Sensitivity, Specificity, and Safety of a Novel ESAT6-CFP10 Skin Test for Tuberculosis Infection in China: 2 Randomized, Self-Controlled, Parallel-Group Phase 2b Trials.

BACKGROUND: Diagnostics to identify tuberculosis infection are limited. We aimed to assess the diagnostic accuracy and safety of ESAT6-CFP10 (EC) skin test for tuberculosis infection in Chinese adults. METHODS: We conducted 2 randomized, parallel-group clinical trials in healthy participants and tuberculosis patients. All participants were tested with the T-SPOT.TB test, then received an EC skin test and tuberculin skin test (TST). The diameter of skin indurations and/or redness at injection sites were measured at different time periods. A bacillus Calmette Guerin (BCG) model was established to assess the diagnosis of tuberculosis infection using an EC skin test. RESULTS: In total, 777 healthy participants and 96 tuberculosis patients were allocated to receive EC skin test at 1.0 µg/0.1 mL or 0.5 µg/0.1 mL. The area under the curve was 0.95 (95% confidence interval [CI], .91-.97) for the EC skin test at 1.0 µg/0.1 mL at 24-72 hours. Compared with the T-SPOT.TB test, the EC skin test demonstrated similar sensitivity (87.5, 95% CI, 77.8-97.2 vs 86.5, 95% CI, 79.5-93.4) and specificity (98.9, 95% CI, 96.0-99.9 vs 96.1, 95% CI, 93.5-97.8). Among BCG vaccinated participants, the EC skin test had high consistency with the T-SPOT.TB test (96.3, 95% CI, 92.0-100.0). No serious adverse events related to the EC skin test were observed. CONCLUSIONS: The EC skin test demonstrated both high specificity and sensitivity at a dose of 1.0 µg/0.1 mL, comparable to the T-SPOT.TB test. The diagnostic accuracy of the EC skin test was not impacted by BCG vaccination. CLINICAL TRIALS REGISTRATION: NCT02389322 and NCT02336542.

UBE2W Improves the Experimental Colitis by Inhibiting the NF-κB Signaling Pathway.

BACKGROUND: The NF-κB signaling cascade regulates immune response and is often dysregulated in tumor development. UBE2W is a novel type I ubiquitin-conjugating enzyme (E2) whose biological function is still unclear. AIMS: This study was designed to investigate whether UBE2W regulates NF-κB signaling pathway and is involved in the progression of experimental colitis. METHODS: At the cellular level, the effect of UBE2W on NF-κB transcriptional activity was measured using a dual-luciferase reporter assay. The influence of UBE2W on NF-κB pathway activation and the entry of p65 into the nucleus were determined by Western blot and immunofluorescence analyses, respectively. Moreover, the colitis model was established by administering 2.5% dextran sulfate sodium (DSS)/water to UBE2W overexpression, UBE2W-knockdown and control mice. Body weight, stool consistency, colon length and clinical severity were examined. Expression of pro-inflammatory cytokines and phosphorylation of p65 and IκB in the colon tissue were measured by qRT-PCR and Western blot, respectively. RESULTS: UBE2W inhibited TNFα-induced NF-κB transcription activity, attenuated IκB and p65 phosphorylation, downregulated TNFα and IL-8 expression and blocked the entry of p65 into the nucleus. In the DSS-induced colitis model, UBE2W-knockdown mice had increased weight loss, more serious diarrhea and mucosal injures compared with the control mice. Moreover, phosphorylation of IκB and p65 and the expression of pro-inflammatory mediators such as TNFα, IL-6 were significantly increased in UBE2W knockdown mice. However, these changes were completely reversed in UBE2W overexpression mice. CONCLUSIONS: The overexpression of UBE2W ameliorates the severity of DSS-induced colitis, which may be mediated by inhibiting the expression of pro-inflammatory mediators and activation of the NF-κB signaling pathway. These findings provide evidence that UBE2W might have potential therapeutic implications in IBD.

