tRF-33-P4R8YP9LON4VDP inhibits gastric cancer progression via modulating STAT3 signaling pathway in an AGO2-dependent manner.

It has been demonstrated that tRNA-derived small RNAs (tsRNAs) perform essential functions in the pathophysiology of cancer. In this study, we focused on the possible mechanisms of tRF-33-P4R8YP9LON4VDP (tRF-33) underlying the development of gastric malignancy. In total, 454 tissue samples with different gastric mucosal lesions were collected. The tRF-33 expression level in different cohorts was determined, and its value for diagnostic efficiency and prognosis evaluation were assessed. Cell proliferation assays, Transwell assay, flow cytometry, and xenotransplantation model were used to evaluate its effect on gastric cancer cells. The molecular mechanism was verified by fluorescence in situ hybridization, dual luciferase assay, Western blot, and RNA binding protein immunoprecipitation. The results showed that the expression of tRF-33 exhibited a gradual modification from normal control samples to gastritis tissues, early and latent stage of gastric cancer tissues. Consequently, tRF-33 holds significant potential as a predictive and diagnostic biomarker for gastric malignancy. Over-expression of tRF-33 inhibited gastric cancer cell progression and metastatic viability, and induced cell apoptosis. Tumorigenicity in nude mice showed the suppressive characteristics of tRF-33. Mechanistic investigation revealed that tRF-33 exerted silencing on STAT3 mRNA via binding to AGO2. In conclusion, tRF-33 exhibited values in diagnosing gastric cancer and evaluating its prognosis, and suppressed tumor cell viability by inhibiting STAT3 signaling pathway. The schematic mechanisms underlying tRF-33 regulating gastric cancer occurrence. tRF-33 binds to AGO2 proteins and then negatively regulates STAT3 expression through targeting its 3'UTR. The downregulated expression of STAT3 results in the decrease of STAT3 and p-STAT3 and further blocks the transcription of the downstream genes and finally inhibits the gastric cancer occurrence. MMP-9, matrix metalloproteinase-9; Bcl-2, B-cell lymphoma-2; STAT3, signal transducer and activator of transcription 3; UTR, untranslated region.

Global progress and future prospects of early gastric cancer screening.

Gastric cancer is a prevalent malignancy that poses a serious threat to global health. Despite advances in medical technologies, screening methods, and public awareness, gastric cancer remains a significant cause of morbidity and mortality worldwide. Early gastric cancer frequently does not present with characteristic symptoms, while advanced stage disease is characterized by a dismal prognosis. As such, early screening in gastric cancer is of great importance. In recent years, advances have been made globally in both clinical and basic research for the screening of early gastric cancer. The current predominant screening methods for early gastric cancer include imaging screening, endoscopic screening and serum biomarker screening. Imaging screening encompasses upper gastrointestinal barium meal, multidimensional spiral computed tomography (MDCT), Magnetic resonance imaging (MRI), and ultrasonography. Endoscopic screening methods include white light endoscopy, chromoendoscopy, computed virtual chromoendoscopy, and other endoscopic techniques like endocytoscopy, confocal laser endomicroscopy, optical coherence tomography and so on. Biomarkers screening involves the assessment of conventional biomarkers such as CEA, CA19-9 and CA72-4 as well as more emerging biomarkers such as peptides (PG, G-17, GCAA, TAAs and others), DNA (cfDNA, DNA methylation, MSI), noncoding RNA (miRNA, lncRNA, circRNA, and tsRNA) and others. Each screening method has its strengths and limitations. This article systematically summarizes worldwide progress and future development of early gastric cancer screening methods to provide new perspectives and approaches for early diagnostic and treatment advancements in gastric cancer worldwide.

EIF4A3-Bound hsa_circ_0006847 Exerts a Tumor-Suppressive Role in Gastric Cancer.

