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Sulfur is a critical element for plant growth and development, serving as a component of amino acids (cysteine and methionine), iron-sulfur clusters, proteins, glutathione, coenzymes, and auxin precursors. Deficiency or low concentrations of sulfur in the soil can lead to significant growth retardation in plants. The objective of our study was to examine the effects of sulfur (S) deficiency and excess on morphological symptoms, sulfur and nitrogen (N) metabolism, as well as antioxidant activity in soybean. We found that S starvation decreased the fine root length, biomass, and activity, and the chlorophyll content was reduced, while excess sulfur promotes lateral root growth. In contrast to sulfur excess, sulfur deficiency inhibits N and S metabolism levels in both subsurface and above-ground parts, and induced the expression of some sulfur transporters (SULTRs). In this study, we created soybean hairy root lines overexpressing the SULTR gene ( GmSULTR2;1a ) to observe metabolic changes following sulfur deficiency treatment. The results showed that GmSULTR2;1a saved the sulfur-deficient phenotype, and the antioxidant enzyme activity was much higher than that of the wildtype in the absence of sulfur. Our study revealed the important role of sulfur element in soybean growth and development and the regulation of sulfur deficiency by GmSULTR2;1a .

Membrane ruffles are cell actin-based membrane protrusions that have distinct structural characteristics. Linear ruffles with columnar spike-like and veil-like structures assemble at the leading edge of cell membranes. Circular dorsal ruffles (CDRs) have no supporting columnar structures but their veil-like structures, connecting from end to end, present an enclosed ring-shaped circular outline. Membrane ruffles are involved in multiple cell functions such as cell motility, macropinocytosis, receptor internalization, fluid viscosity sensing in a two-dimensional culture environment, and protecting cells from death in response to physiologically compressive loads. Herein, we review the state-of-the-art knowledge on membrane ruffle structure and function, the growth factor-induced membrane ruffling process, and the growth factor-independent ruffling mode triggered by calcium and other stimulating factors, together with the respective underlying mechanisms. We also summarize the inhibitors used in ruffle formation studies and their specificity. In the last part, an overview is given of the various techniques in which the membrane ruffles have been visualized up to now.

Spinal cord injury (SCI) is a debilitating central nervous system (CNS) disorder that leads to significant motor and sensory impairments. Given the limited regenerative capacity of adult mammalian neurons, this study presents an innovative strategy to enhance axonal regeneration and functional recovery by identifying a novel factor that markedly promotes axonal regeneration. Employing a zebrafish model with targeted single axon injury in Mauthner cells (M-cells) and utilizing the Tg (Tol056: EGFP) transgenic line for in vivo monitoring, we investigate the intrinsic mechanisms underlying axonal regeneration. This research specifically examines the role of amino acid transport, emphasizing the role of the solute carrier 1A4 amino acid transporter in axonal regeneration. Our findings demonstrate that Slc1a4 overexpression significantly enhances axonal regeneration in M-cells, whereas Slc1a4 deficiency impedes this process, which is concomitant with the downregulation of the P53/Gap43 signaling pathway. By elucidating the fundamental role of Slc1a4 in axonal regeneration and uncovering its underlying mechanisms, this study thus provides novel insights into therapeutic strategies for SCI.

Programmed cell death (PCD) is a form of cell death distinct from accidental cell death (ACD) and is also referred to as regulated cell death (RCD). Typically, PCD signaling events are precisely regulated by various biomolecules in both spatial and temporal contexts to promote neuronal development, establish neural architecture, and shape the central nervous system (CNS), although the role of PCD extends beyond the CNS. Abnormalities in PCD signaling cascades contribute to the irreversible loss of neuronal cells and function, leading to the onset and progression of neurodegenerative diseases. In this review, we summarize the molecular processes and features of different modalities of PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and other novel forms of PCD, and their effects on the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), multiple sclerosis (MS), traumatic brain injury (TBI), and stroke. Additionally, we examine the key factors involved in these PCD signaling pathways and discuss the potential for their development as therapeutic targets and strategies. Therefore, therapeutic strategies targeting the inhibition or facilitation of PCD signaling pathways offer a promising approach for clinical applications in treating neurodegenerative diseases.

Long non-coding RNAs (lncRNAs), a class of important regulatory factors for many biological processes in plants, have received much attention in recent years. To explore the molecular roles of lncRNAs in sweet cherry fruit ripening, we conducted widely targeted metabolome, transcriptome and lncRNA analyses of sweet cherry fruit at three ripening stages (yellow stage, pink stage, and dark red stage). The results show that the ripening of sweet cherry fruit involves substantial metabolic changes, and the rapid accumulation of anthocyanins (cyanidin 3-rutinoside, cyanidin 3-O-galactoside, and cyanidin 3-O-glucoside) is the main cause of fruit coloration. These ripening-related alterations in the metabolic profile are driven by specific enzyme genes related to the synthesis and decomposition of abscisic acid (ABA), cell wall disintegration, and anthocyanin biosynthesis, as well as transcription factor genes, such as MYBs , bHLHs , and WD40s . LncRNAs can target these ripening-related genes to form regulatory modules, incorporated into the sweet cherry fruit ripening regulatory network. Our study reveals that the lncRNA-mRNA module is an important component of the sweet cherry fruit ripening regulatory network. During sweet cherry fruit ripening, the differential expression of lncRNAs will meditate the spatio-temporal specific expression of ripening-related target genes (encoding enzymes and transcription factors related to ABA metabolism, cell wall metabolism and anthocyanin metabolism), thus driving fruit ripening.

Gibberellic acid-stimulated Arabidopsis sequences ( GASAs ) are a subset of the gibberellin (GA)-regulated gene family and play crucial roles in various physiological processes. However, the GASA genes in Brassica rapa have not yet been documented. In this study, we identified and characterized 16 GASA genes in Chinese cabbage ( Brassica rapa L. ssp. pekinensis ). Analysis of the conserved motifs revealed significant conservation within the activation segment of BraGASA genes. This gene family contains numerous promoter elements associated with abiotic stress tolerance, including those for abscisic acid (ABA) and methyl jasmonate (MeJA). Expression profiling revealed the presence of these genes in various tissues, including roots, stems, leaves, flowers, siliques, and callus tissues. When plants were exposed to drought stress, the expression of BraGASA3 decreased notably in drought-sensitive genotypes compared to their wild-type counterparts, highlighting the potentially crucial role of BraGASA3 in drought stress. Additionally, BraGASAs exhibited various functions in sexual reproduction dynamics. The findings contribute to the understanding of the function of BraGASAs and provide valuable insights for further exploration of the GASA gene function of the BraGASA gene in Chinese cabbage.

Core-shell nanostructures are powerful platforms for the development of novel nanoscale drug delivery systems with sustained drug release profiles. Coaxial electrospinning is facile and convenient for creating medicated core-shell nanostructures with elaborate designs with which the sustained-release behaviors of drug molecules can be intentionally adjusted. With resveratrol (RES) as a model for a poorly water-soluble drug and cellulose acetate (CA) and PVP as polymeric carriers, a brand-new electrospun core-shell nanostructure was fabricated in this study. The guest RES and the host CA molecules were designed to have a reverse gradient distribution within the core-shell nanostructures. Scanning electron microscope and transmission electron microscope evaluations verified that these nanofibers had linear morphologies, without beads or spindles, and an obvious core-shell double-chamber structure. The X-ray diffraction patterns and Fourier transform infrared spectroscopic results indicated that the involved components were highly compatible and presented in an amorphous molecular distribution state. In vitro dissolution tests verified that the new core-shell structures were able to prevent the initial burst release, extend the continuous-release time period, and reduce the negative tailing-off release effect, thus ensuring a better sustained-release profile than the traditional blended drug-loaded nanofibers. The mechanism underlying the influence of the new core-shell structure with an RES/CA reverse gradient distribution on the behaviors of RES release is proposed. Based on this proof-of-concept demonstration, a series of advanced functional nanomaterials can be similarly developed based on the gradient distributions of functional molecules within electrospun multi-chamber nanostructures.

