Mutational landscape of TP53 and CDH1 in gastric cancer.

In this editorial we comment on an article published in a recent issue of the World J Gastrointest Surg. A common gene mutation in gastric cancer (GC) is the TP53 mutation. As a tumor suppressor gene, TP53 is implicated in more than half of all tumor occurrences. TP53 gene mutations in GC tissue may be related with clinical pathological aspects. The TP53 mutation arose late in the progression of GC and aided in the final switch to malignancy. CDH1 encodes E-cadherin, which is involved in cell-to-cell adhesion, epithelial structure maintenance, cell polarity, differentiation, and intracellular signaling pathway modulation. CDH1 mutations and functional loss can result in diffuse GC, and CDH1 mutations can serve as independent prognostic indicators for poor prognosis. GC patients can benefit from genetic counseling and testing for CDH1 mutations. Demethylation therapy may assist to postpone the onset and progression of GC. The investigation of TP53 and CDH1 gene mutations in GC allows for the investigation of the relationship between these two gene mutations, as well as providing some basis for evaluating the prognosis of GC patients.

Microwave synthesis of chitosan-based carbon dots for Al3+ detection and biological application.

Yellow fluorescent carbon dots (Y-CDs) were prepared via microwave method using chitosan and o-phenylenediamine as the main raw materials. The obtained Y-CDs possesses good water solubility, excellent biocompatibility and luminous stability. During the microwave pyrolysis carbonization process, the surface of Y-CDs was modified with the functional groups such as amino and carboxyl, which can bind to Al3+ by forming complexes, further improving the selectivity and sensitivity of the Al3+ detection. And the fluorescence of Y-CDs was quenched by Al3+ by static quenching process. More importantly, Y-CDs as fluorescent sensor was further applied for the determination of Al3+ in the real water samples with high reliability and accuracy. In addition, Y-CDs present potential application in biological imaging. The cultivated zebrafish embryos with Y-CDs displayed clearly in vivo uptake and metabolic fluorescence images, further confirming its low toxicity and excellent biocompatibility.

Rapid Preparation of Long-Wavelength Emissive Carbon Dots for Information Encryption Using the Microwave-Assisted Method.

The synthesis of long-wavelength emission fluorescent carbon dots is not common, and it is even more difficult to quickly synthesize within 10 min. In this experiment, yellow, orange, and red B, N codoped fluorescent carbon dots were successfully synthesized using a microwave-assisted method with o-phenylenediamine as the carbon-nitrogen source, boric acid as the boron source, and potassium chloride as the catalyst in just 7 min. Based on the different contents of B, N element doping, there are differences in their surface structures, resulting in differences in the luminescence properties of the synthesized carbon dots. Long-wavelength carbon dots can avoid interference from the blue fluorescence of filter papers and have a clearer display in information encryption. Therefore, three types of carbon dots were mixed with PVP to produce fluorescent inks, and anticounterfeiting and encryption patterns were designed on the filter paper, displaying different fluorescence information under sunlight and UV light. In addition, the rich fluorescent colors were combined ingeniously to enable secondary encryption of information in the form of binary codes that increase the difficulty of decoding. These indicate that the three synthesized long-wavelength carbon dots have good application prospects in information encryption.

Echoes in a "tree hole": A qualitative study on the service needs and responses at an antidrug helpline in China.

INTRODUCTION: China's antidrug measures have been slowly shifting from police-intervention and punitive approaches to supportive services. However, the system is still highly stigmatizing. Helpline services emerged to engage drug users, families, and friends and provide needed support as they seek rehabilitation. This study aimed to explore service needs expressed during helpline calls, operators' use of techniques when responding to different needs, and operators' experiences working at and views toward the helpline. METHODS: We conducted a qualitative mixed-method study using two sources of data. One source was 47 call recordings collected at a drug helpline in China, and the other was five individual and two focus group interviews conducted with 18 helpline operators. Using a six-step thematic analysis method, we explored the patterns of needs expression and response, and the operators' experiences of interacting with callers. RESULTS: We found that typical callers were drug users and their relatives or friends. Interactions between the callers and operators involved the expression of and response to needs that emerged from involvement with drugs. Informational and emotional needs were the most common. Operators would respond to these needs with different counseling techniques, such as providing information, advising, normalizing, focusing, and instilling hope. The operators developed a system of practices, such as internal supervision, case summaries, and listening back, to enhance competence and ensure quality of services. The helpline work also prompted their critical reflections on the current antidrug system and gradually reshaped their views toward the population they serve. CONCLUSIONS: Antidrug workers who engaged in answering helpline calls employed varying techniques to facilitate callers' expressed needs. They helped by providing much-needed informational and emotional support for drug users, families, and friends. Helpline services opened a private channel for people involved in drug use to express their needs and seek formal help in China's still stigmatizing and punitive antidrug system. Experiences working with anonymous help-seekers outside the statutory rehabilitation system helped workers at the helpline to gain unique reflective insight into the antidrug system and drug users.

