HT29, DLD1, and HCT116 attenuated NF-κB transactivation compared to WT-PRMT5, confirming that S15 phosphorylation is critical for the activation of NF-κB by PRMT5. Furthermore, the S15A mutant when compared to WT-PRMT5, could downregulate a subset of IL-1β-inducible NF-κB-target genes which correlated with attenuated promoter occupancy of p65 at its target genes. Additionally, the S15A mutant reduced IL-1β-induced methyltransferase activity of PRMT5 and disrupted the interaction of PRMT5 with p65. Furthermore, our data indicate that blockade of PKCι-regulated PRMT5-mediated activation of NF-κB was likely through phosphorylation of PRMT5 at S15. Finally, inhibition of PKCι or overexpression of the S15A mutant attenuated the growth, migratory, and colony-forming abilities of CRC cells compared to the WT-PRMT5. Collectively, we have identified a novel PKCι/PRMT5/NF-κB signaling axis, suggesting that pharmacological disruption of this pivotal axis could serve as the basis for new anti-cancer therapeutics. [ABSTRACT FROM AUTHOR]

The nuclear factor kappa B (NF-κB) is a ubiquitous transcription factor central to inflammation and various malignant diseases in humans. The regulation of NF-κB can be influenced by a myriad of post-translational modifications (PTMs), including phosphorylation, one of the most popular PTM formats in NF-κB signaling. The regulation by phosphorylation modification is not limited to NF-κB subunits, but it also encompasses the diverse regulators of NF-κB signaling. The differential site-specific phosphorylation of NF-κB itself or some NF-κB regulators can result in dysregulated NF-κB signaling, often culminating in events that induce cancer progression and other hyper NF-κB related diseases, such as inflammation, cardiovascular diseases, diabetes, as well as neurodegenerative diseases, etc. In this review, we discuss the regulatory role of phosphorylation in NF-κB signaling and the mechanisms through which they aid cancer progression. Additionally, we highlight some of the known and novel NF-κB regulators that are frequently subjected to phosphorylation. Finally, we provide some future perspectives in terms of drug development to target kinases that regulate NF-κB signaling for cancer therapeutic purposes.