Search

Summary Background The use of magnetically controlled capsules for gastroscopy is in the early stages of clinical adoption. We aimed to evaluate the safety and efficacy of a fully automated magnetically controlled capsule endoscopy (FAMCE) system in clinical practice for gastroscopy and small bowel examination. Methods We did a prospective, comparative study to evaluate the safety and efficacy of FAMCE. Patients from two hospitals in Chongqing, China were consecutively enrolled. Eligible participants were aged 18–80 years with suspected gastric pathology and no previous surgery. Participants underwent FAMCE for screening of gastric lesions, then conventional transoral gastroscopy 2 h later, and stomach examination results were compared. The primary outcome was the rate of complete detection of gastric anatomy landmarks (cardia, fundus, body, angulus, antrum, and pylorus) by FAMCE. Secondary outcomes were the time required for gastric completion by FAMCE, the rate of detection of gastric lesions by FAMCE compared with conventional transoral gastroscopy, and the rate of complete small bowel examination. Adverse events were also evaluated. The study was registered in the Chinese Clinical Trial Registry, ChiCTR2000040507. Findings Between May 12 and Aug 17, 2020, 114 patients (mean age 44·0 years [IQR 34·0–55·0]; 63 [55%] female) were enrolled. The rate of complete detection of gastric anatomical structures by FAMCE was 100% (95% CI 99·3–100·0). The concordance between FAMCE and conventional transoral gastroscopy was 99·61% (99·45–99·78). The mean completion time of a gastroscopy with FAMCE was 19·17 min (SD 1·43; median 19·00, IQR 19·00–20·00), compared with 5·21 min (2·00; 5·18, 3·68–6·45) for conventional transoral gastroscopy. In 114 enrolled patients, 214 lesions were detected by FAMCE and conventional transoral gastroscopy. Of those, 193 were detected by both modalities. FAMCE missed five pathologies (four cases of gastritis and one polyp), whereas conventional transoral gastroscopy missed 16 pathologies (12 cases of gastritis, one polyp, one fundal xanthoma, and two antral erosions). FAMCE was able to provide a complete small bowel examination for all 114 patients and detected intestinal lesions in 50 (44%) patients. During the study, two (2%) patients experienced adverse events. No serious adverse events were recorded, and there was no evidence of capsule retention. Interpretation The performance of FAMCE is similar to conventional transoral gastroscopy in completion of gastric examination and lesion detection. Furthermore, it can provide a complete small bowel examination. Therefore, FAMCE could be effective method for examination of the gastrointestinal tract. Funding Chinese National Key Research and Development Program.

Interleukin-16 (IL-16), as a lymphocyte chemoattractant cytokine, plays a crucial role in regulating cellular activities and anti-pathogen immunity. In teleost, the information about the antibacterial effect of IL-16 is scarce. In our study, we examined the immune functions of an IL-16 homologue (CsIL-16) from tongue sole Cynoglossus semilaevis. The CsIL-16 precursor (proCsIL-16) is comprised of 1181 amino acid residues, sharing 21.1%-67.3% identities with IL-16 precursor from invertebrate and vertebrate. The C-terminal proCsIL-16 containing two PDZ domains was designated as mature CsIL-16 which was released into the supernatant of peripheral blood leukocytes (PBLs). CsIL-16 was expressed in various tissues and regulated by bacterial invasion. Recombinant CsIL-16 (rCsIL-16), as a homodimer, was able to bind to the membrane of PBLs and played essential roles in regulating chemotaxis and activation of PBLs, which in vitro inhibited intracellular survival of E. tarda. Under in vivo condition, rCsIL-16 could dramatically regulate the induction of inflammatory genes, and suppress the bacterial dissemination in fish tissues. Collectively, our results reveal that CsIL-16 plays positive roles in antibacterial immunity, and provide insights into the immune function of CsIL-16.

GOAL: The purpose of this study was to evaluate the effectiveness of vitamin C solution (VCS) in reducing adverse reactions caused by painless Lugol chromoendoscopy. BACKGROUND: Lugol chromoendoscopy is an effective method for screening superficial esophageal squamous cell carcinoma, although Lugol iodine solution (LIS) causes mucosal irritation. STUDY: In 4 hospitals in China, patients were randomized and divided into a distilled water (DW) group, an sodium thiosulfate solution (STS) group and a VCS group. Patients' esophageal mucosal surfaces were stained with either 1.2% or 0.5% LIS and then sprayed with DW, STS, or VCS at various concentrations. For the current randomized study, 1610 patients were enrolled in the 1.2% LIS group and 1355 patients were enrolled in the 0.5% LIS group. In addition, 150 patients were enrolled to assess the discoloration effect. The primary outcome for evaluation was the incidence of acute or late adverse reactions after Lugol iodine staining. The secondary outcome for evaluation was the discoloration effect on esophageal iodine-stained mucosa. RESULTS: VCS significantly reduced the occurrence of acute adverse reactions due to staining from 1.2% LIS. The effect of VCS was similar to that of STS but better than that of DW (P

