Genomic Epidemiology of SARS-CoV-2 in Guangdong Province, China.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA-positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China, we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain because of low virus genetic variation early in the pandemic. Our results illustrate how the timing, size, and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required, because the number of cases imported from other countries has increased.

CRKL but not CRKII contributes to hemin-induced erythroid differentiation of CML.

Destruction of erythropoiesis process leads to various diseases, including thrombocytopenia, anaemia, and leukaemia. miR-429-CT10 regulation of kinase-like (CRKL) axis involved in development, progression and metastasis of cancers. However, the exact role of miR-429-CRKL axis in leukaemic cell differentiation are still unknown. The current work aimed to uncover the effect of miR-429-CRKL axis on erythropoiesis. In the present study, CRKL upregulation was negatively correlated with miR-429 downregulation in both chronic myeloid leukaemia (CML) patient and CR patient samples. Moreover, CRKL expression level was significantly decreased while miR-429 expression level was increased during the erythroid differentiation of K562 cells following hemin treatment. Functional investigations revealed that overexpression and knockdown of CRKL was remarkably effective in suppressing and promoting hemin-induced erythroid differentiation of K562 cells, whereas, miR-429 exhibited opposite effects to CRKL. Mechanistically, miR-429 regulates erythroid differentiation of K562 cells by downregulating CRKL via selectively targeting CRKL-3'-untranslated region (UTR) through Raf/MEK/ERK pathway. Conversely, CRKII had no effect on erythroid differentiation of K562 cells. Taken together, our data demonstrated that CRKL (but not CRKII) and miR-429 contribute to development, progression and erythropoiesis of CML, miR-429-CRKL axis regulates erythropoiesis of K562 cells via Raf/MEK/ERK pathway, providing novel insights into effective diagnosis and therapy for CML patients.

The proportion of tumour stroma predicts response to treatment of immune checkpoint inhibitor in combination with chemotherapy in patients with stage IIIB-IV non-small cell lung cancer.

AIMS: Immunotherapy has brought a new era to cancer treatment, yet we lack dependable predictors for its effectiveness. This study explores the predictive significance of intratumour stroma proportion (iTSP) for treatment success and prognosis in non-small cell lung cancer (NSCLC) patients undergoing treatment with immune check-point inhibitors (ICIs) together with chemotherapy. METHODS AND RESULTS: We retrospectively collected data from patients with unresectable stage IIIB-IV NSCLC who were treated with first-line ICIs and chemotherapy. Each patient received a confirmed pathological diagnosis, and the pathologist evaluated the iTSP on haematoxylin and eosin (H&E)-stained sections of diagnostic tissue slides. Among the 102 H&E-stained biopsy samples, 61 (59.8%) were categorised as stroma-L (less than 50% iTSP), while 41 (40.2%) were classified as stroma-H (more than 50% iTSP). We observed that the stroma-L group exhibited a significantly better objective response rate (ORR) (72.1 versus 51.2%, P = 0.031) and deeper response depth (DpR) (-50.49 ± 28.79% versus -35.83 ± 29.91%, P = 0.015) compared to the stroma-H group. Furthermore, the stroma-L group showed longer median progression-free survival (PFS) (9.6 versus 6.0 months, P = 0.011) and overall survival (OS) (24.0 versus 12.2 months, P = 0.001) compared to the stroma-H group. Multivariate Cox proportional hazards regression analysis indicated that iTSP was a highly significant prognostic factor for both PFS [hazard ratio (HR) = 1.713; P = 0.030] and OS (HR = 2.225; P = 0.003). CONCLUSION: Our findings indicate that a lower iTSP corresponds to improved clinical outcomes and greater DpR in individuals with stage IIIB-IV NSCLC treated with first-line ICIs and chemotherapy. The iTSP could potentially serve as a predictive biomarker for ICIs therapy response.

Genomic epidemiology of CVA10 in Guangdong, China, 2013-2021.

