eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction.

Helicobacter pylori is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between H. pylori and the human gastric epithelium has not been fully investigated. In this study, using dual RNA sequencing technology, we characterized a cytotoxin-associated gene A (cagA)-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, metQ and HP_0888, upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by cagA, leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed the downregulation of multiple splicing regulators due to bacterial infection, resulting in aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. Moreover, we demonstrated a protective effect of gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, Muribaculaceae, selectively enriched in the colons of H. pylori-pre-colonized mice, which may contribute to the restoration of intestinal barrier function damaged by DSS treatment. Collectively, this study presents the first dual-transcriptome analysis of H. pylori during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which H. pylori promotes infection and pathogenesis in the human gastric epithelium. IMPORTANCE: Simultaneous profiling of the dynamic interaction between Helicobacter pylori and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of H. pylori when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A (cagA). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. We demonstrated a protective effect of gastric H. pylori colonization against chronic DSS-induced colitis through both in vitro and in vivo experiments. These findings significantly enhance our understanding of how H. pylori promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies.

Bridging Component Strategy in Phosphomolybdate-Based Sensors for Electrochemical Determination of Trace Cr(VI).

Rapid and sensitive electrochemical determination of trace carcinogenic Cr(VI) pollutants remains an urgent and important task, which requires the development of active sensing materials. Herein, four cases of reduced phosphomolybdates with formulas of the (H2bib)3[Zn(H2PO4)]2{Mn[P4Mo6O31H7]2}·6H2O (1), (H2bib)2[Na(H2O)]2[Mn(H2O)]2{Mn[P4Mo6O31H6]2}·5H2O (2), (H2bib)3[Mo2(µ2-O)2(H2O)4]2{Ni[P4Mo6O31H2]2}·4H2O (3), and (H2bib)2{Ni[P4Mo6O31H9]2}·9H2O (4) (bib = 4,4'-bis(1-imidazolyl)-biphenyl) were hydrothermally synthesized under the guidance of a bridging component strategy, which function as effective electrochemical sensors to detect trace Cr(VI). The difference of hybrids 1-4 is in the inorganic moiety, in which the reduced phosphomolybdates {M[P4MoV6O31]2} (M{P4Mo6}2) exhibited different arrangements bridged by different cationic components ({Zn(H2PO4)} subunit for 1, [Mn2(H2O)2]4+ dimer for 2, and [MoV2(µ2-O)2(H2O)4]6+ for 3). As a result, hybrids 1 and 3 display noticeable Cr(VI) detection activity with low detection limits of 14.3 nM (1.48 ppb) for 1 and 6.61 nM (0.69 ppb) for 3 and high sensitivities of 97.3 and 95.3 µA·mM-1, respectively, which are much beyond the World Health Organization's detection threshold (0.05 ppm) and superior to those of the contrast samples (inorganic Mn{P4Mo6}2 salt and hybrid 4), even the most reported noble-metal catalysts. This work supplies a prospective pathway to build effective electrochemical sensors based on phosphomolybdates for environmental pollutant treatment.

Preparation of paramagnetic ferroferric oxide-calcined layered double hydroxide core-shell adsorbent for selective removal of anionic pollutants.

Adsorption is one of the most common methods of pollution treatment. The selectivity for pollutants and recyclability of adsorbents are crucial to reduce the treatment cost. Layered double hydroxide (LDH) materials are one type of adsorbent with poor recyclability. Prussian blue (PB) is a sturdy and inexpensive metal-organic framework material that can be used as the precursor for synthesizing paramagnetic ferroferric oxide (Fe3O4). It is intriguing to build some reusable adsorbents with magnetic separation by integrating LDH and PB. In this work, paramagnetic Fe3O4-calcined LDH (Fe3O4@cLDH) core-shell adsorbent was designed and prepared by the calcination of PB-ZnAl layered double hydroxide (PB@LDH) core-shell precursor, which exhibits high anionic dyes selectivity in wastewater solutions. The paramagnetism and adsorption capability of Fe3O4@cLDH come from the Fe3O4 core and calcined ZnAl-LDH shell, respectively. Fe3O4@cLDH shows an adsorption capacity of 230 mg g-1 for acid orange and a high selectivity for anionic dyes in cation-anion mixed dye solutions. The regeneration process indicates that the high selectivity for anions is related to the specific hydration recovery process of ZnAl-LDH. The synergistic effect of the paramagnetic Fe3O4 core and calcined ZnAl-LDH shell makes Fe3O4@cLDH an excellent magnetic separation adsorbent with high selectivity to anions.