Objective To confirm the role of long noncoding RNA differentiation antagonizing non‐protein coding RNA (DANCR) in chondrocyte inflammatory injury in osteoarthritis (OA) in vitro, as well as its molecular mechanism. Methods Human primary chondrocytes were treated with lipopolysaccharide (LPS) to construct a chondrocyte inflammatory injury in human OA cell model. Gene expression was detected using real‐time quantitative polymerase chain reaction. Cell inflammatory injury was evaluated by Cell Counting Kit‐8 assay, flow cytometry, and enzyme‐linked immunosorbent assay. The interplay between miRNA‐19a‐3p (miR‐19a) and DANCR was validated by dual‐luciferase reporter assay and RNA immunoprecipitation. Results Expression of DANCR was upregulated, and miR‐19a was downregulated in human OA cartilage and LPS‐treated primary chondrocytes in vitro. Moreover, DANCR expression was inversely correlated with miR‐19a in OA patients. LPS reduced cell viability and increased the apoptotic rate and secretion of interleukin (IL)‐1β, IL‐6, IL‐8, as well as tumor necrosis factor (TNF)‐α in primary chondrocyte cells in vitro, suggesting an inflammatory injury model of OA. Functionally, knockdown of DANCR could attenuate LPS‐induced apoptosis and inflammatory response, as evidenced by improved cell viability, and reduced apoptotic rate and products of IL‐1β, IL‐6, IL‐8, and TNF‐α. Notably, DANCR negatively regulated miR‐19a expression, presumably via sponging. Furthermore, miR‐19a deletion eliminated the effect of DANCR knockdown on apoptosis and the inflammatory response of primary chondrocytes under LPS stress. Conclusion Differentiation antagonizing non‐protein coding RNA silencing could protect human chondrocyte cells against LPS‐induced inflammatory injury and apoptosis through targeting miR‐19a, suggesting a vital role of the DANCR/miR‐19a axis in OA., Highlights Expression of DANCR and miR‐19a was upregulated and downregulated in human OA cartilage, respectively.Silencing DANCR alleviated LPS‐induced apoptosis and inflammatory response in primary chondrocytes, which could be counteracted by deleting miR‐19a.DANCR functioned as a sponge for miR‐19a.

Cancer-associated fibroblast (CAF) secretes extracellular vesicle (EV)-encapsulated microRNAs (miRNAs) which have been underlined great promise for therapeutic target for diseases and cancers. Our study aimed to explore the role of EV-encapsulated miR-10a-5p from CAFs in angiogenesis in cervical cancer. Expression of miR-10a-5p in clinical samples of cervical cancer and cancer cells was detected by in situ hybridization and RT-qPCR. Results demonstrated that miR-10a-5p expression was upregulated in both cancer tissues and cells. CAFs and normal fibroblasts (NFs) from cervical cancer patient tissues were characterized under transmission electron microscopy, followed by EV isolation from CAFs. The EVs labeled with PKH67 were cultured with cervical squamous cell carcinoma (CSCC) cell line (SiHa) and HUVECs. Data indicated that CAF-EVs were internalized by cancer cells and promoted cell proliferation and tube formation. CAF-EVs then were transfected with miR-10a-5p inhibitor and then injected into nude mice. While injection of CAF-EVs promoted tumor growth and increased VEGFR and CD31 expression level, miR-10a-5p inhibitor-treated CAF-EVs resulted in decreased tumor volume and amount of vessel around tumor. Of note, dual-luciferase reporter gene assay and bioinformatic analysis indicated TBX5 as a target gene of miR-10a-5p. Moreover, EV-derived miR-10a-5p promoted angiogenesis in vivo and in vitro through activation of Hedgehog signaling via downregulation of TBX5. Taken altogether, miR-10a-5p in CAF-EVs promoted CSCC cell angiogenesis and tumorigenicity via activation of Hh signaling by inhibition of TBX5, providing insight into novel treatment based on miR-10a-5p against CSCC.

We aimed to explore the anti-inflammatory activity of mollugin extracted from Rubia cordifolia L, a traditional Chinese medicine, on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. Thirty C57BL/6 mice were divided into a control group (n=6), a model group (n=6), and three experimental groups (40, 20, 10 mg/kg of mollugin, n=6 each). DSS solution (3%) was given to mice in the model group and experimental groups from day 4 to day 10 to induce the mouse UC model. Mice in the experimental groups were intragastrically administrated mollugin from day 1 to day 10. Animals were orally given distilled water in the control group for the whole experiment time and in the model group from day 1 to day 3. The changes in colon pathology were detected by hematoxylin and eosin (HE) staining. Interleukin-1β (IL-1β) in the serum, and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN) in the tissues were measured by enzyme linked immunosorbent assay. Expression levels of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 in the colon tissues were detected by immunohistochemistry. Results showed that mollugin could significantly reduce weight loss and the disease activity index in the DSS-induced UC mouse model. HE examinations demonstrated that mollugin treatment effectively improved the histological damage (P

Background: Wound complications are a major source of morbidity after cesarean section (CS) and contribute to increased risks in subsequent pregnancies. In the present study, we aim to investigate the wound healing potential of a kind of oligopeptide compound, mainly derived from the marine fish peptides (MFPs), in rats after CS by biomechanical, biochemical, and histological methods. Methods: Eighty-four pregnant Sprague–Dawleyrats were randomly assigned to four groups, namely the control group and 1.1, 2.2, and 4.4 mg/kg MFP groups, respectively. The MFPs or normal saline of the equal volume was intragastrically administered every morning on the second day after CS. On days 5, 10, and 15 after the surgery, seven rats from each group were randomly selected. The samples of skin wound and uterus were harvested and then used for the following experiments and analyses. Results: Using the CS rat model, this study demonstrated that in the MFP groups, the skin tensile strength, uterine bursting pressure, and hydroxyproline (Hyp) were significantly higher than those in the control group at all three time points (P < 0.05). The formation of collagen and smooth muscle fibers and the expression of CD34 and connective tissue growth factor at the incision site were increasingly observed in the MFP groups (P < 0.05). Conclusions: MFPs have a great potential to accelerate the process and quality of wound healing in rats after CS.

