TYMSOS drives the proliferation, migration, and invasion of gastric cancer cells by regulating ZNF703 via sponging miR-4739.

Gastric cancer (GC) is a kind of malignancy originating from the epithelium of gastric mucosa. Long noncoding RNAs (lncRNAs) are tightly related to the GC progression. Herein, our research was meant to investigate a novel lncRNA thymidylate synthetase opposite strand (TYMSOS) in GC. Quantitative real-time polymerase chain reaction was used to analyze TYMSOS expression in GC cells. 5-Ethynyl-2'-deoxyuridine, flow cytometry analysis, and transwell assay detected the influence of TYMSOS on GC cell proliferation, apoptosis, migration, and invasion. Subcellular fractionation and fluorescent in situ hybridization assays determined the cellular localization of TYMSOS in GC cells. Bioinformatics programs, RNA-binding protein immunoprecipitation, RNA pull-down, and luciferase reporter assays measured the molecular interplays of TYMSOS in GC cells. In brief, TYMSOS was highly expressed in GC cells, and TYMSOS silence inhibited GC cell proliferation, migration, and invasion while elevating cell apoptosis. Functionally, TYMSOS functioned as a competing endogenous RNA to posttranscriptionally modulate GC progression. TYMSOS interacted with miR-4739 to regulate its target gene zinc finger protein 703. Collectively, our study proved the tumor-promoting role of TYMSOS in GC cells, which might offer the utility value for GC treatment.

Histone modifications induced by MDV infection at early cytolytic and latency phases.

BACKGROUND: Marek's disease (MD) is a highly contagious, lymphomatous disease of chickens induced by a herpesvirus, Marek's disease virus (MDV) that is the cause of major annual losses to the poultry industry. MD pathogenesis involves multiple stages including an early cytolytic phase and latency, and transitions between these stages are governed by several host and environmental factors. The success of vaccination strategies has led to the increased virulence of MDV and selective breeding of naturally resistant chickens is seen as a viable alternative. While multiple gene expression studies have been performed in resistant and susceptible populations, little is known about the epigenetic effects of infection. RESULTS: In this study, we investigated temporal chromatin signatures induced by MDV by analyzing early cytolytic and latent phases of infection in the bursa of Fabricius of MD-resistant and -susceptible birds. Major global variations in chromatin marks were observed at different stages of MD in the two lines. Differential H3K27me3 marks were associated with immune-related pathways, such as MAP kinase signaling, focal adhesion and neuroactive ligand receptor interaction, and suggested varying degrees of silencing in response to infection. Immune-related microRNAs, e.g. gga-miR-155 and gga-miR-10b, bore chromatin signatures, which suggested their contribution to MD-susceptibility. Finally, several members of the focal adhesion pathway, e.g. THBS4 and ITGA1, showed marked concordance between gene expression and chromatin marks indicating putative epigenetic regulation in response to MDV infection. CONCLUSION: Our comprehensive analysis of chromatin signatures, therefore, revealed further clues about the epigenetic effects of MDV infection although further studies are necessary to elucidate the functional implications of the observed variations in histone modifications.

Research progress on molecular mechanism of pyroptosis caused by Helicobacter pylori in gastric cancer.

Gastric cancer (GC) is a prevalent malignancy worldwide. Helicobacter pylori (H. pylori), a Gram-negative spiral bacterium, has the ability to colonize and persist in the human gastric mucosa. Persistent H. pylori infection has been identified as a major risk factor for ~80% of GC cases. The interplay between H. pylori pathogenicity, genetic background, and environmental factors collectively contribute to GC transformation. Eradicating H. pylori infection is beneficial in reducing the recurrence of gastric cancer and residual cancer. However, the underlying molecular mechanisms involved in GC remain incompletely understood. Additionally, H. pylori reshapes the immune microenvironment within the stomach which may compromise immunotherapy efficacy in infected individuals. Clinical eradication of H. pylori infection still faces numerous challenges. In this review, the authors summarize recent research progress on elucidating the molecular mechanisms underlying H. pylori infection in GC development. Notably, CagA protein-a carcinogenic virulence factor predominantly expressed by Asian strains of H. pylori-induces inflammation and excessive ROS production within gastric mucosa cells. Dysregulation of multiple pyroptosis signalling pathways can lead to malignant transformation of these cells. MiRNA-1290 plays a crucial role in GC initiation and progression while serving as an indicator for disease progression dynamics. Pyroptosis exhibits dual roles both promoting carcinogenesis and inhibiting tumour growth; thus it holds potential clinical applications for drug-resistant GC treatment strategies. Furthermore, pyroptosis may play a regulatory role within the immune system during gastric cancer development. Lastly, the authors provide an overview on current concepts regarding pyroptosis as well as insights into miRNA-1290's pathogenicity and clinical value within immune mechanisms associated with GC, aiming to serve as reference material for researchers.

