Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids.

Background: Hypoxia is the typical characteristic of keloids. The development of keloids is closely related to the abnormal phenotypic transition of macrophages. However, the role of exosomal microRNAs (miRNAs) derived from hypoxic macrophages in keloids remains unclear. This study aimed to explore the role of hypoxic macrophage-derived exosomes (HMDE) in the occurrence and development of keloids and identify the critical miRNA. Methods: The expression of CD206+ M2 macrophage in keloids and normal skin tissues was examined through immunofluorescence. The polarization of macrophages under a hypoxia environment was detected through flow cytometry. The internalization of macrophage-derived exosomes in human keloid fibroblasts (HKFs) was detected using a confocal microscope. miRNA sequencing was used to explore the differentially expressed miRNAs in exosomes derived from the normoxic and hypoxic macrophage. Subsequently, the dual-luciferase reporter assay verified that phosphatase and tension homolog (PTEN) was miR-26b-5p's target. The biological function of macrophage-derived exosomes, miR-26b-5p and PTEN were detected using the CCK-8, wound-healing and Transwell assays. Western blot assay was used to confirm the miR-26b-5p's underlying mechanisms and PTEN-PI3K/AKT pathway. Results: We demonstrated that M2-type macrophages were enriched in keloids and that hypoxia treatment could polarize macrophages toward M2-type. Compared with normoxic macrophages-derived exosomes (NMDE), HMDE promote the proliferation, migration and invasion of HKFs. A total of 38 differential miRNAs (18 upregulated and 20 downregulated) were found between the NMDE and HMDE. miR-26b-5p was enriched in HMDE, which could be transmitted to HKFs. According to the results of the functional assay, exosomal miR-26b-5p produced by macrophages facilitated HKFs' migration, invasion and proliferation via the PTEN-PI3K/AKT pathway. Conclusions: The highly expressed miR-26b-5p in HMDE promotes the development of keloids via the PTEN-PI3K/AKT pathway.

Genome-wide identification of U-box gene family and expression analysis in response to saline-alkali stress in foxtail millet (Setaria italica L. Beauv).

E3 ubiquitin ligases are central modifiers of plant signaling pathways that regulate protein function, localization, degradation, and other biological processes by linking ubiquitin to target proteins. E3 ubiquitin ligases include proteins with the U-box domain. However, there has been no report about the foxtail millet (Setaria italica L. Beauv) U-box gene family (SiPUB) to date. To explore the function of SiPUBs, this study performed genome-wide identification of SiPUBs and expression analysis of them in response to saline-alkali stress. A total of 70 SiPUBs were identified, which were unevenly distributed on eight chromosomes. Phylogenetic and conserved motif analysis demonstrated that SiPUBs could be clustered into six subfamilies (I-VI), and most SiPUBs were closely related to the homologues in rice. Twenty-eight types of cis-acting elements were identified in SiPUBs, most of which contained many light-responsive elements and plant hormone-responsive elements. Foxtail millet had 19, 78, 85, 18, and 89 collinear U-box gene pairs with Arabidopsis, rice, sorghum, tomato, and maize, respectively. Tissue specific expression analysis revealed great variations in SiPUB expression among different tissues, and most SiPUBs were relatively highly expressed in roots, indicating that SiPUBs may play important roles in root development or other growth and development processes of foxtail millet. Furthermore, the responses of 15 SiPUBs to saline-alkali stress were detected by qRT-PCR. The results showed that saline-alkali stress led to significantly differential expression of these 15 SiPUBs, and SiPUB20/48/70 may play important roles in the response mechanism against saline-alkali stress. Overall, this study provides important information for further exploration of the biological function of U-box genes.

Genome-wide identification of AAAP gene family and expression analysis in response to saline-alkali stress in foxtail millet (Setaria italica L.).