Bio-Inspired FeMo2S4 Microspheres as Bifunctional Electrocatalysts for Boosting Hydrogen Oxidation/Evolution Reactions in Alkaline Solution.

Developing robust and effectual nonprecious electrocatalysts for the bifunctional hydrogen oxidation and evolution reactions (HOR and HER) in alkaline electrolyte is of critical significance for the realization of future hydrogen economy but challenging. Herein, this work demonstrates a new routine for the preparation of bio-inspired FeMo2S4 microspheres via the one-step sulfuration of Keplerate-type polyoxometalate {Mo72Fe30}. The bio-inspired FeMo2S4 microspheres feature potential-abundant structural defects and atomically precise iron doping and act as an effective bifunctional electrocatalyst for hydrogen oxidation/reduction reactions. The FeMo2S4 catalyst presents an impressive alkaline HOR activity compared to FeS2 and MoS2 with the high mass activity of 1.85 mA·mg-1 and high specific activity as well as excellent tolerance to carbon monoxide poisoning. Meanwhile, FeMo2S4 electrocatalyst also displayed prominent alkaline HER activity with a low overpotential of 78 mV at a current density of 10 mA·cm-2 and robust long-term durableness. Density functional theory (DFT) calculations indicate that the bio-inspired FeMo2S4 with a unique electron structure possesses the optimal hydrogen adsorption energy and enhanced adsorption of hydroxyl intermediates, which accelerates the potential-determining Volmer step, thus promoting the HOR and HER performance. This work provides a new pathway for designing efficient noble-metal-free electrocatalysts for the hydrogen economy.

Three-Dimensional Silver-Containing Polyoxotungstate Frameworks for Photocatalytic Aerobic Oxidation of Benzyl Alcohol.

Photocatalytic organic transformation derived by functionalized polyoxometalate (POM)-based metal-organic frameworks provides a feasible route for fine chemical synthesis. Herein, three kinds of photoactive three-dimensional silver-containing polyoxotungstate frameworks are synthesized with the formulas [Ag3L2(OH)][Na(H2O)0.5][PW12O40]·H2O (1), [Ag4L3][SiW12O40] (2), and [Ag(H2O)][Ag4L3][BW12O40]·9H2O (3) (L = 1,4-di(4H-1,2,4-triazol-4-yl)benzene). In compounds 1-3, the cationic Ag-triazole clusters with diverse nuclei serve as nodes to assemble with rigid bridging ligands (L) and polyoxoanions to extend into stable three-dimensional frameworks, in which Keggin-type anions act as guests or pendants. When using them as heterogeneous photocatalysts, compounds 1-3 show high catalytic activity and selectivity for the photocatalytic aerobic oxidation of benzyl alcohol to benzoic acid under 10 W 365 nm light irradiation. Among them, compound 1 exhibits the highest performance with ca. 99% benzyl alcohol conversion and 99% selectivity of benzoic acid in 9 h. Compounds 2 and 3 show ca. 79 and 88% conversions of benzyl alcohol, respectively, which are higher than those of the individual Keggin-type precursors. Moreover, mechanism investigation suggests that the synergistic cooperation occurring between cationic Ag-triazole clusters and Keggin-type polyoxoanions modulates the energy band structures of compounds 1-3, resulting in the efficient separation of photogenerated carriers and accelerating the aerobic oxidation of benzyl alcohol. This work provides some important guidance for the design and development of efficient POM-based photocatalysts for practical organic transformation.

[Research on the pathogeny of black tooth stain and association between black tooth stain and primary dentition caries in children].

