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Objective To explore the complex mechanisms of keloid, new approaches have been developed by different strategies. However, conventional treatment did not significantly reduce the recurrence rate. This study aimed to identify new biomarkers and mechanisms for keloid progression through bioinformatics analyses.Methods In our study, microarray datasets for keloid were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified by R software. Multiple bioinformatics tools were used to identify hub genes, and reverse predict upstream miRNAs and lncRNA molecules of target hub genes. Finally, the total RNA-sequencing technique and miRNA microarray were combined to validate the identified genes.Results Thirty-one DEGs were screened out and the upregulated hub gene SPP1 was finally identified, which was consistent with our RNA-sequencing analysis results and validation dataset. In addition, a ceRNA network of mRNA (SPP1)-miRNA (miR-181a-5p)-lncRNA (NEAT1, MALAT1, LINC00667, NORAD, XIST and MIR4458HG) was identified by the bioinformatics databases. The results of our miRNA microarray showed that miR-181a-5p was upregulated in keloid, also we found that the lncRNA NEAT1 could affect keloid progression by retrieving the relevant literature.Conclusions We speculate that SPP1 is a potential candidate biomarker and therapeutic target for patients with keloid, and NEAT1/miR-181a-5p/SPP1 might be the RNA regulatory pathway that regulates keloid formation.

Abstract Background The significance of sugarcane as a major crop is due to the production of sucrose and a significant source of ethanol. Sucrose phosphate synthase (SPS), Sucrose synthase (SuSy), and cell wall invertase (CWIN) genes regulate sucrose metabolism and accumulation in high sucrose sugarcane; such genes are significant for manipulating sucrose content. The current study explored the genes associated with sucrose metabolism and accumulation in a high sucrose sugarcane mutant clone GXB9 compared to its low sucrose parental clone B9. Results A total of 100, 262 differentially expressed genes were obtained, and 69, 637 (69.46%) got annotation in public databases COG, GO, KEGG, KOG, Pfam, eggNOG, NR, and Swiss-Prot. The SPS5 gene was significantly up-regulated in the maturing internodes of GXB9 and downregulated in B9. The SuSy and CWIN genes were up-regulated in the immature internodes; however, no expression was found in the maturing internodes of GXB9. The genes involved in trehalose synthesis were downregulated in GXB9 while up-regulated in B9. The cellulose synthase (CeS) genes were significantly up-regulated in the immature internodes than in maturing internodes of GXB9. Conclusions The key finding of this research suggests that the SPS5 gene has a predominant role in enhancing the sucrose accumulation ability of GXB9. No expression of SuSy and CWIN genes in maturing internodes and downregulation of trehalose genes in GXB9 may also have contributed to the higher sucrose accumulation in the stalk of high sucrose mutant. The current finding is a source for sugarcane breeding, particularly improving sucrose content. Graphical Abstract

Autophagy plays a critical role in the physiology and pathophysiology of hepatocytes. High level of homocysteine (Hcy) promotes autophagy in hepatocytes, but the underlying mechanism is still unknown. Here, we investigate the relationship between Hcy-induced autophagy level and the expression of nuclear transcription factor EB (TFEB). The results show that Hcy-induced autophagy level is mediated by upregulation of TFEB. Silencing of TFEB decreases the level of autophagy-related protein LC3BII/I and increases p62 expression level in hepatocytes after exposure to Hcy. Moreover, the effect of Hcy on the expression of TFEB is regulated by hypomethylation of the TFEB promoter catalyzed by DNA methyltransferase 3b (DNMT3b). In summary, this study shows that Hcy can activate autophagy by inhibiting DNMT3b-mediated DNA methylation and upregulating TFEB expression. These findings provide another new mechanism for Hcy-induced autophagy in hepatocytes.