A meta-analysis examined the effect of topical nursing application of antimicrobial as a prophylaxis for the stoppage of surgical wound infection in colorectal surgery.

To assess the impact of topical antimicrobial (TA) as a prophylaxis for the stoppage of surgical wound infection (SWI) in colorectal surgery (CS), we lead a meta-analysis. 9160 participants with CS were enrolled in the chosen studies; 4719 of them used TA, while 4441 served as controls. To assess the effectiveness of TA application in lowering SWIs following CS, odds ratios (OR) with 95% confidence intervals (CIs) were computed with a dichotomous technique with a fixed- or random-effect model. Significantly lower SWIs post CS for TA as whole (OR, 0.50; 95% CI, 0.38-0.64; P < .001), gentamicin collagen sponge and beads (OR, 0.52; 95% CI, 0.32-0.86; P = .01), triclosan impregnated fascial suture (OR, 0.57; 95% CI, 0.38-0.84; P = .005), antibiotic powder, ointment, lavage, or injection for the abdominal wound (OR, 0.35; 95% CI, 0.21-0.59; P < .001), and ionised silver dressing on the closed abdominal wound (OR, 0.45; 95% CI, 0.27-0.77; P = .003) compared to control. Significantly lower SWIs post CS for TA as a whole, gentamicin collagen sponge and beads, triclosan impregnated fascial sutures, antibiotic powder, ointment, lavage, or injection for the abdominal wound, and ionised silver dressing on the closed abdominal wound compared with control. The low sample size of 8 out of the 39 included studies in this meta-analysis calls for precaution when analysing the outcomes.

Biocontrol of Wheat Crown Rot Using Bacillus halotolerans QTH8.

Fusarium pseudograminearum causes crown rot in wheat. This study aimed to assess the effects of the bacterial strain QTH8 isolated from Cotinus coggygria rhizosphere soil against F. pseudograminearum. Bacterial strain QTH8 was identified as Bacillus halotolerans in accordance with the phenotypic traits and the phylogenetic analysis of 16S rDNA and gyrB gene sequence. Culture filtrates of bacterial strain QTH8 inhibited the mycelial growth of F. pseudograminearum and resulted in mycelial malformation such as tumor formation, protoplast condensation, and mycelial fracture. In addition, bacterial strain QTH8 also inhibited the mycelial growth of Hainesia lythri, Pestalotiopsis sp., Botrytis cinerea, Curvularia lunata, Phyllosticta theaefolia, Fusarium graminearum, Phytophthora nicotianae, and Sclerotinia sclerotiorum. The active compounds produced by bacterial strain QTH8 were resistant to pH, ultraviolet irradiation, and low temperature, and were relatively sensitive to high temperature. After 4 h exposure, culture filtrates of bacterial strain QTH8-when applied at 5%, 10%, 15%, 20%, 25%, and 30%-significantly reduced conidial germination of F. pseudograminearum. The coleoptile infection assay proved that bacterial strain QTH8 reduced the disease index of wheat crown rot. In vivo application of QTH8 to wheat seedlings decreased the disease index of wheat crown rot and increased root length, plant height, and fresh weight. Iturin, surfactin, and fengycin were detected in the culture extract of bacterial strain QTH8 by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Bacterial strain QTH8 was identified for the presence of the ituC, bacA, bmyB, spaS, srfAB, fend, and srfAA genes using the specific polymerase chain reaction primers. B. halotolerans QTH8 has a vital potential for the sustainable biocontrol of wheat crown rot.

Two citrus KNAT-like genes, CsKN1 and CsKN2, are involved in the regulation of spring shoot development in sweet orange.

