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Objective: To explore the operational accuracy and operative time of oral surgery robot-assisted endodontic microsurgery on a head-simulator for clinical reference. Methods: Three pairs of surgical simulation models were set up on head-simulator. Each model included 10 positions anteriorly and posteriorly, 20 teeth for each technique, for a total of 60 teeth. An attending physician with more than 3 years clinical experience in endodontic microsurgery completed fixed-point osteotomy and apicoectomy in three groups of endodontic microsurgery under freehand (FH), static navigation (SN), and surgery robot (SR). The duration of each operation was recorded. Cone-beam CT was taken before the operation and the surgical path was planned in the software; after surgery, a plug gauge (precision gauge for measuring hole dimensions) was inserted into the surgical path for intraoral scanning. Surgical accuracy (starting point, end point, and angular deviation) was assessed in all 3 groups, and surgery time was compared. Results: The deviation at the starting point and the end point, and angular deviation was (0.37±0.11), (0.37±0.10) mm, and 0.71°±0.17°in the SR group. The deviations in the SR group were significantly lower than those in the SN group [(0.59±0.14), (0.65±0.18) mm, and 2.64°±0.75°] (P<0.05), and both groups were significantly lower than the FH group [(1.37±0.31), (1.10±0.21) mm, and 9.84°±3.15°] (P<0.05). The operative time in the SN group [(1.20±0.03) min] was significantly less than that in the SR group [(2.18±0.03) min] (P<0.05), and both groups were significantly less than that in the FH group [(8.70±3.15) min] (P<0.05). Starting point deviation, end point deviation, and angular deviation [(1.09±0.10), (0.90±0.07) mm, 7.22°±1.13°] in anterior teeth using the FH was significantly lower than the starting deviation, endpoint deviation, and angular deviation [(1.65±0.14), (1.30±0.06) mm, 12.46°±2.10°] in the posterior teeth using FH (P<0.05), and the operative time in the anterior teeth using the FH [(5.75±0.57) min] was significantly less than that in the posterior teeth using [(11.65±1.14) min] (P<0.05). The difference in accuracy and operative time between using SN and SR on anterior and posterior teeth was not statistically significant (P>0.05). Conclusions: Oral surgery robot-assisted endodontic microsurgery helps improving the accuracy of clinicians' operations and shorten the operation time.

Objective: The preliminary results was reported regarding the treatment of mesenteric torsion by mesenteric fixation in the last decade, especially preventing recurrence of mesenteric torsion by mesenteric fan-shaped fixation. Methods: We selected 12 patients who received emergency operation in Chongqing Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from December 2010 to March 2022. All of them were made a definite diagnose of mesenteric torsion by the preoperative CT scan or exploratory laparotomy. The recurrence of mesenteric torsion will be prevented by taking the operation of mesenteric fan-shaped fixation. This technique is suitable for the patient who is suffering total mesenteric torsion, but enteric necrosis is excluded affirmatively. The operation is consists of the following progress: (1) Exploratory laparotomy to check for necrosis of the bowel and for lesions other than torsion. (2) Mesenteric torsion derotation.(3) Mesenteric linear fixation; the right posterior lower border of the small mesentery (terminal ileal mesentery) is intermittently sutured to the posterior peritoneum of the right lower quadrant to increase the width of the base of the small mesentery. (4) Mesenteric fan-shaped fixation, which is fan-shaped to the lower left and fixed in the posterior peritoneum, shortening the length of the mesentery and further increasing the width of the mesentery and posterior peritoneal fixation. Results: A total of 12 patients with mesenteric torsion were treated by operation for 15 times in all. Among them, 3 cases received resection of most small bowel were performed without recurrence; 3 patients received only derotation for a total of 4 times, 2 cases recurred, 1 of them recurred twice; 4 cases underwent derotation and mesenteric linear fixation,and 1 case recurred. Four patients with derotation and mesenteric fan-shaped fixation recovered well without recurrence. Conclusion: Mesenteric fan-shaped fixation may be an effective operative type to reduce or avoid postoperative recurrence of mesenteric torsion.

Background: Extensive data suggest that exposure to cigarette smoke can induce pulmonary epithelial barrier dysfunction. However, the effects of cigarette smoke on the nasal epithelial barrier are still unclear. Here, we investigated the consequence and mechanism of cigarette smoke on the nasal epithelial barrier., Methods: Sprague Dawley rats were exposed to cigarette smoke for 3 or 6 months, and changes in inflammatory markers and nasal barrier function were evaluated. Moreover, underlying mechanisms were explored. Finally, normal human bronchial epithelial cells were cultured with or without tumor necrosis factor-alpha (TNF-α) in vitro, and the levels of continuity and tight junction-associated proteins were measured., Results: In vivo experiments showed that the nasal mucosal barrier function of rats exposed to cigarette smoke was disturbed. Indeed, proteins associated with tight junctions were decreased, and the levels of inflammatory factors, such as IL-8, IL-6, and TNF-α, were dramatically increased in comparison to those of control animals. In vitro, TNF-α was shown to disrupt the continuity of proteins associated with tight junctions and to downregulate the expression of these proteins in bronchial epithelial cells., Conclusions: We found that cigarette smoke disrupted the nasal mucosal barrier, and the extent of the damage was correlated with the duration of cigarette smoke exposure. We showed that TNF-α can disrupt the continuity and attenuate the expression of tight junction proteins in human bronchial epithelial cells. Therefore, cigarette smoke may induce nasal epithelial barrier dysfunction through TNF-α., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chronic wounds that fail to progress through normal phases of healing present a significant healthcare burden owing to prolonged treatment and associated costs. Traditional wound care typically involves regular dressing changes, which can be painful. Recent approaches have explored the use of lidocaine to manage pain and red-light irradiation (RLI), known for its anti-inflammatory and cell proliferation effects, to potentially enhance wound healing., Aim: To investigate the therapeutic efficacy of lidocaine wet compression (LWC) combined with RLI for chronic wounds., Methods: We enrolled 150 patients with chronic wounds from the Wound and Ostomy Outpatient Clinic of the Second Hospital of Anhui Medical University from April to September 2022. The wounds were treated with dressing changes. The patients were randomly assigned to the control and experimental groups using a random number table and given the same first dressing change (2% LWC for 5 min and routine dressing change). From the second dressing change, in addition to 2% LWC for 5 min and routine dressing change, the experimental group received RLI, whereas the control group continued to receive the same LWC and dressing change. The first and second dressing changes were performed on days 1 and 2, respectively. The third dressing change was performed 3 d after the second change. The frequency of subsequent dressing changes was determined based on wound exudation and pain. Pain during the first three dressing changes was evaluated in both groups. The average number of dressing changes within 28 d and the degree of wound healing on day 28 were also recorded., Results: During the initial dressing change, no noticeable differences were observed in the pain levels experienced by the two groups, indicating similar pain tolerance. However, during the second and third dressing changes, the experimental group reported significantly less pain than the control group. Furthermore, over 28 d, the experimental group required fewer dressing changes than the control group., Conclusion: Notably, the effectiveness of wound healing on the 28 th day was significantly higher in the experimental group than that of in the control group. The combination of LWC and RLI was effective in reducing early-stage pain, promoting wound healing, decreasing the frequency of dressing changes, and enhancing patients' overall quality of life with chronic wounds., Competing Interests: Conflict-of-interest statement: All authors declare that there are no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity characterized by intrahepatic ectopic steatosis. As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle, the incidence of NAFLD has surpassed that of viral hepatitis, making it the most common cause of chronic liver disease globally. Huangqin decoction (HQD), a Chinese medicinal formulation that has been used clinically for thousands of years, has beneficial outcomes in patients with liver diseases, including NAFLD. However, the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood., Aim: To evaluate the ameliorative effects of HQD in NAFLD, with a focus on lipid metabolism and insulin resistance, and to elucidate the underlying mechanism of action., Methods: High-fat diet-induced NAFLD rats and palmitic acid (PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action. Phytochemicals in HQD were analyzed by high-performance liquid chromatography (HPLC) to identify the key components., Results: Ten primary chemical components of HQD were identified by HPLC analysis. In vivo , HQD effectively prevented rats from gaining body and liver weight, improved the liver index, ameliorated hepatic histological aberrations, decreased transaminase and lipid profile disorders, and reduced the levels of pro-inflammatory factors and insulin resistance. In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation, inflammation, and insulin resistance in HepG2 cells. In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathway-modulated lipogenesis and inflammation, contributing to its beneficial actions, which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD., Conclusion: In summary, our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Tranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in patients after surgery. The choice of antithrombotic agents for venous thromboembolism (VTE) prevention after TKA is controversial. Therefore, this study aimed to compare the effects of different antithrombotic agents on patients after primary unilateral TKA in the context of applied TXA., Methods: A total of 180 patients undergoing primary unilateral TKA from October 2020 to December 2021 were included in this study. All patients were given an intraoperative drip of 60 mg/kg TXA. Thereafter, patients were divided into three groups (n = 60 each). Baseline data were comparable among the three groups. The average follow-up time was 3.02 ± 0.09 months. Group 1 enrolled patients receiving oral rivaroxaban (RA) at 10 mg, Group 2 included patients who received subcutaneous Dalteparin sodium at 2500 IU, while Group 3 included patients taking oral aspirin (ASA) at 100 mg. Patients in all the three groups received treatment once a day for 30 days at 12 h postoperatively. The primary outcomes in this study were post-treatment drainage volume and thrombotic complication rate. The secondary outcomes included hematologic parameters, transfusion rate, intraoperative blood loss, total blood loss (TBL), and bleeding complication rate., Results: The average drainage volume after treatment was significantly lower in Group 3 than in Group 1 and Group 2 (205.2 ± 69.0 vs 243.4 ± 72.5 vs 295.4 ± 72.5 ml, P < 0.001), and there was a significant difference between Group 1 and Group 2 (243.4 ± 72.5 mL vs 295.4 ± 72.5 mL, P < 0.001). The blood transfusion rate of Group 2 dramatically increased compared with Group 1 and Group 3 (20.0% vs 6.7% vs 5.0%, P = 0.01). The bleeding complication rate in Group 1 apparently increased relative to Group 2 and Group 3 (26.7% vs 10.0% vs 8.3%, P = 0.008). Besides, there was no significant difference in the thrombotic complication rate among the three groups., Conclusion: Under the background of TXA application, ASA, RA, and Dalteparin sodium were all effective on preventing VTE after TKA. In addition, ASA effectively reduced post-treatment Hemoglobin (Hb) loss, drainage volume, TBL, transfusion rate, and bleeding complications compared with RA and Dalteparin sodium., Trial Registration: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200060169). Date of Registration: 21/05/2022., (© 2023. The Author(s).)