Hand, Foot and Mouth Disease (HFMD) is a highly contagious viral illness primarily affecting children globally. A significant epidemiological transition has been noted in mainland China, characterized by a substantial increase in HFMD cases caused by non-Enterovirus A71 (EV-A71) and non-Coxsackievirus A16 (CVA16) enteroviruses (EVs). Our study conducts a retrospective examination of 36,461 EV-positive specimens collected from Guangdong, China, from 2013 to 2021. Epidemiological trends suggest that, following 2013, Coxsackievirus A6 (CVA6) and Coxsackievirus A10 (CVA10) have emerged as the primary etiological agents for HFMD. In stark contrast, the incidence of EV-A71 has sharply declined, nearing extinction after 2018. Notably, cases of CVA10 infection were considerably younger, with a median age of 1.8 years, compared to 2.3 years for those with EV-A71 infections, possibly indicating accumulated EV-A71-specific herd immunity among young children. Through extensive genomic sequencing and analysis, we identified the N136D mutation in the 2 A protein, contributing to a predominant subcluster within genogroup C of CVA10 circulating in Guangdong since 2017. Additionally, a high frequency of recombination events was observed in genogroup F of CVA10, suggesting that the prevalence of this lineage might be underrecognized. The dynamic landscape of EV genotypes, along with their potential to cause outbreaks, underscores the need to broaden surveillance efforts to include a more diverse spectrum of EV genotypes. Moreover, given the shifting dominance of EV genotypes, it may be prudent to re-evaluate and optimize existing vaccination strategies, which are currently focused primarily target EV-A71.

Terahertz beam characterization by temporal-spatial mapping with a reflecting echelon.

A terahertz beam imaging method was proposed that involves scanning a reflecting echelon with temporal-spatial mapping inversion based on self-developed translation-scan and rotation-scan temporal-spatial mapping (TTSM and RTSM) algorithms. The beam characteristics of a terahertz time-domain spectroscopy (TDS) system, such as its size, shape, and energy distribution, were obtained. Besides the weak terahertz beam emitted from a TDS system, this scheme is also suitable for imaging large-size terahertz or laser beams in time-domain systems where existing beam imaging is impractical.

A novel framework for vegetation change characterization from time series landsat images.

Understanding terrestrial ecosystem dynamics requires a comprehensive examination of vegetation changes. Remote sensing technology has been established as an effective approach to reconstructing vegetation change history, investigating change properties, and evaluating the ecological effects. However, current remote sensing techniques are primarily focused on break detection but ignore long-term trend analysis. In this study, we proposed a novel framework based on a change detection algorithm and a trend analysis method that could integrate both short-term disturbance detection and long-term trends to comprehensively assess vegetation change. With this framework, we characterized the vegetation changes in Zhejiang Province from 1990 to 2020 using Landsat and landcover data. Benefiting from combining break detection and long-term trend analysis, the framework showcased its capability of capturing a variety of dynamics and trends of vegetation. The results show that the vegetation was browning in the plains while greening in the mountains, and the overall vegetation was gradually greening during the study period. By comparison, detected vegetation disturbances covered 57.71% of the province's land areas (accounting for 66.92% of the vegetated region) which were mainly distributed around the built-up areas, and most disturbances (94%) occurred in forest and cropland. There were two peak timings in the frequency of vegetation disturbances: around 2003 and around 2014, and the proportions of more than twice disturbances in a single location were low. The results illustrate that this framework is promising for the characterization of regional vegetation growth, including long-term trends and short-term features. The proposed framework enlightens a new direction for the continuous monitoring of vegetation dynamics.

Pollution and risk assessment of potentially toxic elements in soils from industrial and mining sites across China.

Potentially toxic elements in soils (SPTEs) from industrial and mining sites (IMSs) often cause public health issues. However, previous studies have either focused on SPTEs in agricultural or urban areas, or in a single or few IMSs. A systematic assessment of the pollution and risk levels of SPTEs from IMS at the national scale is lacking. Here, we obtained SPTE (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) concentrations from IMSs across China based on 188 peer-reviewed articles published between 2004 and 2022 and quantified their pollution and risk levels using the pollution index and risk assessment model, respectively. The results indicated that the average concentrations of the eight SPTEs were 4.42-270.50 times the corresponding background values, and 19.58% of As, 14.39% of Zn, 12.79% of Pb, and 8.03% of Cd exceeded the corresponding soil risk screening values in these IMSs. In addition, 27.13% of the examined IMS had one or more SPTE pollution, mainly distributed in the southwest and south central China. On the examined IMSs, 81.91% had moderate or severe ecological risks, which were mainly caused by Cd, Hg, As, and Pb; 23.40% showed non-carcinogenic risk and 11.70% demonstrated carcinogenic risk. The primary exposure pathways of the former were ingestion and inhalation, while that for the latter was ingestion. A Monte Carlo simulation also confirmed the health risk assessment results. As, Cd, Hg, and Pb were identified as priority control SPTEs, and Hunan, Guangxi, Guangdong, Yunnan, and Guizhou were selected as the key control provinces. Our results provide valuable information for public health and soil environment management in China.