Background The cystic fibrosis transmembrane conductance regulator (CFTR) and nuclear factor κB (NF-κB) signalling pathways are currently regarded as co-regulators of the occurrence of cervical cancer. However, the detailed mechanism of CFTR- and NF-κB-mediated effects in cervical cancer remains to be elucidated. This study aimed to investigate the mechanism by which CFTR and NF-κB influence the development of cervical cancer. Patients and methods CFTR ΔF508 mutation and CFTR promoter methylation were detected in cervical tissue samples. NF-κB p65 and IκBα protein levels were tested in HeLa cells with CFTR overexpression and knockdown by Western blotting. The effects of CFTR on cell proliferation, migration, and invasion were examined in HeLa cells by WST-1 and soft agar assays, cell wound scratch assay, and Matrigel invasion assays, respectively. The protein-protein interaction (PPI) network was constructed by using GeneMANIA. GeneCoDis3 was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis on genes in the PPI network. Results CFTR mutation and CFTR promoter methylation were not associated with the occurrence of cervical cancer. NF-κB p65 protein levels were decreased in CFTR overexpression lines and increased in CFTR knockdown lines, and IκBα levels were affected in the opposite manner, indicating that CFTR inhibited the NF-κB signalling pathway. CFTR also regulated the cell proliferation, migration, and invasion ability of cervical cancer cells. When CFTR was overexpressed, cell proliferation, migration, and invasion ability were decreased. There were 20 genes that interacted with CFTR. KEGG pathway analysis showed enrichment in the gastric acid secretion, chemokine signalling, bile secretion and apoptosis pathways. Conclusion CFTR plays an important role in cancer cell proliferation, migration and invasion by inhibiting the NF-κB signalling pathway in cervical cancer.

Interleukin-10 (IL-10) is a pleiotropic cytokine and plays a crucial role in immunity. In the current study, we examined the expression patterns and biological functions of tongue sole Cynoglossus semilaevis IL-10 (CsIL-10). CsIL-10 is composed of 186 amino acid residues and shares 46.3%-71.7% identities with other teleost IL-10. Csil-10 expression occurred in multiple tissues and was regulated by bacterial infection. Recombinant CsIL-10 (rCsIL-10) in the form of a dimer bound to a wide range of bacterial species but did not affect bacterial growth. rCsIL-10 could interact with peripheral blood leukocytes (PBL) and significantly reduce the phagocytic activity, ROS production, and apoptosis of PBL. When injected in vivo, rCsIL-10 significantly suppressed the expression of proinflammatory cytokines and promoted bacterial dissemination in tongue sole tissues. Consistently, knockdown of Csil-10 significantly inhibited bacterial infection in tongue sole. Taken together, these results indicate that CsIL-10 plays a negative regulatory role in the immune response against bacterial infection.

Lignin, a characteristic component of terrestrial plants. Rivers transport large amounts of vascular plant organic matter into the oceans where lignin can degrade over time; however, microorganisms involved in this degradation have not been identified. In this study, several bacterial strains were isolated from marine samples using the lignin-derived compound vanillic acid (4-hydroxy-3-methoxybenzoic acid) as the sole carbon and energy source. The optimum growth temperature for all isolates ranged from 30 to 35°C. All isolates grew well in a wide NaCl concentration range of 0 to over 50 g/L, with an optimum concentration of 22.8 g/L, which is the same as natural seawater. Phylogenetic analysis indicates that these strains are the members of Halomonas, Arthrobacter, Pseudoalteromonas, Marinomonas, and Thalassospira. These isolates are also able to use other lignin-derived compounds, such as 4-hydroxybenzoic acid, ferulic acid, syringic acid, and benzoic acid. Vanillic acid was detected in all culture media when isolates were grown on ferulic acid as the sole carbon source; however, no 4-hydroxy-3-methoxystyrene was detected, indicating that ferulic acid metabolism by these strains occurs via the elimination of two side chain carbons. Furthermore, the isolates exhibit 3,4-dioxygenase or 4,5-dioxygenase activity for protocatechuic acid ring-cleavage, which is consistent with the genetic sequences of related genera. This study was conducted to isolate and characterize marine bacteria of degrading lignin-derived compounds, thereby revealing the degradation of aromatic compounds in the marine environment and opening up new avenues for the development and utilization of marine biological resources.

Interleukin (IL)-11 is a multifunctional cytokine belonging to the IL-6 family, which plays essential roles in immune response. However, much less is known about the immunological functions of IL-11 in teleost. In this study, we investigated the immune properties of a teleost IL-11 homologue (CsIL-11) from tongue sole Cynoglossus semilaevis. CsIL-11 possesses four conserved α-helices and conserved CsIL-11 receptor binding residues L86 and R187, and shares 23.3%-80.1% identities with other IL-11 homologues. CsIL-11 expression was constitutive in tissues, with most abundant in blood and least abundant in spleen, and upregulated by bacterial challenge in blood, spleen, and head kidney. Recombinant CsIL-11 (rCsIL-11) in the native form of monomer, could bind to peripheral blood leukocytes (PBLs) membrane and enhance the activation and phagocytosis of PBLs. When administered in vivo, rCsIL-11 could markedly promote the host to defend against microbial infection. Overall, our findings show that CsIL-11 plays a pivotal role in regulating PBLs phagocytosis and antibacterial immunity.

Background and Objectives Calcium-sensing receptor (CaSR) is known to regulate hypoxia-induced pulmonary hypertension (HPH) and vascular remodeling via the phenotypic modulation of pulmonary arterial smooth muscle cells (PASMCs) in small pulmonary arteries. Moreover, autophagy is an essential modulator of VSMC phenotype. But it is not clear whether CaSR can regulate autophagy involving the phenotypic modulation under hypoxia. Methods The viability of human PASMCs was detected by cell cycle and BrdU. The expressions of proliferation protein, phenotypic marker protein, and autophagy protein in human PASMCs were determined by western blot. Results Our results showed that hypoxia-induced autophagy was considerable at 24 h. The addition of NPS2390 decreased the expression of autophagy protein and synthetic phenotype marker protein osteopontin and increased the expression of contractile phenotype marker protein SMA-ɑ and calponin via suppressing downstream PI3K/Akt/mTOR signal pathways. Conclusions Our study demonstrates that treatment of NPS2390 was conducive to inhibit the proliferation and reverse phenotypic modulation of PASMCs by regulating autophagy levels.

