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Accumulating studies have shown that the dysregulation of microRNAs is related to the carcinogenesis and development of gastric cancer (GC), and the role of miR-635 in GC remains largely unknown. miR-635 and Kinesin Family Member C1 (KIFC1) mRNA expression in GC tissues and paracancerous tissues and cells were detected by quantitative real-time PCR. KIFC1 protein expression in GC tissues and paracancerous normal tissues and cells was detected by immunohistochemistry and western blot. Cell proliferation was monitored by Cell Counting Kit-8 assay and 5-bromo-2'-deoxyuridine assay. Transwell assay was employed to detect the migration and invasion of GC cells. The dual-luciferase reporter gene assay was adopted to detect the targeting relationship between miR-635 and KIFC1. Compared with paracancerous tissues, miR-635 expression was remarkably decreased in GC tissues; conversely, KIFC1 expression was significantly increased. Compared with human normal gastric epithelial cell GSE-1, miR-635 expression was markedly decreased in GC cell lines. Meanwhile, KIFC1 expression was significantly increased, and the Kaplan-Meier Plotter database showed that its high expression was remarkably associated with poor prognosis. Additionally, miR-635 can negatively regulate KIFC1. miR-635 can target KIFC1 to inhibit proliferation, migration and invasion of GC cells. Collectively, miR-635 is lowly expressed in GC, and it inhibits proliferation, migration and invasion of GC cells via regulating KIFC1. [ABSTRACT FROM AUTHOR]

Rutile titania (TiO2) was successfully prepared via hydrolysis of TiCl4 in the presence of AlCl3. The powders were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) surface area analysis. In the present system, AlCl3 functions as a nucleating agent and induces the formation of rutile TiO2. The influences of HCl and isopropanol concentrations on the purity and morphology of the rutile TiO2 were investigated. The purity of the rutile TiO2 increased with increasing concentration of HCl. Evenly dispersed rutile TiO2 particles with a spherical morphology were obtained when the HCl and isopropanol concentrations were 0.5 and 1 mol·L−1, respectively. Furthermore, the prepared TiO2 powders were used in adsorption tests of the heavy metal pollutant Cr(VI). Rutile TiO2 sample S-9 demonstrated greater adsorption performance and a removal efficiency that was greater than 99.95% after 60 min of adsorption when the Cr(VI) concentration was 200 mg·L−1 The maximum adsorption capacity on rutile TiO2 was 28.9 mg·g−1. This work provides an easy path to prepare a high-performance rutile TiO2 adsorbent with potential applications in water pollution treatment. [ABSTRACT FROM AUTHOR]

Aseptic loosening of artificial joints is the leading cause of failure for patients who receive total joint arthroplasty. Prior reports indicate that bone marrow mesenchymal stem cells (BSMC) are critical in the stabilization of implanted artificial joints, and that deregulated interaction between BMSCs and artificial joint derived particles is a risk factor for aseptic loosening with an unknown mechanism. In the present study, the pathomechanisms whereby titanium and its alloy derived particles facilitate aseptic loosing were investigated in vitro. It was demonstrated that nano-sized titanium alloy particles significantly inhibited the proliferation of BMSCs in a time and concentration dependent manner. Furthermore, it was demonstrated that the particles promoted the apoptosis of BMSCs in the same manner. Bax and Caspase-3 expression of BMSCs were elevated when cultured with the particles. As BMSCs exhibit a critical role in the stabilization of artificial joints, the results of the present study may provide a novel direction for the management of aseptic loosening in clinics. [ABSTRACT FROM AUTHOR]

Dual metal–organic frameworks (MOFs, i.e., MIL‐100(Fe) and ZIF‐8) are thermally converted into Fe–Fe3C‐embedded Fe–N‐codoped carbon as platinum group metal (PGM)‐free oxygen reduction reaction (ORR) electrocatalysts. Pyrolysis enables imidazolate in ZIF‐8 rearranged into highly N‐doped carbon, while Fe from MIL‐100(Fe) into N‐ligated atomic sites concurrently with a few Fe–Fe3C nanoparticles. Upon precise control of MOF compositions, the optimal catalyst is highly active for the ORR in half‐cells (0.88 V in base and 0.79 V versus RHE in acid in half‐wave potential), a proton exchange membrane fuel cell (0.76 W cm−2 in peak power density) and an aprotic Li–O2 battery (8749 mAh g−1 in discharge capacity), representing a state‐of‐the‐art PGM‐free ORR catalyst. In the material, amorphous carbon with partial graphitization ensures high active site exposure and fast charge transfer simultaneously. Macropores facilitate mass transport to the catalyst surface, followed by oxygen penetration in micropores to reach the infiltrated active sites. Further modeling simulations shed light on the true Fe–Fe3C contribution to the catalyst performance, suggesting Fe3C enhances oxygen affinity, while metallic Fe promotes *OH desorption as the rate‐determining step at the nearby Fe–N–C sites. These findings demonstrate MOFs as model system for rational design of electrocatalyst for energy‐based functional applications. [ABSTRACT FROM AUTHOR]

