The diagnostic value of serum exosomal SNORD116 and SNORA21 for NSCLC patients.

PURPOSE: Non-small cell lung cancer (NSCLC) is a widespread and serious global malignancy. This study aimed to examine the clinical relevance of serum exosomal SNORD116 and SNORA21 as novel diagnostic biomarkers for NSCLC. METHODS: Serum exosomes from 226 healthy controls and 305 NSCLC patients were isolated by ultracentrifugation. Characterization of exosomes was conducted by qNano, transmission electron microscopy (TEM) and Western immunoblotting. RT-PCR revealed snoRNAs that were differentially expressed. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance. RESULTS: In NSCLC patients, the levels of serum exosomal SNORD116 and SNORA21 were significantly reduced compared to those in healthy controls (P < 0.0001 for both). ROC curves showed AUC values of 0.738 and 0.761. By combining SNORD116 and SNORA21 with traditional blood biomarkers CYFRA21-1 and carcinoembryonic antigen (CEA), the AUC increased to 0.917. Moreover, these two exosomal snoRNAs distinguished between patients with metastatic NSCLC (n = 132) and those with non-metastatic NSCLC (n = 173) significantly (P < 0.0001 for both). The ROC curves gave AUC values of 0.743 and 0.694, respectively. The combined analysis raised the AUC to 0.751. The diagnostic power of these two exosomal snoRNAs combined with CYFRA21-1 and CEA increased to 0.784. CONCLUSION: This study demonstrated that serum exosomal SNORD116 and SNORA21 can be used as potential promising non-invasive diagnostic biomarkers for NSCLC.

Effects of Apatinib combined with Temozolomide on levels of sPD-1 and sPD-L1 in patients with drug-resistant recurrent glioblastoma.

OBJECTIVE: This study aimed to explore the effects of Apatinib combined with Temozolomide (TMZ) on the levels of Soluble PD-1 (sPD-1) and Soluble Programmed Death-1 Ligand (sPD-L1) in patients with drug-resistant recurrent Glioblastoma (GB). STUDY DESIGN: A total of 69 patients with recurrent GB from September 2020 to March 2022 were recruited and assigned to the control group (n = 34) and observation group (n = 35) according to different treatment options after tumor recurrence. The control group was treated with TMZ, and the observation group was treated with Apatinib combined with TMZ. Levels of sPD-1 and spd-l1, clinical efficacy, survival time and adverse reactions were observed and compared between the two groups. RESULTS: General data including gender, age, body mass index, and combined diseases indicated no statistical significance between groups (p > 0.05). Before the intervention, sPD-1 and sPD-L1 levels were not significantly different in the two groups (p > 0.05). After interventions, levels of PD-1 and sPD-L1 levels decreased significantly (p < 0.05). The objective remission rate and clinical benefit rate of the observation group were higher and overall survival and progression-free survival were longer than those of the control group (p < 0.05). No significant difference was observed in major adverse reactions among patients (p > 0.05). CONCLUSIONS: Apatinib combined with TMZ is safe and effective in the treatment of recurrent GB. The combined application of the two can reduce the levels of sPD-1 and sPD-L1, which has important clinical application value.

Simultaneous photocatalytic removal of tetracycline and hexavalent chromium by BiVO4/0.6CdS photocatalyst: Insights into the performance, evaluation, calculation and mechanism.

In this study, a novel Z-scheme heterojunction on bismuth vanadium/cadmium sulfide (BiVO4/0.6CdS) was developed and evaluated for simultaneous photocatalytic removal of combined tetracycline (TC) and hexavalent chromium Cr(Ⅵ) pollution under visible light. Based on the analysis of intermediate products and theoretical calculation, the property of the intermediate products of TC degradation and the effect of built-in electric field (IEF) of composite materials on photo-generated carrier separation were illustrated. According to the experiments and evaluation results, the performance of BiVO4/0.6CdS is higher than CdS 2.83 times and 4.82 times under the visible light conditions, with the aspect of simultaneous oxidizing TC and reducing Cr(Ⅵ), respectively. The catalyst has a faster removal rate in the binary composite pollution system than the single one. Therefore, the photocatalytic degradation of TC using BiVO4/0.6CdS can reduce the toxic effect of TC on the environment. The aforementioned evaluation provides a new design strategy for Z-scheme heterojunction to simultaneous photocatalytic degradation of composite organic and inorganic pollutants.

LTBP2 regulates cisplatin resistance in GC cells via activation of the NF-κB2/BCL3 pathway.