Direct C(sp3)-H Polyfluoroarylation: Access to Polyfluoroaryl Amino Acids via Rh-Catalyzed Selective C-F Bond Cleavage.

A catalytic selective C-F bond alkylation method for polyfluoroarene with glycinates and derivatives in the presence of a DavePhos-ligated Rh catalyst was developed. This method avoids the preactivation of alkylating reagents and provides an efficient and straightforward route to synthesize a series of polyfluoroaryl amino acids via C(sp3)-H functionalization. This reaction proceeds under mild conditions and exhibits high reactivity and excellent chemoselectivities. Meanwhile, the synthetic potential of this method was demonstrated by gram-scale synthesis, and further transformations proved the application value of the products as well.

Transamidation and Decarbonylation of N-Phthaloyl-Amino Acid Amides Enabled by Palladium-Catalyzed Selective C-N Bond Cleavage.

Amides are important functional synthons that have been widely used in the construction of peptides, natural products, and drugs. The C-N bond cleavage provides the direct method for amide conversion. However, amides, especially secondary amides, tend to be chemically inert due to the resonance of the amide bond. Here, we describe an efficient Pd-catalyzed transamidation and decarbonylation of multiamide structure molecules through C-N bond cleavage with excellent chemoselectivity. The transamidation of secondary amides and the decarbonylation of phthalimide provide meaningful tools for the modification of amino acid derivatives. Moreover, further transformations of azidation and C(sp3)-H monoarylation emphasized the potential utility of this selective C-N bond cleavage method.

Active projection nonlinear γ correction method for fringe projection profilometry.

In fringe projection profilometry (FPP), the luminance nonlinearity generated by the superimposed γ effect of the projector and camera can lead to distortion of the intensity of the sinusoidal phase-shift fringe, resulting in a reduction of measurement precision and resolution. Traditional phase error compensation and γ-correction methods need to focus on the projector's optimal performance. However, commercial projectors often have huge apertures and are, therefore, unable to project a perfectly focused sinusoidal fringe image. This paper proposes an easy-to-implement active projection error correction method with high precision that is insensitive to projector defocus. After calibrating the projector to establish the nonlinear γ-response model of the optical measurement system, inverse γ compensation is performed. By generating and projecting a set of precorrected sinusoidal fringes, the camera can capture the high-quality sinusoidal fringe image and decrease the phase measurement error caused by the nonlinear γ effect of the FPP system. Computer simulations and experiments verify the effectiveness and feasibility of the proposed method for estimating and correcting the nonlinear γ distortion of the FPP system. The experimental results show that using the proposed active projection method to compensate for the error of the three-step phase-shift algorithm can achieve a high-precision measurement, and the influence of the system's nonlinear γ effect on the measurement accuracy is significantly suppressed.

Study on the thermal washing of oily sludge used by rhamnolipid/sophorolipid binary mixed bio-surfactant systems.

Demulsification and crude oil desorption are usually a necessary step for the treatment of oily sludge in the petroleum industry. In this study a binary mixed bio-surfactant (rhamnolipid / sophorolipid, RL/SL) was used to strengthen the removing oil efficiency for oily sludge by thermal washing method. Surface tension values of the single and the mixed surfactants were carried out to investigate the effect of mixing systems on reducing critical micelle concentrations (CMC) value. The models proposed by Clint, Rubingh and Gibbs et al. had been employed to interpret the formation of mixed micelles and synergism and found out in case of the mass ratios of 4:6 the synergism was the strongest in RL and SL mixed surfactant systems, which was selected as the washing agents to treat the oily sludge produced from Huabei oilfield. Through the optimization of oil washing process parameters, the oil removal rate reached the maximum value (95.66%, residual oil rate 1.98%) at the condition of heating temperature of 45 °C, detergents concentration of 500 mg/L, washing time of 3 h, liquid/solid mass ratio of 1:4, stirring speed of 300 r/min, and washing 4 times. The factors affecting the oil washing effect were analyzed from the composition and performance characteristics of oily sludge samples, washing oil system and washing process parameters. The results showed that low oil content of oily sludge, small specific surface area, strong wetting and solubilization of the oil-washing system all can increase the oil-washing effect and the washing time and temperature had a great influence on the oil-washing effect. Compared with the results of other researchers, the oil washing temperature and the concentration of oil washing agent were significantly lower and high oil removal rate and low residual oil rate were obtained in this study. It was confirmed that thermal oil washing method using RT/SL binary bio-surfactant mixing system was proved to a high-efficiency, low-consumption and wide range of applications technology.