Wafer-Scale Growth of One-Dimensional Transition-Metal Telluride Nanowires.

The development of bulk synthetic processes to prepare functional nanomaterials is crucial to achieve progress in fundamental and applied science. Transition-metal chalcogenide (TMC) nanowires, which are one-dimensional (1D) structures having three-atom diameters and van der Waals surfaces, have been reported to possess a 1D metallic nature with great potential in electronics and energy devices. However, their mass production remains challenging. Here, a wafer-scale synthesis of highly crystalline transition-metal telluride nanowires is demonstrated by chemical vapor deposition. The present technique enables formation of either aligned, atomically thin two-dimensional (2D) sheets or random networks of three-dimensional (3D) bundles, both composed of individual nanowires. These nanowires exhibit an anisotropic 1D optical response and superior conducting properties. The findings not only shed light on the controlled and large-scale synthesis of conductive thin films but also provide a platform for the study on physics and device applications of nanowire-based 2D and 3D crystals.

Decreased expression of long noncoding RNA XLOC_013703 promotes cell growth via NF-κB pathway in multiple myeloma.

Long noncoding RNAs (lncRNAs) are dysregulated in cancer and involved in oncogenic or tumor inhibitory processes. The aim of the study was to investigate the expression pattern of lncRNA XLOC_013703 in multiple myeloma (MM) and to evaluate its biological role and potential significance. We found that XLOC_013703 was significantly decreased in CD138 positive plasma cells and serum of MM patients compared to normal controls, and the decreased XLOC_013703 expression was correlated with ß2-MG, serum-free light chain (s-FLC) and revised international staging system. RNA-fluorescence in situ hybridization results revealed that XLOC_013703 was distributed both in the nucleus and in the cytoplasm of MM cells including H929, RPMI8226, and U266. Overexpression of XLOC_013703 inhibited the proliferation of U266 cells and blocked the cell cycle in G1 stage, thus contributing to MM cell apoptosis. By contrast, knockdown of XLOC_013703 promoted the growth of H929 cells. Western blot analysis confirmed that the expression of p-IκBα and nuclear P65 was substantially increased in shRNA transfection groups compared to control groups, whereas overexpression of XLOC_013703 reduced these expressions. In conclusion, we confirmed that the decreased expression of a novel lncRNA, XLOC_013703, in MM. XLOC_013703 was involved in MM cell survival and proliferation via nuclear factor-κB pathway which represents a potential therapeutic target for MM. © 2019 IUBMB Life, 71(9):1240-1251, 2019.

[Regulation of Chrysophanol-mediated TLR4/NF-κB Pathway on Renal Injury and Immune Response in IgA Nephropathy Rats].

OBJECTIVE: To investigate the regulatory effect and its mechanism of chrysophanol (CP) on renal injury and immune response in immunoglobin A (IgA) nephropathy rats. METHODS: IgA nephropathy rat model was established by the method of lipopolysaccharide + bovine serum protein + carbon tetrachloride. Then the rats were randomly divided into 5 groups: control group, IgA group, IgA+low, medium and high dose of CP groups(2.5, 5 and 10 mg/kg for each group respectively). IgA+CP groups were intraperitoneally injected with different doses of chrysophanol once a day for 4 weeks, and the control group and IgA group were given isovolumetric saline. Urine protein content, serum creatinine and urea nitrogen were detected at 24 h after the administration of drugs. Kidney histopathological damage and apoptosis were measured by HE and TUNEL staining. The expression levels of Caspase-3 and Caspase-9 were detected by RT-PCR and Western blot; The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and (glutathione peroxidase, Gpx) were detected by enzyme-linked immunosorbent assay (ELISA). The expression of interleukin-1ß, -6 (IL-1ß, IL-6) and tumor necrosis factor (TNF-α) in serum and kidney tissue were measured by ELISA and Western blot, respectively. The mRNA and protein expression levels of toll-like receptro 4 (TLR4), nuclear factor-κB P65 (NF-κB P65) were also detected by RT-PCR and Western blot, and vascular cell adherin molecule (VCAM-1) protein level was deteted by Western blot. RESULTS: In IgA nephropathy rats, the administration of CP reduced proteinuria, serum creatinine and urea nitrogen in a dose-dependent manner (P < 0.01). It also improved the pathological damage of kidney tissue, reduced the apoptosis rate (P < 0.01), and decreased the mRNA and protein expression levels of apoptosis-related proteins Caspase-3 and Caspase-9 (P < 0.01). CP inhibited MDA production while increased the activities of antioxidant enzymes Gpx and SOD (P < 0.01), and decreased the levels of serum and protein expression of IL-1ß, IL-6 and TNF-α (P < 0.01), as well as the expression levels of TLR4, NF-κB P65 and VCAM-1 (P < 0.01). CONCLUSION: Chrysophanol could play a protective role in IgA nephropathy rats, and its mechanism may be related to alleviating kidney injury and regulating immune response.