Background The population of left-behind children is growing rapidly in China in recent years. Without parents' company, left-behind children may develop severe emotional problems, which can trigger extreme behaviours such as self-harm and suicide. Previous literature suggests that mindfulness-based intervention could effectively alleviate a variety of sufferings such as anxiety and suicide ideation. The current study sought to examine the effectiveness of mindfulness-based intervention on suicide ideation among left-behind children in China. Methods This study investigated the effects of an 8-week mindfulness training programme on suicide ideation of left-behind children in China. Forty-nine left-behind children completed a pretest and posttest on mindfulness level, social anxiety, self-esteem, and suicide ideation, with 21 in the mindfulness training group and 28 in the waitlist control group. Results Adjusting for pretest differences analyses of covariance found that, compared with waitlist control group, the mindfulness training group showed a significant improvement in mindfulness level and decreases in social anxiety and suicide ideation after the 8-week mindfulness training. Conclusion The findings from this study support that the use of mindfulness-based intervention can effectively reduce the suicide ideation and social anxiety of left-behind children in China.

Background Trait emotional intelligence and fear of cancer recurrence could predict quality of life, but the mechanism between the three is poorly understood. Methods The aim of this study was to investigate the associations between trait emotional intelligence, fear of cancer recurrence and quality of life in patients with breast cancer. A cross-sectional study was conducted with 215 breast cancer patients recruited from two hospitals in China. Data were collected from December 2018 to April 2019. Questionnaires measured demographic and medical characteristics, trait emotional intelligence, fear of cancer recurrence and quality of life. Pearson correlation analysis and structural equation modelling were conducted to analyse the data. Results As expected, trait emotional intelligence was positively related to quality of life and negatively correlated with fear of cancer recurrence. Fear of cancer recurrence was negatively associated with quality of life. This relationship between trait emotional intelligence and quality of life was mediated by fear of cancer recurrence. Conclusions These results shed light on underlying mechanisms by which trait emotional intelligence affects quality of life. Trait emotional intelligence training could reduce fear of cancer recurrence to improve quality of life for cancer patients.

The objective of this study was to investigate the inhibitory effect of miR-135a in regulating JAK/STAT signaling pathway on airway inflammation in asthmatic mice. An asthma model was established by sensitization and stimulation with ovalbumin (OVA), and the corresponding drug intervention was given from the day of stimulation by means of nasal drops. Airway hyperresponsiveness was tested. The content of miR-135a in the lung tissue of mice was detected by RT-PCR. The pathological changes of lung tissue were evaluated by HE staining. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-5, and eotaxin in bronchoalveolar lavage fluid (BALF) and lung tissue were detected by ELISA and immunohistochemistry, respectively. The expression of JAK/STAT signaling pathway-related protein in lung tissue was detected by western blot. To further validate the effect of miR-135a overexpression on the JAK/STAT signaling pathway, pathway activators and inhibitors were added. Compared with the OVA group, the airway hyperresponsiveness of the mice was significantly decreased after treatment with the miR-135a agonist. The expression of miR-135a was significantly increased in the lung tissue and the pathological changes of the lung tissue were alleviated. The contents of TNF-α, IL-6, IL-5, and eotaxin in BALF and lung tissues were decreased. The expression of JAK/STAT signaling pathway-related proteins p-JAK3/JAK3, p-STAT1/STAT1, and p-STAT3/STAT3 were significantly reduced in lung tissue (P

Objective: Reading small bowel capsule endoscopy (SBCE) is a tedious task. We aim to evaluate the performance of a Convolutional Neural Network (CNN) algorithm (SmartScan)-assisted reading in the setting of real-life clinical care. Design: A total of 5,825 SBCE examinations (comprising 295,314,067 images) performed in 51 Chinese medical centres were collected. 2,927 SBCE examinations from 29 medical centres were used to train SmartScan to detect 17 CEST findings. SmartScan was later validated in 2,898 SBCE examinations collected from 22 medical centres. All 2,898 SBCE examinations were read with both Conventional Reading (CR) and SmartScan-Assisted Reading (SSAR) by eight specialist gastroenterologists. If finding(s)/results by both types of reading in a patient were concordant, the result was taken as the Combined Agreed Comparator (CAC) for that case. In discordant cases, the consensus result by three expert readers was taken as the CAC for the case. Results: SSAR achieved an overall higher detection rate (79.30%) for CEST findings compared to CR (70.67%); from a total of 6,084 SB findings, SSAR detected 95.89%, significantly higher compared to CR (76.10%). Furthermore, SSAR achieved overall higher sensitivity (98.80%), for the 17 CEST subtypes of findings, 10.75% higher than CR (88.05%). With SSAR, the number of images requiring review per SB CE video was reduced to 779.17 ±337.18, with reading time was shortened to 5.37 ±1.51min. C Conclusion: A commercially available CNN algorithm (SmartScan) can increase the detection rate of SB findings while reducing SB CE reading times. Trial Registration: This clinical trial study was registered in the Chinese Clinical Trial Registry (reg no. CHiCTR2100042455). Funding: This work was supported by the National Key Research and Development Program (NO. 2016YFC0107000) and Special project of National Health Committee (NO. 201502013). Declaration of Interest: The authors declare no competing interests. Ethical Approval: The whole study was performed in accordance with guidelines approved by Medical Ethics Committee of Second Affiliated Hospital of the Third Medical University (NO.2020-yan-134-01).

[This corrects the article DOI: 10.1371/journal.pone.0240187.].