Shoot-tip abortion is a very common phenomenon in some perennial woody plants and it affects the height, architecture, and branch orientation of trees; however, little is currently known about the underlying mechanisms. In this study, we identified a gene in sweet orange (Citrus sinensis) encoding a KNAT-like protein (CsKN1) and found high expression in the shoot apical meristem (SAM). Overexpression of CsKN1 in transgenic plants prolonged the vegetative growth of SAMs, whilst silencing resulted in either the loss or inhibition of SAMs. Yeast two-hybrid analysis revealed that CsKN1 interacted with another citrus KNAT-like protein (CsKN2), and overexpression of CsKN2 in lemon and tobacco caused an extreme multiple-meristem phenotype. Overexpression of CsKN1 and CsKN2 in transgenic plants resulted in the differential expression of numerous genes related to hormone biosynthesis and signaling. Yeast one-hybrid analysis revealed that the CsKN1-CsKN2 complex can bind to the promoter of citrus floral meristem gene LEAFY (CsLFY) and inhibit its expression. These results indicated that CsKN1 might prolong the vegetative growth period of SAMs by delaying flowering. In addition, an ethylene-responsive factor (CsERF) was found to bind to the CsKN1 promoter and suppresses its transcription. Overexpression of CsERF in Arabidopsis increased the contents of ethylene and reactive oxygen species, which might induce the occurrence of shoot-tip abscission. On the basis of our results, we conclude that CsKN1 and CsKN2 might work cooperatively to regulate the shoot-tip abscission process in spring shoots of sweet orange.

Feasibility and Preliminary Efficacy of a Community-Based Addiction Rehabilitation Electronic System in Substance Use Disorder: Pilot Randomized Controlled Trial.

BACKGROUND: Drug use disorder has high potential for relapse and imposes an enormous burden on public health in China. Since the promulgation of the Anti-drug law in 2008, community-based rehabilitation has become the primary approach to treat drug addiction. However, multiple problems occurred in the implementation process, leading to a low detoxification rate in the community. Mobile health (mHealth) serves as a promising tool to improve the effectiveness and efficiency of community-based rehabilitation. Community-based addiction rehabilitation electronic system (CAREs) is an interactive system for drug users and their assigned social workers. OBJECTIVE: The study aimed to examine the feasibility and preliminary efficacy of CAREs in community-based rehabilitation from the perspective of drug users and social workers in Shanghai, China. METHODS: In this pilot randomized controlled trial, 40 participants were recruited from the community in Shanghai from January to May 2019. Participants randomized to the intervention group (n=20) received CAREs + community-based rehabilitation, while participants in the control group (n=20) received community-based rehabilitation only for 6 months. CAREs provided education, assessment, and SOS (support) functions for drug users. The assigned social workers provided service and monitored drug use behavior as usual except that the social workers in the intervention group could access the webpage end to obtain drug users' information and fit their routine workflow into CAREs. The primary outcome was the feasibility of CAREs, reflected in the overall proportion and frequency of CAREs features used in both app and webpage end. The secondary outcomes were the effectiveness of CAREs, including the percentage of drug-positive samples, longest period of abstinence, contact times with social workers, and the change of Addiction Severity Index (ASI) from baseline to the 6-month follow-up. RESULTS: The number of participants logged in to the app ranged from 7 to 20 per week, and CAREs had relatively high levels of continued patient use. Drug users preferred assessment and education features in the app end while their social workers showed high levels of use in urine results record and viewing assessment results on the webpage end. After the 6-month intervention, 3.3% (17/520) of samples in the intervention group and 7.5% (39/520) in the control group were drug-positive (F=4.358, P=.04). No significant differences were noted between the control and intervention groups in terms of longest duration of abstinence, number of contact times and ASI composite scores. CONCLUSIONS: The study preliminarily demonstrated that with relatively good feasibility and acceptability, CAREs may improve the effectiveness and efficiency of the community-based rehabilitation, which provided instruction for further improvement of the system. TRIAL REGISTRATION: ClinicalTrials.gov NCT03451344; https://clinicaltrials.gov/ct2/show/NCT03451344. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3389/fpsyt.2018.00556.

miR-26a-5p mediates TLR signaling pathway by targeting CTGF in LPS-induced alveolar macrophage.

To explore the regulation mechanism of miR-26a-5p and connective tissue growth factor (CTGF) in lipopolysaccharide (LPS)-induced alveolar macrophages, which is a severe pneumonia cell model. MH-S cells were grouped into Normal group, Model group, negative control (NC) group, miR-26a-5p mimic group, oe-CTGF group, miR-26a-5p mimic + oe-CTGF group. The expression level of miR-26a-5p, CTGF and Toll-like receptor (TLR) signaling related molecules (TLR2, TLR4 and nuclear factor-κB p65) were detected by qRT-PCR and WB, respectively. The cell viability and apoptosis rate were detected by methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. Compared with the Normal group, the expression level of miR-26a-5p was significantly decreased, while CTGF protein level was significantly increased in the Model group. Compared with the Model group, MH-S cells with miR-26a-5p overexpression showed enhanced cell viability, decreased apoptosis rate, declined expression level of TLR signaling related molecules and reduced level of tumor necrosis factor-α (TNF-α), interleukin (IL) 6 (IL-6) and IL-1ß, while those with CTGF overexpression had an opposite phenotype. In conclusion, miR-26a-5p can inhibit the expression of CTGF and mediate TLR signaling pathway to inhibit the cell apoptosis and reduce the expression of proinflammatory cytokines in alveolar macrophages which is a cell model of severe pneumonia.