Mutation of MET D1228N as an Acquired Potential Mechanism of Crizotinib Resistance in NSCLC with MET Y1003H Mutation.

Mesenchymal-epithelial transition (MET) gene has been identified as a promising target for treatments. However, different sites of the MET mutation show different effects to MET inhibition. Here, we reported a non-small cell lung cancer (NSCLC) patient harboring MET Y1003H mutation who achieved a durable partial response to crizotinib with a PFS of 22.4 months. Furthermore, we report for the first time the identification of MET D1228N as a possible mechanism of acquired resistance to crizotinib in a patient with MET Y1003H mutation during disease progression.

Efficient reduction of CO2 and inhibition of hydrogen precipitation by polyoxometalate photocatalyst modified with the metal Mn.

Photocatalytic reduction of CO2 to chemical fuels is attractive for solving both the greenhouse effect and the energy crisis, but the key challenge is to design and synthesize photocatalysts with remarkable performance under visible light irradiation. Efficient catalytic carbon dioxide reduction (CO2RR) with light is considered a promising sustainable and clean approach to solve environmental problems. Herein, we found a new photocatalyst ([Mn(en)2]6[V12B18O54(OH)6]) (abbreviated as Mn6V12) based on the modifiability of polyoxometalates, in which Mn acts as a modifying unit to efficiently reduce CO2 to CO and effectively inhibit the hydrogen precipitation reaction. This Mn modified polyoxometalate catalyst has a maximum CO generation rate of 4625.0 µmol g-1 h-1 and a maximum H2 generation rate of 499.6 µmol g-1 h-1, with a selectivity of 90.3% for CO generation and 9.7% for H2 generation. This polyoxometalate photocatalyst can effectively reduce CO and inhibit the hydrogen precipitation reaction. It provides a new idea for the efficient photocatalytic carbon dioxide reduction (CO2RR) with polyoxometalate catalysts.

One-Dimensional Single-Crystal Mesoporous TiO2 Supported CuW6O24 Clusters as Photocatalytic Cascade Nanoreactor for Boosting Reduction of CO2 to CH4.

Constructing nanoreactors with multiple active sites in well-defined crystalline mesoporous frameworks is an effective strategy for tailoring photocatalysts to address the challenging of CO2 reduction. Herein, one-dimensional (1-D) mesoporous single-crystal TiO2 nanorod (MS-TiO2-NRs, ≈110 nm in length, high surface area of 117 m2 g-1, and uniform mesopores of ≈7.0 nm) based nanoreactors are prepared via a droplet interface directed-assembly strategy under mild condition. By regulating the interfacial energy, the 1-D mesoporous single-crystal TiO2 can be further tuned to polycrystalline fan- and flower-like morphologies with different oxygen vacancies (Ov). The integration of single-crystal nature and mesopores with exposed oxygen vacancies make the rod-like TiO2 nanoreactors exhibit a high-photocatalytic CO2 reduction selectivity to CO (95.1%). Furthermore, photocatalytic cascade nanoreactors by in situ incorporation of CuW6O24 (W-Cu) clusters onto MS-TiO2-NRs via Ov are designed and synthesized, which improved the CO2 adsorption capacity and achieved two-step CO2-CO-CH4 photoreduction. The second step CO-to-CH4 reaction induced by W-Cu sites ensures a high generation rate of CH4 (420.4 µmol g-1 h-1), along with an enhanced CH4 selectivity (≈94.3% electron selectivity). This research provides a platform for the design of mesoporous single-crystal materials, which potentially extends to a range of functional ceramics and semiconductors for various applications.

