Predictive value of PD-L1 and TMB for short-term efficacy prognosis in non-small cell lung cancer and construction of prediction models.

Objective: To investigate the correlation between programmed death ligand 1(PD-L1), tumor mutation burden (TMB) and the short-term efficacy and clinical characteristics of anti-PD-1 immune checkpoint inhibitor combination chemotherapy in NSCLC patients. The efficacy of the prediction model was evaluated. Methods: A total of 220 NSCLC patients receiving first-line treatment with anti-PD-1 immune checkpoint inhibitor combined with chemotherapy were retrospectively collected. The primary endpoint was short-term efficacy ORR. The correlation between short-term efficacy, PD-L1, TMB, and clinical characteristics using χ2 test or t-test was evaluated. Screen the independent prognostic factors using univariate and multivariate logistic regression analyses, and construct a nomogram prediction model using the "rms" package in R software. Using receiver operating characteristic (ROC) curve analysis to evaluate the independent Prognostic factors and the prediction model. Using decision curve analysis (DCA) to verify the superiority of the prediction model. Results: The mean values of PD-L1, TMB, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, and albumin were the highest in the ORR group, PD-L1 expression and TMB correlated with epidermal growth factor receptor expression. Multivariate analyses showed that PD-L1, TMB, and neutrophil were independent prognostic factors for ORR. The area under the ROC curve (AUC) values of the ROC constructed based on these three indicators were 0.7104, 0.7139, and 0.7131, respectively. The AUC value under the ROC of the nomogram model was 0.813. The DCA of the model showed that all three indicators used together to build the prediction model of the net return were higher than those of the single indicator prediction model. Conclusion: PD-L1, TMB, and neutrophils are independent prognostic factors for short-term efficacy. The nomogram prediction model constructed using these three indicators can further improve predictive efficacy of ICIs in patients with NSCLC.

Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Elemental geochemical evidence for the river-derived sources of trace metals in surface sediments from Hangzhou Bay, East China Sea.

Coastal estuaries are often heavily subject to riverine influences by the inputs of sediment from terrestrial sources. Hangzhou Bay (HZB) is threatened by the riverine derived trace metals from two large rivers of Qiantang River (QTR) and Yangtze River (YZR). However, previous studies mainly focused on the incidental transport from the largest river in China (YZR) and failed to simultaneously evaluate the contributions of these two rivers, especially the directly flowing river of QTR, by their trace elemental geochemical composition and distribution. Herein, a comprehensive study identified the river-derived sources of multiple trace metals in surface sediments which transported from both of the rivers. The sampling stations were separated into three regions of YZR, HZB, and QTR based on their spatial distributions of sediment grain size and components. The significant variations for most of the trace metals concentrations, except for Cd, Th, and U, were found among three regions (χ2 ≥ 8.22, p ≤ 0.016). The highest concentrations in HZB were mainly resulted from the grain size effect (68.82% of the total variance), while the highest concentrations of Sr, Cd, and Ba in YZR and Zr and Hf in QTR were attributed to the anthropogenic source (11.90%) and mineral composition (6.21%) of river basins. After normalized the diversity of multiple trace metals concentrations and the influence of grain size by ratios of Igeo and EFLi, three regions were effectively distinguished. It was indicated that As, Cd, and Sb were enriched in the sediments of rivers by anthropogenic source (EFLi > 1.5 and/or Igeo > 1). The results evidenced that, after removing the influence of grain size, elemental geochemical composition of the surface sediments confidently identified the river-derived anthropogenic sources of the enriched trace metals from two major rivers, and largely from YZR.

An update to the taxonomy of Serica MacLeay, 1819 (sensu lato) from China (Coleoptera, Scarabaeidae, Sericinae, Sericini).

In this paper we update the knowledge on the species of Serica McLeay, 1819 (sensu lato) occurring in Yunnan, Sichuan, and Shaanxi provinces, China. Three new species are described: Sericaallonanhua Liu, Ahrens, Li & Su, sp. nov., S.breviantennalis Liu, Ahrens, Li & Su, sp. nov., and S.fengensis Liu, Ahrens, Li & Su, sp. nov. The key to the species groups and species is updated. The habitus and male genitalia of the new species are illustrated, and a map showing their distribution is provided. New distributional data are given for four species.