Amino acid/auxin permease (AAAP) genes encode a large family of protein transporters that play important roles in various aspects of plant growth and development. Here, we performed genome-wide identification of members in the foxtail millet (Setaria italica L.) AAAP family (SiAAAP) and their saline-alkali stress-induced expression patterns, resulting in the identification of 65 SiAAAP genes, which could be divided into eight subfamilies. Except for SiAAAP65, the remaining 64 genes were located on nine chromosomes of foxtail millet. Gene structure and conserved motif analyses indicated that the members in the same subfamily are highly conserved. Gene duplication event analysis suggested that tandem duplication may be the main factor driving the expansion of this gene family, and Ka/Ks analysis indicated that all the duplicated genes have undergone purifying selection. Transcriptome analysis showed differential expression of SiAAAPs in roots, stems, leaves, and tassel inflorescence. Analysis of cis-acting elements in the promoter indicated that SiAAAPs contain stress-responsive cis-acting elements. Under saline-alkali stress, qRT-PCR analysis showed that SiAAP3, SiLHT2, and SiAAP16 were differentially expressed between salt-alkali tolerant millet variety JK3 and salt-alkali sensitive millet variety B175. These results suggest that these genes may be involved in or regulate the response to saline-alkali stress, providing a theoretical basis for further studying the function of SiAAAPs.

CXC ligand 13 orchestrates an immunoactive microenvironment and enhances immunotherapy response in head and neck squamous cell carcinoma.

Objectives: This study aims to systematically explore the role of chemokine CXC ligand 13 (CXCL13) in head and neck squamous cell carcinoma (HNSCC). Methods: The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases provided the RNA-seq data for cancer and normal tissues, respectively. Gene set enrichment analysis was applied to search the cancer hallmarks associated with CXCL13 expression. TIMER2.0 was the main platform used to investigate the immune cell infiltration related to CXCL13. Immunohistochemistry was applied to explore the relationship between CXCL13 and patients' prognosis and the relationship between CXCL13 and tertiary lymphoid structures (TLSs). Results: The expression of CXCL13 was upregulated in most tumors, including HNSCC. The higher expression of CXCL13 was closely related to the positive prognosis of HNSCC. CXCL13 was mainly expressed in B cells and CD8 + T cells, revealing the relationship between its expression and immune activation in the tumor microenvironment. Furthermore, immunohistochemistry and multiple fluorescence staining analysis of HNSCC samples showed a powerful correlation between CXCL13 expression, TLSs formation, and positive prognosis. Finally, CXCL13 significantly increased the response to cancer immunotherapy. Conclusions: CXCL13 may function as a potential biomarker for predicting prognosis and immunotherapy response and associate with TLSs in HNSCC.

[Identification and expression analysis of TCP family members in tobacco (Nicotiana tabacum L.)].

TCP family as plant specific transcription factor, plays an important role in different aspects of plant development. In order to screen TCP family members in tobacco, the homologous sequences of tobacco and Arabidopsis TCP family were identified by genome-wide homologous alignment. The physicochemical properties, phylogenetic relationships and cis-acting elements were analyzed by bioinformatics. The homologous genes of AtTCP3/AtTCP4 were screened, and RT-qPCR was used to detect the changes of gene expression upon 20% PEG6000 treatment. The results show that tobacco contains 63 TCP family members. Their amino acid sequence length ranged from 89 aa to 596 aa, and their protein hydropathicity grand average of hydropathicity (GRAVY) ranged from -1.147 to 0.125. The isoelectric point (pI) ranges from 4.42 to 9.94, the number of introns is 0 to 3, and the subcellular location is all located in the nucleus. The results of conserved domain and phylogenetic relationship analysis showed that the tobacco TCP family can be divided into PCF, CIN and CYC/TB1 subfamilies, and each subfamily has a stable sequence. The results of cis-acting elements in gene promoter region showed that TCP family genes contain low docile acting elements (LTR) and a variety of stress and metabolic regulation related elements (MYB, MYC). Analysis of gene expression patterns showed that AtTCP3/AtTCP4 homologous genes (NtTCP6, NtTCP28, NtTCP30, NtTCP33, NtTCP42, NtTCP57, NtTCP63) accounted for 20% PEG6000 treatment significantly up-regulated/down-regulated expression, and NtTCP30 and NtTCP57 genes were selected as candidate genes in response to drought. The results of this study analyzed the TCP family in the tobacco genome and provided candidate genes for the study of drought-resistance gene function and variety breeding in tobacco.

Proteomic analysis of leaves and roots during drought stress and recovery in Setaria italica L.

