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Human coronaviruses are a group of pathogens that primarily cause respiratory and intestinal diseases. Infection can easily cause respiratory symptoms, as well as a variety of serious complications. There are several types of human coronaviruses, such as SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, and SARS-CoV-2. The prevalence of COVID-19 has led to a growing focus on drug research against human coronaviruses. The main protease (Mpro) from human coronaviruses is a relatively conserved that controls viral replication. X77 was discovered to have extremely high inhibitory activity against SARS-CoV-2 Mpro through the use of computer-simulated docking. In this paper, we have resolved the crystal structure of the HCoV-NL63 Mpro complexed with X77 and analyzed their interaction in detail. This data provides essential information for solving their binding modes and their structural determinants. Then, we compared the binding modes of X77 with SARS-CoV-2 Mpro and HCoV-NL63 Mpro in detail. This study illustrates the structural basis of HCoV-NL63 Mpro binding to the inhibitor X77. The structural insights derived from this study will inform the development of new drugs with broad-spectrum resistance to human coronaviruses. • The crystal structure of X77 HCoV-NL63 Mpro in complex with inhibitor X77. • The structural basis of HCoV-NL63 Mpro binding to the inhibitor X77. • Structural comparison of X77 with SARS-CoV-2 Mpro and HCoV-NL63 Mpro. [ABSTRACT FROM AUTHOR]

The primary cilium is a hair-like projection that controls cell development and tissue homeostasis. Although accumulated studies identify the molecular link between cilia and cilia-related diseases, the underlying etiology of ciliopathies has not been fully understood. In this paper, we determine the function of Rab34, a small GTPase, as a key regulator for controlling ciliogenesis and type I collagen trafficking in craniofacial development. Mechanistically, Rab34 is required to form cilia that control osteogenic proliferation, survival, and differentiation via cilia-mediated Hedgehog signaling. In addition, Rab34 is indispensable for regulating type I collagen trafficking from the ER to the Golgi. These results demonstrate that Rab34 has both ciliary and non-ciliary functions to regulate osteogenesis. Our study highlights the critical function of Rab34, which may contribute to understanding the novel etiology of ciliopathies that are associated with the dysfunction of RAB34 in humans. • Deletion of Rab34 results in multiple ciliopathies-like phenotypes such as craniofacial defects. • Rab34 is required to form cilia that control osteogenesis via cilia-mediated Hedgehog signaling. • Rab34 is critical for regulating type I collagen trafficking from the ER to the Golgi in osteogenesis. [ABSTRACT FROM AUTHOR]

Living systems at all scales are compartmentalized into interacting subsystems. This paper reviews a mechanism that drives compartmentalization in generic systems at any scale. It first discusses three symmetries of generic physical interactions in a quantum-theoretic description. It then shows that if one of these, a permutation symmetry on the inter-system boundary, is spontaneously broken, the symmetry breaking is amplified by the Free Energy Principle (FEP). It thus shows how compartmentalization generically results from permutation symmetry breaking under the FEP. It finally notes that the FEP asymptotically restores the broken symmetry, showing that the FEP can be regarded as a theory of fluctuations away from a permutation-symmetric boundary, and hence from an entangled joint state of the interacting systems. [ABSTRACT FROM AUTHOR]

Cancer poses a significant risk to human well-being. Among the crucial characteristics of cancer is metabolic reprogramming. To meet the relentless metabolic needs, cancer cells enhance cholesterol metabolism within the adverse tumor microenvironment. Reprograming cholesterol metabolism includes a series of modifications in the synthesis, absorption, esterification, and metabolites associated with cholesterol. These adjustments have a strong correlation with the proliferation, invasion, metastasis, and other characteristics of malignant tumors. FDFT1, also known as farnesyl diphosphate farnesyltransferase 1, is an enzyme crucial in the process of cholesterol biosynthesis. Its significant involvement in tumor metabolism has garnered considerable interest. The significance of FDFT1 in cancer metabolism cannot be overstated, as it actively interacts with cancer cells. This paper aims to analyze and consolidate the mechanism of FDFT1 in cancer metabolism and explore its clinical application. The goal is to contribute new strategies and targets for the prevention and treatment of cancer metabolism. • FDFT1: Bidirectional Regulation of Cancer Cell Proliferation and Metastasis. • Mechanism of FDFT1 in Cancer Metabolism:The downstream and upstream pathways. • Clinical Application of FDFT1 in Cancer Therapy and Prognosis. [ABSTRACT FROM AUTHOR]