Guanylate binding protein 5 (GBP5) is a member of the interferon (IFN)-inducible large guanosine triphosphate hydrolases (GTPase) family that regulates cell-autonomous immunity and malignant tumor transformation. However, its specific roles and underlying mechanisms GBP5 in gastric cancer (GC) remain unknown. In this study, we aimed to determine the role GBP5 and underlying mechanism of GBP5 in GC cell progression. Potential oncogenic roles of GBP5 in GC as well as its relationship with the tumor immune microenvironment (TIME) were comprehensively evaluated using bioinformatics analysis. Protein expression levels of GBP5 and their correlation with clinicopathological features of patients were assessed using immunohistochemistry. In addition, diverse in vitro functional experiments were performed to identify the functions of GBP5 in GC. Downstream targets of GBP5 were identified using RNA-sequencing analysis and verified using western blotting or quantitative polymerase chain reaction analysis in different cell lines. GBP5 expression is commonly upregulated and promotes the proliferation and migration of GC cells. Mechanistically, GBP5 was regulated by the IFNγ-Janus kinase (JAK1)-signal transducer and activator of transcription 1 (STAT1) axis and induced CXCL8 expression. Interestingly, GBP5 -induced CXCL8 regulated the JAK1-STAT1 signaling pathway to form a positive feedback loop. Moreover, GBP5 is closely related to the TIME and may be used as a biomarker for predicting the efficacy of immunotherapy. Our findings revealed a new JAK1-STAT1/GBP5/CXCL8 pathway and highlighted the value of GBP5 as a predictive biomarker and novel target for GC intervention., Competing Interests: None., (AJCR Copyright © 2023.)

We use 84 rainfall samples collected during June to September 2017 from the Dongkemadi basin, source region of the Yangtze River, China, to analyze the characteristics and influencing factors of stable isotopes in groundwater, and further discuss the groundwater recharge sources. The results showed that the range of groundwater δ 18 O values in this permafrost region varied from -15.3‰ to -12.5‰ (mean -14.0‰). The range of δ D values in groundwater varied from -108.9‰ to -91.7‰ (mean -100.2‰). Compared with local atmospheric precipitation, groundwater isotopes were relatively enriched. The slope and intercept of the groundwater line (GL) in the study area were both lower than of those of the global and local meteoric water lines (GMWL and LMWL), thus indicating that groundwater in the study area was subjected to evaporation during rainfall recharge of groundwater. The d -excess values of groundwater varied from 4.9‰ to 25.0‰ (mean 11.6‰), which was close to the average d -excess value determined for global average rainfall (10‰), but lower than that of rainfall in the study area (15.1‰). The influencing factors on the composition and variation of groundwater isotopes were different in different periods. The permafrost active layer was relatively thin during periods of increasing air temperature, and groundwater isotopes were significantly affected by air temperature. A temperature decrease during the latter part of the sampling period, when the thickness of the permafrost active layer was still increasing, further increased the retention time of infiltrating rainfall in the soil, thereby eventually leading to evaporation that strengthened the enrichment of heavy isotopes in the groundwater. According to the topographic characteristics of the Dongkemadi basin, the isotopic characteristics of the groundwater, and the factors influencing the isotopic composition, we conclude that rainfall was the main source of groundwater recharge. The results of this study provide a scientific basis for studying water cycle processes in the permafrost regions of the source region of the Yangtze River.