A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer.

BACKGROUND: Mecapegfilgrastim, a long-acting granulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. OBJECTIVE: We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. METHOD: Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. RESULTS: The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. CONCLUSION: In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

Single nucleotide polymorphisms, haplotypes and combined genotypes in MYH3 gene and their associations with growth and carcass traits in Qinchuan cattle.

MYH3 is a major contractile protein which converts chemical energy into mechanical energy through the ATP hydrolysis. MYH3 is mainly expressed in the skeletal muscle in different stages especially embryonic period, and it has a role in the development of skeletal muscle and heart. In this study, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to analyze the genetic variations of the MYH3 gene and verify the effect on growth and carcass traits in a total of 365 Qinchuan cattles. The PCR product was digested with some restriction enzyme and demonstrated the polymorphism in the population, the single nucleotide polymorphisms (SNPs) at nucleotides g. +1215T>C, g. +3377C>T, and g. +28625C>T were in linkage disequilibrium with each other. The result of haplotype analysis showed that nineteen different haplotypes were identified among the five SNPs. The statistical analyses indicated that the five SNPs were significant association with growth and carcass traits (P < 0.05, N = 365); whereas the five SNPs were no significant association between 18 combined genotypes of MYH3 gene and growth and carcass traits. Taken together, our results provide the evidence that polymorphisms in MYH3 are associated with growth and carcass traits in Qinchuan cattle, and may be used as a possible candidate for marker-assisted selection and management in beef cattle breeding program.

An introduction to retrodictive qualitative modeling as an emerging method on affective variables in SLA research.

Investigating second language acquisition (SLA) via a complex dynamic systems theory (CDST) involves much intuition, and operationalizing the dynamic constructs is hard in research terms. In the present study, we contend that the commonly used quantitative data analysis methods such as correlational works or structural equation modeling fail to examine variables as part of a system or network. They are mostly based on linear rather than non-linear associations. Considering the major challenges of dynamic systems research in SLA, we recommend that innovative analytical models such as retrodictive qualitative modeling (RQM) be used more. RQM manages to reverse the usual direction of research by actually beginning from the end. More especially from certain outcomes and then moves backward to find why specific elements of the system led to one outcome rather than the others. The analytical procedures of RQM will be elaborated on and also exemplified in the SLA research, more specifically for investigating language learners' affective variables. The limited body of research using RQM in the SLA domain is also reviewed followed by some conclusive remarks and suggestions for further research into the variables of interest.

Two copper(II) compounds derived from tetrazole carboxylates for chemodynamic therapy against hepatocellular carcinoma cells.

Two Cu(II) compounds based on tetrazole-carboxylate ligands, [Cu(phtza)2(H2O)2]∙3H2O (1) and [Cu(atzipa)2]∙2H2O (2) (phtza = 2,2'-(5,5'-(1,3-phenylene)bis(2H-tetrazole-5,2-diyl))diacetate, atzipa = 3-(5-amino-1H-tetrazol-1-yl)isopropanoic anion), were designed and synthesized by hydrothermal reactions. The X-ray diffraction results show that the two compounds show two-dimensional (2D) layer structures. Nanoprecipitation with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000) contributes to the formation of the nanoparticles (NPs) with excellent water dispersity. In vitro study indicates that the two NPs exert considerable cytotoxicity toward human hepatocellular carcinoma cells (HepG2 and Huh7) with low half-maximal inhibitory concentration (IC50). However, the cytotoxicity of such NPs is negligible in normal cells (HL-7702). The cytotoxicity of these NPs was also investigated by the flow cytometry and Calcein-AM/PI (live/dead) co-stained experiments. The results promise the great potential of these NPs for chemodynamic therapy against cancer cells.

The prognostic value of NLRP1/NLRP3 and its relationship with immune infiltration in human gastric cancer.