Drought is a major environmental factor that limits agricultural crop productivity and threatens food security. Foxtail millet is a model crop with excellent abiotic stress tolerance and is consequently an important subject for obtaining a better understanding of the molecular mechanisms underlying plant responses to drought and recovery. Here the physiological and proteomic responses of foxtail millet (cultivar Yugu1) leaves and roots to drought treatments and recovery were evaluated. Drought-treated foxtail millet exhibited increased relative electrolyte leakage and decreased relative water content and chlorophyll content compared to control and rewatering plants. A global analysis of protein profiles was evaluated for drought-treated and recovery treatment leaves and roots. We also identified differentially abundant proteins in drought and recovery groups, enabling comparisons between leaf and root tissue responses to the conditions. The principal component analysis suggested a clear distinction between leaf and root proteomes for the drought-treated and recovery treatment plants. Gene Ontology enrichment and co-expression analyses indicated that the biological responses of leaves differed from those in roots after drought and drought recovery. These results provide new insights and data resources to investigate the molecular basis of tissue-specific functional responses of foxtail millet during drought and recovery, thereby significantly informing crop breeding.

Effect of nicosulfuron on dynamic changes in the starch-sugar interconversion in sweet maize (Zea mays L.).

Starch is an important reserve of sugar, and starch-sugar conversion in plants plays an important role in the response of plants to various abiotic stresses. Nicosulfuron is a post-emergence herbicide commonly applied to maize fields. However, it is unclear how sucrose and starch in sweet corn are converted to accommodate nicosulfuron stress. Field and pot experiments were conducted to study the effects of nicosulfuron on the sugar metabolism enzymes, starch metabolism enzymes, non-enzyme substances, and expression of key enzyme genes in leaves and roots of sweet maize seedlings. Accordingly, this research compared the responses of the sister lines HK301 and HK320, which are nicosulfuron tolerant and sensitive, respectively. Under nicosulfuron stress, compared with HK301 seedlings, the accumulation of stem and root dry matter of HK320 seedlings was significantly reduced, resulting in a lower root-to-shoot ratio. Compared with HK320 seedlings, nicosulfuron stress significantly increased the sucrose, soluble sugar, and starch contents in HK301 leaves and roots. This may be related to the enhanced carbohydrate metabolism under nicosulfuron stress, including significant changes in sugar metabolism enzyme activity and the levels of SPS and SuSys expression. Further, under nicosulfuron stress, sucrose transporter genes (SUC 1, SUC 2, SWEET 13a, and SWEET 13b) in the leaves and roots of HK301 seedlings were significantly upregulated. Our results emphasize that changes in sugar distribution, metabolism, and transport can improve the adaptability of sweet maize to nicosulfuron stress.

SUMOylation mediates the disassembly of the Smad4 nuclear export complex via RanGAP1 in KELOIDS.

Sentrin/small ubiquitin-like modifier (SUMO) has emerged as a powerful mediator regulating biological processes and participating in pathophysiological processes that cause human diseases, such as cancer, myocardial fibrosis and neurological disorders. Sumoylation has been shown to play a positive regulatory role in keloids. However, the sumoylation mechanism in keloids remains understudied. We proposed that sumoylation regulates keloids via a complex. RanGAP1 acted as a synergistic, functional partner of SUMOs in keloids. Nuclear accumulation of Smad4, a TGF-ß/Smad pathway member, was associated with RanGAP1 after SUMO1 inhibition. RanGAP1*SUMO1 mediated the nuclear accumulation of Smad4 due to its impact on nuclear export and reduction in the dissociation of Smad4 and CRM1. We clarified a novel mechanism of positive regulation of sumoylation in keloids and demonstrated the function of sumoylation in Smad4 nuclear export. The NPC-associated RanGAP1*SUMO1 complex functions as a disassembly machine for the export receptor CRM1 and Smad4. Our research provides new perspectives for the mechanisms of keloids and nucleocytoplasmic transport.

Introducing oxygen vacancies in a bi-metal oxide nanosphere for promoting electrocatalytic nitrogen reduction.

The sluggish breakage of the N-N triple bond, as well as the existence of a competing hydrogen evolution reaction (HER), restricts the nitrogen reduction reaction process. Modification of the catalyst surface to boost N2 adsorption and activation is essential for nitrogen fixation. Herein, we introduced surface oxygen vacancies in bimetal oxide NiMnO3 by pyrolysis at 450 °C (450-NiMnO3) to achieve remarkable NRR activity. The NiMnO3 3D nanosphere with a rough surface could increase catalytically active metal sites and introduce oxygen vacancies that are able to enhance N2 adsorption and further improve the reaction rate. Benefiting from the introduced oxygen vacancies in NiMnO3, 450-NiMnO3 showed excellent performance for nitrogen reduction to ammonia with a high NH3 yield of 31.44 µg h-1 mgcat-1 (at -0.3 V vs. RHE) and a splendid FE of 14.5% (at -0.1 V vs. RHE) in 0.1 M KOH. 450-NiMnO3 also shows high long-term electrochemical stability with excellent selectivity for NH3 formation. 15N isotope labeling experiments further verify that the source of produced ammonia is derived from 450-NiMnO3. The present study opens new avenues for the rational construction of efficient electrocatalysts for the synthesis of ammonia from nitrogen.