Septic acute kidney injury (AKI) is characterized by inflammation. Pyroptosis often occurs during AKI and is associated with the development of septic AKI. This study found that induction of insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to a higher level can induce pyroptosis in renal tubular cells. Meanwhile, macrophage migration inhibitory factor (MIF), a subunit of NLRP3 inflammasomes, was essential for IGF2BP1-induced pyroptosis. A putative m6A recognition site was identified at the 3'-UTR region of E2F transcription factor 1 (E2F1) mRNA via bioinformatics analyses and validated using mutation and luciferase experiments. Further actinomycin D (Act D) chase experiments showed that IGF2BP1 stabilized E2F1 mRNA dependent on m6A. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) indicated that E2F1 acted as a transcription factor to promote MIF expression. Thus, IGF2BP1 upregulated MIF through directly upregulating E2F1 expression via m6A modification. Experiments on mice with cecum ligation puncture (CLP) surgery verified the relationships between IGF2BP1, E2F1, and MIF and demonstrated the significance of IGF2BP1 in MIF-associated pyroptosis in vivo . In conclusion, IGF2BP1 was a potent pyroptosis inducer in septic AKI through targeting the MIF component of NLRP3 inflammasomes. Inhibiting IGF2BP1 could be an alternate pyroptosis-based treatment for septic AKI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aberrant DNA methylation of genes is closely linked to many aspects of tumor development. This study focuses on the effect of DNA hypermethylation of von Willebrand factor C domain containing 2 (VWC2) on colorectal cancer (CRC) progression and the underpinning mechanism. According to data in the bioinformatic systems, VWC2 had the highest degree of DNA methylation in colonic adenocarcinoma, and it showed DNA hypermethylation in rectal adenocarcinoma as well. CRC and the para-tumorous tissues were collected from 86 patients. VWC2 was expressed at low levels in CRC samples and inversely correlated with tumor stage and tumor biomarker expression. DNA hypermethylation and reduced expression of VWC2 were also detected in CRC cell lines HCT-116 and HT29. VWC2 overexpression suppressed the malignant growth of cells in vitro and in vivo. Co-immunoprecipitation and western blot assays showed that small ubiquitin-like modifier 1 (SUMO1) mediated SUMOylation of DNA methyltransferase 1 (DNMT1) and strengthened its protein stability, which promoted DNA methylation and suppression of the VWC2 gene. In summary, this study demonstrates that SUMO1-mediated activation of DNMT1 induces DNA methylation and downregulation of VWC2 in CRC to augment cancer development.

The microstructure and mechanical properties of extruded AZ31 + x TiCN ( x = 0, 0.4, 0.8, 1.2 wt%) were investigated, and the strengthening mechanism was discussed. X-ray diffraction and energy dispersive spectroscopy (EDS) confirmed that the Al 4 C 3 and Al 2 MgC 2 duplex phase particles were generated in situ by TiCN and Al particles, which act as the nucleation precursors of Mg grains during solidification. The grain size decreased and then increased with increasing TiCN addition. The yield strength (YS) and ultimate tensile strength (UTS) increased with increasing TiCN addition reaching a maximum (217.5 MPa) at 0.4 wt%, and in contrast, the elongation index (EI) continuously decreased with increasing TiCN addition., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The effects of general anesthetics on the developing brain have aroused much attention in recent years. Sevoflurane, a commonly used inhalation anesthetic especially in pediatric anesthesia, can induce developmental neurotoxicity. In this study, the differentially expressed mRNAs in the hippocampus of newborn rats exposed to 3% sevoflurane for 6 h were detected by RNA-Sequencing. Those data indicated that the mRNA of Klotho was increased after exposure to sevoflurane. Moreover, the protein expression of Klotho was assayed by Western Blot. Besides over-expression and under-expression of Klotho protein, we also detected changes of cell proliferation, ROS, JC-1, and Bcl-2/Bax ratio in PC12 cells exposed to sevoflurane. After exposure to 3% sevoflurane, the expression of Klotho protein increased in the hippocampus of neonatal rats. In PC12 cells, exposure to sevoflurane could increase cellular ROS level, reduce mitochondrial membrane potential and Bcl-2/Bax ratio. While overexpression of Klotho alleviated the above changes, knockdown of Klotho aggravated the injury of sevoflurane. Klotho protein could reduce oxidative stress and mitochondrial injury induced by sevoflurane in the neuron., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

2D van der Waals materials are crystals composed of atomic layers, which have atomic thickness scale layers and rich distinct properties, including ultrafast optical response, surface effects, light-mater interaction, small size effects, quantum effects and macro quantum tunnel effects. With the exploration of saturable absorption characteristic of 2D van der Waals materials, a series of potential applications of 2D van der Waals materials as high threshold, broadband and fast response saturable absorbers (SAs) in ultrafast photonics have been proposed and confirmed. Herein, the photoelectric characteristics, nonlinear characteristic measurement technique of 2D van der Waals materials and the preparation technology of SAs are systematically described. Furthermore, the ultrafast pulsed fiber lasers based on classical 2D van der Waals materials including graphene, transition metal chalcogenides, topological insulators and black phosphorus have been fully summarized and analyzed. On this basis, opportunities and directions in this field, as well as the research results of ultrafast pulsed fiber lasers based on the latest 2D van der Waals materials (such as PbO, FePSe 3 , graphdiyne, bismuthene, Ag 2 S and MXene etc), are reviewed and summarized., (© 2021 IOP Publishing Ltd.)