Logic gate controlled theranostic nanoagents for in situ microwave thermal therapeutic efficacy evaluation.

In vivo monitoring of treatment response is of great significance for tumor therapy in clinical trials, but it remains a formidable challenge. Herein, we demonstrate a logic AND gate theranostic nanoagent that responds to the coexistence of endogenous and exogenous stimuli, namely HAuCl4@1-Tetradecanol@Gd-based metal-organic framework@SiO2 nanocomposites (APGS NCs). Upon microwave (MW) irradiation, HAuCl4 in the inner part of APGS NCs reacts with the tumor-associated glutathione (GSH). Subsequently, it transforms into an active luminescent form of Au@1-Tetradecanol@Gd-MOF@SiO2 nanocomposites (AuPGS NCs). The intensity of generated fluorescence is correlated with the tumor thermal-injury status. Thus, the generation of AuPGS NCs with high intensity fluorescence under the co-activation of MW and GSH can visualize the treatment effects during MW thermal therapy and instantly modulate the irradiation time and range for optimal outcomes. Hence, this logic gate controlled APGS NCs makes MW thermal therapy eliminate tumor cells completely. This research offers an effective strategy for the design and preparation of activatable theranostic nanoagents for precise tumor imaging and therapy.

Transcription Factor GLI1 Induces IL-6-Mediated Inflammatory Response and Facilitates the Progression of Adamantinomatous Craniopharyngioma.

Adamantinomatous craniopharyngioma (ACP) is a neuroendocrine tumor whose pathogenesis remains unclear. This study investigated the role of glioma-associated oncogene family zinc finger 1 (GLI1), a transcription factor in the sonic hedgehog (SHH) signaling pathway, in ACP. We discovered that GLI1 regulates the expression of IL-6, thereby triggering inflammatory responses in ACP and influencing the tumor's progression. Analyzing the Gene Expression Omnibus (GEO) database chip GSE68015, we found that GLI1 is overexpressed in ACP, correlating positively with the spite of ACP and inflammation markers. Knockdown of GLI1 significantly inhibited the levels of tumor necrosis factor α, interleukin-6 (IL-6), and IL-1ß in ACP cells, as well as cell proliferation and migration. We further identified a binding site between GLI1 and the promoter region of IL-6, demonstrating that GLI1 can enhance the expression of IL-6. These findings were verified in vivo, where activation of the SHH pathway significantly promoted GLI1 and IL-6 expressions in nude mice, inducing inflammation and tumor growth. Conversely, GLI1 knockdown markedly suppressed these processes. Our study uncovers a potential molecular mechanism for the occurrence of inflammatory responses and tumor progression in ACP.

Boosting Microwave Thermo-Dynamic Cancer Therapy of TiMOF via COF-Coating.

Microwave (MW) dynamic therapy (MDT) can efficiently eliminate tumor residue resulting from MW thermal therapy. However, MDT is currently in its infancy, and luck of effective MDT sensiters severely limits its clinical therapeutic effect. Herein, based on TiMOF (TM), a high-efficiency MW sensitizer is designed for MW thermo-dynamic therapy. TM can generate heat and cytotoxic reacyive oxygen species (ROS) under MW irradiation and has the potential to be used as an MW sensitizer, while the suboptimal MW dynamic sensitization effect of TM limits its application. Inorder to improve the MW dynamic sensitization performance, a covalent organic framework (COF) with good stability and a large conjugate system is used to cover TM, which is conductive to electron and energy transfer, thus increasing the ROS generation rate and prolonging the ROS lifetime. In addition, loading Ni NPs endow nanomaterials with magnetic resonance imaging capabilities. Therefore, this work develops an MW sensitizer based on TM for the first time, and the mechanism of COF coating to enhance the MW dynamic sensitization of TM is preliminarily explored, which provides a new idea for the further development of MW sensitizer with great potential.