Gastric cancer (GC) often develops resistance to cisplatin treatment, but while latent transforming growth factor ß-binding protein (LTBP2) is recognized as a potential regulator in GC, its specific role in cisplatin resistance is not fully understood. This study investigated LTBP2's impact on cisplatin resistance in GC. LTBP2 expression was assessed in various GC cell lines, and its correlation with cisplatin sensitivity was determined through cell viability assays. Lentivirus-mediated LTBP2 silencing in HGC-27 cells demonstrated enhanced cisplatin sensitivity, reduced cell proliferation, and inhibition of the NF-κB2/Bcl-3/cyclin D1 pathway. Additionally, transient transfection overexpressed the NFκB2 gene in LTBP2-silenced HGC-27/DDPR cells, restoring cisplatin sensitivity and upregulating p52/Bcl-3/cyclin D1. In conclusion, silencing LTBP2 could effectively inhibit cell proliferation and mitigate cisplatin resistance via the NFKB noncanonical pathway NFKB2 p52/Bcl-3/cyclin D1. These findings propose LTBP2 as a potential therapeutic target for overcoming cisplatin resistance in GC patients.

Effects of Apatinib combined with Temozolomide on levels of sPD-1 and sPD-L1 in patients with drug-resistant recurrent glioblastoma

Abstract Objective This study aimed to explore the effects of Apatinib combined with Temozolomide (TMZ) on the levels of Soluble PD-1 (sPD-1) and Soluble Programmed Death-1 Ligand (sPD-L1) in patients with drug-resistant recurrent Glioblastoma (GB). Study design A total of 69 patients with recurrent GB from September 2020 to March 2022 were recruited and assigned to the control group (n = 34) and observation group (n = 35) according to different treatment options after tumor recurrence. The control group was treated with TMZ, and the observation group was treated with Apatinib combined with TMZ. Levels of sPD-1 and spd-l1, clinical efficacy, survival time and adverse reactions were observed and compared between the two groups. Results General data including gender, age, body mass index, and combined diseases indicated no statistical significance between groups (p > 0.05). Before the intervention, sPD-1 and sPD-L1 levels were not significantly different in the two groups (p > 0.05). After interventions, levels of PD-1 and sPD-L1 levels decreased significantly (p < 0.05). The objective remission rate and clinical benefit rate of the observation group were higher and overall survival and progression-free survival were longer than those of the control group (p < 0.05). No significant difference was observed in major adverse reactions among patients (p > 0.05). Conclusions Apatinib combined with TMZ is safe and effective in the treatment of recurrent GB. The combined application of the two can reduce the levels of sPD-1 and sPD-L1, which has important clinical application value.

In vitro evaluation for estrogenic mechanisms of the disinfectant benzalkonium chloride as an emerging contaminant.

This study aimed to evaluate in vitro the possible mechanisms underlying the estrogenic potential of benzalkonium chloride (BAC) as a disinfectant emerging contaminant. Effects of BAC at the environmentally-relevant concentrations on estrogen synthesis and estrogen receptor (ER) signaling were assessed using the H295R steroidogenesis assay and the MCF-7 proliferation assay, respectively. Results showed that exposure to BAC at concentrations of 1.0-1.5 mg/L for 48 h significantly increased estradiol production of H295R cells in a concentration-dependent manner. Transcription of steroidogenic genes 3ß-HSD2, 17ß-HSD1, 17ß-HSD4, and CYP19A were significantly enhanced by BAC. In ER-positive MCF-7 cells, exposure to 0.5-1.5 mg/L BAC for 48 h significantly promoted cell proliferation and increased the expressions of ERα and G-protein coupled estrogen receptor 1. Flow cytometry analysis showed that 0.5-1.5 mg/L BAC significantly decreased the percentage of cells in G0/G1 phase, increased the percentage in S phase, and BAC at concentrations of 1.0 and 1.5 mg/L increased the G2/M phase cells. Findings of the study suggested that BAC at environmentally-relevant concentrations might act as a xenoestrogen through its inhibitory effect on steroidogenesis and ER-mediated mechanism.

Abnormal expression of miRNA-122 in cerebral infarction and related mechanism of regulating vascular endothelial cell proliferation and apoptosis by targeting CCNG1.

OBJECTIVE: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. METHOD: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People's Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. RESULT: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3'UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122. CONCLUSION: Serum miRNA-122 increased significantly after ACI, which may be a diagnostic marker of ACI. miRNA-122 may be involved in the pathological process of ACI and is related to the degree of neurological impairment and short-term prognosis in patients with ACI. miRNA-122 may play a regulatory role in ACI by inhibiting cell proliferation, increasing apoptosis, and inhibiting vascular endothelial cell regeneration through the CCNG1 channel.