Propionibacterium acnes plays a major role in acne vulgaris. In the pre-experiment, the growth of P. acnes was inhibited effectively using surfactin; however, the antibacterial mechanism has not been described. Therefore, the aim of this study was to evaluate antibacterial activity and analyse the mechanism of surfactin against P. acnes. Minimum inhibitory concentration, time-killing kinetics and scanning electron microscopy were used to evaluate the activity of surfactin against P. acnes, which showed that 128 μg ml -1 effectively inhibited growth. Cell wall permeability was evaluated by detecting the extracellular alkaline phosphatase activity, which increased to 1·83- and 2·32-fold after incubating with 128 and 256 μg ml -1 of surfactin for 10 h, respectively. Propidium iodide fluorescence, leakage of nucleic acid, protein, K + , and Ca 2+ , membrane potential and the leakage of calcein from small unilamellar vesicles all increased after incubation with surfactin, indicating that its strong biological activities act mainly by altering membrane integrity. In a mouse model of acne, surfactin significantly reduced P. acnes-induced epidermal swelling and erythema. These results indicate that surfactin effectively inhibited the growth of P. acnes by destroying the cell wall and membrane, and is a potential candidate for acne treatment., (© 2021 The Society for Applied Microbiology.)

Androgenetic alopecia (AGA) is the most common type of hair loss dysfunction. Secreted frizzled related protein 1 (SFRP1) is found to be associated with hair loss, but its role in AGA and the regulation mechanism of its transcription level is unclear. The aim of our study is to explore the expression of SFRP1 in AGA samples and its transcriptional mechanism. Male frontal and occipital scalp hair follicles from AGA patients were collected, and human dermal papilla cells (DPCs) were isolated and cultured. SFRP1 gene was cloned and constructed into recombinant plasmids to perform dual-luciferase reporter assay. Transcription factor binding sites were predicted through the Jaspar website and further confirmed by the chromatin immunoprecipitation (ChIP) assay. Expression of genes in DPCs was determined by immunofluorescence (IF) staining, quantitative real-time PCR (qRT-PCR) and western blotting. Our findings showed that SFRP1 was highly expressed in DPCs of AGA patients. The core promoter region of SFRP1 was from -100 to +50 bp and was found to be positively regulated by forkhead box C1 (FOXC1), a transcription factor related to hair growth, both at mRNA and protein level in DPCs. Our study suggests that FOXC1 plays an important role in regulating SFRP1 transcription, which may provide new insights into the development of therapeutic strategies for the treatment of AGA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Sepsis is a systemic inflammatory response syndrome caused by infection, resulting in organ dysfunction. Sepsis-induced acute kidney injury (AKI) is one of the most common potential complications. Increasing reports have shown that M1 and M2 macrophages both take part in the progress of AKI by influencing the level of inflammatory factors and the cell death, including pyroptosis. However, whether M1 and M2 macrophages regulate AKI by secreting exosome remains unknown. In the present study, we isolated the exosomes from M1 and M2 macrophages and used Western blot and enzyme-linked immunosorbent assay (ELISA) to investigate the effect of M1 and M2 exosomes on cell pyroptosis. miRNA sequencing was used to identify the different miRNA in M1 and M2 exosomes. Luciferase reporter assay was used to verify the target gene of miRNA. We confirmed that exosomes excreted by macrophages regulated cell pyroptosis in vitro by using Western blot and ELISA. miRNA sequencing revealed the differentially expressed level of miRNAs in M1 and M2 exosomes, among which miR-93-5p was involved in the regulation of pyroptosis. By using bioinformatics predictions and luciferase reporter assay, we found that thioredoxin-interacting protein (TXNIP) was a direct target of miR-93-5p. Further in vitro and in vivo experiments indicated that exosomal miR-93-5p regulated the TXNIP directly to influence the pyroptosis in renal epithelial cells, which explained the functional difference between different phenotypes of macrophages. This study might provide new targets for the treatment of sepsis-induced AKI., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Multiple types of stem cells have been proposed for the treatment of spinal cord injury, but their comparative information remains elusive. In this study, a rat model of T10 contusion spinal cord injury was established by the impactor method. Human umbilical cord-derived mesenchymal stem cells (UCMSCs) or human adipose tissue-derived mesenchymal stem cells (ADMSCs) (2.5 μL/injection site, 1 × 10 5 cells/μL) was injected on rostral and caudal of the injury segment on the ninth day after injury. Rats injected with mesenchymal stem cell culture medium were used as controls. Our results show that although transplanted UCMSCs and ADMSCs failed to differentiate into neurons or glial cells in vivo, both significantly improved motor and sensory function. After spinal cord injury, UCMSCs and ADMSCs similarly promoted spinal neuron survival and axonal regeneration, decreased glial scar and lesion cavity formation, and reduced numbers of active macrophages. Bio-Plex analysis of spinal samples showed a specific increase of interleukin-10 and decrease of tumor necrosis factor α in the ADMSC group, as well as a downregulation of macrophage inflammatory protein 3α in both UCMSC and ADMSC groups at 3 days after cell transplantation. Upregulation of interleukin-10 and interleukin-13 was observed in both UCMSC and ADMSC groups at 7 days after cell transplantation. Isobaric tagging for relative and absolute quantitation proteomics analyses showed that UCMSCs and ADMSCs induced changes of multiple genes related to axonal regeneration, neurotrophy, and cell apoptosis in common and specific manners. In conclusion, UCMSC and ADMSC transplants yielded quite similar contributions to motor and sensory recovery after spinal cord injury via anti-inflammation and improved axonal growth. However, there were some differences in cytokine and gene expression induced by these two types of transplanted cells. Animal experiments were approved by the Laboratory Animal Ethics Committee at Jinan University (approval No. 20180228026) on February 28, 2018, and the application of human stem cells was approved by the Medical Ethics Committee of Medical College of Jinan University of China (approval No. 2016041303) on April 13, 2016., Competing Interests: None

SHANK2 is a scaffold protein that serves as a protein anchor at the postsynaptic density in neurons. Genetic variants of SHANK2 are strongly associated with synaptic dysfunction and the pathophysiology of autism spectrum disorder. Recent studies indicate that early neuronal developmental defects play a role in the pathogenesis of autism spectrum disorder, and that insulin-like growth factor 1 has a positive effect on neurite development. To investigate the effects of SHANK2 knockdown on early neuronal development, we generated a sparse culture system using human induced pluripotent stem cells, which then differentiated into neural progenitor cells after 3-14 days in culture, and which were dissociated into single neurons. Neurons in the experimental group were infected with shSHANK2 lentivirus carrying a red fluorescent protein reporter (shSHANK2 group). Control neurons were infected with scrambled shControl lentivirus carrying a red fluorescent protein reporter (shControl group). Neuronal somata and neurites were reconstructed based on the lentiviral red fluorescent protein signal. Developmental dendritic and motility changes in VGLUT1 + glutamatergic neurons and TH + dopaminergic neurons were then evaluated in both groups. Compared with shControl VGLUT1 + neurons, the dendritic length and arborizations of shSHANK2 VGLUT1 + neurons were shorter and fewer, while cell soma speed was higher. Furthermore, dendritic length and arborization were significantly increased after insulin-like growth factor 1 treatment of shSHANK2 neurons, while cell soma speed remained unaffected. These results suggest that insulin-like growth factor 1 can rescue morphological defects, but not the change in neuronal motility. Collectively, our findings demonstrate that SHANK2 deficiency perturbs early neuronal development, and that IGF1 can partially rescue the neuronal defects caused by SHANK2 knockdown. All experimental procedures and protocols were approved by the Laboratory Animal Ethics Committee of Jinan University, China (approval No. 20170228010) on February 28, 2017., Competing Interests: None

The effects of seed size and drought stress on the growth and physiological characteristics of Quercus wutaishanica seedlings were investigated under shading conditions of a pot experiment in greenhouse. There were four treatments, including 80% field water content (FWC), 60% FWC, 40% FWC, and 20% FWC [CK, light drought stress (LDS), medium drought stress (MDS), and high drought stress (HDS), respectively]. The results showed that leaf area per plant, total dry mass, and root-shoot ratio of Q. wutaishanica seedlings regenerated from large seeds (3.05±0.38 g) were significantly higher than those from small seeds (1.46±0.27 g) in all four treatments. Shoot height, basal stem diameter, leaf number, specific leaf area, relative growth rate, and net assimilation rate of the seedlings from large seeds were higher than those of seedlings from small seeds under the treatments of LDS, MDS and HDS. Activities of peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) in large-seeded seedlings were higher than those of small-seeded seedlings under all treatments, while the contents of MDA, soluble protein, free proline, and total chlorophyll of large-seeded seedlings were higher than those of small-seeded seedlings only under some drought stress treatments. All growth parameters except the root-shoot ratio decreased with the increases of drought stress. The HDS treatment resulted in 19.4% and 20.0% decline in total dry mass of large- and small-seeded seedlings respectively, compared with those of CK. With increasing drought stress, the activities of POD, CAT, and SOD decreased after an initial increase. POD activity of large- and small-seeded seedling under MDS treatment was 126.7% and 142.1% higher than CK, while CAT was 170.0% and 151.9% higher than CK, respectively. However, the MDA content of seedlings from large and small seeds under HDS treatment was 86.5% and 68.9% higher than that of CK, respectively. The contents of soluble protein, free proline, and total chlorophyll rose at first and then fell with increasing drought stress, and soluble protein content in large- and small-seeded seedlings experienced MDS enhanced 320.7% and 352.7%, respectively. Those results indicated that large-seeded seedlings of Q . wutaishanica had stronger drought tolerance than small-seeded seedlings due to their growth and physiology advantages. Large-seeded seedlings with stronger resistance to drought stress should be applied to artificial regeneration of the degraded secondary Q . wutaishanica plantations.