PURPOSE: To investigate the relationship between polymorphism of cytochrome P450, family 2, subfamily A, polypeptide 6(CYP2A6) and periodontitis, the expression of inflammatory cytokines in 123 Han smokers. METHODS: From October 2018 to October 2019, a total of 123 smokers with periodontitis were selected as the experimental group, and 125 non-smokers as the control group. The general data of the patients were collected, including age, gender, body mass index (BMI), chewing and brushing habits, as well as molar condition; plaque index (PLI), gingival bleeding index (BI), periodontal probing depth (PD) and attachment loss (AL) were detected. CYP2A6 was amplified by PCR. The level of interleukin (IL)-17, IL-1, IL-6, IL-23 and tumor necrosis factor-α (TNF-α) in GCF was detected by enzyme-linked immunosorbent assay(ELISA). SPSS 25.0 software package was used for statistical analysis of the data. RESULTS: There was significant difference in gender, PLI, IL-17, IL-1, IL-6, IL-23, TNF-α level in GCF between the two groups(P＜0.05). All samples were amplified by PCR. Among them, 23 were not amplified, which were identified as CYP2A6 deletion type (CYP2A6del), including 5 in the experimental group and 18 in the control group; 225 were amplified and identified as CYP2A6 wild type(CYP2A6wt), including 118 in the experimental group and 107 in the control group. There was significant difference in CYP2A6 genotype between the two groups(P＜0.05). In the experimental group, the level of IL-1 and PLI of different CYP2A6 genotypes was significantly different(P＜0.05); and in the control group, the level of IL-17 and PLI of different CYP2A6 genotypes was also significantly different(P＜0.05). CONCLUSIONS: There are differences in CYP2A6 genotype between smokers and non-smokers in Han population with periodontitis, but the relationship between CYP2A6 genotype and inflammatory cytokines is not clear.

Bifunctional Sensors Based on Phosphomolybdates for Detection of Inorganic Hexavalent Chromium and Organic Tetracycline.

Exploring effective sensors for detecting possible hazards in a water system are greatly significant. This work proposed a strategy for stable and effective bifunctional sensors via incorporating hourglass-type phosphomolybdates into metal-organic fragments to construct a high-dimensional framework. Two hourglass-type phosphomolybdate-based electrochemical sensors toward heavy metal ion Cr(VI) and tetracycline (TC) detection were designed with the formula [CoII2(H2O)4NaI2][CoII(Hbpe)][NaI(bpe)1.5]{CoII[PV4MoV6O31H6]2}·9H2O (1) and [CoII(H2O)4NaI3][CoII(Hbpe)][CoII(bpe)]{CoII[PV4MoV6O31H6]2}·9H2O (2) [bpe = 1,2-di(4-pyridyl)ethylene]. Structural analysis showed that hybrids 1 and 2 possess three-dimensional POM-supported network features with favorable stability and exhibit reversible redox properties. Experiments found that this kind of hybrids as efficient sensors have excellent electrochemical performance toward Cr(VI) detection with high sensitivities of 0.111 µA·µM-1 for 1 and 0.141 µA·µM-1 for 2, fast response time of 1 s, and low detection limits of 30 nM for 1 and 27 nM for 2, which far meet the standard of WHO for drinking water. Moreover, hybrids 1-2 also exhibit fast responses to TC detection with sensitivities of 0.0073 and 0.022 µA·mM-1 and detection limits of 0.426 and 0.084 mM. This work offers a novel strategy for the purposeful design of efficient POM-based electrochemical sensors for accurate determination of contaminants in a practical water system.

Polyoxometalate-Incorporated Metal-Organic Network as a Heterogeneous Catalyst for Selective Oxidation of Aryl Alkenes.

Selective oxidation of aryl alkenes is important for chemical synthesis reactions, in which the key lies in the rational design of efficient catalysts. Herein, four polyoxometalate (POM)-incorporated metal-organic networks, with the formulas of [Co(ttb)(H2O)3]2[SiMo12O40]·2H2O (1), [Co(ttb)(H2O)2]2[SiW12O40]·8H2O (2), [Zn(Httb)(H2ttb)][BW12O40]·9H2O (3) and {[Zn(H2O)3(ttb)]4[Zn3(H2O)6]}[H3SiW10.5Zn1.5O40]2·24H2O (4) (ttb = 1,3,5-tri(1,2,4-triazol-1-ylmethyl)-2,4,6-trimethylbenzene), were hydrothermally synthesized and structurally characterized. Structural analysis showed that compound 1 consists of a POM-encapsulated three-dimensional (3-D) supramolecular framework; compound 2 is composed of a POM-supported 3-D coordination network; and compounds 3-4 show POM-incorporated 3-D supramolecular networks. Using selective catalytic oxidation of styrene as the model reaction, compounds 1-4 as heterogeneous catalysts display excellent performance with the double advantages of high styrene conversion and benzaldehyde selectivity owing to the synergistic effect among POM anions and transition metal (TM) centers. Among them, compound 1 exhibits the highest performance with ca. 96% styrene conversion and ca. 99% benzaldehyde selectivity in 3 h. In addition, compound 1 also displays excellent substrate compatibility, good reusability, and structural stability. Thus, a plausible reaction pathway for the selective oxidation of styrene is proposed. This study on the structure-function relationship paves a way for the rational design of POM-based heterogeneous catalysts for important catalysis applications.

miR-122 and miR-197 expressions in hepatic carcinoma patients before and after chemotherapy and their effect on patient prognosis.