Mono-2-ethylhexyl phthalic acid (MEHP) is the most toxic metabolite of plasticizer di-2-ethylhexyl phthalic acid (DEHP), and there is limited information available on the effects of MEHP on neurotoxicity. This study aims to examine the neurotoxicity of MEHP and preliminarily explore its potential molecular mechanisms. We found that MEHP impeded the growth of zebrafish embryos and the neurodevelopmental-related gene expression at environmentally relevant concentrations. MEHP exposure also induces oxidative stress response and brain cell apoptosis accompanied by a decrease in acetylcholinesterase (AChE) activity in zebrafish larvae. RNA-Seq and bioinformatics analysis showed that MEHP treatment altered the nervous system, neurogenic diseases, and visual perception pathways. The locomotor activity in dark-to-light cycles and phototaxis test confirmed the abnormal neural behavior of zebrafish larvae. Besides, the immune system has produced a large number of differentially expressed genes related to neural regulation. Inflammatory factor IL1β and IL-17 signaling pathways highly respond to MEHP, indicating that inflammation caused by immune system imbalance is a potential mechanism of MEHP-induced neurotoxicity. This study expands the understanding of the toxicity and molecular mechanisms of MEHP, providing a new perspective for in-depth neurotoxicity exploration of similar compounds.

Accumulating evidence has shown that the apoptosis of trophoblast cells plays an important role in the pathogenesis of preeclampsia, and an intricate interplay between DNA methylation and polycomb group (PcG) protein-mediated gene silencing has been highlighted recently. Here, we provide evidence that the expression of nervous system polycomb 1 (NSPc1), a BMI1 homologous polycomb protein, is significantly elevated in trophoblast cells during preeclampsia, which accelerates trophoblast cell apoptosis. Since NSPc1 acts predominantly as a transcriptional inactivator that specifically represses HOXA11 expression in trophoblast cells during preeclampsia, we further show that NSPc1 is required for DNMT3a recruitment and maintenance of the DNA methylation in the HOXA11 promoter in trophoblast cells during preeclampsia. In addition, we find that the interplay of DNMT3a and NSPc1 represses the expression of HOXA11 and promotes trophoblast cell apoptosis. Taken together, these results indicate that the cooperation between NSPc1 and DNMT3a reduces HOXA11 expression in preeclampsia pathophysiology, which provides novel therapeutic approaches for targeted inhibition of trophoblast cell apoptosis during preeclampsia pathogenesis.

Long noncoding RNAs (lncRNAs) are increasingly being implicated as key regulators of cell proliferation, apoptosis, and differentiation. However, the molecular mechanisms of specific lncRNAs in the context of hypertrophic scar remain largely unclear. Here, we find that the lncRNA FPASL (fibroblast proliferation-associated LncRNA) is downregulated in HS, and FPASL reduces fibroblast proliferation and colony formation and blocks cell cycle progression. Using GO annotation enrichment analysis along with AZC (a specific inhibitor of DNA methylation), we identify that DNA methylation is responsible for downregulating FPASL in hypertrophic scar. Subsequent studies demonstrate that high expression of DNMT3b inhibits FPASL expression in HS. Mechanistic study reveals a significant increase in fibroblast proliferation after transfection with LNA-FPASL, which is further inhibited by knockdown of DNMT3b. Thus, our study reveals that DNMT3b mediates hypermethylation of the lncRNA FPASL promoter and the downregulation of lncRNA FPASL promotes fibroblast proliferation in hypertrophic scar.

Hypertrophic scar is a problem for numerous patients, especially after burns, and is characterized by increased fibroblast proliferation and collagen deposition. Increasing evidence demonstrates that lncRNAs contribute to the development and progression of various diseases. However, the function of lncRNAs in hypertrophic scar formation remains poorly characterized. In this study, a novel fibroblast proliferation-associated lncRNA, named lncRNA FPASL (MSTRG.389905.1), which is mainly localized in the cytoplasm, is found to be downregulated in hypertrophic scar, as detected by lncRNA microarray and qRT-PCR. The full-length FPASL is characterized and further investigation confirms that it has no protein-coding potential. FPASL knockdown in fibroblasts triggers fibroblast proliferation, whereas overexpression of FPASL directly attenuates the proliferation of fibroblasts. Furthermore, target genes of the differentially expressed lncRNAs in hypertrophic scars and the matched adjacent normal tissues are enriched in fibroblast proliferation signaling pathways, including the PI3K/AKT and MAPK signaling pathways, as determined by GO annotation and KEGG enrichment analysis. We also demonstrate that knockdown of FPASL activates the PI3K/AKT and MAPK signaling pathways, and specific inhibitors of the PI3K/AKT and MAPK signaling pathways can reverse the proliferation of fibroblasts promoted by FPASL knockdown. Our findings contribute to a better understanding of the role of lncRNAs in hypertrophic scar and suggest that FPASL may act as a potential novel therapeutic target for hypertrophic scar.