Nicosulfuron stress on the glyoxalase system and endogenous hormone content in sweet maize seedlings.

To reduce the harmful effects of nicosulfuron on sweet corn, the physiological regulation mechanism of sweet corn detoxification was studied. This study analyzed the effects of nicosulfuron stress on the glyoxalase system, hormone content, and key gene expression of nicosulfuron-tolerant "HK301" and nicosulfuron-sensitive "HK320" sweet corn seedling sister lines. After spraying nicosulfuron, the methylglyoxal (MG) content in HK301 increased first and then decreased. Glyoxalase I (GlyI) and glyoxalase II (GlyII) activities, non-enzymatic glutathione (GSH), and the glutathione redox state glutathione/(glutathione + glutathione disulfide) (GSH/(GSH + GSSG)) showed a similar trend as the MG content. Abscisic acid (ABA), gibberellin (GA), and zeatin nucleoside (ZR) also increased first and then decreased, whereas the auxin (IAA) increased continuously. In HK301, all indices after spraying nicosulfuron were significantly greater than those of the control. In HK320, MG accumulation continued to increase after nicosulfuron spraying and GlyI and GlyII activities, and GSH first increased and then decreased after 1 day of stress. The indicators above were significantly greater than the control. The GSH/(GSH + GSSG) ratio showed a decreasing trend and was significantly smaller than the control. Furthermore, ABA and IAA continued to increase, and the GA and ZR first increased and then decreased. Compared with HK320, HK301 significantly upregulated the transcription levels of GlyI and GlyII genes in roots, stems, and leaves. Comprehensive analysis showed that sweet maize seedlings improved their herbicide resistance by changing the glyoxalase system and regulating endogenous hormones. The results provide a theoretical basis for further understanding the response mechanism of the glyoxalase system and the regulation characteristics of endogenous hormones in maize under nicosulfuron stress.

Targeting cellular metabolism in head and neck cancer precision medicine era: A promising strategy to overcome therapy resistance.

Head and neck squamous cell carcinoma (HNSCC) is among the most prevalent cancer worldwide, with the most severe impact on quality of life of patients. Despite the development of multimodal therapeutic approaches, the clinical outcomes of HNSCC are still unsatisfactory, mainly caused by relatively low responsiveness to treatment and severe drug resistance. Metabolic reprogramming is currently considered to play a pivotal role in anticancer therapeutic resistance. This review aimed to define the specific metabolic programs and adaptations in HNSCC therapy resistance. An extensive literature review of HNSCC was conducted via the PubMed including metabolic reprogramming, chemo- or immune-therapy resistance. Glucose metabolism, fatty acid metabolism, and amino acid metabolism are closely related to the malignant biological characteristics of cancer, anti-tumor drug resistance, and adverse clinical results. For HNSCC, pyruvate, lactate and almost all lipid categories are related to the occurrence and maintenance of drug resistance, and targeting amino acid metabolism can prevent tumor development and enhance the response of drug-resistant tumors to anticancer therapy. This review will provide a better understanding of the altered metabolism in therapy resistance of HNSCC and promote the development of new therapeutic strategies against HNSCC, thereby contribute to a more efficacious precision medicine.

Unicystic ameloblastoma: A retrospective study on recurrent factors from a single institute database.

OBJECTIVE: Unicystic ameloblastomas are a variant of ameloblastoma with a definite recurrence rate because of the biological behaviours of the tumour. The risk factors associated with disease recurrence were analysed in this retrospective study. METHODS: A total of 132 patients with primary unicystic ameloblastoma reported in a tertiary hospital from 2005 to 2015 were analysed to identify the clinic-pathological and radiological factors associated with recurrence using univariate and multivariate Cox regression analyses. RESULTS: The mean volume was 30.54cm3  ± 12.55 cm3 , and this value differed significantly according to recurrence (p < 0.001). Root resorption and bone cortex/soft tissue invasion were also significantly associated with recurrence among unicystic ameloblastoma patients (p = 0.017 vs. p < 0.001, respectively). A new stage classification system was developed to predict disease recurrence of patients. The multivariate Cox regression analysis revealed that the new stage classification system was the only predictor of disease recurrence in unicystic ameloblastoma patients (p < 0.001), regardless of root resorption, position and site characteristics. CONCLUSIONS: Volume, root resorption and bone cortex/soft tissue invasion were risk factors for disease recurrence among unicystic ameloblastoma patients. The new stage classification was an independent predictor of disease recurrence in patients with unicystic ameloblastoma.