OBJECTIVE: To quantify the miR-122 and miR-197 expression levels in liver cancer (LC) patients before and after chemotherapy and to determine their prognostic implications. METHODS: The present study included 169 patients with LC who were admitted to our hospital from January 2005 to December 2010. The miR-122 and miR-197 expression levels in the patients' cancerous and adjacent tissues were quantified, and their peripheral blood levels before and after chemotherapy were analyzed, as well as their prognostic implications. RESULTS: The miR-122 and miR-197 levels in the LC tissues were lower than they were in the adjacent tissues, and they increased in the peripheral blood after chemotherapy. Higher miR-122 and miR-197 expression levels were observed in the LC tissues of sorafenib-sensitive patients. ROC curves demonstrated that miR-122 and miR-197 are predictive markers for the therapeutic effect of sorafenib. As shown by a K-M survival curve and a log-rank test, low miR-122 and miR-197 levels are responsible for low 5-year patient survival rates. Moreover, a univariate Cox analysis uncovered the association between the 5-year survival and the miR-122 and miR-197 expression levels, the size and number of tumors, vascular invasion, and TNM and BCLC staging. Also, a multivariate Cox analysis indicated that the independent risk factors for 5-year survival in LC included the miR-122 and miR-197 levels, the number of tumors, vascular invasion, and TNM and BCLC staging. CONCLUSION: miR-122 and miR-197 expression levels can predict LC patient responses to sorafenib chemotherapy, and their levels increase after chemotherapy. Moreover, decreased miR-122 and miR-197 levels are independent risk factors for LC progression.

Organic Moiety-Regulated Photocatalytic Performance of Phosphomolybdate Hybrids for Hexavalent Chromium Reduction.

Visible-light-driven photocatalytic Cr(VI) reduction is a promising pathway to moderate environmental pollution, in which the development of photocatalysts is pivotal. Herein, three hourglass-type phosphomolybdate-based hybrids with the formula of: (H2 bpe)3 [Zn(H2 PO4 )][Zn(bpe)(H2 O)2 ]H{Zn[P4 Mo6 O31 H6 ]2 } ⋅ 6H2 O (1) Na6 [H2 bz]2 [ZnNa4 (H2 O)5 ]{Zn [P4 Mo6 O31 H3 ]2 } ⋅ 2H2 O (2) and (H2 mbpy) {[Zn(mbpy)(H2 O)]2 [Zn(H2 O)]2 }{Zn[P4 Mo6 O31 H6 ]2 } ⋅ 10H2 O (3) (bpe=trans-1,2-bi(4-pyridyl)-ethylene; bz=4,4'-diaminobiphenyl; mbpy=4,4'-dimethyl-2,2'bipyridine) were synthesized under the guidance of the functional organic moiety modification strategy. Structural analysis showed that hybrids 1-3 have similar 2D layer-like spatial arrangements constructed by {Zn[P4 Mo6 ]2 } clusters and organic components with different conjugated degree. With excellent redox properties and wide visible-light absorption capacities, hybrids 1-3 display favourable photocatalytic activity for Cr(VI) reduction with 79%, 70% and 64% reduction rates, which are superior to that of only inorganic {Zn[P4 Mo6 ]2 } itself (21%). The investigation of organic components on photocatalytic performance of hybrids 1-3 suggested that the organic counter cations (bpe, bz and mbpy) can effectively affect the visible-light absorption, as well as the recombination of photogenerated carriers stemmed from {Zn[P4 Mo6 ]2 } clusters, further promoting their photocatalytic performances towards Cr(VI) reduction. This work provides an experimental basis for the design of functionalized photocatalysts via the modification of organic species.

A Bicadmium-Substituted Polyoxometalate Network Based on a Vanadosilicate Cluster for the Selective Oxidation of Styrene to Benzaldehyde.