Marine algal toxins have garnered significant attention in the research community for their unique biochemical properties and potential medical applications. These bioactive compounds, produced by microalgae, pose significant risks due to their high toxicity, yet offer promising therapeutic benefits. Despite extensive research identifying over 300 marine algal toxins, including azaspiracids, brevetoxins, cyclic imines, and yessotoxins, gaps remain in the understanding of their pharmacological potential. In this paper, we critically review the classification, bioactive components, toxicology, pharmacological activities, and mechanisms of these toxins, with a particular focus on their clinical applications. Our motivation stems from the increasing interest in marine algal toxins as candidates for drug development, driven by their high specificity and affinity for various biological receptors. We aim to bridge the gap between toxicological research and therapeutic application, offering insights into the advantages and limitations of these compounds in comparison to other bioactive substances. This review not only enhances the understanding of marine algal toxins' complexity and diversity, but also highlights their extensive application potential in medicine and bioscience, providing a foundation for future research and development in this field.

DNA methylation plays a critical role in regulating gene expression during testicular development. However, few studies report on candidate genes related to the DNA methylation regulation of porcine testicular development. This study examined the differentially expressed genes (DEGs) and their methylation levels in testicular tissues from pigs at 60 days of age (60 d) and 180 days of age (180 d) using RNA-Seq and whole genome bisulfite sequencing (WGBS). It was determined that DNA methylation primarily occurs in the cytosine-guanine (CG) context, and the analysis identified 106,282 differentially methylated regions (DMRs) corresponding to 12,385 differentially methylated genes (DMGs). Further integrated analysis of RNA-Seq and WGBS data revealed 1083 DMGs negatively correlated with the expression of DEGs. GO analysis showed that these genes were significantly enriched in spermatogenesis, germ cell development, and spermatid differentiation. The screening of enriched genes revealed that hyper-methylation repressed ADAM30 , ADAM3A , DPY19L2 , H2BC1 , MAK , RPL10L , SPATA16 , and YBX2 , while hypo-methylation elevated CACNA1I , CADM1 , CTNNB1 , JAM2 , and PAFAH1B3 expression. Additionally, the methylation status of the key genes ADAM3A , ADAM30 , YBX2 , JAM2 , PAFAH1B3 , and CTNNB1 was detected by bisulfite sequencing PCR (BSP). This study offers insights into the epigenetic regulation mechanisms underlying porcine testicular development.

Sulfate transporters (SULTRs) are essential for the transport and absorption of sulfate in plants and serve as critical transport proteins within the sulfur metabolism pathway, significantly influencing plant growth, development, and stress adaptation. A bioinformatics analysis of SULTR genes in soybean was performed, resulting in the identification and classification of twenty-eight putative GmSULTRs into four distinct groups. In this study, the characteristics of the 28 GmSULTR genes, including those involved in collinearity, gene structure, protein motifs, cis -elements, tissue expression patterns, and the response to abiotic stress and plant hormone treatments, were systematically analyzed. This study focused on conducting a preliminary functional analysis of the GmSULTR3;1a gene, wherein a high expression level of GmSULTR3;1a in the roots, stems, and leaves was induced by a sulfur deficiency and GmSULTR3;1a improved the salt tolerance. A further functional characterization revealed that GmSULTR3;1a- overexpressing soybean hairy roots had higher SO 4 2- , GSH, and methionine (Met) contents compared with the wild-type (WT) plant. These results demonstrate that the overexpression of GmSULTR3;1a may promote the sulfur assimilation metabolism and increase the content of sulfur-containing amino acids in plants.

Exopolysaccharides (EPSs) are carbohydrate polymers that are synthesized and secreted into the extracellular during the growth of microorganisms. Bacillus thuringiensis (Bt) is a type of entomopathogenic bacterium, that produces various insecticidal proteins and EPSs. In our previous study, the EPSs produced by Bt strains were first found to enhance the toxicity of insecticidal crystal proteins against Plutella xylostella . However, the response of the intestinal bacterial communities of P. xylostella under the action of EPSs is still unelucidated. In this study, 16S rRNA amplicon sequencing was used to characterize the intestinal bacterial communities in P. xylostella treated with EPSs alone, Cry1Ac protoxin alone, and both the Cry1Ac protoxin and EPSs. Compared with the control group, alpha diversity indices, the Chao1 and ACE indices were significantly altered after treatment with EPSs alone, and no significant difference was observed between the groups treated with Cry1Ac protoxin alone and Cry1Ac protoxin + EPSs. However, compared with the gut bacterial community feeding on Cry1Ac protoxin alone, the relative abundance of 31 genera was significantly changed in the group treated with Cry1Ac protoxin and EPSs. The intestinal bacteria, through the oral of Cry1Ac protoxin and EPSs, significantly enhanced the toxicity of the Cry1Ac protoxin towards the axenic P. xylostella . In addition, the relative abundance of the 16S rRNA gene in the chloroplasts of Brassica campestris decreased after adding EPSs. Taken together, these results show the vital contribution of the gut microbiota to the Bt strain-killing activity, providing new insights into the mechanism of the synergistic insecticidal activity of Bt proteins and EPSs.

Lipid metabolism is a critical component in preserving homeostasis and health, and lipids are significant chemicals involved in energy metabolism in living things. With the growing interest in lipid metabolism in recent years, an increasing number of studies have demonstrated the close relationship between abnormalities in lipid metabolism and the development of numerous human diseases, including cancer, cardiovascular, neurological, and endocrine system diseases. Thus, understanding how aberrant lipid metabolism contributes to the development of related diseases and how it works offers a theoretical foundation for treating and preventing related human diseases as well as new avenues for the targeted treatment of related diseases. Therefore, we discuss the processes of aberrant lipid metabolism in various human diseases in this review, including diseases of the cardiovascular system, neurodegenerative diseases, endocrine system diseases (such as obesity and type 2 diabetes mellitus), and other diseases including cancer.

The hair follicle is the basis of hair regeneration, and the dermal papilla is one of the most important structures in hair regeneration. New intervention and reversal strategies for hair loss may arise due to the prevention of oxidative stress. GC/MS analysis was used to determine the compounds contained in NSO. Then, NSO was applied to DPC for cell proliferation and oxidative stress experiments. RNA-seq was performed in cells treated with NSO and minoxidil. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify the gene expression. The effects of NSO on hair length, weight, the number and depth of hair follicles, and the dermal thickness were also studied. GC/MS analysis showed that the main components of NSO were eicosapentaenoic acid, palmitic acid, and linoleic acid. NSO promotes DPC proliferation and reduces H 2 O 2 -mediated oxidative damage. NSO can also activate hair growth-related pathways and upregulate antioxidant-related genes analyzed by gene profiling. The topical application of NSO significantly promotes hair growth and increases hair length and weight in mice. NSO extract promotes hair growth and effectively inhibits oxidative stress, which is beneficial for the prevention and treatment of hair loss.