Nanopesticide Formulation from Pyraclostrobin and Graphene Oxide as a Nanocarrier and Application in Controlling Plant Fungal Pathogens.

Efficient and environment-friendly nanopesticide delivery systems are critical for the sustainable development of agriculture. In this study, a graphene oxide nanocomposite was developed for pesticide delivery and plant protection with pyraclostrobin as the model pesticide. First, graphene oxide-pyraclostrobin nanocomposite was prepared through fast adsorption of pyraclostrobin onto graphene oxide with a maximum loading of 87.04%. The as-prepared graphene oxide-pyraclostrobin nanocomposite exhibited high stability during two years of storage, suggesting its high potential in practical application. The graphene oxide-pyraclostrobin nanocomposite could achieve temperature (25 °C, 30 °C and 35 °C) and pH (5, 7 and 9) slow-release behavior, which overcomes the burst release of conventional pyraclostrobin formulation. Furthermore, graphene oxide-pyraclostrobin nanocomposite exhibited considerable antifungal activities against Fusarium graminearum and Sclerotinia sclerotiorum both in vitro and in vivo. The cotoxicity factor assay revealed that there was a synergistic interaction when graphene oxide and pyraclostrobin were combined at the ratio of 1:1 against the mycelial growth of Fusarium graminearum and Sclerotinia sclerotiorum with co-toxicity coefficient values exceeding 100 in vitro. The control efficacy of graphene oxide-pyraclostrobin nanocomposite was 71.35% and 62.32% against Fusarium graminearum and Sclerotinia sclerotiorum in greenhouse, respectively, which was higher than that of single graphene oxide and pyraclostrobin. In general, the present study provides a candidate nanoformulation for pathogenic fungal control in plants, and may also expand the application of graphene oxide materials in controlling plant fungal pathogens and sustainable agriculture.

Comprehensive Analysis of Circular RNA Expression in ceRNA Networks and Identification of the Effects of hsa_circ_0006867 in Keloid Dermal Fibroblasts.

Circular RNAs (circRNAs) play a crucial role in the pathogenesis of various fibrotic diseases, but the potential biological function and expression profile of circRNAs in keloids remain unknown. Herein, microarray technology was applied to detect circRNA expression in four patient-derived keloid dermal fibroblasts (KDFs) and normal dermal fibroblasts (NDFs). A total of 327 differentially expressed (DE) circRNAs (fold change > 1.5, p < 0.05) were identified with 195 upregulated and 132 downregulated circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the upregulated circRNAs were mainly enriched in the cytoskeleton and tight junctions, while the downregulated circRNAs were related to morphogenesis of the epithelium and axonal guidance. To explore the function of DE circRNAs, a circRNA-miRNA-mRNA network, including five circRNAs, nine miRNAs, and 235 correlated mRNAs, was constructed using bioinformatics analyses. The expression of five DE circRNAs was validated by qRT-PCR in 18 pairs of KDFs and NDFs, and hsa_circ_0006867 showed promising regulatory function in keloids in vitro. Silencing hsa_circ_00006867 suppressed the proliferation, migration, and invasion of keloid fibroblasts. RNA-binding protein immunoprecipitation (RIP) assays indicated that hsa_circ_00006867 may serve as a platform for miRNA binding to Argonaute (AGO) 2. In addition, hsa-miR-29a-5p may be a potential target miRNA of hsa_circ_00006867. Taken together, our research provided multiple novel clues to understand the pathophysiologic mechanism of keloids and identified hsa_circ_0006867 as a biomarker of keloids.

Responses of photosynthesis, antioxidant enzymes, and related gene expression to nicosulfuron stress in sweet maize (Zea mays L.).