A new bicadmium-substituted vanadosilicate, [Cd(en)2]2[(en)2Cd2Si8V12O40(OH)8(H2O)0.5]·5H2O (1; en = ethylenediamine), had been hydrothermally synthesized and characterized. Structural analysis revealed that the kind of new [(en)2Cd2Si8V12O40(OH)8(H2O)0.5]4- polyoxoanionic cluster was derived from the classical {V18O42} cluster by replacing six {VO5} square pyramids with four {Si2O7} and two [Cd(en)]2+ groups. Notably, such mixed substitution of both main-group and transition metals in polyoxovanadates is much less developed. Furthermore, compound 1 displays efficient catalytic activity toward the selective oxidation of styrene to benzaldehyde with a conversion of 97% and a selectivity of 87% in 8 h.

Tribological Performance of Micro-Groove Tools of Improving Tool Wear Resistance in Turning AISI 304 Process.

AISI 304 has good physical and chemical properties and thus is widely used. However, due to the low thermal diffusivity, the cutting temperature of AISI 304 is high accelerating the wear of the tool. Therefore, tool wear is a major problem in machining hard cutting materials. In this study, we developed a new type of micro-groove tool whose rake surface was distributed with micro-groove by powder metallurgy based on the finite element temperature field morphology. We compared the wear of the proposed micro-groove tool with an untreated one by using a scanning electron microscope (SEM) and an X-ray energy spectrum. The abrasive, adhesive, and oxidation wear of the rake and the flank face of the micro-groove tool were lower than that of the untreated one. Due to the micro-groove on the rake face of the tool, the contact length between the tool and chip was reduced, leaving more extension space. Furthermore, chip extrusion deformation was avoided, and the energy caused by chip deformation was reduced. After 70 min of cutting, the counterpart reached the specified wear amount while the main cutting force, the feed resistance, and the cutting depth resistance of the proposed micro-groove tool were reduced by 16.1%, 33.9%, and 40.1%, respectively. With regard to steady state, the cutting temperature was reduced by 17.2% and the wear width of the flank face was reduced by 36.7%.

MoS2 quantum dots decorated ultrathin NiO nanosheets for overall water splitting.

Atomically thin 2D materials with high surface areas allow engineering its physical and chemical properties with help of combining or decorating with different classes of materials. The hybrid or heterostructure of two different atomically thin materials exhibits completely different chemical and electronics behavior as compared to its parent components. Here, MoS2 quantum dots (QDs) are decorated onto ultrathin NiO nanosheets (NSs) by using a one-pot hydrothermal process. Uniformly dispersed MoS2 QDs and ultrathin NiO NSs hybrid/heterostructure can provide more active reaction sites and accelerate the charge transfer rate. Benefiting from the heterointerfaces synergistic effect between MoS2 QDs and NiO NSs, the MoS2 QDs/NiO NSs electrode exhibits excellent electrocatalytic activity towards both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). As a bifunctional electrocatalyst, the MoS2 QDs/NiO NSs electrode has achieved highly efficient overall water splitting activity, which needs a low voltage of 1.61 V to deliver a 10 mA cm-2 with superior stability.

Stable monovalent aluminum(i) in a reduced phosphomolybdate cluster as an active acid catalyst.

Low-valent aluminum Al(i) chemistry has attracted extensive research interest due to its unique chemical and catalytic properties but is limited by its low stability. Herein, a hourglass phosphomolybdate cluster with a metal-center sandwiched by two benzene-like planar subunits and large steric-hindrance is used as a scaffold to stabilize low-valent Al(i) species. Two hybrid structures, (H3O)2(H2bpe)11[AlIII(H2O)2]3{[AlI(P4MoV 6O31H6)2]3·7H2O (abbr. Al6{P4Mo6}6) and (H3O)3(H2bpe)3[AlI(P4MoV 6O31H7)2]·3.5H2O (abbr. Al{P4Mo6}2) (bpe = trans-1,2-di-(4-pyridyl)-ethylene) were successfully synthesized with Al(i)-sandwiched polyoxoanionic clusters as the first inorganic-ferrocene analogues of a monovalent group 13 element with dual Lewis and Brønsted acid sites. As dual-acid catalysts, these hourglass structures efficiently catalyze a solvent-free four-component domino reaction to synthesize 1,5-benzodiazepines. This work provides a new strategy to stabilize low-valent Al(i) species using a polyoxometalate scaffold.