[Influence of Pre-treatment Lymphocyte/Monocyte Ratio and Neutrophil/Lymphocyte Ratio on the Prognosis of Patients with Extranodal NK/T-Cell Lymphoma].

OBJECTIVE: To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS. RESULTS: The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high ß2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL. CONCLUSION: Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.

A phase I clinical trial of sonodynamic therapy combined with temozolomide in the treatment of recurrent glioblastoma.

PURPOSE: The prognosis of recurrent glioblastoma (rGBM) is poor, and there is currently no effective treatment strategy. Sonodynamic therapy (SDT) is a new method for cancer treatment that uses a combination of low-frequency ultrasound and sonosensitisers to produce antitumor effects, which have shown good therapeutic effects in preclinical studies. Therefore, we initiated an open, prospective pilot study to evaluate the safety, tolerability, and efficacy of SDT for the treatment of rGBM. METHODS: Nine patients with rGBM were enrolled who had received multiple treatments, but the nidus continued to progress without additional standard treatments. After MRI localisation, porphyrin drugs were injected, and intermittent low-frequency ultrasound therapy was performed for five days. RESULTS: None of the nine patients in this clinical trial showed any clinical, neurological, haematological, or skin-targeted adverse effects associated with SDT. After the completion of the trial, one patient maintained stable disease, and eight patients experienced disease progression. Among the eight with progressive disease, the median progression-free survival time was 84 days. Four patients died, and the median overall survival duration after recurrence was 202.5 days. CONCLUSION: The number of patients in this study was small; therefore, a long-term survival benefit was not demonstrated. However, this study suggests that SDT has potential as a treatment for rGBM and warrants further exploration. Trial information: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ): ChiCTR2200065992. November 2, 2022, retrospectively registered.

CircMAN1A2 contributes to nasopharyngeal carcinoma progression via enhancing the ubiquitination of ATMIN through miR-135a-3p/UBR5 axis.

Recently, the dysregulation of circRNAs has been increasingly implicated in the pathogenesis of nasopharyngeal carcinoma (NPC). Among these circRNAs, circMAN1A2 has been highlighted for the up-regulated expression in NPC, whereas the underlying mechanisms have not been clearly established. Thus, the aim of this study was to delineate the tumor-supporting role of circMAN1A2 in the oncogenesis and metastases of NPC. We validated through qRT-PCR that circMAN1A2 was highly expressed in NPC tissues and NPC cells. Survival analysis through Kaplan-Meier method showed that the overall survival, disease-free survival, and distant metastasis-free survival of patients was negatively correlated with the expression of circMAN1A2. Then, gain- and loss-of function assays demonstrated that circMAN1A2 knockdown could impede the proliferation, migration, invasion, and EMT in NPC cells. Further, we conducted dual luciferase reporter gene, RIP, and RNA pull down assays, unveiling that circMAN1A2 functioned as a sponge of miR-135a-3p, and miR-135a-3p targeted UBR5. Additionally, UBR5 interacted with ATMIN to foster the ubiquitination of ATMIN, thereby expediting the malignant behaviors of NPC cells as well as the lung and inguinal lymph node metastases of NPC tumors in vivo. Together, our study uncovered the tumor-initiating and pro-metastatic role of circMAN1A2-miR-135a-3p-UBR5-ATMIN axis in NPC regulation that may be a potential therapeutic target for human NPC.

Long non-coding RNA ZNF667-AS1 retards the development of esophageal squamous cell carcinoma via modulation of microRNA-1290-mediated PRUNE2.