Salinity is a common abiotic stress that limits crop productivity. Although there is a wealth of evidence suggesting that miRNA and lncRNA play important roles in the response to salinity in rice seedlings and reproductive stages, the mechanism by which competing endogenous RNAs (ceRNAs) influence salt tolerance and yield in rice has been rarely reported. In this study, we conducted full whole-transcriptome sequencing of rice panicles during the reproductive period to clarify the role of ceRNAs in the salt stress response and yield. A total of 214 lncRNAs, 79 miRNAs, and 584 mRNAs were identified as differentially expressed RNAs under salt stress. Functional analysis indicates that they play important roles in GO terms such as response to stress, biosynthesis processes, abiotic stimuli, endogenous stimulus, and response to stimulus, as well as in KEGG pathways such as secondary metabolite biosynthesis, carotenoid biosynthesis, metabolic pathways, and phenylpropanoid biosynthesis. A ceRNA network comprising 95 lncRNA-miRNA-mRNA triplets was constructed. Two lncRNAs, MSTRG.51634.2 and MSTRG.48576.1, were predicted to bind to osa-miR172d-5p to regulate the expression of OsMYB2 and OsMADS63 , which have been reported to affect salt tolerance and yield, respectively. Three lncRNAs, MSTRG.30876.1, MSTRG.44567.1, and MSTRG.49308.1, may bind to osa-miR5487 to further regulate the expression of a stress protein (LOC_Os07g48460) and an aquaporin protein (LOC_Os02g51110) to regulate the salt stress response. This study is helpful for understanding the underlying molecular mechanisms of ceRNA that drive the response of rice to salt stress and provide new genetic resources for salt-resistant rice breeding.

The role of Chitinase-3-like protein 1 (CHI3L1) in tumor progression has been gradually clarified in different kinds of solid tumors. Hence, we aim to elucidate its prognostic value for glioma. In this study, we analyzed RNA sequencing data combined with corresponding clinical information obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. Differentially expressed genes (DEGs) were acquired based on CHI3L1 expression profiles and were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Cox regression, least absolute shrinkage and selection operator (LASSO) regression methods, along with a nomogram, were employed to establish a predictive model. Compared with the corresponding non-tumor tissues, CHI3L1 expression was significantly upregulated in various types of solid tumors, correlating with poor clinical outcomes including glioma. GO analysis identified oxidative stress-related genes (ORGs) that were differentially expressed and modulated by CHI3L1, with 11 genes subsequently identified as potential predictors, using Univariate-Cox regression and LASSO regression. In addition, an index of oxidative stress-related genes (ORGI) was established, demonstrating its prognostic value in conjunction with CHI3L1 expression. The aberrant expression of CHI3L1 was proved in glioma patients through immunohistochemistry (IHC). Meanwhile, the knockdown of CHI3L1 inhibited glioma growth in vitro, and real-time Quantitative PCR (qPCR) confirmed decreased ORG expression upon CHI3L1 knockdown, suggesting the potential prognostic value of CHI3L1 as a therapeutic target for glioma.

Chronic Hepatitis B virus (CHB) infection is a global health challenge, causing damage ranging from hepatitis to cirrhosis and hepatocellular carcinoma. In our study, single-cell RNA sequencing (scRNA-seq) analysis was performed in livers from mice models with chronic inflammation induced by CHB infection and we found that endothelial cells (ECs) exhibited the largest number of differentially expressed genes (DEGs) among all ten cell types. NF-κB signaling was activated in ECs to induce cell dysfunction and subsequent hepatic inflammation, which might be mediated by the interaction of macrophage-derived and cholangiocyte-derived VISFATIN/Nampt signaling. Moreover, we divided ECs into three subclusters, including periportal ECs (EC_Z1), midzonal ECs (EC_Z2), and pericentral ECs (EC_Z3) according to hepatic zonation. Functional analysis suggested that pericentral ECs and midzonal ECs, instead of periportal ECs, were more vulnerable to HBV infection, as the VISFATIN/Nampt- NF-κB axis was mainly altered in these two subpopulations. Interestingly, pericentral ECs showed increasing communication with macrophages and cholangiocytes via the Nampt-Insr and Nampt-Itga5/Itgb1 axis upon CHB infection, which contribute to angiogenesis and vascular capillarization. Additionally, ECs, especially pericentral ECs, showed a close connection with nature killer (NK) cells and T cells via the Cxcl6-Cxcr6 axis, which is involved in shaping the microenvironment in CHB mice livers. Thus, our study described the heterogeneity and functional alterations of three subclusters in ECs. We revealed the potential role of VISFATIN/Nampt signaling in modulating ECs characteristics and related hepatic inflammation, and EC-derived chemokine Cxcl16 in shaping NK and T cell recruitment, providing key insights into the multifunctionality of ECs in CHB-associated pathologies.

Iron is an essential nutrient for humans and microbes, such as bacteria. Iron deficiency commonly occurs in critically ill patients, but supplementary iron therapy is not considered during the acute phase of critical illness since it increases iron availability for invading microbes and oxidative stress. However, persistent iron deficiency in the recovery phase is harmful and has potential adverse outcomes such as cognitive dysfunction, fatigue, and cardiopulmonary dysfunction. Therefore, it is important to treat iron deficiency quickly and efficiently. This article reviews current knowledge about iron-related biomarkers in critical illness with a focus on patients with sepsis, and provides possible criteria to guide decision-making for iron supplementation in the recovery phase of those patients., Competing Interests: The authors declare no conflict of interest.

Drought stress is one of the significant abiotic stresses that limit soybean ( Glycine max [L.] Merr.) growth and production. Ankyrin repeat (ANK) proteins, being highly conserved, occupy a pivotal role in diverse biological processes. ANK genes were classified into nine subfamilies according to conserved domains in the soybean genome. However, the function of ANK-TM subfamily proteins (Ankyrin repeat proteins with a transmembrane domain) in the abiotic-stress response to soybean remains poorly understood. In this study, we first demonstrated the subcellular localization of GmANKTM21 in the cell membrane and nucleus. Drought stress-induced mRNA levels of GmANKTM21 , which encodes proteins belonging to the ANK-TM subfamily, Transgenic 35S:GmANKTM21 soybean improved drought tolerance at the germination and seedling stages, with higher stomatal closure in soybean, lower water loss, lower malondialdehyde (MDA) content, and less reactive oxygen species (ROS) production compared with the wild-type soybean (Dongnong50). RNA-sequencing (RNA-seq) and RT-qPCR analysis of differentially expressed transcripts in overexpression of GmANKTM21 further identified potential downstream genes, including GmSPK2 , GmSPK4 , and GmCYP707A1 , which showed higher expression in transgenic soybean, than those in wild-type soybean and KEGG enrichment analysis showed that MAPK signaling pathways were mostly enriched in GmANKTM21 overexpressing soybean plants under drought stress conditions. Therefore, we demonstrate that GmANKTM21 plays an important role in tolerance to drought stress in soybeans.

Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.

Salinity is an environmental stress that severely impacts rice grain yield and quality. However, limited information is available on the molecular mechanism by which salinity reduces grain quality. In this study, we investigated the milling, appearance, eating and cooking, and nutritional quality among three japonica rice cultivars grown either under moderate salinity with an electrical conductivity of 4 dS/m or under non-saline conditions in a paddy field in Dongying, Shandong, China. Moderate salinity affected rice appearance quality predominantly by increasing chalkiness rate and chalkiness degree and affected rice eating and cooking and nutritional quality predominantly by decreasing amylose content and increasing protein content. We compared the expression levels of genes determining grain chalkiness, amylose content, and protein content in developing seeds (0, 5, 10, 15, and 20 days after flowering) of plants grown under saline or non-saline conditions. The chalkiness-related gene Chalk5 was up-regulated and WHITE-CORE RATE 1 was repressed. The genes Nuclear factor Y and Wx, which determine amylose content, were downregulated, while protein-content-associated genes OsAAP6 and OsGluA2 were upregulated by salinity in the developing seeds. These findings suggest some target genes that may be utilized to improve the grain quality under salinity stress conditions via gene-pyramiding breeding approaches.