Vitamin D3 activates the autolysosomal degradation function against Helicobacter pylori through the PDIA3 receptor in gastric epithelial cells.

Helicobacter pylori (H. pylori) is a common human pathogenic bacterium. Once infected, it is difficult for the host to clear this organism using the innate immune system. Increased antibiotic resistance further makes it challenging for effective eradication. However, the mechanisms of immune evasion still remain obscure, and novel strategies should be developed to efficiently eliminate H. pylori infection in stomachs. Here we uncovered desirable anti-H. pylori effect of vitamin D3 both in vitro and in vivo, even against antibiotic-resistant strains. We showed that H. pylori can invade into the gastric epithelium where they became sequestered and survived in autophagosomes with impaired lysosomal acidification. Vitamin D3 treatment caused a restored lysosomal degradation function by activating the PDIA3 receptor, thereby promoting the nuclear translocation of PDIA3-STAT3 protein complex and the subsequent upregulation of MCOLN3 channels, resulting in an enhanced Ca2+ release from lysosomes and normalized lysosomal acidification. The recovered lysosomal degradation function drives H. pylori to be eliminated through the autolysosomal pathway. These findings provide a novel pathogenic mechanism on how H. pylori can survive in the gastric epithelium, and a unique pathway for vitamin D3 to reactivate the autolysosomal degradation function, which is critical for the antibacterial action of vitamin D3 both in cells and in animals, and perhaps further in humans. Abbreviations: 1,25D3: 1α, 25-dihydroxyvitamin D3; ATG5: autophagy related 5; Baf A1: bafilomycin A1; BECN1: beclin 1; CagA: cytotoxin-associated gene A; CFU: colony-forming unit; ChIP-PCR: chromatin immunoprecipitation-polymerase chain reaction; Con A: concanamycin A; CQ: chloroquine; CRISPR: clustered regularly interspaced short palindromic repeats; CTSD: cathepsin D; GPN: Gly-Phe-ß-naphthylamide; H. pylori: Helicobacter pylori; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MCOLN1: mucolipin 1; MCOLN3: mucolipin 3; MCU: mitochondrial calcium uniporter; MOI: multiplicity of infection; NAGLU: N-acetyl-alpha-glucosaminidase; PDIA3: protein disulfide isomerase family A member 3; PMA: phorbol 12-myristate 13-acetate; PRKC: protein kinase C; SQSTM1: sequestosome 1; STAT3: signal transducer and activator of transcription 3; SS1: Sydney Strain 1; TRP: transient receptor potential; VacA: vacuolating cytotoxin; VD3: vitamin D3; VDR: vitamin D receptor.

Nuclear receptor ERRα and transcription factor ERG form a reciprocal loop in the regulation of TMPRSS2:ERG fusion gene in prostate cancer.

The TMPRSS2:ERG (T:E) fusion gene is generally believed to be mainly regulated by the activated androgen receptor (AR) signaling in androgen-dependent prostate cancer. However, its persistent expression in castration-resistant and neuroendocrine prostate cancers implies that other transcription factors might also regulate its expression. Here, we showed that up-regulation of nuclear receptor estrogen-related receptor alpha (ERRα) was closely associated with the oncogenic transcription factor ERG expression in prostate cancer, and their increased coexpression patterns were closely associated with high Gleason scores and metastasis in patients. Both ERRα and ERG exhibited a positive expression correlation in a castration-resistant prostate cancer (CRPC) xenograft model VCaP-CRPC. We showed that ERRα could directly transactivate T:E fusion gene in both AR-positive and -negative prostate cancer cells via both ERR-binding element- and AR-binding element-dependent manners. Ectopic T:E expression under ERRα regulation could promote both in vitro invasion and in vivo metastasis capacities of AR-negative prostatic cells. Intriguingly, ERG expressed by the T:E fusion could also transactivate the ERRα (ESRRA) gene. Hereby, ERRα and ERG can synergistically regulate each other and form a reciprocal regulatory loop to promote the advanced growth of prostate cancer. Inhibition of ERRα activity by ERRα inverse agonist could suppress T:E expression in prostate cancer cells, implicating that targeting ERRα could be a potential therapeutic strategy for treating the aggressive T:E-positive prostate cancer.