Numerous studies have shown that circular RNAs are associated with the occurrence and development of various cancers, but the biological functions and mechanisms of hsa_circ_0006847 (circASPHD1) in gastric cancer (GC) remain unclear. The expression of hsa_circ_0006847 in GC cell lines, tissue, and plasma from GC patients was assayed by quantitative real-time reverse transcription-polymerase chain reaction. Hsa_circ_0006847 expression in cells was downregulated or upregulated by transfected small interfering RNA (siRNA) or overexpression plasmid. The role of hsa_circ_0006847 in GC was investigated with Cell Counting Kit-8, EdU, Transwell, flow cytometry assays, and in a subcutaneous xenograft tumor model. In addition, the interaction of eukaryotic translation initiation factor 4A3 (EIF4A3) and hsa_circ_0006847 was determined with western blot, biotin-labeled RNA pull-down, and RNA immunoprecipitation assays. Co-immunoprecipitation and mass spectrometry were used to validate the combination of EIF4A3 and synaptopodin-2 (SYNPO2). The expression of hsa_circ_0006847 was decreased in GC tissues and cells and indicated poor survival and prognosis. Overexpression of hsa_circ_0006847 inhibited cell proliferation, migration, and invasion. Flow cytometry showed that upregulation of hsa_circ_0006847 resulted in promotion of apoptosis of GC cells and inhibited their progression through the G0/G1 phase. Downregulation of hsa_circ_0006847 expression had the opposite effects. Overexpression of hsa_circ_0006847 in subcutaneous tumor xenografts inhibited tumor growth. Mechanically, hsa_circ_0006847 promoted the binding of EIF4A3 to SYNPO2 by recruiting EIF4A3, which inhibited the growth of GC. The tumor suppressor activity of hsa_circ_0006847, inhibition of the occurrence and development of GC, was mediated by promotion of EIF4A3 and the binding of EIF4A3 to SYNPO2. The results support the study of hsa_circ_0006847 as a novel therapeutic target for the treatment of GC.

Circular RNA CircSLC22A23 Promotes Gastric Cancer Progression by Activating HNRNPU Expression.

BACKGROUND: Circular RNAs (CircRNAs) play essential roles in cancer occurrence as regulatory RNAs. However, circRNA-mediated regulation of gastric cancer (GC) remains poorly understood. AIM: The purpose of this study was to investigate the molecular mechanism of circSLC22A23 (hsa_circ_0075504) underlying GC occurrence. METHODS: CircSLC22A23 levels were first quantified by quantitative real-time reverse transcription-polymerase chain reaction in GC cell lines, 80 paired GC tissues and adjacent normal tissues, and 27 pairs of plasma samples from preoperative and postoperative patients with GC. Then circSLC22A23 was knocked-down with short hairpin RNA to analyze its oncogenic effects on the proliferation, migration, and invasion of GC cells. Finally, circRNA-binding proteins and their downstream target genes were identified by RNA pulldown, mass spectrometry, RNA immunoprecipitation, quantitative real-time reverse transcription-polymerase chain reaction, and Western blot assays. RESULTS: CircSLC22A23 was found to be highly expressed in GC cells, GC tissues, and plasma from GC patients. Knockdown of circSLC22A23 inhibited GC cell proliferation, migration and invasion. RNA pulldown and RNA immunoprecipitation assays verified the interaction between circSLC22A23 and heterogeneous nuclear ribonucleoprotein U (HNRNPU). Knockdown of circSLC22A23 decreased HNRNPU protein levels. Moreover, rescue assays showed that the tumor suppressive effect of circSLC22A23 knockdown was reversed by HNRNPU overexpression. Finally, epidermal growth factor receptor (EGFR) was found to be one of the downstream target genes of HNRNPU that was up regulated by circSLC22A23. CONCLUSION: CircSLC22A23 regulated the transcription of EGFR through activation of HNRNPU in GC cells, suggesting that circSLC22A23 may serve as a potential therapeutic target for the treatment of GC.

Characteristics, sources, and health risk assessment of atmospheric particulate mercury in Guanzhong Basin.

Mercury (Hg) has received increasing public attention owing to its high toxicity and global distribution capability via long-range atmospheric transportation. Guanzhong Basin (GB) is vital for the industrial and economic development of Shaanxi Province. To determine the concentration, spatial distribution, seasonal variation, sources, and health risks of particulate-bound mercury (PBM), PM2.5 samples were collected at three sampling sites representing urban, rural, and remote areas during winter and summer in GB. The three sampling sites were in Xi'an (XN), Taibai (TB), and the Qinling Mountains (QL). The mean PBM concentrations in XN, TB, and QL in winter were 130 ± 115 pg m-3, 57.5 ± 47.3 pg m-3, and 53.6 ± 38.5 pg m-3, respectively, higher than in summer (13.7 ± 7.11 pg m-3, 8.01 ± 2.86 pg m-3, and 7.75 ± 2.85 pg m-3, respectively). PBM concentrations are affected by precipitation, meteorological conditions (temperature and mixed boundary layer), emission sources, and atmospheric transport. During the sampling period, the PBM dry deposition in XN, TB, and QL was 1.90 µg m-2 (2 months), 0.835 µg m-2 (2 months), and 0.787 µg m-2 (2 months), respectively, lower than the range reported in national megacities. According to backward trajectory and potential source contribution factor (PSCF) analysis, mercury pollution in XN is mainly affected by local pollution source emissions, whereas the polluted air mass in TB and QL originates from local anthropogenic emissions and long-distance atmospheric transmission. The non-carcinogenic health risk values of PBM in XN, TB, and QL in winter and summer were less than 1, indicating that the risk of atmospheric PBM to the health of the residents was negligible.