Abstract Sugarcane (Saccharum spp. hybrid) is a noteworthy crop in the world for sugar and bioenergy production. In the present study, transcriptomic analysis was steered for a high sucrose mutant Guixuan B9 (GXB9) and the low sucrose mother genotype B9 of sugarcane during sugar accumulating stage. A total of 112,170 unigenes were obtained, and 106,026 (94.52%) were annotated by using the available public databases nonredundant, Gene ontology, COG, Kyoto Encyclopedia of Genes and Genomes, Swiss‐Prot, and Pfam. Functional assignment analysis of unigenes exhibited that they were active in a diversity of metabolic pathways. The vital unigenes for sucrose metabolism and accumulation were relatively characterized in the immature internodes (int. 5, 6) and maturing internodes (int. 13, 14) of GXB9 in comparison with B9. The differentially expressed unigenes (DEGs) encoding sucrose phosphate synthase (SPS, EC2.4.1.14), sucrose synthase (SuSy, EC2.4.1.13), and invertase (EC3.2.1.26), which are the vital enzymes functioning in the biosynthesis and splitting of sucrose, in the internodal tissues were revealed by using Illumina Hiseq 2000 platform, and verified by quantitative reverse transcription‐polymerase chain reaction analysis. The DEGs encoding SPS proteins SPS1, SPS2, SPS4, and SPS5 were upregulated in the maturing internodes of GXB9 compared with B9. The DEGs encoding SuSy proteins were majorly upregulated in the immature internodes of GXB9, and those encoding the enzymes involved in trehalose synthesis were downregulated in GXB9 compared with B9. The results in this study have revealed the opportunities for future sugarcane improvement by concentrating on the DEGs linked to sucrose metabolic pathways by applying omics technologies.

As one of the most environmentally toxic heavy metals, cadmium (Cd) has attracted the attention of researchers globally. In particular, Guangxi, a province in southwestern China, has been subjected to severe Cd pollution due to geogenic processes and anthropogenic activities. Cd can be accumulated in aquatic animals and transferred to the human body through the food chain, with potential health risks. The aim of the present study was to explore the effects of waterborne Cd exposure (0.5 mg/L and 1.5 mg/L) on the intestinal microbiota of mudsnail, Cipangopaludina cathayensis, which is favored by farmers and consumers in Guangxi. Gut bacterial community composition was investigated using high-throughput sequencing of the V3–V4 segment of the bacterial 16S rRNA gene. Our results indicated that C. cathayensis could tolerate low Cd (0.5 mg/L) stress, while Cd exposure at high doses (1.5 mg/L) exerted considerable effects on microbiota composition. At the phylum level, Proteobacteria, Bacteroidetes, and Firmicutes were the dominant phyla in the mudsnail gut microbiota. The relative abundances of Bacteroidetes increased significantly under high Cd exposure (H14) (p < 0.01), with no significant change in the low Cd exposure (L14) treatment. The dominant genera with significant differences in relative abundance were Pseudomonas, Cloacibacterium, Acinetobacter, Dechloromonas, and Rhodobacter. In addition, Cd exposure could significantly alter the pathways associated with metabolism, cellular processes, environmental information processing, genetic information processing, human diseases, and organismal systems. Notably, compared to the L14 treatment, some disease-related pathways were enriched, while some xenobiotic and organic compound biodegradation and metabolism pathways were significantly inhibited in the H14 group. Overall, Cd exposure profoundly influenced community structure and function of gut microbiota, which may in turn influence C. cathayensis gut homeostasis and health.