GHR is involved in gastric cell growth and apoptosis via PI3K/AKT signalling.

Growth hormone receptor (GHR), the cognate receptor of growth hormone (GH), is a membrane bound receptor that belongs to the class I cytokine receptor superfamily. GH binding GHR induces cell differentiation and maturation, initiates the anabolism inside the cells and promotes cell proliferation. Recently, GHR has been reported to be associated with various types of cancer. However, the underlying mechanism of GHR in gastric cancer has not been defined. Our results showed that silence of GHR inhibited the growth of SGC-7901 and MGC-803 cells, and tumour development in mouse xenograft model. Flow cytometry showed that GHR knockout significantly stimulated gastric cancer cell apoptosis and caused G1 cell cycle arrest, which was also verified by Western blot that GHR deficiency induced the protein level of cleaved-PARP, a valuable marker of apoptosis. In addition, GHR deficiency inhibited the activation of PI3K/AKT signalling pathway. On the basis of the results, that GHR regulates gastric cancer cell growth and apoptosis through controlling G1 cell cycle progression via mediating PI3K/AKT signalling pathway. These findings provide a novel understanding for the role of GHR in gastric cancer.

Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus first identified in December 2019. Notable features that make SARS-CoV-2 distinct from most other previously identified betacoronaviruses include a receptor binding domain and a unique insertion of 12 nucleotides or 4 amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS-CoV-2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN). These deletions were verified by multiple sequencing methods. In vitro results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero-E6 cells; however, the deletion of QTQTN may restrict late-phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and 12 of 24 in vitro-isolated viruses, while the deletion of NSPRRAR was identified in 3 in vitro-isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS-CoV-2 replication or infection in vitro and in vivo; (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage; and (iii) the PRRA insertion, which is unique to SARS-CoV-2, is not fixed during virus replication in vitro These findings provide information to aid further investigation of SARS-CoV-2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here.IMPORTANCE The spike protein determines the infectivity and host range of coronaviruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has two unique features in its spike protein, the receptor binding domain and an insertion of 12 nucleotides at the S1/S2 boundary resulting in a furin-like cleavage site. Here, we identified two deletion variants of SARS-CoV-2 that either directly affect the furin-like cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN), and we investigated these deletions in cell isolates and clinical samples. The absence of the polybasic cleavage site in SARS-CoV-2 did not affect virus replication in Vero or Vero-E6 cells. Our data indicate the PRRAR sequence and the flanking QTQTN sequence are not fixed in vitro; thus, there appears to be distinct selection pressures on SARS-CoV-2 sequences in vitro and in vivo Further investigation of the mechanism of generating these deletion variants and their infectivity in different animal models would improve our understanding of the origin and evolution of this virus.

Molecular surveillance of coxsackievirus A16 in southern China, 2008-2019.

A national surveillance system on hand, foot, and mouth disease (HFMD) was launched in 2008 in China. Since then, millions of HFMD cases have been reported each year, with enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6) as the major causative pathogens. Long-term surveillance of viral infection rates and genetic changes is essential for understanding the disease epidemiology pattern. Here, we analyzed molecular surveillance data on CV-A16 covering a period of 12 years (2008-2019) in Guangdong, China, one of the regions reporting the largest number of HFMD cases. Full VP1 sequences of 456 strains were determined to examine the genetic diversity and changes in the distribution of CV-A16 variants. Our study revealed an irregular pattern of CV-A16 infections in Guangdong. Different from the cyclic epidemics observed in some Asia-Pacific regions, there was a continuously high CV-A16 infection rate from 2008 to 2014, and after a period of lower epidemic activity in 2015-2017, an upsurge of CV-A16 infection was observed in 2018-2019. Cocirculation of subgenotypes B1a and B1b was observed, but while subgenotype B1a was predominant from 2008 to 2012, it appears to have been replaced by B1b, which has circulated as the predominant subgenotype since 2013. Phylogenetic analysis showed that most of the circulating CV-A16 strains are endemic, with occasional transmission between neighboring regions. The re-emergence of B1a in 2016-2019 in Guangdong was likely the result of introduction(s) from Southeast Asia. These results highlight the importance of continuous molecular surveillance from different areas, which will improve our understanding of the origin of the epidemic and facilitate the development of strategies for HFMD disease control.