Abnormal long non-coding RNAs (lncRNAs) have been detected in esophageal squamous cell carcinoma (ESCC). Here, we focused on lncRNA ZNF667-AS1 and its downstream mechanism in ESCC progression. Differentially expressed lncRNAs in ESCC were predicted by bioinformatics analysis. ZNF667-AS1, microRNA-1290 (miR-1290), and prune homolog 2 with BCH domain (PRUNE2) expression was determined with their relationship in cell biological processes analyzed also by means of gain- and loss-of-function assays. Xenograft mouse models were performed to re-produce the in vitro findings. We found a decline in ZNF667-AS1 expression in ESCC tissues and cell lines. ZNF667-AS1 overexpression indicated a favorable prognosis of ESCC sufferers. ZNF667-AS1 overexpression suppressed ESCC cell malignant potentials. ZNF667-AS1 reduced miR-1290 to result in upregulation of the miR-1290 target gene PRUNE2. The inhibiting property of ZNF667-AS1 on the malignant characteristics of ESCC cells was achieved by disrupting the miR-1290-mediated downregulation of PRUNE2. ZNF667-AS1 suppressed the tumorigenesis of ESCC in vivo. Collectively, our study demonstrates that ZNF667-AS1 can function as a tumor suppressor in ESCC by upregulating PRUNE2 and downregulating miR-1290.

Hyperthermia inhibits growth of nasopharyngeal carcinoma through degradation of c-Myc.

BACKGROUND: Hyperthermia is a widely used adjunct treatment for different cancers including nasopharyngeal carcinoma (NPC). The protooncogene c-Myc is up-regulated in NPC and its expression is associated with poor prognosis. OBJECTIVE: We hypothesized that c-Myc constitutes an important hyperthermia treatment target, and we investigated its contribution to hyperthermia responses in NPC. METHODS: The growth of the human NPC cell lines CNE1 and CNE2 was analyzed using CCK-8 and clonogenicity assays after 43 °C hyperthermia, knockdown or overexpression of c-Myc. Flow cytometry measurements assessed cell cycle parameters and apoptosis, while levels of c-Myc together with key transcriptional targets were determined using qPCR and Western blotting. Parallel experiments were undertaken using NPC xenografts in nude mice and lastly, global transcriptomic changes were determined using 'RNAseq'. RESULTS: Hyperthermia increased the ubiquitination and proteasomal destruction of c-Myc, causing a rapid decline in c-Myc protein levels in NPC cells. Similar to c-Myc knockdown, NPC cells treated with hyperthermia showed growth inhibition associated with the downregulation of c-Myc target genes. Moreover, low levels of c-Myc could be sustainably repressed in NPC cells through repeated hyperthermia treatments. Importantly, the key findings of growth inhibition and decreased c-Myc protein levels were reproduced in NPC tumor xenografts. Bioinformatic analyses showed that downregulation of c-Myc constituted a central node in the hyperthermia response of NPC cells. CONCLUSION: Our study reveals that hyperthermia can readily destabilize c-Myc levels in NPC cells and inhibit tumor growth. This proposes new strategies for implementing hyperthermia to target c-Myc-driven cancers to improve therapeutic efficacy.

Survival Effects of Radiotherapy on Patients Newly Diagnosed with Distant Metastatic Nasopharyngeal Carcinoma in Non-High-Incidence Areas.

PURPOSE: To analyze the effects of radiotherapy and its timing on the survival and safety of patients with newly diagnosed distant metastatic NPC in non-high-incidence areas. PATIENTS AND METHODS: We retrospectively analyzed 94 newly diagnosed NPC patients with distant metastatic admitted to our hospital from January 2011 to June 2018. They were divided into three groups: no radiotherapy group received chemotherapy alone, early radiotherapy group was combined with radiotherapy during 1 to 3 cycles of chemotherapy, and late radiotherapy group was combined with radiotherapy after 4-6 cycles of chemotherapy were effective. The efficacy and side effects of the three groups were compared, and the prognostic factors were analyzed. RESULTS: The 6-month, 1-year and 2-year PFS were 53.6%, 14.3% and 3.6% in no radiotherapy group, 71.0%, 38.7% and 19.4% in early radiotherapy group, 88.6%, 48.6% and 22.9% in late radiotherapy group; the radiotherapy groups were better than the no radiotherapy group, and the difference was statistically significant (P < 0.017). The 1-year, 2-year and 3-year OS were 75.0%, 32.1% and 0 in no radiotherapy group, 77.4%, 54.8% and 12.9% in early radiotherapy group, 85.7%, 71.4% and 31.4% in late radiotherapy group; the radiotherapy groups were better than the no radiotherapy group, and the differences were statistically significant (P < 0.017). There was no significant difference in OS and PFS between the two radiotherapy groups. Univariate and multivariate analysis showed that HBV (P = 0.031), number of metastases (P = 0.002), liver metastases (P = 0.038), radiotherapy (P < 0.001) and treatment response (P = 0.011) were related to OS. There was no significant difference in the incidence of adverse events (P > 0.017). CONCLUSION: Early and late combined radiotherapy had similar clinical efficacy and both prolonged PFS and OS for patients with newly diagnosed distant metastatic NPC in non-high-risk areas. If chemotherapy response is expected to be poor, radiotherapy can be received early.