Sugarcane is a significant crop plant with the capability of accumulating higher amount of sucrose. In the present study, a high sucrose content sugarcane mutant clone, GXB9, has been studied in comparison to the low sucrose mother clone B9 on morphological, agronomical and physiological level in order to scrutinize the variation because of mutation in GXB9 in field under normal environmental condition. The results showed that GXB9 has less germination, tillering rate, stalk height, leaf length, leaf width, leaf area, number of internodes, internode length and internode diameter than B9. Qualitative traits of leaf and stalk displayed significant variation between GXB9 and B9. Endogenous hormones quantity was also showed variation between the two clones. The relative SPAD reading and chlorophyll a, b concentrations also showed variation between GXB9 and B9. The photosynthetic parameter analysis indicated that the GXB9 has significantly higher net photosynthetic rate (Pn), stomatal conductance (gs) and transpiration rate (Tr) than B9. The qRT-PCR analysis of genes encoding enzymes like SPS, SuSy, CWIN, and CeS showed upregulation in GXB9 and downregulation in B9. However, these genes were significantly differentially expressed between the immature and maturing internodes of GXB9. The cane quality trait analysis showed that GXB9 had higher juice rate, juice gravity purity, brix, juice sucrose content and cane sucrose content than B9. The yield and component investigation results indicated that GXB9 had lower single stalk weight, however higher number of millable stalks per hectare than B9, and GXB9 had lower theoretical cane yield than B9. SSR marker analysis showed genetic variation between GXB9 and B9. This study has shown significant variation in the traits of GXB9 in comparison to B9 which advocates that GXB9 is a high sugar mutant clone of B9 and an elite source for future breeding.

The incidence of chronic wounds has been increasing over the past 20 years. However, the standardized diagnosis and treatment practice of chronic refractory wounds have not been established. In addition, the properties of the wound are characterized by morphology and thus correct description of the wound in medical history collection plays a vital role, which directly affects the definitive diagnosis. To develop more accurate format of clinical history record which can correctly reflect a patient’s course and treatment progress, and to standardize the medical history record of chronic refractory wounds, at the national or regional level, we designed the WoundCareLog APP. It acts as a recording and communication tool for wound healing specialists at all levels of medical institutions in China. The WoundCareLog APP is fully compatible to meet the criteria and requirements of conventional medical records by embedding 9 modules. In addition, the demands for morphological description of wounds in wound healing diagnosis and treatment have been fulfilled by enroll of digital imaging technology to overcome the inadequacies of traditional medical history records. Keywords: Mobile applications, Wound healing, Chronic wound, Diagnosis and treatment

The mud snail Cipangopaludina cathayensis is a widely distributed species in China. Particularly in Guangxi province, mud snail farming contributes significantly to the economic development. However, global warming in recent decades poses a serious threat to global aquaculture production. The rising water temperature is harmful to aquatic animals. The present study explored the effects of high temperature on the intestinal microbiota of C. cathayensis. Snail intestinal samples were collected from the control and high-temperature groups on days 3 and 7 to determine the gut microbiota composition and diversity. Gut bacterial community composition was investigated using high-throughput sequencing of the V3–V4 region of bacterial 16S rRNA genes. Our results suggested that thermal stress altered the gut microbiome structure of C. cathayensis. At the phylum level, Proteobacteria, Bacteroidetes, and Firmicutes were dominant in C. cathayensis gut microbiota. The T2 treatment (32 ± 1 °C, day 7) significantly decreased the relative abundance of Firmicutes, Actinobacteria, and Deinococcus-Thermus. In T2, the abundance of several genera of putatively beneficial bacteria (Pseudomonas, Aeromonas, Rhodobacter, and Bacteroides) decreased, whereas the abundance of Halomonas—a pathogenic bacterial genus—increased. The functional prediction results indicated that T2 treatment inhibited some carbohydrate metabolism pathways and induced certain disease-related pathways (e.g., those related to systemic lupus erythematosus, Vibrio cholerae infection, hypertrophic cardiomyopathy, and shigellosis). Thus, high temperature profoundly affected the community structure and function of C. cathayensis gut microbiota. The results provide insights into the mechanisms associated with response of C. cathayensis intestinal microbiota to global warming.