Hedera helix is a traditional medicinal plant. Its primary active ingredients are oleanane-type saponins, which have extensive pharmacological effects such as gastric mucosal protection, autophagy regulation actions, and antiviral properties. However, the glycosylation-modifying enzymes responsible for catalyzing oleanane-type saponin biosynthesis remain unidentified. Through transcriptome, cluster analysis, and PSPG structural domain, this study preliminarily screened four candidate UDP-glycosyltransferases (UGTs), including Unigene26859, Unigene31717, CL11391.Contig2, and CL144.Contig9. In in vitro enzymatic reactions, it has been observed that Unigene26859 ( HhUGT74AG11 ) has the ability to facilitate the conversion of oleanolic acid, resulting in the production of oleanolic acid 28- O -glucopyranosyl ester. Moreover, HhUGT74AG11 exhibits extensive substrate hybridity and specific stereoselectivity and can transfer glycosyl donors to the C -28 site of various oleanane-type triterpenoids (hederagenin and calenduloside E) and the C -7 site of flavonoids (tectorigenin). Cluster analysis found that HhUGT74AG11 is clustered together with functionally identified genes AeUGT74AG6 , CaUGT74AG2 , and PgUGT74AE2 , further verifying the possible reason for HhUGT74AG11 catalyzing substrate generalization. In this study, a novel glycosyltransferase, HhUGT74AG11 , was characterized that plays a role in oleanane-type saponins biosynthesis in H. helix, providing a theoretical basis for the production of rare and valuable triterpenoid saponins.

The advancement of exosome studies has positioned engineered exosomes as crucial biomaterials for the development of advanced drug delivery systems. This study focuses on developing a hybrid exosome system by fusing mesenchymal stem cells (MSCs) exosomes with folate-targeted liposomes. The aim was to improve the drug loading capacity and target modification of exosome nanocarriers for delivering the first-line chemotherapy drug paclitaxel (PTX) and its effectiveness was assessed through cellular uptake studies to evaluate its ability to deliver drugs to tumor cells in vitro. Additionally, in vivo experiments were conducted using a CT26 tumor-bearing mouse model to assess the therapeutic efficacy of hybrid exosomes loaded with PTX (ELP). Cellular uptake studies demonstrated that ELP exhibited superior drug delivery capabilities to tumor cells in vitro. Moreover, in vivo experiments revealed that ELP significantly suppressed tumor growth in the CT26 tumor-bearing mouse model. Notably, for the first time, we examined the tumor microenvironment following intratumoral administration of ELP. We observed that ELP treatment activated CD4 + and CD8 + T cells, reduced the expression of M2 type tumor-associated macrophages (TAMs), polarized TAMs towards the M1 type, and decreased regulatory T cells (Tregs). Our research highlights the considerable therapeutic efficacy of ELP and its promising potential for future application in cancer therapy. The development of hybrid exosomes presents an innovative approach to enhance drug delivery and modulate the tumor microenvironment, offering exciting prospects for effective cancer treatment strategies.

Inherited retinal degenerative diseases (IRDs) are a group of rare diseases that lead to a progressive loss of photoreceptor cells and, ultimately, blindness. The overactivation of cGMP-dependent protein kinase G (PKG), one of the key effectors of cGMP-signaling, was previously found to be involved in photoreceptor cell death and was studied in murine IRD models to elucidate the pathophysiology of retinal degeneration. However, PKG is a serine/threonine kinase (STK) with several hundred potential phosphorylation targets and, so far, little is known about the specificity of the target interaction and downstream effects of PKG activation. Here, we carried out both the kinome activity and phosphoproteomic profiling of organotypic retinal explant cultures derived from the rd10 mouse model for IRD. After treating the explants with the PKG inhibitor CN03, an overall decrease in peptide phosphorylation was observed, with the most significant decrease occurring in seven peptides, including those from the known PKG substrate cyclic-AMP-response-element-binding CREB, but also Ca 2+ /calmodulin-dependent kinase (CaMK) peptides and TOP2A. The phosphoproteomic data, in turn, revealed proteins with decreased phosphorylation, as well as proteins with increased phosphorylation. The integration of both datasets identified common biological networks altered by PKG inhibition, which included kinases predominantly from the so-called AGC and CaMK families of kinases (e.g., PKG1, PKG2, PKA, CaMKs, RSKs, and AKTs). A pathway analysis confirmed the role of CREB, Calmodulin, mitogen-activated protein kinase (MAPK) and CREB modulation. Among the peptides and pathways that showed reduced phosphorylation activity, the substrates CREB, CaMK2, and CaMK4 were validated for their retinal localization and activity, using immunostaining and immunoblotting in the rd10 retina. In summary, the integrative analysis of the kinome activity and phosphoproteomic data revealed both known and novel PKG substrates in a murine IRD model. This data establishes a basis for an improved understanding of the biological pathways involved in cGMP-mediated photoreceptor degeneration. Moreover, validated PKG targets like CREB and CaMKs merit exploration as novel (surrogate) biomarkers to determine the effects of a clinical PKG-targeted treatment for IRDs.

Nucleic acid modifications play important roles in biological activities and disease occurrences, and have been considered as cancer biomarkers. Due to the relatively low amount of nucleic acid modifications in biological samples, it is necessary to develop sensitive and reliable qualitative and quantitative methods to reveal the content of any modifications. In this review, the key processes affecting the qualitative and quantitative analyses are discussed, such as sample digestion, nucleoside extraction, chemical labeling, chromatographic separation, mass spectrometry detection, and data processing. The improvement of the detection sensitivity and specificity of analytical methods based on mass spectrometry makes it possible to study low-abundance modifications and their biological functions. Some typical nucleic acid modifications and their potential as biomarkers are displayed, and efforts to improve diagnostic accuracy are discussed. Future perspectives are raised for this research field.

Porcine epidemic diarrhea virus (PEDV), a member of the Alpha-coronavirus genus in the Coronaviridae family, induces acute diarrhea, vomiting, and dehydration in neonatal piglets. This study aimed to investigate the genetic dependencies of PEDV and identify potential therapeutic targets by using a single-guide RNA (sgRNA) lentiviral library to screen host factors required for PEDV infection. Protein kinase C θ (PKCθ), a calcium-independent member of the PKC family localized in the cell membrane, was found to be a crucial host factor in PEDV infection. The investigation of PEDV infection was limited in Vero and porcine epithelial cell-jejunum 2 (IPEC-J2) due to defective interferon production in Vero and the poor replication of PEDV in IPEC-J2. Therefore, identifying suitable cells for PEDV investigation is crucial. The findings of this study reveal that human embryonic kidney (HEK) 293T and L929 cells, but not Vero and IPEC-J2 cells, were suitable for investigating PEDV infection. PKCθ played a significant role in endocytosis and the replication of PEDV, and PEDV regulated the expression and phosphorylation of PKCθ. Apoptosis was found to be involved in PEDV replication, as the virus activated the PKCθ-B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) axis in HEK293T and L929 cells to increase viral endocytosis and replication via mitochondrial apoptosis. This study demonstrated the suitability of HEK293T and L929 cells for investigating PEDV infection and identified PKCθ as a host factor essential for PEDV infection. These findings provide valuable insights for the development of strategies and drug targets for PEDV infection.