BACKGROUND: Inflammasomes are related to tumorigenesis and immune-regulation. Here, we investigated the prognostic value of the NLR family pyrin domain containing (NLRP) 1/NLRP3 inflammasome and its potential mechanisms in immune-regulation in gastric cancer (GC). METHODS: We analyzed the differential expression of NLRP1/NLRP3 between tumor and normal tissues using the Oncomine and Tumor Immune Estimate Resource (TIMER) databases. Immunohistochemistry and western blotting were used to detect NLRP1/NLRP3 protein expression in GC tissues. Correlations between NLRP1/NLRP3 expression levels and patient survival were analyzed using Kaplan-Meier survival curves. The relationships of NLRP1/NLRP3 expression and tumor-infiltrating immune cells/marker genes were assessed using the TIMER database. NLRP1/NLRP3 and immune checkpoint gene correlations were verified by single-gene co-expression analyses, and tumor immune-related pathways involving NLRP1/NLRP3 were analyzed using gene set enrichment analysis (GSEA). RESULTS: Elevated NLRP1/NLRP3 expression was significantly correlated with lymph node metastasis, poor survival, immune-infiltrating cell abundances, and immune cell markers. NLRP3 showed stronger correlations with immune infiltration and the prognosis of gastric cancer. NLRP1 and NLRP3 might be involved in the same tumor immune-related pathways. Thus, high NLRP1/NLRP3 expression promotes immune cell infiltration and poor prognosis in GC. NLRP1/NLRP3, particularly NLRP3, may have important roles in immune infiltration and may serve as a prognostic biomarker for GC. CONCLUSIONS: NLRP1/NLRP3, particularly NLRP3, may have important roles in immune infiltration and may serve as a prognostic biomarker for GC.

Corrigendum: Rational design of a Gd(III)-Cu(II) nanobooster for chemodynamic therapy against cancer cells.

[This corrects the article DOI: 10.3389/fchem.2022.856495.].

Rational Design of a Gd(III)-Cu(II) Nanobooster for Chemodynamic Therapy Against Cancer Cells.

Copper (II) containing coordination complexes have attracted much attention for chemodynamic therapy (CDT) against cancer cells. In this study, the bimetallic nanobooster [Gd2Cu(L)2(H2O)10]·6H2O was prepared by a solvothermal method based on tetrazole carboxylic acid ligand H4L [H4L = 3,3-di (1H-tetrazol-5-yl) pentanedioic acid]. It showed considerable cytotoxicity toward three kinds of human cancer cells (HeLa, HepG2, and HT29). The MTT assay showed that the IC50 (half-maximal inhibitory concentration) of the complex NPs on HeLa cells (4.9 µg/ml) is superior to that of HepG2 (11.1 µg/ml) and HT29 (5.5 µg/ml). This result showed that [Gd2Cu(L)2(H2O)10]·6H2O NPs can inhibit cell proliferation in vitro and may be potential candidates for chemodynamic therapy. In addition, the cytotoxicity was also confirmed by the trypan blue staining experiment. The results promise the great potential of Gd(III)-Cu(II) for CDT against cancer cells.

Efficacy and safety of apatinib as second or later-line therapy in extensive-stage small cell lung cancer: a prospective, exploratory, single-arm, multi-center clinical trial.

Background: A paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active anti-tumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC. Methods: In this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964. Results: From 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3-8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5-24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6-7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed. Conclusions: Apatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.

Effect of genetic variation of CEBPA gene on body measurement and carcass traits of Qinchuan cattle.

In our study, genetic variation in coding region of cattle CCAAT enhancer binding protein alpha(namely CEBPA)gene was detected by PCR-RFLP and DNA sequencing methods in 215 individuals from Qinchuan cattle breed. Two haplotypes (A and B) and three observed genotypes (AA, AB, and BB) were detected. The result of DNA sequence showed one mutation by comparisons with NC_007316. The mutation at nt963 (T>G) were located in coding region of the CEBPA gene. Associations between the CEBPA gene genetic variation and the carcass traits were revealed in Qinchuan cattle. Least squares analysis revealed a significant statistical effect of the CEBPA gene different genotypes on slaughter weight and carcass weight in Qinchuan cattle. Individuals with BB genotype showed higher slaughter weight and carcass weight than individuals with AA and AB genotypes. Therefore, these results suggest that the CEBPA gene is a strong candidate gene that affects carcass traits in Qinchuan cattle.