Study on the treatment of oily sludge in oil fields with lipopeptide/sophorolipid complex bio-surfactant.

A systematic study had been carried out to get insight into the micellar behavior of anionic lipopeptide (LT) and nonionic sophorolipid (SL) in their different mass ratio mixed state using the technique of tensiometry. The models proposed by Clint, Rubingh and Gibbs et al. had been employed to interpret the formation of mixed micelles and found out synergism. The obtained experimental critical micelle concentrations (CMC) were lower than the ideal CMCs, indicating negative deviation from ideal behavior for all multi-component mixed micelles formation. A suited binary bio-surfactant mixing system was selected as the washing agents to treat the oily sludge produced from Huabei oilfield by the thermal bio-surfactant washing method. The results showed that in case of the mass ratios of 8:2 the CMC was dramatically decreased and synergism was the strongest in LT and SL bi mixed surfactant systems. The studied binary mixed bio-surfactant system showed higher washing efficiency for oily sludge than single surfactant system. In addition, the washing power of binary mixed bio-surfactants towards oily sludge was the best at below washing conditions: (a) the concentration of the mixed system (100 mg/L), (b) temperature (55 â„ƒ), (c) ratio of sludge/liquid (1:3), (d) washing time (3 h), and (e) stirring speed (300 rpm). Certainly, the washing abilities of the selected surfactants not only depend on their mixing ratio and washing conditions but also associate with microstructure and mineral components of oily sludge.

Hsp27 Responds to and Facilitates Enterovirus A71 Replication by Enhancing Viral Internal Ribosome Entry Site-Mediated Translation.

Enterovirus 71 (EV-A71) is a human pathogen that causes hand, foot, and mouth disease (HFMD) and fatal neurological diseases, and no effective treatment is available. Characterization of key host factors is important for understanding its pathogenesis and developing antiviral drugs. Here we report that Hsp27 is one of the most upregulated proteins in response to EV-A71 infection, as revealed by two-dimensional gel electrophoresis-based proteomics studies. Depletion of Hsp27 by small interfering RNA or CRISPR/Cas9-mediated knockout significantly inhibited viral replication, protein expression, and reproduction, while restoration of Hsp27 restored such virus activities. Furthermore, we show that Hsp27 plays a crucial role in regulating viral internal ribosome entry site (IRES) activities by two different mechanisms. Hsp27 markedly promoted 2Apro-mediated eukaryotic initiation factor 4G cleavage, an important process for selecting and initiating IRES-mediated translation. hnRNP A1 is a key IRES trans-acting factor (ITAF) for enhancing IRES-mediated translation. Surprisingly, knockout of Hsp27 differentially blocked hnRNP A1 but not FBP1 translocation from the nucleus to the cytoplasm and therefore abolished the hnRNP A1 interaction with IRES. Most importantly, the Hsp27 inhibitor 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone (TDP), a compound isolated from a traditional Chinese herb, significantly protected against cytopathic effects and inhibited EV-A71 infection. Collectively, our results demonstrate new functions of Hsp27 in facilitating virus infection and provide novel options for combating EV-A71 infection by targeting Hsp27.IMPORTANCE Outbreaks of infections with EV-A71, which causes hand, foot, and mouth disease, severe neurological disorders, and even death, have been repeatedly reported worldwide in recent decades and are a great public health problem for which no approved treatments are available. We show that Hsp27, a heat shock protein, supports EV-A71 infection in two distinct ways to promote viral IRES-dependent translation. A small-molecule Hsp27 inhibitor isolated from a traditional Chinese medicinal herb effectively reduces virus yields. Together, our findings demonstrate that Hsp27 plays an important role in EV-A71 infection and may serve as an antiviral target.

Promotive effect of Talin-1 protein on gastric cancer progression through PTK2-PXN-VCL-E-Cadherin-CAPN2-MAPK1 signaling axis.