NAC transcription factors are commonly involved in the plant response to drought stress. A transcriptome analysis of root samples of the soybean variety 'Jiyu47' under drought stress revealed the evidently up-regulated expression of GmNAC19 , consistent with the expression pattern revealed by quantitative real-time PCR analysis. The overexpression of GmNAC19 enhanced drought tolerance in Saccharomyces cerevisiae INVSc1. The seed germination percentage and root growth of transgenic Arabidopsis thaliana were improved in comparison with those of the wild type, while the transgenic soybean composite line showed improved chlorophyll content. The altered contents of physiological and biochemical indices (i.e., soluble protein, soluble sugar, proline, and malondialdehyde) related to drought stress and the activities of three antioxidant enzymes (i.e., superoxide dismutase, peroxidase, and catalase) revealed enhanced drought tolerance in both transgenic Arabidopsis and soybean. The expressions of three genes (i.e., P5CS , OAT , and P5CR ) involved in proline synthesis were decreased in the transgenic soybean hairy roots, while the expression of ProDH involved in the breakdown of proline was increased. This study revealed the molecular mechanisms underlying drought tolerance enhanced by GmNAC19 via regulation of the contents of soluble protein and soluble sugar and the activities of antioxidant enzymes, providing a candidate gene for the molecular breeding of drought-tolerant crop plants.

Light is one of the most important environmental factors for plant growth. In the production process of tung oil tree cultivation, due to the inappropriate growth of shading conditions, the lower branches are often dry and dead, which seriously affects the yield of tung oil trees. However, little is known about the key factors of light-induced tree photomorphogenesis. In this study, a total of 22 VfBBX family members were identified to provide a reference for candidate genes in tung tree seedlings. All members of the VfBBX family have different numbers of highly conserved B-box domains or CCT domains. Phylogenetic evolution clustered the VfBBX genes into four categories, and the highest density of members was on chromosome 6. Interspecific collinearity analysis suggested that there were six pairs of duplicate genes in VfBBX members, but the expression levels of all family members in different growth and development stages of the tung tree were significantly divergent. After different degrees of shading treatment and physiological data determination of tung tree seedlings, the differential expression level and chlorophyll synthesis genes correlation analysis revealed that VfBBX9 was a typical candidate nuclear localization transcription factor that was significantly differentially expressed in light response. This study systematically identified the VfBBX gene family and provided a reference for studying its molecular function, enhanced the theoretical basis for tung tree breeding, and identified excellent varieties.

Acute colitis is a complex disease that can lead to dysregulation of the gut flora, inducing more complex parenteral diseases. Dandelion polysaccharides (DPSs) may have potential preventive and therapeutic effects on enteritis. In this study, LPS was used to induce enteritis and VC was used as a positive drug control to explore the preventive and therapeutic effects of DPS on enteritis. The results showed that DPS could repair the intestinal barrier, down-regulate the expression of TNF-α, IL-6, IL-1β, and other pro-inflammatory factors, up-regulate the expression of IL-22 anti-inflammatory factor, improve the antioxidant capacity of the body, and improve the structure of intestinal flora. It is proved that DPS can effectively prevent and treat LPS-induced acute enteritis and play a positive role in promoting intestinal health.

Homeostatic maintenance is essential for pulp function. Disrupting pulp homeostasis may lead to pulp degeneration, such as fibrosis and calcifications. Sensory nerves constitute a crucial component of the dental pulp. However, the precise involvement of sensory nerves in pulp homeostasis remains uncertain. In this study, we observed the short-term and long-term histological changes in the dental pulp after inferior alveolar nerve transection. Additionally, we cultured primary dental pulp cells (DPCs) from the innervated and denervated groups and compared indicators of cellular senescence and cellular function. The results revealed that pulp fibrosis occurred at 2 w after the operation. Furthermore, the pulp area, as well as the height and width of the pulp cavity, showed accelerated reductions after sensory denervation. Notably, the pulp area at 16 w after the operation was comparable to that of 56 w old rats. Sensory denervation induced excessive extracellular matrix (ECM) deposition and increased predisposition to mineralization. Furthermore, sensory denervation promoted the senescence of DPCs. Denervated DPCs exhibited decelerated cell proliferation, arrest in the G2/M phase of the cell cycle, imbalance in the synthesis and degradation of ECM, and enhanced mineralization. These findings indicate that sensory nerves play an essential role in pulp homeostasis maintenance and dental pulp cell fate decisions, which may provide novel insights into the prevention of pulp degeneration.

The function of the respiratory chain is closely associated with kidney function, and the dysfunction of the respiratory chain is a primary pathophysiological change in chronic kidney failure. The incidence of chronic kidney failure caused by defects in respiratory-chain-related genes has frequently been overlooked. Correcting abnormal metabolic reprogramming, rescuing the "toxic respiratory chain", and targeting the clearance of mitochondrial reactive oxygen species are potential therapies for treating chronic kidney failure. These treatments have shown promising results in slowing fibrosis and inflammation progression and improving kidney function in various animal models of chronic kidney failure and patients with chronic kidney disease (CKD). The mitochondrial respiratory chain is a key target worthy of attention in the treatment of chronic kidney failure. This review integrated research related to the mitochondrial respiratory chain and chronic kidney failure, primarily elucidating the pathological status of the mitochondrial respiratory chain in chronic kidney failure and potential therapeutic drugs. It provided new ideas for the treatment of kidney failure and promoted the development of drugs targeting the mitochondrial respiratory chain.

Avian metapneumovirus subgroup C (aMPV/C) causes respiratory diseases and egg dropping in chickens and turkeys, resulting in severe economic losses to the poultry industry worldwide. Integrin β1 (ITGB1), a transmembrane cell adhesion molecule, is present in various cells and mediates numerous viral infections. Herein, we demonstrate that ITGB1 is essential for aMPV/C infection in cultured DF-1 cells, as evidenced by the inhibition of viral binding by EDTA blockade, Arg-Ser-Asp (RSD) peptide, monoclonal antibody against ITGB1, and ITGB1 short interfering (si) RNA knockdown in cultured DF-1 cells. Simulation of the binding process between the aMPV/C fusion (F) protein and avian-derived ITGB1 using molecular dynamics showed that ITGB1 may be a host factor benefiting aMPV/C attachment or internalization. The transient expression of avian ITGB1-rendered porcine and feline non-permissive cells (DQ cells and CRFK cells, respectively) is susceptible to aMPV/C infection. Kinetic replication of aMPV/C in siRNA-knockdown cells revealed that ITGB1 plays an important role in aMPV/C infection at the early stage (attachment and internalization). aMPV/C was also able to efficiently infect human non-small cell lung cancer (A549) cells. This may be a consequence of the similar structures of both metapneumovirus F protein-specific motifs (RSD for aMPV/C and RGD for human metapneumovirus) recognized by ITGB1. Overexpression of avian-derived ITGB1 and human-derived ITGB1 in A549 cells enhanced aMPV/C infectivity. Taken together, this study demonstrated that ITGB1 acts as an essential receptor for aMPV/C attachment and internalization into host cells, facilitating aMPV/C infection.

The newly released 'Snow White' (SW), a white-fleshed loquat ( Eriobotrya japonica Lindl.) cultivar, holds promise for commercial production. However, the specifics of the phenolic composition in white-fleshed loquats, along with the antioxidant substances and their regulatory mechanisms, are not yet fully understood. In this study, we examined the dynamic changes in the phenolic compounds, enzyme activities, antioxidant capacity, and gene expression patterns of SW during the key stages of fruit development and ripening. A total of 18 phenolic compounds were identified in SW, with chlorogenic acid, neochlorogenic acid, and coniferyl alcohol being the most predominant. SW demonstrated a stronger antioxidant capacity in the early stages of development, largely due to total phenolics and flavonoids. Neochlorogenic acid may be the most significant antioxidant contributor in loquat. A decline in enzyme activities corresponded with fruit softening. Different genes within a multigene family played distinct roles in the synthesis of phenolics. C4H1 , 4CL2 , 4CL9 , HCT , CCoAOMT5 , F5H , COMT1 , CAD6 , and POD42 were implicated in the regulation of neochlorogenic acid synthesis and accumulation. Consequently, these findings enhance our understanding of phenolic metabolism and offer fresh perspectives on the development of germplasm resources for white-fleshed loquats.