Background: Anastomotic leakage (AL) is one of the most severe early complications after rectal cancer surgery. Many studies and meta-analysis results show that the indentation of transanal drainage tubes (TDT) can prevent and reduce the incidence of AL. However, the size and material of drainage tubes are rarely reported. Herein, we compare the effect of three kinds of TDT and analyze the use of TDT material and size to prevent AL, which may better prevent the occurrence of AL., Methods: The clinical data of 182 patients who underwent laparoscopic anterior resection of rectal cancer were retrospectively analyzed between January 2016 and March 2019. According to the types of indwelling TDT after the operation, they were divided into Fr32 silicone tubes (81 cases), Fr24 silicone tubes (54 cases), Fr24 latex tubes (47 cases). The first drainage, exhaust, defecation, abdominal distension and anastomotic leakage of the patients with three different types of TDT were compared., Results: There was no significant difference in the degree of first exhaust, abdominal distension and anastomotic leakage among three different types of TDT; the time of first drainage and defecation of the Fr32 silicone tube was significantly earlier than that of Fr24 silicone tube and Fr24 latex tube., Conclusion: The drainage effect of the Fr32 silicone tube is better than that of Fr24 silicone tube and Fr24 latex tube after anterior resection for rectal cancer, Fr32 silicone may better prevent the occurrence of AL, but randomized controlled studies are needed.

Aim: To identify proangiogenic factors engaged in neovascular age-related macular degeneration (AMD) except vascular endothelial growth factor (VEGF) from human retinal pigment epithelial (hRPE) cells and investigate the underlying mechanisms., Methods: VEGF receptor 2 (VEGFR2) in ARPE-19 cells was depleted by siRNA transfection or overexpressed through adenovirus infection. The mRNA and the protein levels of interleukin-8 (IL-8) in ARPE-19 cells were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay respectively. The protein levels of AKT, p-AKT, MEK, p-MEK, ERK1/2, p-ERK1/2, JNK, p-JNK, p38 and p-p38 were detected by Western blotting. A selective chemical inhibitor, LY3214996, was employed to inhibit phosphorylation of ERK1/2. Cell viability was determined by MTT assay., Results: Knockdown of VEGFR2 in ARPE-19 cells robustly augmented IL-8 production at both the mRNA and the protein levels. Silencing VEGFR2 substantially enhanced phosphorylation of MEK and ERK1/2 while exerted no effects on phosphorylation of AKT, JNK and p38. Inhibiting ERK1/2 phosphorylation by LY3214996 reversed changes in VEGFR2 knockdown-induced IL-8 upregulation at the mRNA and the protein levels with no effects on cell viability. VEGFR2 overexpression significantly reduced IL-8 generation at the mRNA and the protein levels., Conclusion: Blockade of VEGF signaling augments IL-8 secretion via MEK/ERK1/2 axis and overactivation of VEGF pathway decreases IL-8 production in hRPE cells. Upregulated IL-8 expression after VEGF signaling inhibition in hRPE cells may be responsible for being incompletely responsive to anti-VEGF remedy in neovascular AMD, and IL-8 may serve as an alternative therapeutic target for neovascular AMD., (International Journal of Ophthalmology Press.)

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA SNHG16 promotes migration and invasion through suppression of CDKN1A in clear cell renal cell carcinoma, by S.-B. Liu, H.-F. Wang, Q.-P. Xie, G. Li, L.-B. Zhou, B. Hu, published in Eur Rev Med Pharmacol Sci 2020; 24 (7): 3572-3578-DOI: 10.26355/eurrev&#95;202004&#95;20818-PMID: 32329831" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20818.

Objectives: The aim of this study was to (1) understand types and amounts of Ebola-related information that health organization employees wanted and obtained through formal, informal, internal, and external organizational communication channels; (2) determine potential discrepancies between information wanted and obtained; and (3) investigate how organizational structure might affect information wanted and obtained through these communication channels., Methods: Primary data were collected from 526 health workers in 9 hospitals and 13 public health departments in Texas from June to November 2015. Survey data were collected for 7 types of Ebola-related information health organization employees wanted and obtained through various types of organizational communication channels. Descriptive statistical analyses, mixed design analysis of variance, regression analyses, and multilevel analyses were used to analyze the data., Results: Hospital employees (mostly nurses in our sample) received more self-care information than they wanted from every communication channel. However, they received less about all other types of information than they wanted from every communication channel separately and combined. Public health department employees wanted more information than they received from every communication channel separately and combined for all 7 types of information., Conclusions: Discrepancies existed between the types of Ebola-related information wanted and obtained by employees of hospitals and public health departments.

Objective: Researchers have discovered the important role of long noncoding RNAs (lncRNAs) in tumorigenesis. In this study, lncRNA SNHG16 was studied to identify whether it influences metastasis of clear cell renal cell carcinoma (ccRCC)., Patients and Methods: SNHG16 expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in both ccRCC cells and tissue samples. The association between prognosis of ccRCC patients and the expression of SNHG16 was analyzed through Kaplan-Meier method. Moreover, functional assays including wound healing assay and transwell assay were conducted. Bioinformatics analysis, qRT-PCR and Western blot assay were used to explore the underlying mechanism. Furthermore, animal experiments were conducted to explore the function of SNHG16 in vivo., Results: SNHG16 expression level was higher in ccRCC samples when compared with that in adjacent ones. Moreover, cell migration and cell invasion capacities were inhibited after SNHG16 was silenced in vitro. In addition, the mRNA and protein expression of CDKN1A was upregulated after silence of SNHG16. Furthermore, the expression level of CDKN1A was negatively related to the expression of SNHG16 in ccRCC tissues. The experiments in vivo showed that silence of SNHG16 remarkably repressed the metastasis of ccRCC., Conclusions: These results suggest that silence of SNHG16 could inhibit cell migration and invasion via upregulating CDKN1A in ccRCC.

α-Synucleinopathies are characterized by autonomic dysfunction and motor impairments. In the pure autonomic failure (PAF), α-synuclein (α-Syn) pathology is confined within the autonomic nervous system with no motor features, but mouse models recapitulating PAF without motor dysfunction are lacking. Here, we show that in TgM83 +/- mice, inoculation of α-Syn preformed fibrils (PFFs) into the stellate and celiac ganglia induces spreading of α-Syn pathology only through the autonomic pathway to both the central nervous system (CNS) and the autonomic innervation of peripheral organs bidirectionally. In parallel, the mice develop autonomic dysfunction, featured by orthostatic hypotension, constipation, hypohidrosis and hyposmia, without motor dysfunction. Thus, we have generated a mouse model of pure autonomic dysfunction caused by α-Syn pathology. This model may help define the mechanistic link between transmission of pathological α-Syn and the cardinal features of autonomic dysfunction in α-synucleinopathy.