Synthesis of Large-Area InSe Monolayers by Chemical Vapor Deposition.

Recently, 2D materials of indium selenide (InSe) layers have attracted much attention from the scientific community due to their high mobility transport and fascinating physical properties. To date, reports on the synthesis of high-quality and scalable InSe atomic films are limited. Here, a synthesis of InSe atomic layers by vapor phase selenization of In2 O3 in a chemical vapor deposition (CVD) system, resulting in large-area monolayer flakes or thin films, is reported. The atomic films are continuous and uniform over a large area of 1 × 1 cm2 , comprising of primarily InSe monolayers. Spectroscopic and microscopic measurements reveal the highly crystalline nature of the synthesized InSe monolayers. The ion-gel-gated field-effect transistors based on CVD InSe monolayers exhibit n-type channel behaviors, where the field effect electron mobility values can be up to ≈30 cm2 V-1 s-1 along with an on/off current ratio, of >104 at room temperature. In addition, the graphene can serve as a protection layer to prevent the oxidation between InSe and the ambient environment. Meanwhile, the synthesized InSe films can be transferred to arbitrary substrates, enabling the possibility of reassembly of various 2D materials into vertically stacked heterostructures, prompting research efforts to probe its characteristics and applications.

Thermoelectric Detection of Multi-Subband Density of States in Semiconducting and Metallic Single-Walled Carbon Nanotubes.

Thermoelectric detection of a multi-subband density of states in semiconducting and metallic single-walled carbon nanotubes is demonstrated by scanning the Fermi energy from electron-doped to hole-doped regions. The Fermi energy is systematically controlled by utilizing the strong electric field induced in electric-double-layer transistor configurations, resulting in the optimization of the thermoelectric power factor.

Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses.

To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1ß, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1ß, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.

CUEDC2 Protects Against Experimental Colitis and Suppresses Excessive Proliferation of Intestinal Mucosa.

BACKGROUND: CUEDC2, a CUE domain-containing protein, is highly expressed in many tumors, which also may be associated with inflammation. AIMS: In this study, we studied whether CUEDC2 plays a role in the progress of inflammatory bowel disease using CUEDC2 knockout (KO) mice and discussed the effects of CUEDC2 on cell proliferation in colonic mucosa. METHODS: CUEDC2 KO mice were administered with drinking dextran sodium sulfate (DSS) to establish colitis mice model. At different time points after DSS administration, body weight and stool consistency of mice were graded. Cytokines in colon tissue such as IL-6 were measured by RT-PCR. NF-κB and STAT3 signaling pathways in colon tissue were assessed by western blotting. Besides, cell proliferation of intestinal mucosa was analyzed by immunohistochemical staining. RESULTS: CUEDC2 alleviated the colonic inflammation, showing elevated body weight loss, worse diarrhea, and more severe colonic mucosal injury in CUEDC2 KO mice than WT mice. Moreover, pro-inflammatory cytokines such as IL-6, TNFα, COX2, and MIP2 were significantly elevated. In CUEDC2 KO mice, the NF-κB and STAT3 signaling pathways were increasingly activated in different stages of progression of the colonic inflammation, and the percentage of proliferating cells as indicated by Ki67, CyclinD1, and BrdU in the inflammatory tissues was significantly increased. CONCLUSIONS: Our findings demonstrate that CUEDC2 plays an important role in protection from colonic inflammation, primarily by inhibiting the NF-κB and STAT3 signaling pathways and preventing excessive proliferation of the inflammatory epithelial cell.