Generating plasmonic heterostructures by cation exchange and redox reactions of covellite CuS nanocrystals with Au3+ ions.

We demonstrate the fabrication of various types of heterostructures, including core-shells and dimers. This is achieved by reacting platelet-shaped covellite (CuS) nanocrystals (NCs) with Au3+ ions under various reaction conditions: the exposure of CuS NCs to Au3+ ions, in the presence or in the absence of ascorbic acid (AA), leads to the formation of CuS@Au core-shell nanostructures; the reaction of CuS NCs with Au3+ ions in the presence of oleylamine (OM) leads to the formation of CuS@Au2S; the presence of both OM and AA leads to the formation of Au/CuS dimers. Depending on which condition is chosen, either cation exchange (CE) between gold and copper ions is predominant (leading to amorphous Au2S) or the reduction of Au3+ leads to the nucleation of metallic Au domains (which are operated by the AA). In the heterostructures achieved by CE, the Au2S shell is almost entirely amorphous, and can be converted to polycrystalline upon electron beam irradiation. Finally, when both oleylamine and AA are present in the reaction environment, Au/CuS dimers are formed due to the reduction of Au3+ to metallic Au domains which nucleate on top of the CuS seeds. The experimental dual plasmonic bands of the CuS@Au core-shells and Au/CuS dimers are in agreement with the theoretical optical simulations. The procedures described here enable the synthesis of core-shell nanostructures with tunable localized surface plasmon resonances (LSPRs) in the near-infrared (NIR) region, and of plasmonic metal/semiconductor heterostructures with LSPRs in both the NIR and the visible regions.

Inhibition of NF-κB pathway in fibroblast-like synoviocytes by α-mangostin implicated in protective effects on joints in rats suffering from adjuvant-induced arthritis.

α-Mangostin (MG) is a bioactive compound isolated from mangosteen. This study was aimed to investigate effects of MG on adjuvant-induced arthritis (AA) in rats and decipher the underlying mechanisms. Clinical severity of AA was evaluated by paw oedema, arthritis score, and hematological parameters. Digital radiography (DR) and histological examinations were employed to assess joints destructions. Immune functions were evaluated by T cell subsets distribution. Effects on NF-κB pathway were investigated by immunohistochemical, western-blot and immunofluorescence methods both in vivo and vitro. It was found MG possessed superior anti-inflammatory effects in vivo, suggested by attenuated paw swelling, reduced inflammatory cells infiltration and decreased the secretion of TNF-α and IL-1ß in serum. Meanwhile MG inhibited fibrous hyperplasia, synovial angiogenesis, cartilage and bone degradation in AA rats. Although MG exerted little effects on CD4+ population, it greatly decreased IFN-γ positive cells and promoted expression of FOXP3 in immune organs, indicating restoration of Th1/Treg cells ratio and recovery of immune homeostasis in vivo. Inhibition of NF-κB induced by MG was indicated by reduced the expression of p-p65 and VEGF in synovium. In vitro experiments found MG at 10 µg/ml significantly suppressed the expression and phosphorylation of key proteins implicated in NF-κB pathway and inhibited nucleus translocation of p65. These changes led to increased apoptosis and proliferation inhibition of HFLS-RA cells. The results demonstrated regulation of immune functions was deeply involved in the therapeutic actions of MG on AA, and it's inhibition on NF-κB in fibroblast-like synoviocytes was associated to the protective effects on joints.

Biotransformation of Dioscorea nipponica by Rat Intestinal Microflora and Cardioprotective Effects of Diosgenin.

Studying the biotransformation of natural products by intestinal microflora is an important approach to understanding how and why some medicines-particularly natural medicines-work. In many cases, the active components are generated by metabolic activation. This is critical for drug research and development. As a means to explore the therapeutic mechanism of Dioscorea nipponica (DN), a medicinal plant used to treat myocardial ischemia (MI), metabolites generated by intestinal microflora from DN were identified, and the cardioprotective efficacy of these metabolites was evaluated. Our results demonstrate that diosgenin is the main metabolite produced by rat intestinal microflora from DN. Further, our results show that diosgenin protects the myocardium against ischemic insult through increasing enzymatic and nonenzymatic antioxidant levels in vivo and by decreasing oxidative stress damage. These mechanisms explain the clinical efficacy of DN as an anti-MI drug.