The insulin growth factor 2 receptor (IGF2R) belongs to insulin growth factor (IGF) pathway and has been proposed as the tumor suppressor in many cancers. However, its role in bladder cancer is unknown. In the current study, we reported that IGF2R expression was decreased in bladder cancer tissues (p<0.05). Immunohistochemistry (IHC) and Cox regression analysis showed that low IGF2R expression was significantly associated with more advanced histological grade; high clinical stage; lymph node metastasis and poorer overall survival for patients with bladder cancer. Moreover, silencing IGF2R promoted cell proliferation of bladder cancer cells in vitro and in vivo (p<0.05). Furthermore, knockdown IGF2R resulted in higher phosphorylation level of AKT. The findings of this study indicated that IGF2R played a tumor suppressor role in bladder cancer. Downregulation IGF2R may promote tumor growth by activating AKT signaling pathway. IGF2R could be considered as a promising candidate for novel biomarker and therapeutic target for human bladder cancer.

Integrase strand transfer inhibitors (INSTIs) are the most recent class of antiretroviral drugs with potent and durable antiviral activity used to treat human immunodeficiency virus type 1 (HIV-1) infection. However, development of drug resistance increases the risk of treatment failure, disease progression and mortality. A better understanding of drug efficacy and resistance against INSTIs is crucial for their efficient use and the development of new antiretrovirals. A meta-analysis of studies reporting efficacy and resistance data on INSTI use in HIV-infected patients was performed. Odds ratios (ORs) of efficacy outcome data favouring INSTI use in different clinical settings demonstrated that INSTIs have higher efficacy compared with drugs of other classes. For combination antiretroviral therapy-naïve patients and virologically-suppressed patients who switched to INSTI-based therapy, the OR was 1.484 (95% CI 1.229-1.790) and 1.341 (95% CI 0.913-1.971), respectively. ORs of resistance data indicated decreased treatment-emergent resistance development to dolutegravir (DTG) upon virological failure than to non-INSTIs (OR = 0.081, 95% CI 0.004-1.849), whereas the opposite was observed for raltegravir (RAL) (OR = 3.137, 95% CI 1.827-5.385) and elvitegravir (EVG) (OR = 1.886, 95% CI 0.569-6.252). Pooled analysis of resistance data indicated that development of resistance to DTG and bictegravir was rare, whereas EVG and RAL had low genetic barriers to resistance and the intensive cross-resistance between them limits INSTI efficiency. Efficient means of monitoring the emergence of resistance to INSTIs and the development of drugs with high genetic barriers are clear paths for future research., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Gastric carcinoma (GC) is one common malignant tumor with high morbidity and mortality rates all over the world. Recently, numerous studies have showed that the microRNAs (miRNAs) dysregulation was implicated in GC carcinogenesis. This research aimed to explore the potential associations between miR-29c and cyclin-dependent kinase 6 (CDK6) in GC., Patients and Methods: GC tissues and corresponding normal tissues were collected from 54 GC patients who underwent surgery at the Second Hospital of Anhui Medical University between 2015 and 2017. We measured the expressions of CDK6 and miR-29c in GC tissues using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). We next investigated the functions of miR-29c in GC cells by performing transwell assays. To further determine the correlation between miR-29c and CDK6 in GC cell invasion and migration, the rescue experiments were performed by co-transfecting miR-29c inhibitor and CDK6 siRNA into AGS cells., Results: MiR-29c expressions were significantly declined in GC tissues and cells. Additionally, functional assays showed that the miR-29c over-expression suppressed the invasion and migration capacities of GC cells. According to TargetScan and dual-luciferase reporter assays, CDK6 was identified as a new miR-29c target. Moreover, the knockout of CDK6 had similar effects as the miR-29c over-expression in GC cells. The current research indicated that miR-29c over-expression could inhibit tumor behaviors in GC partially via down-regulating CDK6., Conclusions: We revealed that miR-29c down-regulated in GC tissues and cells. MiR-29c over-expression effectively suppressed the GC cell invasion and migration. Moreover, CDK6 was identified as a direct functional target of miR-29c in GC. The current study provides new insights for the GC treatment and suggests that miR-29c/CDK6 axis is a therapeutic candidate target for GC patients.

Although it is well established that the Kiss1/GPR54 system stimulates the reproductive axis in mammals, its functional roles, especially in male reproduction of non-mammalian species, is less clear. In this study, we have isolated the full-length kiss2 and gpr54 cDNAs from black porgy (Acanthopagrus schlegelii). The Kiss2 precursor expressed from kiss2 comprises 124 amino acids and contains a highly conserved 10-amino acid sequence, Kiss2-10 (FNFNPFGLRF). GPR54 comprises 375 amino acid residues and contains distinct characteristics of G protein-coupled receptors. Real-time PCR analysis indicated that kiss2 and gpr54 were expressed highly in the brain regions. Moreover, intraperitoneal injection of porgy Kiss2-10 could stimulate genes expression of the gpr54, gnrh1, gnrh3, fshβ, lhβ, p450c17, star, and ar, and the serum testerone level in male black porgy. Our findings demonstrate that the Kisspeptin stimulates the male reproductive axis in black porgy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To study the predictive value of Pediatric Age-adapted Sequential Organ Failure Assessment Score (pSOFA), Pediatric Risk of Mortality Score III (PRISM III), and Pediatric Critical Illness Score (PCIS) in children with severe sepsis., Methods: A retrospective analysis was performed for the clinical data of 193 hospitalized children with severe sepsis. According to the final outcome, these children were divided into a survival group with 151 children and a death group with 42 children. The scores of pSOFA, PRISM III, and PCIS were determined according to the worst values of each index within 24 hours after admission. The receiver operating characteristic (ROC) curve was used to analyze the efficiency of each scoring system in predicting the risk of death due to sepsis. Smooth curve fitting was used to analyze the correlation between the three scoring systems and the threshold effect of each scoring system. Decision curve analysis (DCA) was used to evaluate the application value of each scoring system., Results: The ROC analysis showed that PCIS and pSOFA had a similar predictive value (P=0.182) and that PRISM III and pSOFA had a similar predictive value (P=0.210), while PRISM III had a better predictive value than PCIS (P=0.045). PRISM III had the highest degree of fitting with prognosis, followed by pSOFA and PCIS. The DCA analysis showed that when the risk of death was 0.4 and 0.6 in children with severe sepsis and the three scoring systems were used as the basis for emergency intervention decision-making, pSOFA achieved the highest standardized net benefit, followed by PRISM III and PCIS., Conclusions: All three scoring systems have a certain value in predicting the prognosis of children with severe sepsis, and pSOFA has a better value than PRISM III and PCIS.

Influences from the mother on offspring phenotype, known as maternal effects, are an important cause of adaptive phenotypic plasticity [1, 2]. Eusocial insects show dramatic phenotypic plasticity with morphologically distinct reproductive (queen) and worker castes [3, 4]. The dominant paradigm for honeybees (Apis mellifera) is that castes are environmentally rather than genetically determined, with the environment and diet of young larvae causing caste differentiation [5-9]. A role for maternal effects has not been considered, but here we show that egg size also influences queen development. Queens laid significantly bigger eggs in the larger queen cells than in the worker cells. Eggs laid in queen cells (QE), laid in worker cells (WE), and 2-day old larvae from worker cells (2L) were transferred to artificial queen cells to be reared as queens in a standardized environment. Newly emerged adult queens from QE were heavier than those from the other two groups and had more ovarioles, indicating a consequence of egg size for adult queen morphology. Gene expression analyses identified several significantly differentially expressed genes between newly emerged queens from QE and those from the other groups. These included a disproportionate number of genes involved in hormonal signaling, body development, and immune pathways, which are key traits differing between queens and workers. That egg size influences emerging queen morphology and physiology and that queens lay larger eggs in queen cells demonstrate both a maternal effect on the expression of the queen phenotype and a more active role for the queen in gyne production than has been realized previously., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Several previous researches had found artery stiffness associated skeletal muscle mass, but not considering muscle strength and physical performance, which also were compositions of sarcopenia. This study aims to reveal the relationship of artery stiffness and sarcopenia using the Asian Working Group for Sarcopenia criteria., Methods: Study was performed on 1002 Chinese community dwelling participants aged ≥65 years from November 2016 to March 2017. Body composition, muscle strength, physical performance, and brachial-ankle pulse wave velocity (baPWV) considering as artery stiffness index were measured., Results: In multiple regression analysis, baPWV was associated with handgrip (β=-0.13, P=0.04) and Relative skeletal muscle mass index (ASM/Ht2) (β=-0.02, P<0.01), but not with 4-meter velocity (P=0.21). Multiple logistic regression analysis showed that 1-SD (3.50m/s) increased in baPWV was still associated with a 11% (CI, 4%-20%; P<0.01) higher odds of being sarcopenia. In the gender subgroup analysis, the relationship of baPWV and sarcopenia remain significant in men (OR, 1.23; 95% CI, 1.07-1.42, P<0.01), but not in women (P=0.07)., Conclusions: High brachial-ankle pulse wave velocity is associated with sarcopenia in Chinese community-dwelling elderly, with gender differences., Competing Interests: None of the authors declares a conflict of interest