[Decreases of progressive motility, total motility, and acrosin activity of sperm from oligoasthenoteratospermia males at different time points after sperm activation].

OBJECTIVE: To investigate the progressive motility, (PR), total motility (progressive + non-progressive motility, PR + NP), and acrosin activity of sperm from normal and infertile men at different time points after sperm activation. METHODS: Based on the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen and the results of modified Papanicolaou staining, we divided the semen samples into groups A (normal, n = 28), B (oligoasthenoteratospermia, n = 30), and C (asthenoteratospermia, n = 32). At 1, 24, and 48 hours after sperm activation, we detected sperm PR and PR + NP by CASA and chemical colorimetry, and determined sperm acrosin activity using the modified Kennedy method. RESULTS: Sperm PR and PR + NP were significantly decreased in all the three groups at 1-24 hours and even more significantly at 24-48 hours after sperm activation as compared with the baseline (P < 0.05). Sperm acrosin activity showed remarkable reduction in group A (P = 0. 013) , even more significant at 1-24 hours than at 24-48 hours after sperm activation, but not in groups B and C (P = 0.519 and 0.979). CONCLUSION: Sperm PR, PR + NP, and acrosin activity are all decreased with the extension of time after sperm activation, each in a specific manner. Examination of sperm acrosin activity should be applied as a routine tool in the assessment of male fertility.

Flexible and stretchable thin-film transistors based on molybdenum disulphide.

The outstanding physical and chemical properties of two-dimensional materials, which include graphene and transition metal dichalcogenides, have allowed significant applications in next generation electronics. In particular, atomically thin molybdenum disulphide (MoS2) is attracting widespread attention because of its large bandgap, effective carrier mobility, and mechanical strength. In addition, recent developments in large-area high-quality sample preparation methods via chemical vapour deposition have enabled the use of MoS2 in novel functional applications, such as flexible and stretchable electronic devices. In this perspective, we focus on the current progress in generating MoS2-based flexible and stretchable thin-film transistors. The reported virtues and novelties of MoS2 provide significant advantages for future flexible and stretchable electronics.

Jolkinolide B synergistically potentiates the antitumor activity of GPX4 inhibitors via inhibiting TrxR1 in cisplatin-resistant bladder cancer cells.

Glutathione peroxidase 4 (GPX4) is a promising anticancer therapeutic target; however, the application of GPX4 inhibitors (GPX4i) is limited owing to intrinsic or acquired drug resistance. Hence, understanding the mechanisms underlying drug resistance and discovering molecules that can overcome drug resistance are crucial. Herein, we demonstrated that GPX4i killed bladder cancer cells by inducing lipid reactive oxygen species-mediated ferroptosis and apoptosis, and cisplatin-resistant bladder cancer cells were also resistant to GPX4i, representing a higher half-maximal inhibitory concentration value than that of parent bladder cancer cells. In addition, thioredoxin reductase 1 (TrxR1) overexpression was responsible for GPX4i resistance in cisplatin-resistant bladder cancer cells, and inhibiting TrxR1 restored the sensitivity of these cells to GPX4i. In vitro and in vivo studies revealed that Jolkinolide B (JB), a natural diterpenoid and previously identified as a TrxR1 inhibitor, potentiated the antiproliferative efficacy of GPX4i (RSL3 and ML162) against cisplatin-resistant bladder cancer cells. Furthermore, GPX4 knockdown and inhibition could augment JB-induced paraptosis and apoptosis. Our results suggest that inhibiting TrxR1 can effectively improve GPX4 inhibition-based anticancer therapy. A combination of JB and GPX4i, which is well-tolerated and has several anticancer mechanisms, may serve as a promising therapy for treating bladder cancer.