Transfer RNA-derived fragments as novel biomarkers of the onset and progression of gastric cancer.

Gastric cancer (GC) is a particularly malignant disease; thus, early diagnosis and treatment are especially important. Transfer RNA-derived small RNAs (tsRNAs) have been implicated in the onset and progression of various cancers. Therefore, the aim of this study was to explore the role of tRF-18-79MP9P04 (previously named tRF-5026a) in the onset and progression of GC. Expression levels of tRF-18-79MP9P04 were quantified in gastric mucosa specimens of healthy controls and plasma samples of patients with different stages of GC. The results showed that plasma levels of tRF-18-79MP9P04 were significantly decreased in the early and advanced stages of GC. The results of the nucleocytoplasmic separation assay found that tRF-18-79MP9P04 was localized in the nuclei of GC cells. High-throughput transcriptome sequencing identified genes regulated by tRF-18-79MP9P04 in GC cells, and the function of tRF-18-79MP9P04 was predicted by bioinformatics. Collectively, the findings of this study suggest that tRF-18-79MP9P04 would be useful as non-invasive biomarker for early diagnosis of GC and is related to cornification, the type I interferon signaling pathway, RNA polymerase II activities, and DNA binding.

Absolute quantification of a plasma tRNA-derived fragment for the diagnosis and prognosis of gastric cancer.

Background: The transition from a healthy gastric mucosa to gastric cancer is a multi-step process. Early screening can significantly improve the survival rate of gastric cancer patients. A reliable liquid biopsy for gastric cancer prediction is urgently needed and since tRNA-derived fragments (tRFs) are abundant in various body fluids, tRFs are possible new biomarkers for gastric cancer. Methods: A total of 438 plasma samples from patients with different gastric mucosal lesions as well as healthy individuals were collected. A specific reverse transcription primer, a forward primer, a reverse primer, and a TaqMan probe were designed. A standard curve was constructed and an absolute quantitation method was devised for detection of tRF-33-P4R8YP9LON4VDP in plasma samples of individuals with differing gastric mucosa lesions. Receiver operating characteristic curves were constructed to evaluate the diagnostic values of tRF-33-P4R8YP9LON4VDP for individual with differing gastric mucosa. A Kaplan-Meier curve was established to calculate the prognostic value of tRF-33-P4R8YP9LON4VDP for advanced gastric cancer patients. Finally, a multivariate Cox regression analysis was performed to assess the independent prognostic value of tRF-33-P4R8YP9LON4VDP for advanced gastric cancer patients. Results: A detection method for plasma tRF-33-P4R8YP9LON4VDP was successfully established. Levels of plasma tRF-33-P4R8YP9LON4VDP were shown to reflect a gradient change from healthy individuals to gastritis patients to early and advanced gastric cancer patients. Significant differences were found among individuals with differing gastric mucosa, with reduced levels of tRF-33-P4R8YP9LON4VDP significantly related to a poor prognosis. tRF-33-P4R8YP9LON4VDP was found to be an independent predictor of an unfavorable survival outcome. Conclusions: In this study, we developed a quantitative detection method for plasma tRF-33-P4R8YP9LON4VDP that exhibited hypersensitivity, convenience, and specificity. Detection of tRF-33-P4R8YP9LON4VDP was found to be a valuable means by which to monitor different gastric mucosa and to predict patient prognosis.

Exosomes and circular RNAs: promising partners in hepatocellular carcinoma from bench to bedside.