To deeply understand the foraging behavioral strategies of the rodents in response to seeds of different sizes and tannin contents under different seed densities and its relationship with plant regeneration, field experiments were conducted to explore the effects of artificial seeds of different sizes (large and small) and tannin (T) contents (0%T, 2%T, 8%T, and 15%T) on seed predation and dispersal behavior of rodents during simulated non-mast and mast seeding year in Larix principis-rupprechtii plantation of Liupan Mountains in Ningxia. The results showed that seeds were consumed rapidly by rodents in non-mast seeding year but relatively slow in mast seeding year. No significant difference of in situ predation rate (ISPR) was observed between non-mast and mast seeding year. The predation rates of seeds after dispersal (PRAD) by rodents in non-mast year were significantly higher than those in mast year, while the hoarding rate of seed after dispersal (HRAD) of the former was significantly lower than the latter. Both seed predation distance after dispersal (PDAD) and hoarding distance after dispersal (HDAD) by rodents in non-mast year were substantially higher than those in mast year. In non-mast year, both PDAD and HDAD of large seeds were longer than those of small seeds. Significant difference of the former was observed between large and small seeds for all tannin content seeds, but significant difference of the latter between large and small seeds was detected only for seeds of 2% and 15% tannin. In mast year, significant difference of PDADs and HDADs between large and small seeds was found in all other seeds of tannin contents except for 0% Tannin seeds. The ISPR maximized in medium tannin seeds and minimized in high tannin seeds. Maximums of PRAD were observed in high tannin seeds in non-mast year and 0% tannin seeds in mast year respectively. High tannin seeds had the highest HRAD while medium tannin seeds had the lowest HRAD in both mast and non-mast year. Our results suggested that mast seeding year could delay the seed consumption rate of rodents and increase the HRAD, but reduce the dispersal distance. Hoarding preference of the rodents on large seeds was demonstrated in both mast and non-mast years and the dispersal distance of large seeds was longer than those of small ones. It is probably that rodents prefer to predate in situ seeds of medium tannin and disperse high tannin seeds during both mast and non-mast years.

Background: Standard management has been recommended for obstructive sleep apnea (OSA) by several guidelines, but patient choice in the practical setting is unclear., Methods: A survey nested in two prospective cohort studies of OSA (enrollment: 2001-2010) in China. The last interview was conducted between July 2014 and May 2015, using a comprehensive 10-point questionnaire administered in a face-to-face or telephone interview, and assessed (I) whether the participant had received any OSA treatment; (II) why he or she had decided for or against treatment; (III) what treatment was received; (IV) whether the participant used continuous positive airway pressure (CPAP) or OA daily; and (V) the perceived efficacy of therapy., Results: A total of 4,097 subjects with a mean age of 45 years [37-55] responded to this survey, with a response rate of 79.4% (4,097/5,160); 2,779 subjects (67.8%) did not receive any treatment: 1,485 (53.4%) believed that their condition was not serious, despite severe OSA in 53.7% of the patients. A multivariate regression showed that the decision to receive treatment was associated with: age between 45-59 years [odds ratio (OR) 0.805, 95% CI: 0.691-0.936; P<0.001], female gender (OR 0.492, 95% CI: 0.383-0.631; P<0.001), severe OSA (OR 1.92, 95% CI: 1.01-3.64; P<0.001), hypertension (OR 1.414, 95% CI: 1.209-1.654; P<0.001) and diabetes (OR 1.760, 95% CI: 1.043-2.972; P=0.034). In subjects receiving treatment (n=1,318), 50.9% reported negative perceptions about the treatments., Conclusions: Nearly two thirds of Chinese patients choose not to receive treatment after OSA diagnosis, and nearly half are negative about their treatments for OSA. This requires clinical attention, and warrants further study in different geographic settings., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Living organisms have been exploited as production hosts for a large variety of compounds. To improve the efficiency of bioproduction, metabolic pathways in an organism are usually manipulated by various genetic modifications. However, bottlenecks during the conversion of substrate to a desired product may result from cellular regulations at different levels. Dynamic regulation of metabolic pathways according to the need of cultivation process is therefore essential for developing effective bioprocesses, but represents a major challenge in metabolic engineering and synthetic biology. To this end, switchable biomolecules which can sense the intracellular concentrations of metabolites with different response types and dynamic ranges are of great interest. This chapter summarizes recent progress in the development of biomolecular switches and their applications for improvement of bioproduction via dynamic control of metabolic fluxes. Further studies of bioswitches and their applications in industrial strain development are also discussed.

Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-onset SLE remains elusive. In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE, as seen on quantitative real-time PCR, and the expression of Sp1 and IFN-α was positively correlated with IRF5. In addition to being used as antitumor drugs, a number of histone deacetylase inhibitors (HDACi) display potent anti-inflammatory properties; however, their effects on IRF5 expression remain unclear. In this study, we identified that HDACi trichostatin A (TSA) and histone acetyltransferase (HAT)-p300 downregulated IRF5 promoter activity, mRNA expression, and protein level, whereas the HAT-p300/CBP-associated factor had no effect. Moreover, TSA inhibited the production of TNF-α and IL-6 in differentiated THP-1cells. Furthermore, chromatin immunoprecipitation assays revealed that TSA inhibited DNA binding of Sp1, RNA polymerase II, HDAC3, and p300 to the core promoter region of IRF5. Our results suggest that HDACi may have therapeutic potential in patients with autoimmune diseases such as SLE through repression of IRF5 expression.

Background: Many species of Tephritidae are damaging to fruit, which might negatively impact international fruit trade. Automatic or semi-automatic identification of fruit flies are greatly needed for diagnosing causes of damage and quarantine protocols for economically relevant insects., Results: A fruit fly image identification system named AFIS1.0 has been developed using 74 species belonging to six genera, which include the majority of pests in the Tephritidae. The system combines automated image identification and manual verification, balancing operability and accuracy. AFIS1.0 integrates image analysis and expert system into a content-based image retrieval framework. In the the automatic identification module, AFIS1.0 gives candidate identification results. Afterwards users can do manual selection based on comparing unidentified images with a subset of images corresponding to the automatic identification result. The system uses Gabor surface features in automated identification and yielded an overall classification success rate of 87% to the species level by Independent Multi-part Image Automatic Identification Test., Conclusion: The system is useful for users with or without specific expertise on Tephritidae in the task of rapid and effective identification of fruit flies. It makes the application of computer vision technology to fruit fly recognition much closer to production level. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Interferon regulatory factor 3 (IRF-3) is an important transcription factor for interferon genes. Although its functional activation by viral infection has been widely explicated, the regulatory mechanism of IRF-3 gene expression in cancer cells is poorly understood. In this study, we demonstrated treatment of lung adenocarcinoma A549 cells with trichostatin A (TSA) and valproic acid (VPA), two different classes of histone deacetylase inhibitors, strongly stimulated IRF-3 gene expression. Truncated and mutated IRF-3 promoter indicated that a specific GATA-1 element was responsible for TSA-induced activation of IRF-3 promoter. Chromatin immunoprecipitation and electrophoretic mobility shift assay showed that TSA treatment increased the binding affinity of GATA-1 to IRF-3 promoter. Using immunoprecipitation assay and immunoblotting, we demonstrated that TSA increased the level of acetylated GATA-1 in A549 cells. In summary, our study implied that TSA enhanced IRF-3 gene expression through increased GATA-1 recruitment to IRF-3 promoter and the acetylation level of GATA-1 in lung adenocarcinoma A549 cells., Competing Interests: CONFLICTS OF INTEREST The authors state that there are no conflicts of interest to disclose.