Skeletal muscle differentiation is a precisely coordinated process. While many of the molecular details of myogenesis have been investigated extensively, the dynamic changes and functions of amino acids and related transporters remain unknown. In this study, we conducted a comprehensive analysis of amino acid levels during different time points of C2C12 myoblast differentiation using high-performance liquid chromatography (HPLC). Our findings revealed that the levels of most amino acids exhibited an initial increase at the onset of differentiation, reaching their peak typically on the fourth or sixth day, followed by a decline on the eighth day. Particularly, arginine and branched-chain amino acids showed a prominent increase during this period. Furthermore, we used RNA-seq analysis to show that the gene encoding the arginine transporter, Slc7a2 , is significantly upregulated during differentiation. Knockdown of Slc7a2 gene expression resulted in a significant decrease in myoblast proliferation and led to a reduction in the expression levels of crucial myogenic regulatory factors, hindering the process of myoblast differentiation, fusion, and subsequent myotube formation. Lastly, we assessed the expression level of Slc7a2 during aging in humans and mice and found an upregulation of Slc7a2 expression during the aging process. These findings collectively suggest that the arginine transporter SLC7A2 plays a critical role in facilitating skeletal muscle differentiation and may hold potential as a therapeutic target for sarcopenia.

Swine acute diarrhea syndrome coronavirus (SADS-CoV), a member of the family Coronaviridae and the genus Alphacoronavirus, primarily affects piglets under 7 days old, causing symptoms such as diarrhea, vomiting, and dehydration. It has the potential to infect human primary and passaged cells in vitro, indicating a potential risk of zoonotic transmission. In this study, we successfully generated and purified six monoclonal antibodies (mAbs) specifically targeting the spike protein of SADS-CoV, whose epitope were demonstrated specificity to the S1 A or S1 B region by immunofluorescence assay and enzyme-linked immunosorbent assay. Three of these mAbs were capable of neutralizing SADS-CoV infection on HeLa-R19 and A549. Furthermore, we observed that SADS-CoV induced the agglutination of erythrocytes from both humans and rats, and the hemagglutination inhibition capacity and antigen-antibody binding capacity of the antibodies were assessed. Our study reveals that mAbs specifically targeting the S1 A domain demonstrated notable efficacy in suppressing the hemagglutination phenomenon induced by SADS-CoV. This finding represents the first instance of narrowing down the protein region responsible for SADS-CoV-mediated hemagglutination to the S1 A domain, and reveals that the cell attachment domains S1 A and S1 B are the main targets of neutralizing antibodies.

Although recent research progress on the abundant C-to-U RNA editing events in plant chloroplasts and mitochondria has uncovered many recognition factors and their molecular mechanisms, the intrinsic regulation of RNA editing within plants remains largely unknown. This study aimed to establish a regulatory relationship in Arabidopsis between the plant hormone auxin and chloroplast RNA editing. We first analyzed auxin response elements (AuxREs) present within promoters of chloroplast editing factors reported to date. We found that each has more than one AuxRE, suggesting a potential regulatory role of auxin in their expression. Further investigation unveiled that the depletion of auxin synthesis gene YUC2 reduces the expression of several editing factors. However, in yuc2 mutants, only the expression of CRR4 , DYW1 , ISE2 , and ECD1 editing factors and the editing efficiency of their corresponding editing sites, ndhD -2 and rps14 -149, were simultaneously suppressed. In addition, exogenous IAA and the overexpression of YUC2 enhanced the expression of these editing factors and the editing efficiency at the ndhD -2 and rps14 -149 sites. These results suggested a direct effect of auxin upon the editing of the ndhD -2 and rps14 -149 sites through the modulation of the expression of the editing factors. We further demonstrated that ARF1, a downstream transcription factor in the auxin-signaling pathway, could directly bind to and inactivate the promoters of CRR4 , DYW1 , and ISE2 in a dual-luciferase reporter system, thereby inhibiting their expression. Moreover, the overexpression of ARF1 in Arabidopsis significantly reduced the expression of the three editing factors and the editing efficiency at the ndhD -2 and rps14 -149 sites. These data suggest that YUC2-mediated auxin biosynthesis governs the RNA-editing process through the ARF1-dependent signal transduction pathway.

The contemporary comprehension of breast cancer has progressed to the molecular level. As a heterogeneous malignancy, conventional pathological diagnosis and histological classification could no longer meet the needs of precisely managing breast cancer. Genetic testing based on gene expression profiles and gene mutations has emerged and substantially contributed to the precise diagnosis and treatment of breast cancer. Multigene assays (MGAs) are explored for early-stage breast cancer patients, aiding the selection of adjuvant therapy and predicting prognosis. For metastatic breast cancer patients, testing specific genes indicates potentially effective antitumor agents. In this review, genetic testing in early-stage and metastatic breast cancer is summarized, as well as the advantages and challenges of genetic testing in breast cancer.

Due to the extensive utilization of poly (ethylene terephthalate) (PET), a significant amount of PET waste has been discharged into the environment, endangering both human health and the ecology. As an eco-friendly approach to PET waste treatment, biodegradation is dependent on efficient strains and enzymes. In this study, a screening method was first established using polycaprolactone (PCL) and PET nanoparticles as substrates. A PET-degrading strain YX8 was isolated from the surface of PET waste. Based on the phylogenetic analysis of 16S rRNA and gyrA genes, this strain was identified as Bacillus safensis . Strain YX8 demonstrated the capability to degrade PET nanoparticles, resulting in the production of terephthalic acid (TPA), mono (2-hydroxyethyl) terephthalic acid (MHET), and bis (2-hydroxyethyl) terephthalic acid (BHET). Erosion spots on the PET film were observed after incubation with strain YX8. Furthermore, the extracellular enzymes produced by strain YX8 exhibited the ability to form a clear zone on the PCL plate and to hydrolyze PET nanoparticles to generate TPA, MHET, and BHET. This work developed a method for the isolation of PET-degrading microorganisms and provides new strain resources for PET degradation and for the mining of functional enzymes.

Fluorescence in situ hybridization (FISH) with rRNA-targeted oligonucleotide probes is widely used for the identification of microbes in complex samples, but it suffers from some limitations resulting in the weak or even absence of fluorescence signals of microbe(s), which may lead to the underestimation or misunderstanding of a microbial community. Herein, we explored symbionts in the bacteriomes and fat bodies of cicadas using modified FISH, aiming to improve this technique. We initially revealed that the probes of Candidatus Sulcia muelleri ( Sulcia ) and the yeast-like fungal symbiont (YLS) are suitable for detection of these symbionts in all cicadas and some other species of Auchenorrhyncha, whereas the probe of Candidatus Hodgkinia cicadicola ( Hodgkinia ) is only suitable for detection of Hodgkinia in a few cicada species. The fluorescence signal of Sulcia , Hodgkinia and YLS exhibited weak intensity without the addition of unlabeled oligonucleotides (helpers) and heat shock in some cicadas; however, it can be significantly improved by the addition of both helpers and heat shock. Results of this study suggest that heat shock denaturing rRNA and proteins of related microbe(s) together with helpers binding to the adjacent region of the probe's target sites prevent the re-establishment of the native secondary structure of rRNA; therefore, suitable probe(s) can more easily access to the probe's target sites of rRNA. Our results provide new information for the significant improvement of hybridization signal intensities of microbes in the FISH experiment, making it possible to achieve a more precise understanding of the microbial distribution, community and density in complex samples.