Using 64 precipitation samples collected from June to September 2013 in the Dongkemadi Basin in the source region of the Yangtze River, the pH, conductivity, and main ionic concentration characteristics of precipitation were analyzed. The main ionic sources of precipitation and their relationships with atmospheric circulation were examined using factor analysis, correlation analysis, enrichment factor analysis, and backward trajectory analysis. The results showed that the range of precipitation pH values varied from 5.26 to 9.25 with a weighted average of 6.70, and conductivity ranged from 0.23 to 28.70 μS·cm -1 with a weighted average of 3.45 μS·cm -1 . The conductivity of precipitation was lower than for the Mt. Waliguan basin (China Global Atmosphere Watch baseline observatory). The total ionic concentrations in the precipitation ranged from 7.0 to 376.9 μeq·L -1 with a weighted average of 40.8 μeq·L -1 . The ranked order of ionic concentrations was HCO 3 - > NH 4 + > Ca 2+ > NO 3 - > SO 4 2- > Na + > Cl - > K + > Mg 2+ . HCO 3 - , NH 4 + ,Ca 2+ , and NO 3 - were the dominant ions, which accounted for 74.75% of the total ionic concentration. Fractional acidity (FA) analysis showed that 97.8% of the precipitation acidity was neutralized by alkaline constituents. Neutral factor (NF) analysis indicated that NH 4 + and Ca 2+ were the dominant neutralization constituents in the precipitation. The precipitation ions in this study area were mainly derived from terrestrial material, while input from marine sources was relatively low. Backward trajectory analysis revealed that the total ionic concentrations varied significantly between the different sources, which followed the order of local sources>westerly sources>monsoon sources. This indicates that different atmospheric circulation conditions and air mass sources have a significant influence on the chemical composition of precipitation in this area. To some extent, the chemical characteristics of precipitation could reflect the air quality and background values for remote areas due to the limited effect of human activities. The results of this study provide a scientific basis for the protection of water quality and the assessment of the impact of human activities on the atmospheric environment in the source region of the Yangtze River.

Based on the stable isotopes of 73 precipitation samples continuously collected from May to October 2014 and related meteorological statistics in the Dongkemaldi Basin, the characteristics of δ D, δ 18 O, and d -excess of precipitation, as well as the correlations between δ 18 O and the rainfall amount and air temperature were analyzed. The moisture sources were tracked by the HYSPLIT model to further estimate the contribution of different water vapor sources to the rainfall amount. The results showed that the range of δ 18 O and δ D values varied from -26.5‰ to 1.9‰ and -195.2‰ to 34.0‰, respectively; meanwhile, the δ 18 O and δ D values in precipitation fluctuated greatly with time in response to water vapor transport from different moisture sources of the Qinghai-Tibet Plateau. The slope and intercept of the Local Meteoric Water Line (LMWL) were both higher than those of the Global Meteoric Water Line (GMWL) and close to the LMWL in the northern area of the Qinghai-Tibet Plateau. The relationship between δ 18 O and δ D in different precipitation types showed significant differences, which were mainly related to the source of water vapor and meteorological conditions during the process of precipitation formation. Because of the influence of local evaporation and the transport process of water vapor, the d -excess values of atmospheric precipitation were relatively large; the δ 18 O in precipitation had a significant amount effect, but had no temperature effect, thus indicating that the rainfall amount was more effective in controlling the stable isotope content of atmospheric precipitation than temperature. The modeled trajectory of vapor sources showed that water vapor of precipitation was mainly derived from the marine vapor carried by the southwest monsoon, local moisture, and the westerly water vapor, and their contributions to the rainfall amount were 43%, 36%, and 21%, respectively. The results of this study can contribute to further understanding of the atmospheric circulation characteristics and water cycle process of the Dongkemadi basin in the headwaters of the Yangtze River.

Bone morphogenetic protein 2(BMP2) plays a key role in bone development and reestablishment. In the study, we screened up-regulators of BMP2 among 20 000 compounds through a cell-based high throughput screening model and a positive compound E40071 [2-(4-(5-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-7-yl) piperazin-1-yl)ethan-1-ol] was found as the positive hit. The EC(50) value of E40071 was 2.73 μmol·L(-1). In vitro, E40071 upregulated the m RNA levels of BMP2 and the downstream transcription factors, Runx2 and Osx in MC3T3-E1(subclone 14). Protein expression of Runx2 was up-regulated by E40071 through induction of Smad1/5/8 phosphorylation. The alkaline phosphatase(ALP) activity was increased by E40071. Moreover, E40071 promoted the mineralization of MC3T3-E1(subclone 14) by Alizarin red S staining. In addition, E40071 markedly inhibited osteoclast differentiation of mice macrophage Raw264.7 induced by RANKL and reduced the expression of osteoclast differentiation markers, including MMP9 and NFATc1. The results suggest that E40071 is able to promote bone formation activity of osteoblasts and inhibit differentiation of osteoclasts.