Highly flexible MoS2 thin-film transistors with ion gel dielectrics.

Molybdenum disulfide (MoS(2)) thin-film transistors were fabricated with ion gel gate dielectrics. These thin-film transistors exhibited excellent band transport with a low threshold voltage (<1 V), high mobility (12.5 cm(2)/(V·s)) and a high on/off current ratio (10(5)). Furthermore, the MoS(2) transistors exhibited remarkably high mechanical flexibility, and no degradation in the electrical characteristics was observed when they were significantly bent to a curvature radius of 0.75 mm. The superior electrical performance and excellent pliability of MoS(2) films make them suitable for use in large-area flexible electronics.

Effects of low-dose hydroxychloroquine on expression of phosphorylated Akt and p53 proteins and cardiomyocyte apoptosis in peri-infarct myocardium in rats.

BACKGROUND: Low-dose hydroxychloroquine (HCQ) and ataxia-telangiectasia-mutated (ATM) protein kinase have recently been postulated to be beneficial for the prevention of the age-associated metabolic syndrome including hypertension, hypercholesterolemia and glucose intolerance; however, the effects of low-dose HCQ on the expression of ATM downstream phosphorylated Akt (protein kinase B) and p53 proteins and cardiomyocyte apoptosis in the peri-infarct myocardium remain unclear. OBJECTIVE: To explore the effects of low-dose HCQ on the expression of phosphorylated Akt and p53 proteins and cardiomyocyte apoptosis in the peri-infarct myocardium in a rat model. METHODS: Myocardial infarction (MI) was induced experimentally in a subset of rats, while others underwent sham operation (sham). Three days after operation, surviving Sprague-Dawley male rats were divided into MI+HCQ, MI, sham+HCQ and sham groups. MI+HCQ and sham + HCQ groups were treated with HCQ (3.4 mg/kg); and MI and sham groups were treated with phosphate buffered (ie, physiological) saline (10 mL/kg) by gavage every day for 12 weeks. The expression of phosphorylated Akt and p53 proteins and cardiomyocyte apoptosis in the peri-infarct myocardium was detected by Western blot and terminal deoxynucleotidyl transferase dUTP nick end labelling, respectively. RESULTS: Twelve weeks after treatment, the expression of phosphorylated Akt protein was significantly increased (P<0.05). Expression of phosphorylated p53 protein was not significantly different (P>0.05) in the peri-infarct myocardium of the MI+HCQ group from that in the MI group. The cardiomyocyte apoptosis rate in the peri-infarct myocardium was significantly decreased in the MI+HCQ group compared with the MI group (P<0.05). CONCLUSION: Low-dose HCQ can significantly increase the expression of phosphorylated Akt protein without significantly impacting expression of phosphorylated p53 protein in the peri-infarct myocardium. Accordingly, it can inhibit cardiomyocyte apoptosis in the peri-infarct myocardium.

Simultaneously Cationic and Anionic Dyes Elimination via Magnetic Hydrochar Prepared from Copper Slag and Pinewood Sawdust.