Disruption of mitochondrial oxidative phosphorylation by chidamide eradicates leukemic cells in AML.

PURPOSE: Nowadays, the oxidative phosphorylation (OXPHOS) correlated with leukemogenesis and treatment response is extensive. Thus, exploration of novel approaches in disrupting OXPHOS in AML is urgently needed. MATERIALS AND METHODS: Bioinformatical analysis of TCGA AML dataset was performed to identify the molecular signaling of OXPHOS. The OXPHOS level was measured through a Seahorse XFe96 cell metabolic analyzer. Flow cytometry was applied to measure mitochondrial status. Real-time qPCR and western blot were used to analyze the expression of mitochondrial or inflammatory factors. MLL-AF9-induced leukemic mice were conducted to measure the anti-leukemia effect of chidamide. RESULTS: Here, we reported that AML patients with high OXPHOS level were in a poor prognosis, which was associated with high expression of HDAC1/3 (TCGA). Inhibition of HDAC1/3 by chidamide inhibited cell proliferation and induced apoptotic cell death in AML cells. Intriguingly, chidamide could disrupt mitochondrial OXPHOS as assessed by inducing mitochondrial superoxide and reducing oxygen consumption rate, as well as decreasing mitochondrial ATP production. We also observed that chidamide augmented HK1 expression, while glycolysis inhibitor 2-DG could reduce the elevation of HK1 and improve the sensitivity of AML cells exposed to chidamide. Furthermore, HDAC3 was correlated with hyperinflammatory status, while chidamide could downregulate the inflammatory signaling in AML. Notably, chidamide eradicated leukemic cells in vivo and prolonged the survival time of MLL-AF9-induced AML mice. CONCLUSION: Chidamide disrupted mitochondrial OXPHOS, promoted cell apoptosis and reduced inflammation in AML cells. These findings exhibited a novel mechanism that targeting OXPHOS would be a novel strategy for AML treatment.

Screening crucial lncRNAs and genes in osteoarthritis by integrated analysis

Abstract Background Osteoarthritis (OA) is one of the most frequent chronic diseases with high morbidity worldwide, marked by degradation of the cartilage and bone, joint instability, stiffness, joint space stenosis and subchondral sclerosis. Due to the elusive mechanism of osteoarthritis (OA), we aimed to identify potential markers for OA and explore the molecular mechanisms underlying OA. Methods Expression profiles data of OA were collected from the Gene Expression Omnibus database to identify differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) in OA. Functional annotation and protein-protein interaction (PPI) networks were performed. Then, nearby DEmRNAs of DElncRNAs was obtained. Moreover, GO and KEGG pathway enrichment analysis of nearby DEmRNAs of DElncRNAs was performed. Finally, expression validation of selected mRNAs and lncRNAs was performed by quantitative reverse transcriptase-polymerase chain reaction. Results In total, 2080 DEmRNAs and 664 DElncRNAs were determined in OA. PI3K-Akt signaling pathway, Endocytosis and Rap1 signaling pathway were significantly enriched KEGG pathways in OA. YWHAB, HSPA8, NEDD4L and SH3KBP1 were four hub proteins in PPI network. The AC093484.4/TRPV2 interact pair may be involved in the occurrence and development of OA. Conclusion Our study identified several DEmRNAs and DElncRNAs associated with OA. The molecular characters could provide more information for further study on OA.

In vitro evaluation for estrogenic mechanisms of the disinfectant benzalkonium chloride as an emerging contaminant

This study aimed to evaluate in vitro the possible mechanisms underlying the estrogenic potential of benzalkonium chloride (BAC) as a disinfectant emerging contaminant. Effects of BAC at the environmentally-relevant concentrations on estrogen synthesis and estrogen receptor (ER) signaling were assessed using the H295R steroidogenesis assay and the MCF-7 proliferation assay, respectively. Results showed that exposure to BAC at concentrations of 1.0-1.5 mg/L for 48 h significantly increased estradiol production of H295R cells in a concentration-dependent manner. Transcription of steroidogenic genes 3β‐HSD2, 17β‐HSD1, 17β‐HSD4, and CYP19A were significantly enhanced by BAC. In ER-positive MCF-7 cells, exposure to 0.5-1.5 mg/L BAC for 48 h significantly promoted cell proliferation and increased the expressions of ERα and G-protein coupled estrogen receptor 1. Flow cytometry analysis showed that 0.5-1.5 mg/L BAC significantly decreased the percentage of cells in G0/G1 phase, increased the percentage in S phase, and BAC at concentrations of 1.0 and 1.5 mg/L increased the G2/M phase cells. Findings of the study suggested that BAC at environmentally-relevant concentrations might act as a xenoestrogen through its inhibitory effect on steroidogenesis and ER-mediated mechanism.