Weed control in maize (Zea mays L.) crops is usually undertaken using the postemergence herbicide nicosulfuron. The toxicity of nicosulfuron on maize, especially sweet maize, has been widely reported. In order to examine the effect of nicosulfuron on seedling photosynthetic characteristics, chlorophyll fluorescence, reactive oxygen species production, antioxidant enzyme activities, and gene expressions on sweet maize, nicosulfuron-tolerant "HK310" and nicosulfuron-sensitive "HK320" were studied. All experiment samples were subjected to a water or 80 mg kg-1 of nicosulfuron treatment when sweet maize seedlings grow to the stage of four leaves. After treatment with nicosulfuron, results for HK301 were significantly higher than those for HK320 for net photosynthetic rate, transpiration rate, stomatal conductance, leaf maximum photochemical efficiency of PSII, photochemical quenching of chlorophyll fluorescence, and the electron transport rate. These results were contrary to nonphotochemical quenching and intercellular CO2 concentration. As exposure time increased, associated effects also increased. Both O2·- and H2O2 detoxification is modulated by antioxidant enzymes. Compared to HK301, SOD, POD, and CAT activities of HK320 were significantly reduced as exposure time increase. Compared to HK320, the gene expression for the majority of SOD genes, except for SOD2, increased due to inducement by nicosulfuron, and it significantly upregulated the gene expression of CAT in HK301. Results from this study indicate that plants can improve photosynthesis, scavenging capabilities of ROS, and protective mechanisms to alleviate phytotoxic effect of nicosulfuron. Future research is needed to further elucidate the important role antioxidant systems and gene regulation play in herbicide detoxification in sweet maize.

Formulation of nanopesticide with graphene oxide as the nanocarrier of pyrethroid pesticide and its application in spider mite control.

Nanopesticides with controlled release can achieve more effective utilization of pesticides. Here, to enhance the adsorption of pesticides onto the target organisms, the formulation of pesticides with temperature-responsive release was proposed by combing graphene oxide (GO) and existing pyrethroid pesticides (cyhalothrin, bifenthrin and fenpropathrin). Pesticides were loaded onto GO nanosheets as a carrier via a simple physisorption process, and the GO-pesticide nanocomposites exhibited temperature-responsive release and excellent storage stability, which are of vital importance to the practical application. Furthermore, we assessed the bioactivity of the GO-pesticide nanocomposites against spider mites (Tetranychus urticae Koch) indoors and in the field. As a result, GO-pesticide nanocomposites had many folds higher bioactivity than individual pesticides, and could be adsorbed on the cuticle of T. urticae and surface of bean leaves with highly uniform dispersibility. The easy preparation and higher bioactivity of GO-pesticide nanocomposites indicate their promising application potential in pest control and green agriculture.

Occurrence and risk assessment of emerging contaminants in a water reclamation and ecological reuse project.

Water reclamation and ecological reuse is gradually becoming a popular solution to address the high pollutant loads and insufficient ecological flow of many urban rivers. However, emerging contaminants in water reuse system and associated human health and ecological risks need to be assessed. This study determined the occurrence and human health and ecological risk assessments of 35 emerging contaminants during one year, including 5 types of persistent organic pollutants (POPs), 5 pharmaceutical and personal care products (PPCPs), 7 endocrine disrupting chemicals (EDCs) and 18 disinfection by-products (DBPs), in a wastewater treatment plant (WWTP) and receiving rivers, as well as an unimpacted river for comparison. Results showed that most of PPCPs and EDCs, especially antibiotics, triclosan, estrogens and bisphenol A, occurred frequently at relatively high concentrations, and they were removed from 20.5% to 88.7% with a mean of 58.9% via WWTP. The highest potential noncarcinogenic and carcinogenic risks in different reuse scenarios were assessed using maximal detected concentrations, all below the acceptable risk limits, with the highest total combined risk value of 9.21 × 10-9 and 9.98 × 10-7, respectively. Ecological risk assessment was conducted using risk quotient (RQ) method and indicated that several PPCPs, EDCs and haloacetonitriles (HANs) pose high risk (RQ > 1) to aquatic ecology in the rivers, with the highest RQ up to 83.8. The study suggested that ecological risks need to be urgently addressed by updating and optimizing the process in WWTPs to strengthen the removal efficiencies of emerging contaminants. The study can serve as a reference for safer water reuse in the future, while further studies could be conducted on the health risk of specific groups of people, exposure parameters in water reuse, as well as more emerging contaminants.

Sumoylation enhances the activity of the TGF-ß/SMAD and HIF-1 signaling pathways in keloids.