DNA methylation is a pivotal epigenetic regulatory mechanism in the development of skeletal muscles. Nonetheless, the regulators responsible for DNA methylation in the development of embryonic duck skeletal muscles remain unknown. In the present study, whole genome bisulfite sequencing (WGBS) and transcriptome sequencing were conducted on the skeletal muscles of embryonic day 21 (E21) and day 28 (E28) ducks. The DNA methylation pattern was found to fall mainly within the cytosine-guanine (CG) context, with high methylation levels in the intron, exon, and promoter regions. Overall, 7902 differentially methylated regions (DMRs) were identified, which corresponded to 3174 differentially methylated genes (DMGs). By using integrative analysis of both WGBS with transcriptomics, we identified 1072 genes that are DMGs that are negatively associated with differentially expressed genes (DEGs). The gene ontology (GO) analysis revealed significant enrichment in phosphorylation, kinase activity, phosphotransferase activity, alcohol-based receptors, and binding to cytoskeletal proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGGs) analysis showed significant enrichment in MAPK signaling, Wnt signaling, apelin signaling, insulin signaling, and FoxO signaling. The screening of enriched genes showed that hyper-methylation inhibited the expression of Idh3a , Got1 , Bcl2 , Mylk2 , Klf2 , Erbin , and Klhl38 , and hypo-methylation stimulated the expression of Col22a1 , Dnmt3b , Fn1 , E2f1 , Rprm , and Wfikkn1 . Further predictions showed that the CpG islands in the promoters of Klhl38 , Klf2 , Erbin , Mylk2 , and Got1 may play a crucial role in regulating the development of skeletal muscles. This study provides new insights into the epigenetic regulation of the development of duck skeletal muscles.

The genus Apium, belonging to the family Apiaceae, comprises roughly 20 species. Only two species, Apium graveolens and Apium leptophyllum, are available in China and are both rich in nutrients and have favorable medicinal properties. However, the lack of genomic data has severely constrained the study of genetics and evolution in Apium plants. In this study, Illumina NovaSeq 6000 and Nanopore sequencing platforms were employed to identify the mitochondrial genomes of A. graveolens and A. leptophyllum . The complete lengths of the mitochondrial genomes of A. graveolens and A. leptophyllum were 263,017 bp and 260,164 bp, respectively, and contained 39 and 36 protein-coding genes, five and six rRNA genes, and 19 and 20 tRNA genes. Consistent with most angiosperms, both A. graveolens and A. leptophyllum showed a preference for codons encoding leucine (Leu). In the mitochondrial genome of A. graveolens , 335 SSRs were detected, which is higher than the 196 SSRs found in the mitochondrial genome of A. leptophyllum . Studies have shown that the most common RNA editing type is C-to-U, but, in our study, both A. graveolens and A. leptophyllum exhibited the U-C editing type. Furthermore, the transfer of the mitochondrial genomes of A. graveolens and A. leptophyllum into the chloroplast genomes revealed homologous sequences, accounting for 8.14% and 4.89% of the mitochondrial genome, respectively. Lastly, in comparing the mitochondrial genomes of 29 species, it was found that A. graveolens , A. leptophyllum , and Daucus carota form a sister group with a support rate of 100%. Overall, this investigation furnishes extensive insights into the mitochondrial genomes of A. graveolens and A. leptophyllum , thereby enhancing comprehension of the traits and evolutionary patterns within the Apium genus. Additionally, it offers supplementary data for evolutionary and comparative genomic analyses of other species within the Apiaceae family.

Cold stress is the main factor limiting rice production and distribution. Chaling wild rice can survive in cold winters. AP2/EREBP is a known transcription factor family associated with abiotic stress. We identified the members of the AP2/EREBP transcription factor family in rice, maize, and Arabidopsis , and conducted collinearity analysis and gene family analysis. We used Affymetrix array technology to analyze the expression of AP2/EREBP family genes in Chaling wild rice and cultivated rice cultivar Pei'ai64S, which is sensitive to cold. According to the GeneChip results, the expression levels of AP2/EREBP genes in Chaling wild rice were different from those in Pei'ai64S; and the increase rate of 36 AP2/EREBP genes in Chaling wild rice was higher than that in Pei'ai64S. Meanwhile, the MYC elements in cultivated rice and Chaling wild rice for the Os01g49830 , Os03g08470 , and Os03g64260 genes had different promoter sequences, resulting in the high expression of these genes in Chaling wild rice under low-temperature conditions. Furthermore, we analyzed the upstream and downstream genes of the AP2/EREBP transcription factor family and studied the conservation of these genes. We found that the upstream transcription factors were more conserved, indicating that these upstream transcription factors may be more important in regulating cold stress. Meanwhile, we found the expression of AP2/EREBP pathway genes was significantly increased in recombinant inbred lines from Nipponbare crossing with Chaling wild rice, These results suggest that the AP2/EREBP signaling pathway plays an important role in Chaling wild rice tolerance to cold stress.

Endogenous hydrogen sulfide (H 2 S) produced by cystathionine β-synthase (CBS) and cystathionine-γ lyase (CSE) has emerged as a novel uterine vasodilator contributing to pregnancy-associated increases in uterine blood flow, which safeguard pregnancy health. Uterine artery (UA) H 2 S production is stimulated via exogenous estrogen replacement and is associated with elevated endogenous estrogens during pregnancy through the selective upregulation of CBS without altering CSE. However, how endogenous estrogens regulate uterine artery CBS expression in pregnancy is unknown. This study was conducted to test a hypothesis that endogenous estrogens selectively stimulate UA CBS expression via specific estrogen receptors (ER). Treatment with E 2 β (0.01 to 100 nM) stimulated CBS but not CSE mRNA in organ cultures of fresh UA rings from both NP and P (gestational day 20, GD20) rats, with greater responses to all doses of E 2 β tested in P vs. NP UA. ER antagonist ICI 182,780 (ICI, 1 µM) completely attenuated E 2 β-stimulated CBS mRNA in both NP and P rat UA. Subcutaneous injection with ICI 182,780 (0.3 mg/rat) of GD19 P rats for 24 h significantly inhibited UA CBS but not mRNA expression, consistent with reduced endothelial and smooth muscle cell CBS (but not CSE) protein. ICI did not alter mesenteric and renal artery CBS and CSE mRNA. In addition, ICI decreased endothelial nitric oxide synthase mRNA in UA but not in mesenteric or renal arteries. Thus, pregnancy-augmented UA CBS/H 2 S production is mediated by the actions of endogenous estrogens via specific ER in pregnant rats.