Insects have about 50 neuropeptide genes and about 70 genes, coding for neuropeptide G protein-coupled receptors (GPCRs). An important, but small family of evolutionarily related insect neuropeptides consists of adipokinetic hormone (AKH), corazonin, and AKH/corazonin-related peptide (ACP). Normally, insects have one specific GPCR for each of these neuropeptides. The tick Ixodes scapularis is not an insect, but belongs to the subphylum Chelicerata, which comprises ticks, scorpions, mites, spiders, and horseshoe crabs. Many of the neuropeptides and neuropeptide GPCRs occurring in insects, also occur in chelicerates, illustrating that insects and chelicerates are evolutionarily closely related. The tick I. scapularis is an ectoparasite and health risk for humans, because it infects its human host with dangerous pathogens during a blood meal. Understanding the biology of ticks will help researchers to prevent tick-borne diseases. By annotating the I. scapularis genome sequence, we previously found that ticks contain as many as five genes, coding for presumed ACP receptors. In the current paper, we cloned these receptors and expressed each of them in Chinese Hamster Ovary (CHO) cells. Each expressed receptor was activated by nanomolar concentrations of ACP, demonstrating that all five receptors were functional ACP receptors. Phylogenetic tree analyses showed that the cloned tick ACP receptors were mostly related to insect ACP receptors and, next, to insect AKH receptors, suggesting that ACP receptor genes and AKH receptor genes originated by gene duplications from a common ancestor. Similar duplications have probably occurred for the ligand genes, during a process of ligand/receptor co-evolution. Interestingly, chelicerates, in contrast to all other arthropods, do not have AKH or AKH receptor genes. Therefore, the ancestor of chelicerates might have lost AKH and AKH receptor genes and functionally replaced them by ACP and ACP receptor genes. For the small family of AKH, ACP, and corazonin receptors and their ligands, gene losses and gene gains occur frequently between the various ecdysozoan clades. Tardigrades, for example, which are well known for their survival in extreme environments, have as many as ten corazonin receptor genes and six corazonin peptide genes, while insects only have one of each, or none. [Display omitted] • The tick Ixodes scapularis is a vector for serious human diseases, such as Lyme. • G protein-coupled receptors (GPCRs) play a central role in the physiology of ticks. • GPCRs are also excellent drug targets to fight ticks. • Ticks have as many as five possible GPCR genes for the tick neuropeptide ACP. • We cloned these GPCRs and deorphanized them as being ACP receptors. [ABSTRACT FROM AUTHOR]

Mdivi-1, Mitochondrial DIVIsion inhibitor 1, has been widely employed in research under the assumption that it exclusively influences mitochondrial fusion, but effects other than mitochondrial dynamics have been underinvestigated. This paper provides transcriptome and DNA methylome-wide analysis for Mdivi-1 treated SH-SY5Y human neuroblastoma cells using RNA sequencing (RNA-seq) and methyl capture sequencing (MC-seq) methods. Gene ontology analysis of RNA sequences revealed that p53 transcriptional gene network and DNA replication initiation-related genes were significantly up and down-regulated, respectively, showing the correlation with the arrest cell cycle in the G1 phase. MC-seq, a powerful sequencing method for capturing DNA methylation status in CpG sites, revealed that although Mdivi-1 does not induce dramatic DNA methylation change, the subtle alterations were concentrated within the CpG island. Integrative analysis of both sequencing data disclosed that the p53 transcriptional network was activated while the Parkinson's disease pathway was halted. Next, we investigated several changes in mitochondria in response to Mdivi-1. Copy number and transcription of mitochondrial DNA were suppressed. ROS levels increased, and elevated ROS triggered mitochondrial retrograde signaling rather than inducing direct DNA damage. In this study, we could better understand the molecular network of Mdivi-1 by analyzing DNA methylation and mRNA transcription in the nucleus and further investigating various changes in mitochondria, providing inspiration for studying nuclear-mitochondrial communications. • First reported Mdivi-1-induced DNA methylome shows Mdivi-1 dwindles CGI methylation. • RNA/DNA-methyl sequencing integration unveils Mdivi-1's therapeutic mechanism. • Mdivi-1 modulates retrograde signaling by ROS. [ABSTRACT FROM AUTHOR]