Excessive fibrosis and extracellular matrix deposition resulting from upregulation of target genes expression mediated by transforming growth factor-beta (TGF-ß)/SMAD and hypoxia inducible factor-1 (HIF-1) signaling pathways are the main mechanisms that drive keloid formation. Sumoylation is a protein posttranslational modification that regulates the function of proteins in many biological processes. In the present study, we aimed to investigate the mechanism underlying the effects of sumoylation on the TGF-ß/SMAD and HIF-1 signaling pathways in keloids. We used 2-D08 to block sumoylation and silenced the expression of sentrin sumo-specific protease 1 (SENP1) to enhance sumoylation in human foreskin fibroblasts (HFFs) and human keloid fibroblasts (HKFs). We also reduced and increased intracellular SUMO1 levels by silencing SUMO1 and transfecting cells with a SUMO1 overexpression lentivirus, respectively. Sumoylation has the ability to amplify TGF-ß/SMAD and HIF-1 signals in keloids, while SUMO1, especially the SUMO1-RanGAP1 complex, is the key molecule affecting the TGF-ß/SMAD and HIF-1 signaling pathways. In addition, we also found that hypoxia promotes sumoylation in keloids and that HIF-1α is covalently modified by SUMO1 at Lys 391 and Lys 477 in HKFs. In summary, we elucidated the role and molecular mechanism of sumoylation in the formation of keloids, providing a new perspective for a potential therapeutic target of keloids.

TM4SF1 involves in miR-1-3p/miR-214-5p-mediated inhibition of the migration and proliferation in keloid by regulating AKT/ERK signaling.

AIMS: Transmembrane 4 L six family member 1 (TM4SF1) is a small plasma membrane glycoprotein that is highly expressed in cancers. However, the role of TM4SF1 that plays in keloids remains unknown. We investigated the expression, function and the microRNA (miRNA) regulatory network of TM4SF1 in keloids. MAIN METHODS: Small interfering RNAs and lentivirus were used to alter the expression of TM4SF1 in fibroblasts. Dual-luciferase reporter assays were applied to determine the miRNA targets. Immunohistochemistry, western blotting, qRT-PCR, wound healing assays, Transwell assays, cell count kit-8 assays and flow cytometry were also employed in this study. KEY FINDINGS: TM4SF1 was frequently upregulated in human keloid fibroblasts (HKFs) compared with human normal skin fibroblasts (HSFs). The downregulation of TM4SF1 significantly inhibited proliferation and migration, and induced apoptosis in HKFs. Furthermore, si-TM4SF1 inhibited the AKT/ERK signaling. Meanwhile, the upregulation of TM4SF1 promoted proliferation, migration and the activation of AKT/ERK signaling in human foreskin fibroblasts (HFF-1). Moreover, TM4SF1 can be regulated by miRNAs, which have been validated to play important roles in keloids by posttranscriptional regulation of gene expression. After screening, we found miR-1-3p and miR-214-5p targeted TM4SF1, inhibited TM4SF1 expression, cell proliferation, migration, and induced apoptosis in HKFs. And the level of miR-1-3p and miR-214-5p were found lower in HKFs than in HSFs. SIGNIFICANCE: Our study demonstrates a novel regulatory mechanism by which miR-1-3p, miR-214-5p, and TM4SF1 are involved in proliferation, cell motility, and apoptosis, suggesting that they may be potential targets in therapies for keloids.

Auxiliary usage of botulinum toxin A in plastic surgery in China.

BACKGROUND: Currently, botulinum toxin A (BTA) is mainly used in the treatment of muscle spasms and in cosmetic procedures, and its cosmetic indications are expanding rapidly. There have been sporadic reports focused on the preoperative usage of BTA complementing plastic surgery. We briefly summarize the current experience of BTA complementing plastic surgery in China based on clinical experience. METHODS: We reported a brief review of the preoperative use of BTA as an accessory to plastic surgery (blepharoplasty, chin augmentation, mandibular angle ostectomy, rhinoplasty, hyaluronic acid fillers injection for wrinkle reduction) based on previous studies and our experience. RESULTS: Preoperative treatment with BTA in plastic surgery helps surgeons operate and results in better cosmetic results. CONCLUSIONS: Preoperative BTA treatment can reduce the occurrence of surgical complications as well as improve the surgical results in some plastic surgeries. The procedure is suitable for clinical application and worth promoting.