Hepatocellular carcinoma (HCC) is characterized by high morbidity and mortality, and a low 5-year survival rate. Exploring the potential molecular mechanisms, finding diagnostic biomarkers with high sensitivity and specificity, and determining new therapeutic targets for HCC are urgently needed. Circular RNAs (circRNAs) have been found to play a key role in the occurrence and development of HCC, while exosomes play an important role in intercellular communication; thus, the combination of circRNAs and exosomes may have inestimable potential in early diagnosis and curative therapy. Previous studies have shown that exosomes can transfer circRNAs from normal or abnormal cells to surrounding or distant cells; thereafter, circRNAs influence target cells. This review summarizes the recent progress regarding the roles of exosomal circRNAs in the diagnosis, prognosis, occurrence and development and immune checkpoint inhibitor and tyrosine kinase inhibitor resistance of HCC to provide inspiration for further research.

CircRNA: A new class of targets for gastric cancer drug resistance therapy.

Gastric cancer (GC) is one of the most common malignancies worldwide. Patients with advanced GC need palliative care to ensure survival. This includes the use of chemotherapy agents, such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed, as well as targeted agents. However, the emergence of drug resistance evidence in poor patient outcomes and poor prognosis is a motivation to determine the specific mechanism of drug resistance. Interestingly, circular RNAs (circRNAs) play an important part in the carcinogenesis and progression of GC and are involved in GC drug resistance. This review systematically summarizes the functions and mechanisms of circRNAs underlying GC drug resistance, especially chemoresistance. It also emphasizes that circRNAs can serve as promising targets for improving drug resistance and therapeutic efficacy.

Clinical Diagnostic Values of Transfer RNA-Derived Fragment tRF-41-YDLBRY73W0K5KKOVD and its Effects on the Growth of Gastric Cancer Cells.

Gastric cancer (GC) is a serious disease with high mortality and poor prognosis. It is known that tRNA halves play key roles in the progression of cancer. This study explored the function of the tRNA half tRF-41-YDLBRY73W0K5KKOVD in GC. Quantitative real-time reverse transcription-polymerase chain reaction was used to measure RNA levels. The level of tRF-41-YDLBRY73W0K5KKOVD in GC cells was regulated by its mimics or inhibitor. Cell proliferation was evaluated by using a Cell Counting Kit-8 and EdU cell proliferation assay. A Transwell assay was used to detect cell migration. Flow cytometry was used to measure cell cycle and apoptosis. The results showed that tRF-41-YDLBRY73W0K5KKOVD expression was decreased in GC cells and tissues. Functionally, overexpression of tRF-41-YDLBRY73W0K5KKOVD inhibited cell proliferation, reduced migration, repressed the cell cycle, and promoted cell apoptosis in GC cells. Based on RNA sequencing results and luciferase reporter assays, 3'-phosphoadenosine-5'-phosphosulfate synthase 2 (PAPSS2) was identified as a target gene of tRF-41-YDLBRY73W0K5KKOVD. These findings indicated that tRF-41-YDLBRY73W0K5KKOVD inhibited GC progression, suggesting that tRF-41-YDLBRY73W0K5KKOVD might be a potential therapeutic target in GC.

tRNA derived fragments:A novel player in gene regulation and applications in cancer.

The heterogeneous species of tRNA-derived fragments (tRFs) with specific biological functions was recently identified. Distinct roles of tRFs in tumor development and viral infection, mediated through transcriptional and post-transcriptional regulation, has been demonstrated. In this review, we briefly summarize the current literatures on the classification of tRFs and the effects of tRNA modification on tRF biogenesis. Moreover, we highlight the tRF repertoire of biological roles such as gene silencing, and regulation of translation, cell apoptosis, and epigenetics. We also summarize the biological roles of various tRFs in cancer development and viral infection, their potential value as diagnostic and prognostic biomarkers for different types of cancers, and their potential use in cancer therapy.

The roles and mechanisms of circular RNAs related to mTOR in cancers.