MicroRNA-92a antagonism attenuates lipopolysaccharide (LPS)-induced pulmonary inflammation and injury in mice through suppressing the PTEN/AKT/NF-κB signaling pathway.

Overwhelming lung inflammation is a key feature of acute lung injury (ALI). MicroRNAs (miRNAs) have been implicated in the regulation diverse cellular processes including the inflammatory response. However, little is known about their functions and molecular involvement in regulating the inflammatory process in ALI. Herein, we established a lipopolysaccharide (LPS)-induced ALI mouse model and used miRNA microarray analysis to investigate and compare the miRNA expression profiles in mouse lung tissues. We found that miR-92a was markedly upregulated in the lung tissues of ALI mice compared with that in normal lung tissues. This upregulation of miR-92a in LPS-induced ALI mice was further confirmed in lung tissues, splenocytes and bronchoalveolar lavage fluid (BALF) by quantitative real-time PCR. Inhibition of miR-92a by injection with antagomir-92a markedly reduced LPS-induced pathological changes associated with lung inflammation, and reduces lung wet/dry ratio (W/D ratio), and Evans blue dye extravasation (an indicator of lung epithelial permeability). Moreover, inhibition of miR-92a ameliorated the inflammatory response by reducing the repression of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 in lung tissues. In addition, we identified that miR-92a inhibited the phosphatase and tensin homolog on chromosome ten (PTEN) by binding to its 3'-UTR in RAW264.7 murine macrophage cells. Western blot analysis demonstrated that inhibition of miR-92a may ameliorate inflammatory response through blocking PTEN/AKT/NF-κB signaling pathway in ALI mice. Collectively, these results have revealed a significant role of miR-92a in the lung inflammatory response associated with ALI in mice, and suggest that miR-92a may have potential as a prognostic indicator and novel therapeutic target for the treatment of ALI in future.

Cellular Mechanisms of Hepatoprotection Mediated by M2-Like Macrophages.

BACKGROUND Acute liver injury in the setting of hepatic fibrosis is an intriguing and still unsettled issue. We previously have demonstrated the protective effects conferred by M2-like macrophages in the fibrotic liver. In the present work, we further decipher the cellular mechanisms governing this hepatoprotection. MATERIAL AND METHODS Macrophages were isolated from control mice (M0 macrophages), then polarized into M1 or M2 phenotype using IFN-γ or IL-4, respectively. Conditioned media (CM) from M0, M1, and M2 macrophages were harvested and applied to M1 macrophages. Cell apoptosis was evaluated by immunostaining and real-time PCR. Similarly, human monocyte-derived macrophages were isolated and polarized, then M0, M1, and M2 CM were applied to HL-7702 or HepG2 cells followed by apoptosis induction. Cell apoptosis was assessed by flow cytometry. RESULTS For the mouse conditioned medium experiment, stronger expression of cleaved caspase 3 and higher Bax/Bcl-2 mRNA ratio were found in M1 macrophages pretreated with M2 CM compared to those in M1 macrophages pretreated with M0 or M1 CM. Similarly, exposure of HL-7702 and HepG2 cells to either M0 or M1 CM had no significant effect on cell apoptosis. Nevertheless, the frequency of hepatocyte apoptosis was substantially reduced in HL-7702 (from 32.23±2.99 to 15.37±0.69 for Annexin V+/PI+ staining, p<0.01) and HepG2 cells (from 36.1±7.26 to 15.2±1.2 for Annexin V+/PI+ staining, p<0.01) with M2 CM pretreatment. CONCLUSIONS M2-like macrophages exert their hepatoprotective effect by promoting M1-like macrophage apoptosis but protecting against hepatocyte apoptosis.

Nanoindentation hardness and elastic modulus of nano-grained titanium produced by asymmetric and symmetric rolling.