Histone demethylase KDM4A plays an oncogenic role in nasopharyngeal carcinoma by promoting cell migration and invasion.

Compelling evidence has indicated the vital role of lysine-specific demethylase 4 A (KDM4A), hypoxia-inducible factor-1α (HIF1α) and the mechanistic target of rapamycin (mTOR) signaling pathway in nasopharyngeal carcinoma (NPC). Therefore, we aimed to investigate whether KDM4A affects NPC progression by regulating the HIF1α/DDIT4/mTOR signaling pathway. First, NPC and adjacent tissue samples were collected, and KDM4A protein expression was examined by immunohistochemistry. Then, the interactions among KDM4A, HIF1α and DDIT4 were assessed. Gain- and loss-of-function approaches were used to alter KDM4A, HIF1α and DDIT4 expression in NPC cells. The mechanism of KDM4A in NPC was evaluated both in vivo and in vitro via RT-qPCR, Western blot analysis, MTT assay, Transwell assay, flow cytometry and tumor formation experiments. KDM4A, HIF1α, and DDIT4 were highly expressed in NPC tissues and cells. Mechanistically, KDM4A inhibited the enrichment of histone H3 lysine 9 trimethylation (H3K9me3) in the HIF1α promoter region and thus inhibited the methylation of HIF1α to promote HIF1α expression, thus upregulating DDIT4 and activating the mTOR signaling pathway. Overexpression of KDM4A, HIF1α, or DDIT4 or activation of the mTOR signaling pathway promoted SUNE1 cell proliferation, migration, and invasion but inhibited apoptosis. KDM4A silencing blocked the mTOR signaling pathway by inhibiting the HIF1α/DDIT4 axis to inhibit the growth of SUNE1 cells in vivo. Collectively, KDM4A silencing could inhibit NPC progression by blocking the activation of the HIF1α/DDIT4/mTOR signaling pathway by increasing H3K9me3, highlighting a promising therapeutic target for NPC.

Quantifying the heavy metal risks from anthropogenic contributions in Sichuan panda (Ailuropoda melanoleuca melanoleuca) habitat.

Heavy metals (HM) are ubiquitous in environments, and HM pollution has become a severe global crisis. Previous studies have identified HM levels in Qinling panda habitats but their levels and the associated risks in Sichuan panda habitats are still unknown. Risk-based conservation management is in urgent need and should rely upon identifying risk distributions, quantified risk-source apportionment and collaborative governance. We carried out research in Sichuan panda (Ailuropoda melanoleuca melanoleuca) habitats taking soil, bamboo, and water samples from three different areas (nature reserves, potential habitats, and surrounding regions) of five mountains. The concentrations of HM in the soil were higher than those in bamboo, but both exceeded the background or national standards to varying degrees, suggesting long-term pollution and multi-element contamination. Regional and geographical distribution differences revealed a positive correlation between intensity of human activities and HM pollution. HM contaminants observed in the Sichuan panda habitats, based on their sources, were categorized into coal combustion (34%), industry (44%), and traffic (22%). In particular, our results showed the northern and southern parts of habitat were of highest concern, as they had environmental conditions that could be harmful to the health of giant pandas. Coupling models applying positive matrix factorization model/risk were used to quantify source contributions to various risk types, which was based on real-time monitoring and served as a positive role in multi-step process for developing countermeasures, with the goal of collaboratively reframing the vision and governance of panda conservation in order to incorporate regional disparities.