A novel 18-bp deletion mutation of the AMPD1 gene affects carcass traits in Qinchuan cattle.

The objectives of the present study were focused on detecting deletion mutation in bovine AMPD1 gene, and analyzing its effect on body measurement and carcass traits in Qinchuan cattle by using DNA sequencing and agarose electrophoresis methods. The 198-bp PCR products of AMPD1 gene exhibited three genotypes and two alleles were revealed: A and B. The frequencies of genotype AA/AB/BB in Qinchuan populations was 0.7163, 0.2233 and 0.0605. The χ(2)-test analysis demonstrated that the breed was not in agreement with Hardy-Weinberg equilibrium (P < 0.05). The association of the 18-bp deletion mutation of AMPD1 gene with body measurement and carcass traits of Qinchuan cattle were analyzed. The cattle with AA genotype had slaughter weight and carcass weight than those with genotype AB (P < 0.01 or P < 0.05). These results suggest that the 18-bp deletion mutation may influence the carcass traits in Qinchuan cattle.

Circulating HPV cDNA in the blood as a reliable biomarker for cervical cancer: A meta-analysis.

The applications of liquid biopsy have attracted much attention in biomedical research in recent years. Circulating cell-free DNA (cfDNA) in the serum may serve as a unique tumor marker in various types of cancer. Circulating tumor DNA (ctDNA) is a type of serum cfDNA found in patients with cancer and contains abundant information regarding tumor characteristics, highlighting its potential diagnostic value in the clinical setting. However, the diagnostic value of cfDNA as a biomarker, especially circulating HPV DNA (HPV cDNA) in cervical cancer remains unclear. Here, we performed a meta-analysis to evaluate the applications of HPV cDNA as a biomarker in cervical cancer. A systematic literature search was performed using PubMed, Embase, and WANFANG MED ONLINE databases up to March 18, 2019. All literature was analyzed using Meta Disc 1.4 and STATA 14.0 software. Diagnostic measures of accuracy of HPV cDNA in cervical cancer were pooled and investigated. Fifteen studies comprising 684 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.27 (95% confidence interval [CI], 0.24-0.30) and 0.94(95% CI, 0.92-0.96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 6.85 (95% CI, 3.09-15.21) and 0.60 (95% CI, 0.46-0.78), respectively. The diagnostic odds ratio was 15.25 (95% CI, 5.42-42.94), and the area under the summary receiver operating characteristic curve was 0.94 (95% CI, 0.89-0.99). There was no significant publication bias observed. In the included studies, HPV cDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our meta-analysis suggested that detection of HPV cDNA in patients with cervical cancer could be used as a noninvasive early dynamic biomarker of tumors, with high specificity and moderate sensitivity. Further large-scale prospective studies are required to validate the factors that may influence the accuracy of cervical cancer diagnosis and monitoring.

[An oral DNA vaccine against VEGFR2 inhibits angiogenesis of Lewis lung carcinoma in C57BL/6 mice].

BACKGROUND: It has been known that vascular endothelial growth factor (VEGF) and its receptor (VEGFR2) play important roles in tumor angiogenesis. The aim of this study is to investigate whether an oral DNA vaccine against VEGFR2 has the inhibition effect on tumor growth and angiogenesis, and explore its mechanism in vivo. METHODS: C57BL/6 mice were respectively given the DNA vaccine encoding VEGFR2 (vaccine group), pcDNA3.1 (plasmid group) and saline (saline group). All the mice were then inoculated with Lewis lung carcinoma 3LL cells. Weight, size and microvessel density (MVD) of transplanted tumors were observed. The levels of CD3+ and CD8+ T cells in peripheral blood of mice were detected by flow cytometry. RESULTS: Weight of transplanted tumors in vaccine group was significantly smaller than those in plasmid and saline groups (P < 0.05), and MVD was significantly lower in vaccine group than that in plasmid and saline groups (P < 0.05). After inoculated with 3LL cells, CD3+ and CD8+ T cell levels of vaccine group were markedly higher than those of plasmid and saline groups (P < 0.05). CONCLUSIONS: The oral DNA vaccine can significantly inhibit angiogenesis and growth of transplanted tumor in mice. It may act through killing endothelial cells of tumor.