The topological properties of DNA have long been a focal point in biophysics. In the 1970s, White proposed that the topology of closed DNA double helix follows White's formula: L k = W r + T w. However, there has been controversy in the calculation of DNA twisting number, partly due to discrepancies in the definition of torsion in differential geometry. In this paper, we delved into a detailed study of torsion, revealing that the calculation of DNA twisting number should use the curve's geodesic torsion. Furthermore, we found that the discrepancy in DNA twisting numbers calculated using different torsion is N. This study elucidated the impact of torsion on the calculation of DNA twisting numbers, aiming to resolve controversies in the calculation of DNA topology and provided accurate computational methods and theoretical foundations for related research. • Both as a spatial curve and as a curve lying on a surface, the DNA helix axis is taken into account during the calculation of the twisting number. The torsion derived from each perspective varies. • We have clarified that the torsion mentioned in Fuller's works should refer to the geodesic torsion of the surface where the DNA helix axis resides. • The twisting number computed from the torsion of a surface curve differs from that of a spatial curve by a specific numerical factor. [ABSTRACT FROM AUTHOR]

At present, the physiological roles of various hormones in fish glucose metabolism have been elucidated. Spexin, a 14-amino acids polypeptide, is highly conserved in many species and has functions such as reducing body weight and improving insulin resistance. In this paper, the open reading frame (ORF) of spx2 1 in grass carp (Ctenopharyngodon idella) was cloned, and the tissue distribution of spx1 and spx2 , their direct and indirect regulatory effects on glucose metabolism of grass carp were investigated. The ORF of spx2 gene in grass carp was 279 bp in length. Moreover, spx1 was highly expressed in the adipose tissue, while spx2 was highly expressed in the brain. In vitr o, SPX1 and SPX2 showed opposite effects on the glycolytic pathway in the primary hepatocytes. In vivo , intraperitoneal injection of SPX1 and SPX2 significantly reduced serum glucose levels and increased hepatopancreas glycogen contents. Meanwhile, SPX1 and SPX2 promoted the expression of key genes of glycolysis (pk) and glycogen synthesis (gys) in the hepatopancreas at 3 h post injection. As for indirect effects, 1000 nM SPX1 and SPX2 significantly increased insulin-mediated liver type phosphofructokinase (pfkla) mRNA expression and enhanced the inhibitory effects of insulin on glucose-6-phosphatase (g6pase), phosphoenolpyruvate carboxykinase (pepck), glycogen phosphorylase L (pygl) mRNA expression. Our results show that SPX1 and SPX2 have similar indirect effects on the regulation of glucose metabolism that enhance insulin activity, but they exhibit opposite roles in terms of direct effects. [Display omitted] • SPX1 and SPX2 showed opposite effects on the glycolytic pathway in vitro. • SPX1/2 play a hypoglycemic role in vivo in grass carp. • SPX1 promotes glycolysis and glycogen synthesis, and inhibits gluconeogenesis in vivo. • SPX2 promotes glycolysis and glycogen synthesis in vivo. • SPX1/2 promote insulin-induced glycolysis and glycogen synthesis, inhibit gluconeogenesis. [ABSTRACT FROM AUTHOR]

Secretory myeloid-derived growth factor (MYDGF) exerts beneficial effects on organ repair, probably via a plasma membrane receptor; however, the identity of the expected receptor has remained elusive. In a recent study, MYDGF was reported as an agonist of the sphingosine-1-phosphate receptor 2 (S1PR2), an A-class G protein-coupled receptor that mediates the functions of the signaling lipid, sphingosine-1-phosphate (S1P). In the present study, we conducted living cell-based functional assays to test whether S1PR2 is a receptor for MYDGF. In the NanoLuc Binary Technology (NanoBiT)-based β-arrestin recruitment assay and the cAMP-response element (CRE)-controlled NanoLuc reporter assay, S1P could efficiently activate human S1PR2 overexpressed in human embryonic kidney (HEK) 293T cells; however, recombinant human MYDGF, overexpressed either from Escherichia coli or HEK293 cells, had no detectable effect. Thus, the results demonstrated that human MYDGF is not a ligand of human S1PR2. Considering the high conservation of MYDGF and S1PR2 in evolution, MYDGF is also probably not a ligand of S1PR2 in other vertebrates. • Secretory MYDGF has beneficial effects on organ repair, but its receptor is unknown. • A recent paper reported that MYDGF is an agonist of the lipid receptor S1PR2. • We tested it via β-arrestin recruitment assay and CRE-controlled reporter assay. • MYDGF had no effects on S1PR2 in these living cell-based functional assays. • It seems that MYDGF is not a ligand of S1PR2 in human and other vertebrates. [ABSTRACT FROM AUTHOR]