BACKGROUND: Circular RNAs (circRNAs) are stable molecules with covalently closed structures that have an irreplaceable role in the occurrence, progression, and even treatment of plenty of cancers. Mammalian/mechanistic target of rapamycin (mTOR) is a key regulator in cancers and plays several biological functions, such as proliferation, migration, invasion, autophagy, and apoptosis. METHODS: All data were collected through PubMed and CNKI, using terms including "circRNA," "mTOR," "caner," "signaling pathway," "biomarker," "diagnosis," "treatment." Articles published in Chinese and English were included. RESULTS: In this review, the expression, function, and mechanism of circRNA-associated mTOR in cancers were described. CircRNA-associated-mTOR can regulate the progression and therapy of a variety of cancers in multiple signaling pathways, such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mTOR, mitogen-activated protein kinase (MAPK)/mTOR, and AMP-activated protein kinase (AMPK)/mTOR axis. These cancers including esophageal carcinoma (circLPAR3, ciRS-7), gastric cancer (circNRIP1, hsa_circ_0010882, hsa_circ_0000117, hsa_circ_0072309, and circST3GAL6), colorectal cancer (hsa_circ_0000392, hsa_circ_0084927, hsa_circ_0104631, and circFBXW7), liver cancer (circC16orf62, hsa_circ_100338, hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, hsa_circ_0079299, and hsa_circ_0002130), pancreatic cancer (circ-IARS and circRHOBTB3), renal carcinoma (ciRS-7), bladder cancer (circUBE2K), prostate cancer (circMBOAT2 and circ-ITCH), ovarian cancer (circEEF2, circRAB11FIP1, circMYLK, and circTPCN), endometrial cancer (hsa_circ_0002577 and circWHSC1), lung cancer (circHIPK3, hsa_circ_0001666), thyroid cancer (hsa_circ_0007694 and hsa_circ_0008274), glioma (circGFRA1, circ-MAPK4, circPCMTD1, and hsa_circ_0037251), osteosarcoma (circTCF25), leukemia (circ-PRKDC), and breast cancer (hsa_circ_0000199, circUBAP2, and circWHSC1).

tRNA-derived small RNAs: Mechanisms and potential roles in cancers.

Transfer RNAs (tRNAs) are essential for protein synthesis. Mature or pre-tRNAs may be cleaved to produce tRNA-derived small RNAs (tsRNAs). tsRNAs, divided into tRNA-derived stress-induced RNA (tiRNAs) and tRNA-derived fragments (tRFs), play versatile roles in a number of fundamental biological processes. tsRNAs not only play regulatory roles in gene silencing, RNA stability, reverse transcription, and translation, but are also closely related to cell proliferation, migration, cell cycle, and apoptosis. Their abnormal expression is associated with the occurrence and development of various human diseases, especially cancer. This paper reviews the classification, biogenesis, and mechanism of action of tsRNAs, and the research progress to date on tsRNAs in cancers. These findings provide new opportunities for diagnostic biomarkers and treatment targets of several types of cancers including gastric cancer, colorectal cancer, hepatocellular carcinomas, pancreatic cancer, breast cancer, prostate cancer, renal cell carcinoma, ovarian cancer, lung cancer, bladder cancer, thyroid cancer, oral cancer, and leukemia.

The tumor suppressor function of hsa_circ_0006282 in gastric cancer through PTEN/AKT pathway.

BACKGROUND: Circular RNAs (circRNAs) play key roles in carcinogenesis. However, the roles of circRNAs in gastric cancer are largely unknown. The aim of this study is to study the possible roles of hsa_circ_0006282 in gastric cancer. METHODS: The hsa_circ_0006282 levels in gastric cancer cell lines, 85 gastritis tissues, and 103 paired gastric cancer tissues and non-tumor tissues were first detected by quantitative real-time reverse transcription-polymerase chain reaction. RNA interference and hsa_circ_0006282 expression plasmid were further used to manipulate hsa_circ_0006282 expression in gastric cancer. Finally, biological effects of hsa_circ_0006282 were analyzed by real-time cell analysis, flow cytometry, Transwell, cell cloning assay and Western blot analysis. RESULTS: Hsa_circ_0006282 was down expressed in gastric cancer cells, gastritis tissues, and gastric cancer tissues. The abilities of cell proliferation, cell migration and resistance to apoptosis were enhanced after hsa_circ_0006282 was downregulated, while overexpression of hsa_circ_0006282 got opposite results. Besides, Western blot showed that the levels of protein kinase B (AKT) and cyclin-dependent kinase 2 (CDK2) were significantly increased and decreased after knockdown and up-regulation of hsa_circ_0006282, respectively, while phosphatase and tensin homolog deleted on chromosome ten (PTEN) was significantly opposite regulated. Finally, hsa_circ_0006282 promoted the expression of PTEN by sponging hsa-miR-136-5p. CONCLUSION: By regulating the PTEN/AKT signaling pathway through competitively binding with hsa-miR-136-5p, hsa_circ_0006282 suppresses the growth of gastric cancer.

Extracellular vesicles-associated tRNA-derived fragments (tRFs): biogenesis, biological functions, and their role as potential biomarkers in human diseases.