Data are scarce regarding the comorbid mental disorders and their management among COVID-19 patients. This study described the clinical characteristics and management of COVID-19 patients treated in psychiatric inpatient settings due to comorbid first-onset mental disorders in Wuhan, China. This electronic medical records-based study included 25 COVID-19 patients with first-onset mental disorders and 55 patients with first-onset mental disorders without COVID-19 (control group). Data collected included ICD-10 diagnoses of mental disorders, psychiatric and respiratory symptoms, treatments, and outcomes. Adjustment disorder (n = 11, 44.0%) and acute and transient psychotic disorders, with associated acute stress (n = 6, 24.0%) were main clinical diagnoses in the COVID-19 group while serious mental illnesses (i.e., schizophrenia, 24.5%) and alcohol use disorders (10.9%) were overrepresented in the control group. On admission, the most common psychiatric symptom in COVID-19 patients was insomnia symptoms (n = 18, 72.0%), followed by aggressive behaviors (n = 16, 64.0%), delusion (n = 10, 40.0%), and severe anxiety (n = 9, 36.0%). In addition to respiratory treatments, 76.0% COVID-19 patients received antipsychotics, 40.0% sedative-hypnotics, and 24.0% mood stabilizers. At the end of inpatient treatment, 4 (16.0%) COVID-19 patients were transferred to other hospitals to continue respiratory treatment after their psychiatric symptoms were controlled while the remaining 21 (84.0%) all recovered. Compared to the control group, COVID-19 group had significantly shorter length of hospital stay (21.2 vs. 37.4 days, P

Interleukin (IL)-10, an immune-regulatory cytokine, exerts various biological functions through interaction with IL-10 receptors. In teleost, very limited functional studies on IL-10 receptors have been documented. In this study, we reported the expression patterns of IL-10 receptor 1 (CsIL-10R1) and receptor 2 (CsIL-10R2) of tongue sole (Cynoglossus semilaevis) and examined their biological properties. The expression of CsIL-10R1 and CsIL-10R2 occurred in multiple tissues and were regulated by bacterial challenge. In vitro binding studies showed that recombinant extracellular region of CsIL-10R1 (rCsIL-10R1ex) rather than rCsIL-10R2ex could bind with rCsIL-10. Cellular study showed that both CsIL-10R1 and CsIL-10R2 were expressed on peripheral blood leukocytes (PBLs), and blockade of CsIL-10R1 or CsIL-10R2 by antibody could reduce inhibitory effect of CsIL-10 on ROS production of PBLs. When injected in vivo, anti-rCsIL-10R1 or anti-rCsIL-10R2 antibody dramatically promoted the expression of proinflammatory cytokines and suppressed bacterial dissemination in tongue sole tissues. Consistently, the overexpression of CsIL-10R1 or CsIL-10R2 significantly enhanced bacterial dissemination, and the overexpression of CsIL-10R1M bearing STAT3 site mutation reduced bacterial dissemination. Overall, these results demonstrate for the first time teleost IL-10 receptors play a negative role in antibacterial immunity and add insight into the function of CsIL-10 receptors.

A previous study showed that an attenuated Edwardsiella tarda strain, TXhfq, as a live vaccine could elicit protective immune effects in fish against E. tarda infection. In the current study, in order to clarify the molecular mechanism of fish immune response at the early stage after TXhfq vaccination, RNA-Seq technology was used to compare the transcriptomes of skin, intestine, and spleen between bath-vaccinated and unvaccinated Japanese flounder (Paralichthys olivaceus). An average of 46.6 million clean reads per library was obtained, ~88.04% of which were successfully mapped to the reference genome, and approximately 24,600 genes were detected in each sample. A total of 565, 878, and 1258 differential expression genes (DEGs) were found in skin, intestine, and spleen, respectively, including 1263 up-regulated genes and 1438 down-regulated genes. The DEGs exhibited different characteristics in each tissue. One hundred and sixteen DEGs belonging to six immune related categories were scrutinized, i.e., inflammatory factors, cytokines, complement and coagulation system, mucins, phagocytosis, and antigen processing and presentation. A protein-protein interaction network was constructed to get the interaction network between immune genes during the early stage of immunization. The top six hub genes highly regulated by TXhfq formed complicated interaction relationship with each other, which were involved in immune processes, notably inflammation and phagocytosis. Our results provide valuable information for the understanding of the immune mechanism underlying the protection of live attenuated vaccines in fish.

Pioglitazone (PIO) attenuates cisplatin nephrotoxicity whereas the underlying mechanism remains unknown. Apoptosis is associated with mitochondrial dysfunction and SIRT1 activation can decrease cell apoptosis in cisplatin nephrotoxicity. Therefore, we explored whether the protective effect of PIO in cisplatin nephrotoxicity is achieved by suppressing mitochondria‐mediated apoptosis through SIRT1/p53 signalling regulation. Cell viability, apoptosis, survival rate, renal pathology and function were examined. Moreover, we also analysed the expression of SIRT1, Acetyl‐p53, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial permeability transition pore (mPTP) opening, adenosine triphosphate (ATP) and apoptosis‐related protein in vivo and in vitro. Pioglitazone treatment significantly increased cell viability, promoted SIRT1‐p53 interaction, upregulated Bcl‐2 expression, activated SIRT1 and elevated mitochondrial ATP synthesis after cisplatin treatment. However, PIO decreased the generation of ROS, opening of mPTP, dissipation of MMP and translocation of cytochrome c after cisplatin treatment. Pioglitazone also reduced the activation of caspase‐3 and caspase‐9, lowered the ratio of Bax/Bcl‐2, attenuated kidney pathological damage and dysfunction, down‐regulated the expression of Acetyl‐p53, PUMA‐α and Bax and abated cell apoptosis after cisplatin treatment. The SIRT1 inhibitor, EX527, clearly reversed the protective effects of PIO. These results implied PIO attenuated cisplatin nephrotoxicity by suppressing mitochondria‐mediated apoptosis through regulating SIRT1/p53 signalling.