This study is to explore new lead compounds by inhibition of Pin1 for anticancer therapy using temperature sensitive mutants. As Pin1 is conserved from yeast to human, we established a high-throughput screening method for Pin1 inhibitors, which employed yeast assay. This method led to the identification of one potent hits, 8-11. In vitro, 8-11 inhibited purified Pin1 enzyme activity with IC50 of (10.40 +/- 1.68) micromol x L(-1), induced G1 phase arrest and apoptosis, showed inhibitory effects on a series of cancer cell proliferation, reduced Cyclin D1 expression, was defined as reciprocally matched for protein-ligand complex in virtual docking analysis and reduced cell migration ability. In vivo, we could observe reduction of tumor volume after treatment with 8-11 in xenograft mice compared with vehicle DMSO treatment. Altogether, these results provide for the first time the involvement of 8-11 in the anticancer activity against Pin1.

Objective: To evaluate the value of normalization window of tumor vasculature (NWTV) in patients with unresectable gastric cancer undergoing neoadjuvant chemotherapy., Methods: From October 2010 to March 2011, 93 patients with unresectable advanced or locally advanced gastric carcinoma were prospectively collected and randomly divided to Group A(n=30), Group B(n=29), and Group C(n=34). Group A received FOLFOX4 as conventional neoadjuvant chemotherapy. Group B received FOLFOX4 plus bevacizumab. The treatment was adjusted in Group C according to the hypothesis of NWTV with neoadjuvant chemotherapy delivered 5 days after bevacizumab treatment. The efficacy, drug toxicity and clinical outcome were assessed and compared between the three groups., Results: There were no significant differences among the 3 groups in demographics(P>0.05). All the patients completed the neoadjuvant chemotherapy. Efficacy and toxicity between the three groups were comparable(P>0.05). The rates of tumor downstaging in the three groups were 56.7%(17/30), 72.4%(21/29), 85.3%(29/34), respectively, with a significantly lower downstaging rate in Group C as compared to Group A(P<0.05). R0 resection rates were 23.3%(7/30), 27.6%(8/29), 52.9% (18/34), respectively, with significantly higher R0 resection rate in Group C as compared to Group A and Group B(All P<0.05). There was no perioperative death in this cohort. Postoperative complications were comparable among the 3 groups(P>0.05)., Conclusions: Anti-angiogenesis agent can improve the efficacy of neoadjuvant chemotherapy in unresectable gastric cancer. Furthermore, administration according to NWTV may achieve better outcomes.

In this work, substituted benzothiophene and benzofuran compounds were found to be a new class of potential anabolic agents by enhancing BMP-2 expression. A series of benzothiophene and benzofuran derivatives have been synthesized, and their activities of up-regulating BMP-2 and bone loss prevention efficacies in SAMP6 mice and OVX rats have been studied. Benzothiophenes 1, 3, 14, 4a, 7a, 8a, and benzofuran analogue 2 showed higher BMP-2 up-regulation rates in vitro. Compound 8a was found to significantly affect the bone formation rate of tested SAMP6 mice. Compound 1 showed an improved bone quality in SAMP6 mice and also showed activity in OVX rats. We have demonstrated that substituted benzothiophene and benzofuran derivatives, especially compounds 1 and 8a, enhance BMP-2 expression in vitro and in vivo and stimulate bone formation and trabecular connectivity restoration in vivo. The compounds represent potential leads in the development of a new class of anabolic agents.

Karyotype analysis was carried out by means of culturing whole peripheral blood from 394 pigs, which were produced from three hybridization combinations of 13/17 Robertsonian translocation pig. Three types of karyotype were detected in these hybrids, i.e., the homozygous pigs [2n=36, XY or XX, rob (13; 17)], the heterozygous pigs [2n=37, XY or XX, rob (13; 17)], and the normal karyotype pigs [2n=38, XY or XX]. A Rsa restriction enzyme polymorphic site in a 1 746 bp fragment of porcine POU1F1 gene was detected by PCR-RFLP analysis. While no mutation in exon 4 of porcine POU1F1 gene was detected by PCR-SSCP analysis in the hybrids of the three hybridization combinations. Population genetics analysis showed that for Rsa-RFLP, the frequencies of allele A and genotype AA were significantly higher than allele B and genotype BB in the three hybrid populations and the three type of karyotype populations. The frequency of genotype AB was higher in the heterozygous translocation population than in the other two karyotype populations. Chi-square test suggested that all the populations did not reach Hardy-Weinberg equilibrium. The progeny populations of heterozygous 13/17 translocation pig x heterozygous 13/17 translocation pig, heterozygous 13/17 translocation pig x Yorkshire, and heterozygous pig population had medium polymorphism and others had low polymorphism.