Traditionally, transfer RNAs (tRNAs) specifically decoded messenger RNA (mRNA) and participated in protein translation. tRNA-derived fragments (tRFs), also known as tRNA-derived small RNAs (tsRNAs), are generated by the specific cleavage of pre- and mature tRNAs and are a class of newly defined functional small non-coding RNAs (sncRNAs). Following the different cleavage positions of precursor or mature tRNA, tRFs are classified into seven types, 5'-tRNA half, 3'-tRNA half, tRF-1, 5'U-tRF, 3'-tRF, 5'-tRF, and i-tRF. It has been demonstrated that tRFs have a diverse range of biological functions in cellular processes, which include inhibiting protein translation, modulating stress response, regulating gene expression, and involvement in cell cycles and epigenetic inheritance. Emerging evidences have indicated that tRFs in extracellular vesicles (EVs) seem to act as regulatory molecules in various cellular processes and play essential roles in cell-to-cell communication. Furthermore, the dysregulation of EV-associated tRFs has been associated with the occurrence and progression of a variety of cancers and they can serve as novel potential biomarkers for cancer diagnosis. In this review, the biogenesis and classification of tRFs are summarized, and the biological functions of EV-associated tRFs and their roles as potential biomarkers in human diseases are discussed.

Biological and clinical implications of hsa_circ_0086720 in gastric cancer and its clinical application.

BACKGROUND: Circular RNAs (circRNAs) are thought to be vital participants in carcinogenesis and have the characteristics of being stable, specific, and well conserved. However, their clinical significance and application value in gastric cancer (GC) are still poorly understood. Hsa_circ_0086720 was found to be a dysregulated circRNA in GC by microarray screening and was further explored for its clinical significance and application. METHODS: Hsa_circ_0086720 was detected in GC cell lines, tissues, and plasma, and the clinicopathological correlations were investigated. The existence, stability, origin, and change in the plasma hsa_circ_0086720 level were verified in early GC patients. Moreover, receiver operating characteristic and Kaplan-Meier survival curves were constructed to analyze the diagnostic and prognostic values, and bioinformatics analysis was used to identify the potential functions. Finally, risk factors and nomogram predicting were established. RESULTS: Hsa_circ_0086720 was found to be downregulated in gastric carcinogenesis, and tissue hsa_circ_0086720 was negatively associated with perineural invasion, Borrmann type, disease-free survival, and overall survival. Hsa_circ_0086720 was stable in circulating plasma and was actively secreted by cells in gastric carcinogenesis. As a biomarker for early GC screening, plasma hsa_circ_0086720 had good sensitivity and specificity, and its stability met the clinical application requirements. Bioinformatics analysis suggested that dysregulated hsa_circ_0086720 has important functions in gastric carcinogenesis. Univariate Cox regression analysis identified factors associated with overall survival time and disease-free survival time. The nomograms showed good accuracy of predicting survival time. CONCLUSION: Hsa_circ_0086720 is a novel biomarker for screening early GC and predicting the prognosis of advanced-stage patients.

Characteristics and Predictors of Long-Time Survivors in Non-Metastatic Gastric Signet Ring Cell Carcinoma: A Large Population-Based Study.

Objective: Gastric signet ring cell carcinoma (SRCC) is a distinct entity with a relatively poor prognosis. This study analyzed the clinicopathological characteristics of long-time survivors (LTSs) and identified independent predictors of long-term survival (LTS) in non-metastatic gastric SRCC. Methods: Data from 3906 patients with non-metastatic gastric SRCC were retrieved from Surveillance, Epidemiology and End Results according to the inclusion and exclusion criteria. Patients were randomly divided into training and validation cohorts. Predictors of LTS in the training cohort were identified by multivariate logistic regression. A nomogram-based predictive model for LTS was constructed in non-metastatic gastric SRCC. Results: There were 800 patients who survived for >5 years and were defined as TLSs. Young age, other race (not black or white population), female gender, married status, small tumor size, low tumor infiltration, and negative lymph node involvement were independent predictors of LTS in non-metastatic gastric SRCC. These seven variables were incorporated into a nomogram model for predicting LTS. The calibration curve showed good consistency between observed and predicted probability of LTS, and the receiver operating characteristic curve showed acceptable discriminative capacity in the training and validation cohorts. Conclusion: This study provides an overview of the features of patients with non-metastatic gastric SRCC. Age, race, sex, marital status, tumor size, tumor infiltration, and lymph node involvement were identified as independent predictors of LTS.