Tenascin-C is an extracellular matrix glycoprotein strongly expressed in coronary atherosclerotic plaque. Aptamers are single-stranded oligonucleotides that bind to specific target molecules with high affinity. This study hypothesized that tenascin-C expression at atherosclerotic plaque in vivo could be detected by tenascin-C specific aptamers using positron emission tomography (PET). This paper reports the radiosynthesis of a fluorine-18 (18F)-labeled tenascin-C aptamer for the biodistribution and PET imaging of the tenascin-C expression in apolipoprotein E-deficient (ApoE−/−) mice. The aortas ApoE−/− mice showed significantly increased positive areas of Oil red O staining than control C57BL/6 mice, and tenascin-C expression was detected in foam cells accumulated in the subendothelial lesions of ApoE−/− mice. The ex vivo biodistribution of the 18F-labeled tenascin-C aptamer showed significantly increased uptake at the aorta of ApoE−/− mice, and ex vivo autoradiography of aorta revealed the high accumulation of the 18F-labeled tenascin-C aptamer in the atherosclerotic lesions of ApoE−/− mice, which was consistent with the location of the atherosclerotic plaques detected by Oil red O staining. PET imaging of the 18F-labeled tenascin-C aptamer revealed a significantly higher mean standardized uptake in the aorta of the ApoE−/− mice than the control C57BL/6 mice. These data highlight the potential use of tenascin-C aptamer to diagnose atherosclerotic lesions in vivo. • Tenascin-C expressed in the atherosclerotic lesions of aorta obtained from ApoE−/− mice. • Accumulation and retention of 18F-labeled TNC-specific aptamer in the aorta of ApoE−/− mice is higher than that of the control C57BL/6 mice. • Ex vivo autoradiography of 18F-labeled TNC-specific aptamer visualized the atherosclerotic lesions of aorta obtained from ApoE−/− mice. • PET imaging of 18F-labeled TNC-specific aptamer revealed a higher uptake in the aorta of the ApoE−/− mice than the control C57BL/6 mice. [ABSTRACT FROM AUTHOR]

Mounting studies have showed that tumor microenvironment (TME) is crucial for cervical cancer (CC), and cancer-related fibroblasts (CAFs) play a major role in it. Recently, exosomal miRNAs secreted by CAFs have been found to be potential targets for cancer diagnosis and therapy. In this paper, we aimed to investigate the function of CAFs-mediated exosome miR-18a-5p (CAFs- exo -miR-18a-5p) in CC. First, in combination with bioinformatic data analysis of the GEO database (GSE86100) and RT-qPCR of CC clinical tissue samples and cell lines, miR-18a-5p was discovered to be markedly up-regulated in CC. Next, CAFs-secreted exosomes were isolated and it was found that miR-18a-5p expression was dramatically promoted in CC cell lines when treated with CAFs-exos. The CAFs- exo -miR-18a-5p was then elucidated to stimulate the proliferation and migration and inhibit the apoptosis of CC cells. In order to clarify the underlying mechanism, we further screened the target genes of miR-18a-5p. TMEM170B was selected by bioinformatic data analysis of online databases combined with RT-qPCR of CC clinical tissues and cells. Luciferase reporter gene analysis combined with molecular biology experiments further elucidated that miR-18a-5p suppressed TMEM170B expression in CC. Finally, both cell and animal experiments demonstrated that TMEM170B over-expression attenuated the oncogenic effect of CAFs- exo -miR-18a-5p. In conclusion, our study indicates that CAFs-mediated exosome miR-18a-5p promotes the initiation and development of CC by suppressing TMEM170B signaling axis, which provides a possible direction for the diagnosis and therapy of CC. • CAFs-derived exosomes promoted the development of cervical cancer. • CAFs-derived exosomes-miR-18a-5p inhibited malignant progression of cervical cancer. • Exosomal miR-18a-5p promoted tumor growth by inhibiting TMEM170B expression. [ABSTRACT FROM AUTHOR]