Retinopathy of prematurity, a leading cause of visual impairment in low birth-weight infants, remains a crucial therapeutic challenge. Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor that promotes rod and cone photoreceptor survival and cone outer segment regeneration in the degenerating retina. Ciliary neurotrophic factor expression is regulated by many factors such as all-trans retinoic acid (ATRA). In this study, we found that ATRA increased CNTF expression in mouse retinal pigment epithelial (RPE) cells in a dose- and time-dependent manner, and PKA signaling pathway is necessary for ATRA-induced CNTF upregulation. Furthermore, we showed that ATRA promoted CNTF expression through CREB binding to its promoter region. In addition, CNTF levels were decreased in serum of retinopathy of prematurity children and in retinal tissue of oxygen-induced retinopathy mice. In mouse RPE cells cultured with high oxygen, CNTF expression and secretion were decreased, but could be recovered after treatment with ATRA. In conclusion, our data suggest that ATRA administration upregulates CNTF expression in RPE cells., (Copyright © 2017 John Wiley & Sons, Ltd.)

Specialized castes are considered a key reason for the evolutionary and ecological success of the social insect lifestyle. The most essential caste distinction is between the fertile queen and the sterile workers. Honeybee (Apis mellifera) workers and queens are not genetically distinct, rather these different phenotypes are the result of epigenetically regulated divergent developmental pathways. This is an important phenomenon in understanding the evolution of social insect societies. Here, we studied the genomic regulation of the worker and queen developmental pathways, and the robustness of the pathways by transplanting eggs or young larvae to queen cells. Queens could be successfully reared from worker larvae transplanted up to 3 days age, but queens reared from older worker larvae had decreased queen body size and weight compared with queens from transplanted eggs. Gene expression analysis showed that queens raised from worker larvae differed from queens raised from eggs in the expression of genes involved in the immune system, caste differentiation, body development and longevity. DNA methylation levels were also higher in 3-day-old queen larvae raised from worker larvae compared with that raised from transplanted eggs identifying a possible mechanism stabilizing the two developmental paths. We propose that environmental (nutrition and space) changes induced by the commercial rearing practice result in a suboptimal queen phenotype via epigenetic processes, which may potentially contribute to the evolution of queen-worker dimorphism. This also has potentially contributed to the global increase in honeybee colony failure rates., (© 2016 John Wiley & Sons Ltd.)

Vibriosis is the most common bacterial diseases and brings great economic loss on aquaculture. Vibrio parahaemolyticus (V. parahaemolyticus), a gram-negative bacterium, has been identified as one main pathogens of Vibriosis. The pathogenic mechanism of V. parahaemolyticus is not entirely clear now. In our study, a model of V. parahaemolyticus infection of green-spotted puffer fish (Tetraodon nigroviridis) was established. T. nigroviridis were injected intraperitoneally (i.p.) with 200 μL of V. parahaemolyticus (8 × 10(10) CFU/mL). V. parahaemolyticus infection caused 64% mortality and infected some organs of T. nigroviridis. Histopathology studies revealed V. parahaemolyticus infection induced tissue structural changes, including adipose hollow space in the liver. Immunohistochemistry showed V. parahaemolyticus were present in infected tissue such as liver, head kidney and spleen. In livers of T. nigroviridis infected by V. parahaemolyticus, the alkaline phosphatases (ALP) activity first gradually increased and then backed to normal level, a trend that was on the contrary to the expression profile of the miR-29b. Quantitative real-time PCR analysis showed that the expression level of TLR1, TLR2, TLR5, TLR9, TLR21, NOD1, NOD2 and IL-6 in response to V. parahaemolyticus infection decreased compared to that of non-infected fish. The establishment of the T. nigroviridis model of V. parahaemolyticus infection further confirmed V. parahaemolyticus spreads through the blood circulation system primary as an extracellular pathogen. Meanwhile, liver is an important target organ when infected by V. parahaemolyticus. miR-29b in liver was involved in the progress of liver steatosis during V. parahaemolyticus infection. Moreover, V. parahaemolyticus infection in vivo may have an effect of immunosuppression on host., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The transcription factor, interferon regulatory factor 5 (IRF5), is important in the induction of type I interferon, proinflammatory cytokines and chemokines, and is involved in autoimmune diseases and tumourigenesis. However, the mechanisms underlying the transcriptional regulation of wild‑type IRF5 remain to be fully elucidated. The present study was primarily designed to clarify whether specificity protein 1 (Sp1) was involved in the regulation of IRF5. Initially, the IRF5 promoter region was cloned and its promoter activity was examined using Hela and HEK 293 cells. Deletion analyses revealed that the region spanning ‑179 to +62 was the minimal promoter of IRF5. Bioinformatics analyses showed that this region contained three putative Sp1 binding sites, and mutational analyses revealed that all the Sp1 sites contributed to transcriptional activity. Secondly, the overexpression of Sp1 was found to increase the activity of the IRF5 promoter and the mRNA level of IRF5, determined using reporter gene assays and polymerase chain reaction analysis, respectively. By contrast, treatment with mithramycin and Sp1 small interfering RNA significantly reduced the activity of the IRF5 promoter and the mRNA level of IRF5. Finally, the results of an electrophoretic mobility shift assay and a chromatin immunoprecipitation assay demonstrated that Sp1 bound to the promoter region of IRF5 in vitro and in vivo. These results suggested that the Sp1 transcription factor is the primary determinant for activating the basal transcription of the IRF5.

Objective: To assess the 4-year anti-HBs persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responsive adults., Methods: A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The 892 low-responders were revaccinated with three doses of HepB at 0-1-6 months schedule and the type of HepB was the same as which was used for primary immunization. During the follow-up to low-responders, the following informations were collected: the demographic characteristics (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and four years after revaccination and anti-HBs, anti-HBc and HBsAg (if anti-HBs <10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively. Anti-HBs titer at T1 was grouped according to the level and was considered as the independent variable in the model analysis., Results: A total of 529 participants were identified from 892 low-responders. Among 529 participants, 276 (52.2%) were males and 253 (47.8%) were females. The positive rate was 82.6% (437/529) at T1 and it decreased to 28.2% (149/529) four years after revaccination. The corresponding GMC decreased from 542.06 (95% CI: 466.72-629.56) mU/ml to 27.69 (95% CI: 23.08-33.23) mU/ml. Multivariable analysis showed the positive rate of anti-HBs 4 years after revaccination was independently associated with anti-HBs titer at T1. The positive rate among those whose anti-HBs titer more than 1 000 mU/ml at T1 was significantly higher than those whose anti-HBs titer less than 100 mU/ml. The OR (95%CI) was 39.67 (13.81-114.01). The GMC was associated with HepB type for revaccination and anti-HBs titer at T1. The GMC among those revaccinated 20 μg HepB was significantly higher than those revaccinated 20 μg HepB-CHO, 10 μg HepB-SC and 10 μg HepB-HP. The b (95% CI) was -0.40 (-0.78--0.02), -0.57 (-1.01- -0.15) and -0.63 (-1.03- -0.23), respectively. The GMC among those whose anti-HBs titer 100-999 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T1 were higher than those whose anti-HBs titer <100 mU/ml. The b (95% CI) was 0.93 (0.53-1.33) and 3.31 (2.88-3.73) respectively., Conclusion: Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responsive adults, but still kept good protecion. The anti-HBs persistence after revaccination was associated with HepB type for revaccination and anti-HBs level of titer one month after revaccination.