MicroRNA-155 acts as a diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma.

MicroRNA-155 is over-expressed in many human cancers, but researches on its association with malignant oesophageal squamous cell carcinoma (ESCC) are limited. The aim of the present study was to evaluate the potential value of miR-155 as a biomarker for ESCC diagnosis and prognosis. In this study, we found that miR-155 was significantly increased in ESCC tissues compared with the paired adjacent tissues and healthy normal controls (p < .001), according to qRT-PCR, which suggested that miR-155 might act as an oncogene in ESCC. In addition, clinical features such as the depth of tumour invasion, tumour size, and TNM stage were all proved to impact the expression of miR-155 (p < .01). Then, ROC curve analysis, reaching an AUC of 0.870, and a sensitivity and specificity of 83.5% and 77.5%, respectively, revealed that miR-155 was a predictive factor for ESCC. As well, high expression of miR-155 was associated with poor overall survival of the patients (log-rank test, p = .004), according to Kaplan-Meier analysis. MiR-155 might be an independent predictor for overall survival in ESCC patients, manifested by Cox regression analysis (HR = 16.94, 95%CI = 3.33-86.12, p = .001). Taken together, miR-155 could be an independent diagnostic and prognostic biomarker for ESCC.

Extended ORF8 Gene Region Is Valuable in the Epidemiological Investigation of Severe Acute Respiratory Syndrome-Similar Coronavirus.

Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002-2003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequences of 281 SARS-CoVs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-related CoVs (SARSr-CoVs), a ~430 bp genomic region (from 27 701 bp to 28 131 bp in AY390556.1) with regular variations was investigated. This ~430 bp region overlaps with the ORF8 gene and is prone to deletions and nucleotide substitutions. Its complexity suggested the need for a new genotyping method for coronaviruses related to SARS-similar coronaviruses (SARS-CoV, SARSr-CoV, and SARS-CoV-2). Bat SARSr-CoV presented 3 genotypes, of which type 0 is only seen in bat SARSr-CoV, type I is present in SARS in the early phase, and type II is found in all SARS-CoV-2. This genotyping also shows potential usage in distinguishing the SARS-similar coronaviruses from different hosts and geographic areas. This genomic region has important implications for predicting the epidemic trend and studying the evolution of coronavirus.

Silencing lncRNA LOC101928963 Inhibits Proliferation and Promotes Apoptosis in Spinal Cord Glioma Cells by Binding to PMAIP1.

Long non-coding RNAs (lncRNAs) have been widely highlighted due to their involvement in various types of cancers, including glioma; however, the exact mechanism and function by which they operate in regard to spinal cord glioma remain poorly understood. LOC101928963 was screened out for its differential expression in spinal cord glioma by microarray analysis. Therefore, this study was conducted to investigate the modulatory effects of LOC101928963 on spinal cord glioma by binding to phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1). The expression of LOC101928963 and LOC101928963 was characterized in spinal cord glioma tissues, and their interaction was examined by dual-luciferase reporter gene assay. Cells with LOC101928963 that exhibited elevated or suppressed levels of PMAIP1 were established to substantiate the mechanism between LOC101928963 and PMAIP1. qRT-PCR and western blot methods were subsequently applied to determine the expression of cell-proliferation- and apoptosis-related genes in response to the alterations of LOC101928963 and PMAIP1. Glioma cell proliferation and apoptosis were assessed by MTT assay and flow cytometry. Decreased cell apoptosis and PMAIP1 expression, as well as overexpressed LOC101928963, were exhibited among spinal cord glioma tissues. LOC101928963 overexpression was observed to promote cell proliferation and cell-cycle entry and inhibit the process of apoptosis. PMAIP1, a target of LOC101928963, displayed a downregulated level following the elevation of LOC101928963. The present results strongly emphasize the neutralization effect of PMAIP1 overexpression on spinal cord glioma progression induced by the overexpression of LOC101928963. The data obtained during the study highlighted the inhibitory role of LOC101928963 silencing in spinal cord glioma through the increase in PMAIP1, which suggests a potential target in the treatment of spinal cord glioma.