Neuronal cell types are essential to the comprehensive understanding of the neuronal function and neuron can be categorized by their anatomical property. However, complete morphology data for neurons with a whole brain projection, for example the pyramidal neurons in the cortex, are sparse because it is difficult to trace the neuronal fibers across the whole brain and acquire the neuron morphology at the single axon resolution. Thus the cell types of pyramidal neurons have yet to be studied at the single axon resolution thoroughly. In this work, we acquire images for a Thy1 H-line mouse brain using a fluorescence micro-optical sectioning tomography system. Then we sample 42 pyramidal neurons whose somata are in the layer 5 of the motor cortex and reconstruct their morphology across the whole brain. Based on the reconstructed neuronal anatomy, we analyze the axonal and dendritic fibers of the neurons in addition to the soma spatial distributions, and identify two axonal projection pattern of pyramidal tract neurons and two dendritic spreading patterns of intratelencephalic neurons. The raw image data are available upon request as an additional asset to the community. The morphological patterns identified in this work can be a typical representation of neuron subtypes and reveal the possible input-output function of a single pyramidal neuron.

In this paper, three different types of solid implant bridge (SIB), internal porous implant bridge (IPIB) and external porous implant bridge (EPIB) were modeled to investigate its static mechanical performance. FEA was used to calculate the stress distribution in implant bridges. The 200 N loading was applied to simulate occlusal function. The stress distribution occurred at the gingival surface above the interface in all the groups. The peak stress of IPIB was lower than SIB and EPIB. Further, two porous cylinders with external and internal pore structure were precisely fabricated to better understand its structural responses, stress distribution patterns and micromotions. Results showed that the peak stress and total deformation of internal porous cylinder was much lower than external porous cylinder. This study indicated that IPIB design maintained the better geometric characteristics and exhibited better stress distribution than EPIB design.

Bile acids in host intestine activate larvae of tapeworms and facilitate its invasion. However, the mechanism underlying this process is poorly understood. In order to better understand responses of tapeworms to host biles, we used RNA-Seq profiling method to study the transcriptomes of Cysticercus Pisiformis (larvae of Taenia Pisiformis) after host bile acid treatment. A total of 338.32 million high-quality clean reads were obtained by Illumina Hiseq platform. Totally, 62,009 unigenes were assembled, 38,382 of which were successfully annotated to known databases. A total of 9324 unigenes were identified as differentially expressed genes (DEGs), of which 5380 and 3944 genes were up- and down-regulated in the group treated with bile acids, respectively. Gene Ontology analysis revealed that biosynthesis and energy metabolism potential were significantly strengthened after host bile treatment in C. pisiformis. Similarly, KEGG pathway analysis revealed an enrichment of pathways related to lipid metabolism and carbohydrate metabolism. Among them, 'AMPK signaling pathway' which is critical in balancing cellular energy, was significantly enriched after bile acids activation. In addition, pathways of 'Fatty acid biosynthesis', 'Fatty acid elongation', 'Starch and sucrose metabolism', and 'glycolysis gluconeogenesis' were also significantly changed after bile acid treatment. qRT-PCR analysis confirmed the differential abundances of some key genes in these pathways. Our data suggest that host bile acids remarkably promote the pathways of energy metabolism of this parasite and regulate the genes involved in balancing lipid metabolism and carbohydrate metabolism. These findings provide new insights on the lifecycle of Taenia parasites.

Objectives To investigate the effect and mechanism of macrophage activation and graft damage caused by nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) in acute antibody-mediated rejection (AMR). Methods Acute AMR was induced in different skin-grafted nude mouse models with wild-type NTPDase1 expression, transgene-enhanced NTPDase1 expression, or NTPDase1 gene knockout. Several methods (eg, real-time fluorescence quantitative polymerase chain reaction, high-performance liquid chromatography [HPLC], immunofluorescence, flow cytometry, and luciferin/luciferase assays) were used to study (at the histologic and molecular levels) the extracellular adenosine diphosphate (ADP) concentration, macrophage proliferation, major histocompatibility complex (MHC) class II antigen expression on the surface of macrophages, B-cell activating factor (BAFF) expression in the peripheral blood serum, and the total number of SmIg-positive B cells during acute AMR. The relative activity of NTPDase1 in B cells and epithelial cells, pathologic changes, and the incidence of positive C4d deposition around the capillaries of skin grafts on the different nude mice were studied. Results Macrophages proliferated significantly when acute AMR occurred. The higher the NTPDase1 expression level, the lower the extracellular ADP concentration, the expression of MHC class II antigens on the surface of macrophages, the expression of BAFF in the peripheral blood serum, and the total number of SmIg-positive B cells, indicating negative correlations. The relative activity of NTPDase1 in B cells and epithelial cells of the skin graft was different among the different mice. The higher the NTPDase1 expression level, the lower the degree of pathologic damage to the skin graft. Conclusions Imbalance in extracellular ADP degradation by NTPDase1 may promote macrophage activation, and activated macrophages may be an important cause of graft damage.

Rationale: Nabothian cysts are mucus-filled cervical cysts that are usually asymptomatic unless they become very large. Chronic urinary retention is the persistent inability to empty the bladder despite maintaining an ability to urinate. Chronic urinary retention caused by a large, deep nabothian cyst has not been reported previously. Patient concerns: A 46-year-old woman presented with chronic urinary retention and a cervical cyst that gradually increased in size. Diagnosis: Based on histopathological evidence, our patient was diagnosed with a nabothian cyst. Interventions: A hysterectomy was performed. Outcomes: The urinary symptoms of the patient resolved after she performed clean, intermittent self-catheterizations for 5 days after the operation. She was discharged on postoperative day 6. Lessons: Large nabothian cysts are rare but may account for some unusual symptoms including unexplained urinary difficulties in women. We recommend treating symptomatic nabothian cysts with local cystectomies or hysterectomies.