Aluminum (Al) toxicity is a major limiting factor for plant growth and crop production in acidic soils. This study aims to investigate the effects of γ-aminobutyric acid (GABA) priming on mitigating acid-Al toxicity to creeping bentgrass ( Agrostis stolonifera ) associated with changes in plant growth, photosynthetic parameters, antioxidant defense, key metabolites, and genes related to organic acids metabolism. Thirty-seven-old plants were primed with or without 0.5 mM GABA for three days and then subjected to acid-Al stress (5 mmol/L AlCl 3 ·6H 2 O, pH 4.35) for fifteen days. The results showed that acid-Al stress significantly increased the accumulation of Al and also restricted aboveground and underground growths, photosynthesis, photochemical efficiency, and osmotic balance, which could be effectively alleviated by GABA priming. The application of GABA significantly activated antioxidant enzymes, including superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase, to reduce oxidative damage to cells under acid-Al stress. Metabolomics analysis demonstrated that the GABA pretreatment significantly induced the accumulation of many metabolites such as quinic acid, pyruvic acid, shikimic acid, glycine, threonine, erythrose, glucose-6-phosphate, galactose, kestose, threitol, ribitol, glycerol, putrescine, galactinol, and myo-inositol associated with osmotic, antioxidant, and metabolic homeostases under acid-Al stress. In addition, the GABA priming significantly up-regulated genes related to the transportation of malic acid and citric acid in leaves in response to acid-Al stress. Current findings indicated GABA-induced tolerance to acid-Al stress in relation to scavenging of reactive oxygen species, osmotic adjustment, and accumulation and transport of organic metabolites in leaves. Exogenous GABA priming could improve the phytoremediation potential of perennial creeping bentgrass for the restoration of Al-contaminated soils.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a significant role in health and disease. In this pathway, cGAS, one of the major cytosolic DNA sensors in mammalian cells, regulates innate immunity and the STING-dependent production of pro-inflammatory cytokines, including type-I interferon. Moreover, the cGAS-STING pathway is integral to other cellular processes, such as cell death, cell senescence, and autophagy. Activation of the cGAS-STING pathway by "self" DNA is also attributed to various infectious diseases and autoimmune or inflammatory conditions. In addition, the cGAS-STING pathway activation functions as a link between innate and adaptive immunity, leading to the inhibition or facilitation of tumorigenesis; therefore, research targeting this pathway can provide novel clues for clinical applications to treat infectious, inflammatory, and autoimmune diseases and even cancer. In this review, we focus on the cGAS-STING pathway and its corresponding cellular and molecular mechanisms in health and disease.

Imbalance of the immune system caused by alterations of the gut microbiome is considered to be a critical factor in the pathogenesis of infant eczema, but the exact role of the gut microbiome in adult atopic dermatitis (AD) patients remains to be clarified. To investigate the differences of the gut microbiome between adult AD patients and healthy individuals, stool samples of 234 adults, containing 104 AD patients and 130 healthy subjects, were collected for 16S rRNA gene amplicon. Altered structure and metabolic dysfunctions of the gut microbiome were identified in adult AD patients. Our results illustrated that the adult AD patients were more likely to have allergies, particularly non-food allergies. In addition, the gut microbiome composition of the AD and normal groups were considerably different. Moreover, Romboutsia and Clostridi-um_sensu_stricto_1 was enriched in the normal group, whereas Blautia , Butyricicoccus , Lachnoclostridium , Eubacterium_hallii_group , Erysi-pelatoclostridium , Megasphaera , Oscillibacter , and Flavonifractor dominated in the AD group. Additionally, purine nucleotide degradation pathways were significantly enriched in the AD group, and the enrichment of proteinogenic amino acid biosynthesis pathways was found in the normal group. This study provides insights into new therapeutic strategies targeting the gut microbiome for AD and evidence for the involvement of the gut-skin axis in AD patients.

Depending on their central metal atom, metalloporphyrins (MPs) can attenuate or exacerbate the severity of immune-mediated kidney injury, and this has been attributed to the induction or inhibition of heme oxygenase (HO) activity, particularly the inducible isoform (HO-1) of this enzyme. The role of central metal or porphyrin moieties in determining the efficacy of MPs to attenuate injury, as well as mechanisms underlying this effect, have not been assessed. Using an antibody-mediated complement-dependent model of injury directed against rat visceral glomerular epithelial cells (podocytes) and two MPs (FePPIX, CoPPIX) that induce both HO-1 expression and HO enzymatic activity in vivo but differ in their chelated metal, we assessed their efficacy in reducing albuminuria. Podocyte injury was induced using rabbit immune serum raised against the rat podocyte antigen, Fx1A, and containing an anti-Fx1A antibody that activates complement at sites of binding. FePPIX or CoPPIX were injected intraperitoneally (5 mg/kg) 24 h before administration of the anti-Fx1A serum and on days 1, 3, 6, and 10 thereafter. Upon completion of urine collection on day 14, the kidney cortex was obtained for histopathology and isolation of glomeruli, from which total protein extracts were obtained. Target proteins were analyzed by capillary-based separation and immunodetection (Western blot analysis). Both MPs had comparable efficacy in reducing albuminuria in males, but the efficacy of CoPPIX was superior in female rats. The metal-free protoporphyrin, PPIX, had minimal or no effect on urine albumin excretion. CoPPIX was also the most potent MP in inducing glomerular HO-1, reducing complement deposition, and preserving the expression of the complement regulatory protein (CRP) CD55 but not that of CD59, the expression of which was reduced by both MPs. These observations demonstrate that the metal moiety of HO-1-inducing MPs plays an important role in reducing proteinuria via mechanisms involving reduced complement deposition and independently of an effect on CRPs.

Previous research suggested that the dramatical decrease in CD8 + T cells is a contributing factor in the poor prognosis and disease progression of COVID-19 patients. However, the underlying mechanisms are not fully understood. In this study, we conducted Single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq) analysis, which revealed a proliferative-exhausted MCM + FASLG low CD8 + T cell phenotype in severe/critical COVID-19 patients. These CD8 + T cells were characterized by G2/M cell cycle arrest, downregulation of respiratory chain complex genes, and inhibition of mitochondrial biogenesis. CellChat analysis of infected lung epithelial cells and CD8 + T cells found that the galectin signaling pathway played a crucial role in CD8 + T cell reduction and dysfunction. To further elucidate the mechanisms, we established SARS-CoV-2 ORF3a-transfected A549 cells, and co-cultured them with CD8 + T cells for ex vivo experiments. Our results showed that epithelial galectin-3 inhibited the transcription of the mitochondrial respiratory chain complex III/IV genes of CD8 + T cells by suppressing the nuclear translocation of nuclear respiratory factor 1 (NRF1). Further findings showed that the suppression of NRF1 translocation was associated with ERK-related and Akt-related signaling pathways. Importantly, the galectin-3 inhibitor, TD-139, promoted nuclear translocation of NRF1, thus enhancing the expression of the mitochondrial respiratory chain complex III/IV genes and the mitochondrial biogenesis of CD8 + T cells. Our study provided new insights into the immunopathogenesis of COVID-19 and identified potential therapeutic targets for the prevention and treatment of severe/critical COVID-19 patients.

Members of the tripartite motif (TRIM)-containing protein family have been found to be involved in the progression of hepatocellular carcinoma (HCC). TRIM14 exerts a promotive impact on several cancers. This study aimed to explore the function and mechanism of TRIM14 in HCC. TRIM14 expression in HCC tissues and HCC cell lines was detected. The overexpression or knockdown model of TRIM14 was established in HCC cell lines. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Transwell assay, RT-PCR, Western blot, and immunofluorescence were performed to verify the influence of TRIM14 on cell proliferation, sensitivity to chemotherapy drugs, apoptosis, migration, invasion, and autophagy. A xenograft tumor model was used to confirm the impact of TRIM14 on tumor cell growth. As shown by the data, TRIM14 level was notably higher in the tumor tissues of HCC patients than in the adjacent tissues. The overall survival rate of patients with a high TRIM14 expression was relatively lower than that of patients with a low TRIM14 expression. TRIM14 upregulation enhanced the proliferation, autophagy, migration, and invasion of HCC cells and chemoresistant HCC cells and decreased apoptosis. TRIM14 knockdown contributed to the opposite effects. In in vivo experiments, TRIM14 upregulation bolstered tumor growth. Western blot analysis revealed that TRIM14 upregulation boosted signal transducer and activator of transcription3 (STAT3) and hypoxia-inducible factor-1alpha (HIF-1α) expression, and TRIM14 knockdown suppressed their expression. Moreover, repressing STAT3 and HIF-1α could mitigate the tumor-promoting role of TRIM14 in HCC cells. Overall, TRIM14 facilitated malignant HCC development and induced chemoresistance in HCC cells by activating the STAT3/HIF-1α axis.