OBJECTIVE: Our research group was aim to explore the molecular mechanism of Talin-1 protein affecting gastric cancer progression through PTK2-PXN-VCL-E-Cadherin-CAPN2-MAPK1 signal axis. METHODS: 12 cases of patients with gastric cancer in this hospital from 2018 to 2019 were collected. Immunohistochemistry assay and Western blotting were used to detect the expression of Talin-1, PXN, E-Cadherin, CAPN2, MAPK1 protein in gastric cancer tissue. Cell migration and invasion were measured by Transwell. RESULTS: The results showed that the expression levels of protein Talin-1, PXN and MAPK1 in gastric cancer tissues were significantly higher than that in normal tissue. The number of cell adhesion in the model group was significantly lower than that in the normal group. However, the cell adhesion number in ov-TLN1 was the highest. Transwell results showed that TLN1 could accelerate the migration and invasion abilities of gastric cancer MKN-45 cells. Moreover, Western blotting showed that protein Talin-1, PXN, E-Cadherin, CAPN2, MAPK1 in model group all increased compared with normal group. CONCLUSION: It indicated that talin-1 protein influenced the development of gastric cancer through PTK2-PXN-VCL-E-Cadherin-CAPN2-MAPK1 signal axis.

Trim14 promotes autophagy and chemotherapy resistance of gastric cancer cells by regulating AMPK/mTOR pathway.

OBJECTIVE: To study the relationship between TRIM14 expression and chemotherapy resistance of gastric cancer (GC) cells. METHODS: The expression of TRIM14 in 5-fluorouracil (5-FU)- and oxaliplation (L-OHP)-resistant GC tissues and cells were determined by qRT-PCR and western blotting. PcDNA3.1-TRIM14 and shRNA-TRIM14 vector were transfected to 5-FU-resistant GC cells (SGC7901/5-FU), and the proliferation and apoptosis of cells were measured. Animal experiments on 5-FU-resistant GC mice were performed to study the effect of TRIM14 expression on tumor size and weight, GC cell migration, and proliferation. pcDNA3.1-MK-3903 plasmid was transfected to SGC7901/5-FU cells with TRIM14 silence. The cell proliferation and apoptosis were determined. The protein expressions of Trim14, LC3, and BECLIN1 were measured by western blotting. RESULTS: TRIM14 was significantly upregulated in 5-FU- and L-OHP-resistant GC tissues and cells. The overexpression of TRIM14 promoted the proliferation and autophagy of SGC7901/5-FU cells, and inhibited the apoptosis. Moreover, in vivo experiment verified that the silence of TRIM14 reduced the tumor size and weight, and inhibited the migration and proliferation of GC cells in 5-FU-resistant GC mice. The overexpression of MK-3903 reversed the inhibiting role of TRIM14 knockout on the proliferation and autophagy of SGC7901/5-FU cells. CONCLUSION: TRIM14 promoted chemotherapy resistance of GC cells by regulating AMPK/mTOR pathway, and may be a new biomarker for treating GC.

Combined Chibby and ß-Catenin Predicts Clinical Outcomes in Patients with Hepatocellular Carcinoma.

Chibby is an antagonist of ß-catenin and is considered a potential tumor suppressor protein, but the role of Chibby in hepatocellular carcinoma (HCC) has not been characterized. The expression patterns of Chibby and ß-catenin in HCC specimens and paired adjacent noncancerous tissues were measured by Western blotting and immunohistochemistry. The correlations between Chibby expression and clinicopathological parameters were analyzed. Then the biological functions of Chibby were analyzed in vitro. The Chibby protein was significantly downexpressed in human primary HCC tissues compared to that in matched adjacent normal liver tissue and is a risk factor for HCC recurrence and shorter survival. Furthermore, we found that in HCC tissues the high expression of ß-catenin with low expression of Chibby in the nuclei was an independent predictor for disease-free survival (DFS) (p = 0.012) and overall survival (OS) (p = 0.005). Subsequent genetic manipulation in vitro studies revealed that Chibby knockdown induced the expression of ß-catenin and C-myc, cyclin D1 protein, which promoted cell proliferation and invasiveness. In contrast, overexpression of Chibby decreased ß-catenin expression and inhibited the cell proliferation and invasiveness. Our results suggest that low expression of Chibby was associated with advanced tumor-node-metastasis (TNM) stage and poor differentiation. Furthermore, the combination of Chibby and ß-catenin can predict poor prognosis in patients with HCC. Chibby inhibited HCC progression by blocking ß-catenin signaling in vitro. Chibby is a biomarker and may be a potential therapeutic target for HCC.