In practical wastewater, cationic and anionic dyes usually coexist, while synergistic removal of these pollutants is difficult due to their relatively opposite properties. In this work, copper slag (CS) modified hydrochar (CSHC) was designed as functional material by the one-pot method. Based on characterizations, the Fe species in CS can be converted to zero-valent iron and loaded onto a hydrochar substrate. The CSHC exhibited efficient removal rates for both cationic dyes (methylene blue, MB) and anionic dyes (methyl orange, MO), with a maximum capacity of 278.21 and 357.02 mg·g-1, respectively, which was significantly higher than that of unmodified ones. The surface interactions of MB and MO between CSHC were mimicked by the Langmuir model and the pseudo-second-order model. In addition, the magnetic properties of CSHC were also observed, and the good magnetic properties enabled the adsorbent to be quickly separated from the solution with the help of magnets. The adsorption mechanisms include pore filling, complexation, precipitation, and electrostatic attraction. Moreover, the recycling experiments demonstrated the potential regenerative performance of CSHC. All these results shed light on the co-removal of cationic and anionic contaminates via these industrial by-products derived from environmental remediation materials.

Vapor-Phase Indium Intercalation in van der Waals Nanofibers of Atomically Thin W6Te6 Wires.

One-dimensional (1D) conducting materials are of great interest as potential building blocks for integrated nanocircuits. Ternary 1D transition-metal chalcogenides, consisting of M6X6 wires with intercalated A atoms (M = Mo or W; X = S, Se, or Te; A = alkali or rare metals, etc.), have attracted much attention due to their 1D metallic behavior, superconductivity, and mechanical flexibility. However, the conventional solid-state reaction usually produces micrometer-scale bulk crystals, limiting their potential use as nanoscale conductors. Here we demonstrate a versatile method to fabricate indium (In)-intercalated W6Te6 (In-W6Te6) bundles with a nanoscale thickness. We first prepared micrometer-long, crystalline bundles of van der Waals W6Te6 wires using chemical vapor deposition and intercalated In into the crystal via a vapor-phase reaction. Atomic-resolution electron microscopy revealed that In atoms were surrounded by three adjacent W6Te6 wires. First-principles calculations suggested that their wire-by-wire stacking can transform through postgrowth intercalation. Individual In-W6Te6 bundles exhibited metallic behavior, as theoretically predicted. We further identified the vibrational modes by combining polarized Raman spectroscopy and nonresonant Raman calculations.

Tuina-focused integrative chinese medical therapies for inpatients with low back pain: a systematic review and meta-analysis.

Objective. To evaluate the effectiveness of Tuina-focused integrative Chinese medical therapies (TICMT) on inpatients with low back pain (LBP). Methods. 6 English and Chinese databases were searched for randomized controlled trials (RCTs) of TICMT for in-patients with LBP. The methodological quality of the included RCTs was assessed based on PEDro scale. And the meta-analyses of TICMT for LBP on pain and functional status were conducted. Results. 20 RCTs were included. The methodological quality of the included RCTs was poor. The meta-analyses' results showed that TICMT had statistically significant effects on pain and functional status, especially Tuina plus Chinese herbal medicine (standardised mean difference, SMD: 1.17; 95% CI 0.75 to 1.60 on pain; SMD: 1.31; 95% CI 0.49 to 2.14 on functional status) and Tuina plus acupuncture (SMD: 0.94; 95% CI 0.38 to 1.50 on pain; SMD: 0.53; 95% CI 0.21 to 0.85 on functional status). But Tuina plus moxibustion or hot pack did not show significant improvements on pain. And the long-term evidence of TICMT was far from sufficient. Conclusions. The preliminary evidence from current studies suggests that TICMT might be effective complementary and alternative treatments for in-patients with LBP. However, the poor methodological quality of the included RCTs means that high-quality RCTs with long follow-up are warranted.

Compound heterozygous mutations in PMFBP1 cause acephalic spermatozoa syndrome: A case report.