Objective: To explore anti-HBs persistence four years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to HepB primary immunization., Methods: A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and aged 18-49 years were selected from 79 villages of Zhangqiu County, Shandong Province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were followed up and their basic information and the histories of hepatitis B infection, HepB vaccination, smoking and drinking were investigated. Then they were revaccinated with three doses of HepB with the same schedule as the primary immunization. Blood samples were collected from all of them one month (T1), two years and four years after revaccination and anti-HBs, anti-HBc and HBsAg were detected by CMIA. A total of 356 participants were followed up from 645 low-responders four years after revaccination, and the ratio was 55.2%. The risk factors associated with the positive rate and geometric mean concentration (GMC) of anti-HBs after four years of revaccination were analyzed using multivariate unconditional logistic regression model and multivariate linear regression model, respectively., Results: Among 356 participants, 172 (48.3%) were males and 184 (51.7%) were females. The anti-HBs positive rate was 90.4% (322 cases) at T1 and was 55.9% (199 cases) four years after revaccination. The GMC of anti-HBs was 240.5 (95% CI: 186.4-310.4)mU/ml at T1 and decreased to 15.0 (95%CI: 12.2-18.5) mU/ml four years after revaccination. The average annual decreasing rate of GMC was 50.63% from one month after revaccination to four years after revaccination. The corresponding rate was 64.89% in the first two years, which was 2.12 times the rate in the latter two years (30.57%). When compared with those whose anti-HBs titer was less than 99 mU/ml at T1, the significantly higher anti-HBs four years after revaccination was observed in those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was ≥1 000 mU/ml. The OR (95%CI) was 7.14 (3.90-13.05) and 28.40 (13.16-61.30) respectively. When compared with those whose anti-HBs titer was ≤99 mU/ml at T1, the GMC of anti-HBs four years after revaccination was also significantly higher among those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was ≥1 000 mU/ml. The b (95%CI) was 1.66 (1.26-2.05) and 3.16 (2.72-3.60), respectively., Conclusion: The positive rate and GMC of anti-HBs decreased four years after revaccination among non-responsive adults, but still kept anti-HBs above protective level. The immunity durability after revaccination is mainly associated with anti-HBs titer one month after revaccination.

Objective: To assess the 3-year anti-HBs persistence after primary vaccination with three-dose of hepatitis B vaccine (HepB) among normal and high-responder adults., Methods: A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in local areas for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). During the follow-up to normal and high-responders, the following information was collected: the demographic characteristic (including age and gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and three years after primary vaccination (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively., Results: A total of 4 677 normal and high-responders were identified. Among 4 677 participants, 2 014 (43.06%) were males and 2 663 (56.94%) were females. The positive rate was 100% at T1 and it decreased to 80.99% (3 788/4 677) three years after vaccination. The corresponding GMC was decreased from 1 413.48 (95%CI: 1 358.86-1 470.30) mU/ml to 60.33 (95%CI: 56.97-63.90) mU/ml. When comparing with those vaccinated 20 μg HepB-CHO, the significantly lower positive rate of anti-HBs three years after vaccination was observed in those vaccinated 20 μg HepB-SC, 10 μg HepB-SC and 10 μg HepB-HP. The OR (95%CI) was 0.65 (0.50-0.84), 0.52 (0.41-0.67) and 0.31 (0.28-0.45), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 20 μg HepB-SC, 10 μg HepB-SC and 10 μg HepB-HP. The b (95%CI) was -0.33 (-0.47- -0.20), -0.41 (-0.55- -0.28) and -0.78 (-0.92- -0.65), respectively. The GMC of anti-HBs in those aged 30-39 years old and 40-49 years old were lower than that in 18-29 years. The b (95%CI) was -0.31 (-0.47- -0.15) and -0.24 (-0.39- -0.09), respectively. When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs three years after vaccination was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-9 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 4.97 (3.80-6.49), 7.87 (16.19-10.01) and 9.67 (6.47-14.44), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs three years after vaccination was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was ≥10 000 mU/ml. The b (95%CI) was 1.00 (0.87-1.14), 1.85 (1.74-1.97) and 3.28 (3.12-3.44), respectively. Four subjects showed HBsAg seroconversion and anti-HBc conversion rate was 4.68% at T2., Conclusions: Anti-HBs GMC decreased rapidly three years after primary vaccination among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The anti-HBs persistence after primary vaccination was associated with HepB type, age and GMC of anti-HBs one month after vaccination.

Objective: To evaluate the 5-year antibody persistence and the risk factors associated with the persistence after primary vaccination of hepatitis B vaccine (HepB) among normal or high-response adults., Methods: A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages in north of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). The normal and high-responder was followed up and their demographic characteristic (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases were investigated. Blood samples were collected one month (T1) and five years (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. A total of 1 902 participants were followed up and the risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively., Results: Among 1 902 adults, 824 (43.32%) were male and 1 078 (56.68%) were female. The anti-HBs positive rate was 100% at T1 and it decreased to 73.29% (1 394 cases) at T2. The corresponding GMC was decreased from 1 527.15 (95%CI: 1 437.84-1 622.01) mU/ml at T1 to 35.07 (95%CI: 32.20-38.19) mU/ml at T2. When comparing with those vaccinated 20 μg HepB-SC, the significantly lower positive rate at T2 was observed in those vaccinated 10 μg HepB-SC group and 10 μg HepB-HP group. The OR (95% CI) was 0.41 (0.28-0.61) and 0.27 (0.18-0.39), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 10 μg HepB-SC and 10 μg HepB-HP. The b (95%CI) was -0.20 (-0.28- -0.12) and -0.36 (-0.44- -0.29) , respectively. When comparing with those occasionally drinking, the significantly lower positive rate at T2 was observed in those regular drinking. The OR(95%CI) was 0.51(0.30-0.87). The GMC of anti-HBs in age group of 18-29 was significantly higher than those in 40-49 age group; the b (95%CI) was -0.10(-0.18- -0.01). When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs at T2 was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-2 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 10.11 (6.90-14.82), 20.42 (13.98-29.82) and 54.58 (22.08-134.92), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs at T2 was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was ≥10 000 mU/ml. The b (95%CI) was 0.55 (0.47-0.62), 0.94 (0.88-1.00) and 1.63 (1.54-1.72), respectively. Nobody was found positive to HBsAg at T2 and the conversion rate of anti-HBc was 3.89% (74/1 902) at T2., Conclusion: Anti-HBs GMC decreased rapidly at T2 among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The antibody persistence among normal and high-responder adults at T2 was associated with HepB type, age, history of drinking and GMC of anti-HBs at T1.

Riboswitches are natural RNA elements that regulate gene expression by binding a ligand. Here, we demonstrate the possibility of altering a natural lysine-OFF riboswitch from Eschericia coli (ECRS) to a synthetic lysine-ON riboswitch and using it for metabolic control. To this end, a lysine-ON riboswitch library was constructed using tetA-based dual genetic selection. After screening the library, the functionality of the selected lysine-ON riboswitches was examined using a report gene, lacZ. Selected lysine-ON riboswitches were introduced into the lysE gene (encoding a lysine transport protein) of Corynebacterium glutamicum and used to achieve dynamic control of lysine transport in a recombinant lysine-producing strain, C. glutamicum LPECRS, which bears a deregulated aspartokinase and a lysine-OFF riboswitch for dynamic control of the enzyme citrate synthase. Batch fermentation results of the strains showed that the C. glutamicum LPECRS strain with an additional lysine-ON riboswitch for the control of lysE achieved a 21% increase in the yield of lysine compared to that of the C. glutamicum LPECRS strain and even a 89% increase in yield compared to that of the strain with deregulated aspartokinase. This work provides a useful approach to generate lysine-ON riboswitches for C. glutamicum metabolic engineering and demonstrates for the first time a synergetic effect of lysine-ON and -OFF riboswitches for improving lysine production in this industrially important microorganism. The approach can be used to dynamically control other genes and can be applied to other microorganisms.

Riboswitch, a regulatory part of an mRNA molecule that can specifically bind a metabolite and regulate gene expression, is attractive for engineering biological systems, especially for the control of metabolic fluxes in industrial microorganisms. Here, we demonstrate the use of lysine riboswitch and intracellular l-lysine as a signal to control the competing but essential metabolic by-pathways of lysine biosynthesis. To this end, we first examined the natural lysine riboswitches of Eschericia coli (ECRS) and Bacillus subtilis (BSRS) to control the expression of citrate synthase (gltA) and thus the metabolic flux in the tricarboxylic acid (TCA) cycle in E. coli. ECRS and BSRS were then successfully used to control the gltA gene and TCA cycle activity in a lysine producing strain Corynebacterium glutamicum LP917, respectively. Compared with the strain LP917, the growth of both lysine riboswitch-gltA mutants was slower, suggesting a reduced TCA cycle activity. The lysine production was 63% higher in the mutant ECRS-gltA and 38% higher in the mutant BSRS-gltA, indicating a higher metabolic flux into the lysine synthesis pathway. This is the first report on using an amino acid riboswitch for improvement of lysine biosynthesis. The lysine riboswitches can be easily adapted to dynamically control other essential but competing metabolic pathways or even be engineered as an "on-switch" to enhance the metabolic fluxes of desired metabolic pathways.