Microplastic characteristic in the soil across the Tibetan Plateau.

Microplastics are widely detected in terrestrial environments. However, microplastic features in the soil of remote areas are still sparse. In this study, microplastic pollution in soil across the Tibetan Plateau was systematically investigated. The results revealed that microplastic was ubiquitous in the soil of the Tibetan Plateau with an average abundance of 47.12 items/kg-dry weight (range: 5-340 items/kg). Compared with the published data of soil microplastic pollution in other regions, the microplastic pollution in the Tibetan Plateau was relatively low. Fibers represented 43.54% of microplastic particles detected, followed by fragments (32.20%) and films (23.78%). They mainly consisted of polyvinyl chloride, polyethylene, polypropylene, and polystyrene. Transparent and white microplastics were prevalent, and small microplastics (50-500 µm) occupied approximately 66% of all microplastics. High values of microplastics were found near Lhasa, Naqu, and Linzhi. Furthermore, microplastic pollution was found to be negatively related to the distance to the nearest city (p < 0.01), wind velocity (p = 0.014), altitude (p = 0.181), yet positively related to precipitation (p = 0.024). This work presents new insights into the magnitude of microplastics contamination in the soil across the Tibetan Plateau and supplies valuable data for future research on ecotoxicology, ecosystem impacts, and earth system feedback of microplastics on terrestrial ecosystems.

Hsa_circ_0001020 Serves as a Potential Biomarker for Gastric Cancer Screening and Prognosis.

Circular RNAs (circRNAs) are an intriguing class of RNAs with covalently closed-loop structures. With characteristics of high stability and disease-specific expression, circRNAs are emerging as ideal targets for cancer therapy. However, the screening utility and clinical value of circRNAs in gastric cancer (GC) remain largely elusive. We detected levels of hsa_circ_0001020 in cell lines and tissue and plasma samples and investigated its clinicopathological correlations. Kaplan-Meier survival curves and regression analyses were used to analyze its prognostic value. Receiver operating characteristic curves and biomarker combinations were examined to verify its screening value. Bioinformatics analysis was also performed to predict potential biological functions. Our tests found that hsa_circ_0001020 was significantly upregulated in GC cell lines, GC tissue samples, and even in plasma. High hsa_circ_0001020 expression levels in GC tissues were significantly associated with distal metastasis and blood carbohydrate antigen 19-9 (CA19-9). GC patients with high hsa_circ_0001020 had a lower overall survival and disease-free survival time than the low levels. Regression analysis suggested that the level of hsa_circ_0001020 expression was an independent prognostic factor for survival time. As a biomarker for GC, hsa_circ_0001020 showed a superior AUC, sensitivity, and specificity than carcinoembryonic antigen and CA19-9, and was suitable for combination with clinical tumor biomarkers. Bioinformatics analysis provided valuable clues for the possible oncogenic pathways of GC, such as the FoxO and p53 signaling pathways. In conclusion, our study found that hsa_circ_0001020 in GC could be a reliable biomarker to screen for GC and predict prognosis.

Hsa_circ_0003195 as a biomarker for diagnosis and prognosis of gastric cancer.

PURPOSE: Recent studies have shown that circular RNAs (circRNAs) are closely related to the occurrence and development of gastric cancer. In this paper, we analyzed the value of hsa_circ_0003195 in diagnosis and prognosis of gastric cancer. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the level of hsa_circ_0003195 in 100 paired gastric cancer tissues and paracancerous tissues, 74 paired fasting plasma from gastric cancer patients before and 10 days after operation, and 74 fasting plasmas from healthy controls. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic value. The survival analysis and Cox proportional-hazards model were used to evaluate the efficiency of hsa_circ_0003195 in predicting overall survival (OS) in patients with gastric cancer. RESULTS: The expression of hsa_circ_0003195 was down-regulated in gastric cancer tissues and plasma from patients with gastric cancer. The expression level of hsa_circ_0003195 was correlated with differentiation, TNM stages, lymphatic metastasis, and distal metastasis. The area under the ROC curve (AUC) of tissue and plasma hsa_circ_0003195 was 0.684 and 0.695, respectively. The plasma hsa_circ_0003195 can be used as predictors of survival of patients with gastric cancer. CONCLUSION: Hsa_circ_0003195 may be a new diagnostic and prognostic marker of gastric cancer.