BACKGROUND: Acephalic spermatozoa syndrome (ASS) is an extremely rare form of severe teratozoospermia, where in most of the sperm either appear to lack heads or have disconnected or poorly connected heads and tails. CASE SUMMARY: We reported the case of a male patient with secondary infertility whose sperm showed typical ASS upon morphological analysis. Whole-exome sequencing was performed on the patient's peripheral blood, which revealed two heterozygous variants of the PMFBP1 gene: PMFBP1c.414+1G>T (p.?) and PMFBP1c.393del (p.C132Afs*3). CONCLUSION: It is speculated that the compound homozygous mutation of PMFBP1 may be the cause of ASS. We conducted a literature review in order to provide the basis for genetic counseling and clinical diagnosis of patients with ASS.

Transient receptor potential vanilloid 4 promotes the growth of non-small cell lung cancer by regulating Foxp3.

OBJECTIVE(S): Transient receptor potential vanilloid 4 (TRPV4) participates in malignant tumor. However, the role of TRPV4 in non-small cell lung cancer (NSCLC) remains unclear. In this study, we demonstrated TRPV4 was upregulated in NSCLC tissues and NSCLC cell lines. MATERIALS AND METHODS: TRPV4 level in the NSCLC patients and cell lines were detected, and its function was studied both in vivo and vitro. RESULTS: The level of TRPV4 showed a positive correlation with tumor size of NSCLC patients. Activation TRPV4 by agonist GSK1016790A promoted cell proliferation and decreased apoptosis in A549 cells, and these effects were enhanced when the cells have overexpressed TRPV4. Moreover, GSK1016790A induced inhibitory effects on apoptosis of A549 cells was impaired when GSK1016790A used together with TRPV4 selective antagonist HC-067047, or impaired when the cells have already downregulated TRPV4 expression by TRPV4 siRNA. In vivo study, pharmacological inhibition of TRPV4 prevented A549 cells transplanted tumor growth. It was showed Foxp3 level was significantly increased in the NSCLC tissues, and showed a positive correlation with the level of TRPV4. Deactivation of TRPV4 using TRPV4 siRNA or HC-067047 significantly reduced expression of Foxp3 in GSK1016790A treated NSCLC cells. Moreover, downregulation Foxp3 by transfection of Foxp3 siRNA significantly impaired TRPV4 induced NSCLC cells proliferations in vitro. CONCLUSIONS: Antitumor effects caused by TRPV4 inhibition in NSCLC might be attributed to the suppression of Foxp3 which induced subsequent cell apoptosis. Thus, pharmacological inhibition of TRPV4 may be a promising option for NSCLC treatment.

Large-Scale 1T'-Phase Tungsten Disulfide Atomic Layers Grown by Gas-Source Chemical Vapor Deposition.

The control of crystal polymorphism and exploration of metastable, two-dimensional, 1T'-phase, transition-metal dichalcogenides (TMDs) have received considerable research attention. 1T'-phase TMDs are expected to offer various opportunities for the study of basic condensed matter physics and for its use in important applications, such as devices with topological states for quantum computing, low-resistance contact for semiconducting TMDs, energy storage devices, and as hydrogen evolution catalysts. However, due to the high energy difference and phase change barrier between 1T' and the more stable 2H-phase, there are few methods that can be used to obtain monolayer 1T'-phase TMDs. Here, we report on the chemical vapor deposition (CVD) growth of 1T'-phase WS2 atomic layers from gaseous precursors, i.e., H2S and WF6, with alkali metal assistance. The gaseous nature of the precursors, reducing properties of H2S, and presence of Na+, which acts as a countercation, provided an optimal environment for the growth of 1T'-phase WS2, resulting in the formation of high-quality submillimeter-sized crystals. The crystal structure was characterized by atomic-resolution scanning transmission electron microscopy, and the zigzag chain structure of W atoms, which is characteristic of the 1T' structure, was clearly observed. Furthermore, the grown 1T'-phase WS2 showed superconductivity with the transition temperature in the 2.8-3.4 K range and large upper critical field anisotropy. Thus, alkali metal assisted gas-source CVD growth is useful for realizing large-scale, high-quality, phase-engineered TMD atomic layers via a bottom-up synthesis.