The present study aimed to compare the efficacy and safety of dexmedetomidine and midazolam in patients that are critically ill. Full text articles reporting the clinical effects and complications of dexmedetomidine and midazolam were retrieved from multiple databases. Review Manager 5.0 was adopted for meta-analysis, sensitivity and bias analysis. Finally, a total of 1,379 patients from 8 studies, which met the eligibility criteria, were included. The meta-analysis suggested that the length of stay at the intensive care unit [mean absolute difference (MD)=-1.80; 95% confidence interval (CI), -2.13, -1.48; P

Tudor staphylococcal nuclease (Tudor-SN) is a multifunctional protein involved in a variety of cellular processes and plays a critical role in the regulation of gene expression. Recently, Tudor-SN was found to be upregulated in mammary epithelial cells during lactation in response to prolactin, which further to regulate milk protein synthesis. However, the detailed regulatory mechanism of Tudor-SN to milk protein still remains to be elucidated. In our study, we observed that the levels of Tudor-SN and phosphor-Tudor-SN (Thr103) were both enhanced upon prolactin stimulation. Immunofluorescence assays demonstrated that prolactin treatment facilitated the nuclear transport of Tudor-SN. Further study revealed that the phosphorylation of Tudor-SN was depended on activated JNK. Coimmunoprecipitation assays disclosed that Tudor-SN might be phosphorylated directly by JNK. Using gene mutation assays, we further discovered that mutation of Thr to Ala at site of 103 prevented the nuclear transport of Tudor-SN. Thus, these results suggested the essential mechanism of the activated Tudor-SN in milk protein regulation in response to prolactin, which may provide some new sights into improve milk protein production.

Background and Aims Esophageal stricture is a common adverse event after endoscopic submucosal dissection (ESD) when it involves the entire circumference of the esophagus. We aimed to assess the effectiveness and safety of endoscopic transplantation of autologous esophageal mucosa in preventing stricture formation after circumferential ESD. Methods Nine patients who underwent circumferential ESD for early esophageal cancer were enrolled. After the patients underwent ESD, autologous esophageal mucosal patches were attached to the ulcer surface by using hemoclips and were then fixed with a covered metal mesh stent. The stent was removed 7 days after the procedure. The patients were followed up with endoscopy at scheduled times. Results Epithelialization occurred within a median of 7.1 days, with a graft survival rate of 96.5%. Strictures occurred at a mean of 24.7 days (range 18-34 days) after the procedure. The median number of endoscopic balloon dilatation sessions was 2.7 (range 0-6). Conclusions Transplantation of autologous esophageal mucosa could be a safe way of relieving the severity of esophageal stricture after circumferential ESD.

GPR81 (also named as HCA1) is a member of a subfamily of orphan G-protein coupled receptors (GPCRs), coupled to Gi -type G proteins. GPR81 was discovered in 2001 and identified as the only known endogenous receptor of lactate under physiological conditions in 2008, which opened a new field of research on how lactate may act as a signal molecule along with the GPR81 expression in the roles of metabolic process and inflammatory response. Recent studies showed that the physiological functions of GPR81 include lipid metabolism in adipose tissues, metabolic excitability in the brain, cellular development, and inflammatory response modulation. These findings may reveal a novel therapeutic strategy to treat clinical, metabolic, and inflammatory diseases. This article will summarize past research on GPR81, including its characteristics of distribution and expression, functional residues, pharmacological, and physiological agonists, involvement in signal transduction, and pharmacological applications.

The intracellular fatty acid-binding proteins (FABPs) are a well-conserved family that function as lipid chaperones. Ongoing studies are focused on identification of the mechanistic complexity and vast biological diversity of different isoforms of FABPs. However, the molecular mechanism of FABP5 in the regulation of milk fat synthesis in the mammary gland of dairy cows is still largely unknown. Here, we report that FABP5 acts as a critical regulator of terol response element-binding protein-1c (SREBP-1c) gene expression induced by methionine (Met) and estrogen (E2) in bovine mammary epithelial cells (BMECs). We observed that the expression of FABP5 was markedly higher in dairy cow mammary tissue during the lactating period than the puberty period and the dry period. FABP5 is located in the cytoplasm, and Met and E2 significantly increase the protein levels of FABP5 in BMECs. Using gene function study approaches, we revealed that FABP5 positively regulates SREBP-1c gene expression and promotes milk fat synthesis. We confirmed that FABP5 is required for Met- and E2-induced SREBP-1c gene expression and milk fat synthesis. We further uncovered that fatty acids are needed for FABP5-mediated SREBP-1c gene expression. Thus, our study demonstrates that FABP5 is a critical regulator of Met- and E2-induced SREBP-1c gene expression leading to milk fat synthesis.

In this study, the fungicidal effects and detailed action of chitosan against Ceratocystis fimbriata were evaluated. The results demonstrated that chitosan exhibited strong antifungal activity that restricted the mycelium extension and changed the hyphal morphology. Fluorescein diacetate (FDA) and propidium iodide (PI) double-staining directly visualized decreased cell viability in response to chitosan treatment. Investigation of the PI influx showed that chitosan induced irreversible cell membrane damage. The efflux of potassium ions from the cytosol into the extracellular matrix demonstrated that chitosan induced the leakage of intracellular components. Massive intracellular bis-(1, 3-dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)] accumulation indicated the dissipation of membrane potential. Furthermore, chitosan clearly decreased the activity of H+/K+ ATPase. Fluorescence microscopy revealed that the fluorescence distribution and intensity of fluorescein isothiocyanate (FITC) changed as the incubation time increased. These results indicate that chitosan exerts a fungicidal effect via its ability to disturb fungal membranes.