To understand the nanomechanical properties of nano-grained (NG) Ti produced by combination of asymmetric and symmetric rolling, nanoindentation hardness (H(n)) and elastic modulus (E(n)) of different planes within the NG Ti specimens were measured using continuous stiffness measurement mode at room temperature. For comparison, the nanomechanical properties of the as-received hot-rolled coarse-grained (CG) Ti and ultrafine-grained (UFG) Ti with only asymmetric rolling process were also investigated. It was found that H(n) of the Ti samples increased significantly with the decrease of grain sizes, while E(n) exhibited a slight decrease as the grain sizes decreased from CG to NG regime. The increase of H(n) was expected to be caused by higher density of dislocations and finer grains attained by severer plastic deformation, while the slight decrease of E(n) was considered as a result of the increased density of lattice defects and volume fraction of the grain boundary atoms. Furthermore, the nanomechanical properties of different planes of the Ti specimen exhibited a little difference which can be expressed as H(n(RD-TD)) > H(n(N-RD)) > H(n(TD-ND)) and E(n(RD-TD)) > E(n(ND-RD)) > E(n(TD-ND)). These differences were ascribed to crystallographic textures formed by rolling deformation.

Pilot trial of a recovery management intervention for heroin addicts released from compulsory rehabilitation in China.

China faces the challenge of dual epidemics of drug use and HIV/AIDS. Despite the high relapse rate among heroin addicts released from compulsory rehabilitation facilities, there are few programs available in China to assist these addicts in the community. We pilot-tested in China a Recovery Management Intervention (RMI) program designed to facilitate early detection of relapse and prompt linkage from compulsory rehabilitation to the community and, if participants relapse, to community-based methadone maintenance treatment (MMT) programs. One hundred heroin addicts were randomly assigned to either the Standard Care group (n = 50) or the RMI group (n = 50). At the end of the 3-month trial, participants in the RMI group, relative to the standard care group, demonstrated positive outcomes in recidivism due to relapse (0 vs. 6%, p = .08; d = 0.354), MMT participation (8% vs. 0, p = 0.06; d = 0.417), and employment (33% vs. 2%, p < .001; d = 0.876), although no difference was found in urine testing results (8.5% vs. 8.7%; d = 0.013) among interviewed participants. These pilot study results were based on a small sample size and short-term observation, suggesting the need for more research to further improve and test RMI effectiveness with larger samples over a longer period of time in order to provide evidence in support of RMI as an effective strategy for community reintegration among addicts released from rehabilitation facilities in China.

WebMGA: a customizable web server for fast metagenomic sequence analysis.

BACKGROUND: The new field of metagenomics studies microorganism communities by culture-independent sequencing. With the advances in next-generation sequencing techniques, researchers are facing tremendous challenges in metagenomic data analysis due to huge quantity and high complexity of sequence data. Analyzing large datasets is extremely time-consuming; also metagenomic annotation involves a wide range of computational tools, which are difficult to be installed and maintained by common users. The tools provided by the few available web servers are also limited and have various constraints such as login requirement, long waiting time, inability to configure pipelines etc. RESULTS: We developed WebMGA, a customizable web server for fast metagenomic analysis. WebMGA includes over 20 commonly used tools such as ORF calling, sequence clustering, quality control of raw reads, removal of sequencing artifacts and contaminations, taxonomic analysis, functional annotation etc. WebMGA provides users with rapid metagenomic data analysis using fast and effective tools, which have been implemented to run in parallel on our local computer cluster. Users can access WebMGA through web browsers or programming scripts to perform individual analysis or to configure and run customized pipelines. WebMGA is freely available at http://weizhongli-lab.org/metagenomic-analysis. CONCLUSIONS: WebMGA offers to researchers many fast and unique tools and great flexibility for complex metagenomic data analysis.

[Prospective study of Han's acupoint nerve stimulator for preventing relapse of detoxified heroin addicts].

OBJECTIVE: To assess the efficacy of transcutaneous electrical acupoint stimulation (TEAS) in preventing the relapse of detoxified heroin users in a period of 12 months. METHODS: A total of 164 rehabilitating heroin users in Shanghai area were recruited after compulsory detoxification treatment for a period ranging from 3 months to 3 years. The TEAS was executed by the device named Han's acupoint nerve stimulator (HANS). The patients were treated with HANS for at least 3 months. All the subjects were then followed up for one year and relapse was monitored by monthly heroin/morphine urinalysis. RESULTS: Of 164 rehabilitating former heroin addicts, 53 remained drug-free at the end of 12 months observation period as judged by negative urinalysis while 35 become relapsed as documented by positive urine tests. The rest 76 dropped off due to various reasons and were all counted into the category of "relapsed". Thus, our data indicated 32.3% rehabilitating heroin users could stay sober for at least one year, which is significantly higher than the existing reports that less than 5% detoxified abusers would stay drug free for one year with no further intervention. No obvious correlation was found between the susceptibility of relapse and the duration of compulsory detoxification. CONCLUSION: Compared to the existing literatures, our results indicate that HANS could produce a marked decrease of the relapse rate of rehabilitating heroin users after compulsory detoxification.