In Escherichia coli , the SulA protein is synthesized during the SOS response to arrest cell division. Two possible models of SulA action were proposed: the sequestration and the capping. In current paper, to clarify which model better reflects the SulA effect on cell division upon the SOS response, the FtsZ/SulA ratio was estimated inside cells based on fusion of both FtsZ and SulA to fluorescent protein mNeonGreen. This allowed to quantify this ratio by fluorescence microscopy as well as western blotting; moreover, the effect of SulA on FtsZ distribution patterns in cells was analyzed based on fluorescence microscopy images. The SulA concentration in cells under the SOS response was shown to be several times (about 10) lower than that of FtsZ. The effect of SulA was unequal to corresponding decrease in FtsZ concentration. These results are supported by uneven FtsZ distribution in cells under the SOS response. Together the results of current work indicate that the division arrest by SulA protein in E. coli cells could not be explained by the sequestration model. • FtsZ/SulA ratio is about 10 under the SOS response in E. coli. • SulA action on FtsZ is unequal to corresponding decrease in FtsZ amount. • FtsZ demonstrates uneven distribution in cells under the SOS response. [ABSTRACT FROM AUTHOR]

Allelochemicals are specific secondary metabolites that can exhibit autotoxicity by inhibiting the growth of the same plant species that produced them. These metabolites have been found to affect various physical processes during plant growth and development, including inhibition of seed germination, photosynthesis, respiration, root growth, and nutrient uptake, with diverse mechanisms involving cell destruction, oxidative homeostasis and photoinhibition. In some cases, allelochemicals can also have positive effects on plant growth and development. In addition to their ecological significance, allelochemicals also possess potential as plant growth regulators (PGRs) due to their extensive physiological effects. However, a comprehensive summary of the development and applications of allelochemicals as PGRs is currently lacking. In this review, we present an overview of the sources and categories of allelochemicals, discuss their effects and the underlying mechanisms on plant growth and development. We showcase numerous instances of key phytohormonal allelochemicals and non-phytohormonal allelochemicals, highlighting their potential as candidates for the development of PGRs. This review aims to provide a theoretical basis for the development of economical, safe and effective PGRs utilizing allelochemicals, and emphasizes the need for further research in this area. • Allelochemicals have the potential to be plant growth regulators (PGRs). • The paper highlights the potential of phenols and terpenoids as PGRs. • PGRs developed by allelochemicals are more economical, safe and effective. [ABSTRACT FROM AUTHOR]

Currently, sepsis induced cardiotoxicity is among the major causes of sepsis-related death. The specific molecular mechanisms of sepsis induced cardiotoxicity are currently unknown. Therefore, the purpose of this paper is to identify the key molecule mechanisms for sepsis induced cardiotoxicity. Original data of sepsis induced cardiotoxicity was derived from Gene Expression Omnibus (GEO; GSE63920; GSE44363; GSE159309) dataset. Functional enrichment analysis was used to analysis sepsis induced cardiotoxicity related signaling pathways. Our findings also have explored the relationship of cuproptosis and N6-Methyladenosine (m6A) in sepsis induced cardiotoxicity. Mice are randomly assigned to 3 groups: saline treatment control group, LPS group administered a single 5 mg/kg dose of LPS for 24 h, LPS + CD274 inhibitor group administered 10 mg/kg CD274 inhibitor for 24 h. Overall, expression of cuproptosis-related genes (CRGs) CD274, Ceruloplasmin (CP), Vascular endothelial growth factor A (VEGFA), Copper chaperone for cytochrome c oxidase 11 (COX11), chemokine C–C motif ligand 8 (CCL8), Mitogen-activated protein kinase kinase 1(MAP2K1), Amine oxidase 3 (AOC3) were significantly altered in sepsis induced cardiotoxicity. The results of spearman correlation analysis was significant relationship between differentially regulated genes (DEGs) of CRGs and the expression level of m6A methylation genes. GO and KEGG showed that these genes were enriched in response to interferon-beta, MHC class I peptide loading complex, proteasome core complex, chemokine receptor binding, TAP binding, chemokine activity, cytokine activity and many more. These findings suggest that cuproptosis is strongly associated with sepsis induced cardiotoxicity. In the present study, we found that cuproptosis were associated with sepsis induced cardiotoxicity. The CD274, CP, VEGFA, COX11, CCL8, MAP2K1, AOC3 genes are showing a significant difference expression in sepsis induced cardiotoxicity. Our studies have found significant correlations between CRGs and m6A methylation related genes in sepsis induced cardiotoxicity. These results provide insight into mechanism for sepsis induced cardiotoxicity. • Cuproptosis were associated with sepsis induced cardiotoxicity. • Significant correlations between CRGs and m6A methylation related genes. • CD274 inhibitors can improve sepsis induced cardiotoxicity. [ABSTRACT FROM AUTHOR]