The contamination of food with Aspergillus flavus and subsequent aflatoxins is one of the most serious safety problems in the world. In this study of nerol (NEL)’s antifungal mechanism of action, we observed morphological and physiological changes in Aspergillus flavus. We found that NEL resulted in elevated levels of reactive oxygen species (ROS) and calcium ions (Ca2+). On ROS assays, compared with the controls, the proportion of fluorescent cells treated with concentrations of 0.25, 0.5, 1, and 2 μL/mL NEL increased to 8.4 ± 1.07%, 10.2 ± 1.72%, 13.4 ± 0.50%, and 26.2 ± 4.21%, respectively. Increased mitochondrial dysfunction and oxidative stress induced by the interactions between Ca2+ and ROS subsequently activate the release of cytochrome c and caspase activity. Characteristic changes of apoptosis were also observed via various detection methods, including phosphatidylserine externalization, nuclear condensation, and DNA fragmentation. Meanwhile, we found that the expression of CaMKs increased significantly in NEL-treated cells. In conclusion, our findings indicate that NEL has great potential as an eco-friendly antifungal agent for food preservation.

In mammals, beclin-1 is a key player that regulates autophagic activity. In fish, the immune function of beclin-1 is essentially unknown. In this study, we analyzed the involvement of tongue sole (Cynoglossus semilaevis) beclin-1 (named CsBECN1) in antibacterial immunity. CsBECN1 is composed of 451 amino acid residues and shares 84.5-95.1% overall sequence identities with other teleost beclin-1. CsBECN1 possesses a typical Bcl-2 homology domain 3 and an Atg6 domain. Expression of CsBECN1 occurred in multiple tissues and was upregulated during bacterial infection. Knockdown of CsBECN1 significantly enhanced bacterial dissemination in the tissues of tongue sole, whereas overexpression of CsBECN1 significantly reduced bacterial dissemination. Taken together, these results indicate that CsBECN1 is required for the antibacterial immunity of tongue sole.

In this article, Y2O3-reinforced tungsten composites are fabricated by using an improved wet chemical method combined with the spark plasma sintering (SPS). Triethanolamine (TEA) surfactant addition and an appropriate calcination process are innovatively introduced into this wet chemical method. The results show that ultrafine composite powders with nano-sized Y2O3 dispersions in the tungsten matrix can be obtained through the improved wet chemical method. Using the SPS, the average sizes of Y2O3 particles within tungsten grains and at grain boundaries are identified to be 13.5 and 50 nm, respectively. It is found that the phase interface between W and Y2O3 is a typical semicoherent interface. We observe that the W-Y2O3 composites possess superior mechanical properties compared with the pure tungsten counterparts. The results inferred from atomistic simulations reveal that the added Y2O3 particles can effectively pin the dislocation and impede the dislocation movement, thus enhancing the mechanical performances of W-Y2O3 composites. In addition, the addition of Y2O3 particles is also able to improve the helium ion irradiation resistance of tungsten-based composites. This study is expected to provide a certain reference for the manufacture of large-sized tungsten-based materials.

The essential oil extracted from the black Piper nigrum L. (BPEO) was analyzed for antioxidant, hepatoprotective and antifungal activities. BPEO is rich in total phenolics, total flavonoids and proanthocyanidins, and showed good free radicals and lipid peroxidation scavenging capacities. In a CCl4-induced liver injury mice model, the BPEO treated groups showed increases in the catalase (CAT), glutathione (GSH) and total superoxide dismutase (T-SOD) activities present in the liver and kidney, and reverses the CCl4-elevated total bilirubin (TBIL), glutamate pyruvate transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) and malondialdehyde (MDA) level, which were confirmed in further analyses of kidney tissue sections. BPEO can effectively inhibit the growth of Aspergillus flavus spoilage fungus in maize. Further analyses indicated that BPEO disrupt the permeability barrier of the cell membrane and lead to mitochondrial dysfunction in A. flavus. Therefore, the current study proved BPEO's potential as hepatoprotective products and natural food preservatives.

MiR-150 is a microRNA (miRNA) present in a number of teleost species, but its target and regulation mechanism are unknown. Similarly, lysosome membrane protein 2-like (LMP2L) is a gene identified in fish but with unknown function. In this study, we examined the regulation mechanism and function of flounder miR-150 (named pol-miR-150) and its target gene LMP2L (named PoLMP2L) in association with bacterial and viral infection. We found that pol-miR-150 expression was not only modulated by the bacterial pathogen Streptococcus iniae but also by the viral pathogen megalocytivirus. Pol-miR-150 targeted PoLMP2L by binding to the 3'-untranslated region (3'-UTR) of PoLMP2L and inhibited PoLMP2L expression in vitro and in vivo. PoLMP2L is a member of the CD36 superfamily of scavenger receptors and homologous to but phylogenetically distinct from lysosomal integral membrane protein type 2 (LIMP2). PoLMP2L was localized mainly in the lysosomes and expressed in multiple organs of flounder. In vivo knockdown and overexpression of PoLMP2L enhanced and suppressed, respectively, S. iniae dissemination in flounder tissues, whereas in vivo knockdown and overexpression of pol-miR-150 produced the opposite effects on S. iniae dissemination. In addition, pol-miR-150 knockdown also significantly inhibited the replication of megalocytivirus. The results of this study revealed the regulation mechanism and immune functions of fish miR-150 and LMP2L, and indicated that LMP2L and miR-150 play an important role in the antimicrobial immunity of fish.