Abnormal expression of miRNA-122 in cerebral infarction and related mechanism of regulating vascular endothelial cell proliferation and apoptosis by targeting CCNG1

Abstract Objective: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. Method: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People's Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. Result: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3′UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122.

Muscle injury and sports rehabilitation management in endurance training oriented to winter sports / Lesão muscular e gerenciamento da reabilitação esportiva no treinamento de resistência direcionado aos esportes de inverno / Gestión de las lesiones musculares y de la rehabilitación deportiva en el entrenamiento de resistencia dirigido a los deportes de invierno

ABSTRACT Introduction: Muscle injury in ski sports training has gradually increased, greatly impairing performance in ice and snow sports competitions. Objective: To study muscle injury and muscle movement during ice and snow sports training and the rehabilitation of muscle injuries. Methods: Thirty skiers with knee muscle injuries were selected as subjects and underwent rehabilitation training for six weeks, and the indicators were statistically evaluated. Results: The ski injuries were mainly muscle strain, muscle or ligament strain, and ligament rupture. The indices after treatment were significantly different from those before treatment (P < 0.05); compared with the three rehabilitation programs, the improvement of each index in group C was significantly different from that in the other two groups (P < 0.05), while there was no significant difference in the improvement of each index between the multi-angle isometric training treatment in group A and the proprioceptive neuromuscular stimulation technique in group B (P>0.05). Conclusion: The influence of recovery training technology on knee muscle re-education was proposed, and a rehabilitation plan for skiing was presented. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O quadro de lesão muscular no treinamento esportivo de esqui tem aumentado gradualmente, prejudicando muito o desempenho das competições esportivas de gelo e neve. Objetivo: Estudar a lesão muscular e o movimento muscular durante o treinamento esportivo no gelo e na neve, bem como a reabilitação das lesões musculares. Métodos: Trinta esquiadores com lesão muscular no joelho foram selecionados como sujeitos e submetidos a treinamento de reabilitação por um total de 6 semanas, tendo os indicadores sido avaliados estatisticamente. Resultados: Os tipos de lesões no esqui foram principalmente tensão muscular, tensão muscular ou ligamentar e ruptura ligamentar. Os índices após o tratamento foram significativamente diferentes daqueles antes do tratamento (P < 0,05); comparado com os três programas de reabilitação, a melhora de cada índice no grupo C foi significativamente diferente da dos outros dois grupos (P < 0,05), enquanto não houve diferença significativa na melhora de cada índice entre o tratamento de treinamento isométrico multiangular no grupo A e a técnica de estimulação neuromuscular proprioceptiva no grupo B (P>0,05). Conclusão: A influência da tecnologia de treinamento de recuperação na reeducação muscular do joelho foi proposta, e foi apresentado um plano de reabilitação para a prática de esqui. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El cuadro de lesiones musculares en el entrenamiento de los deportes de esquí ha ido aumentando progresivamente, lo que perjudica en gran medida el rendimiento en las competiciones de deportes de hielo y nieve. Objetivo: Estudiar las lesiones musculares y el movimiento muscular durante el entrenamiento de los deportes de hielo y nieve, así como la rehabilitación de las lesiones musculares. Métodos: Se seleccionaron como sujetos treinta esquiadores con lesiones musculares en la rodilla y se sometieron a un entrenamiento de rehabilitación durante un total de 6 semanas, y se evaluaron estadísticamente los indicadores. Resultados: Los tipos de lesiones de esquí fueron principalmente la distensión muscular, la distensión muscular o de ligamentos y la rotura de ligamentos. Los índices después del tratamiento fueron significativamente diferentes de los anteriores (P < 0,05); en comparación con los tres programas de rehabilitación, la mejora de cada índice en el grupo C fue significativamente diferente de la de los otros dos grupos (P < 0,05), mientras que no hubo diferencias significativas en la mejora de cada índice entre el tratamiento de entrenamiento isométrico multiángulo en el grupo A y la técnica de estimulación neuromuscular propioceptiva en el grupo B (P>0,05). Conclusión: Se propuso la influencia de la tecnología de entrenamiento de recuperación en la reeducación muscular de la rodilla y se presentó un plan de rehabilitación para el esquí. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Clinicopathological and prognostic significance of COX-2 in glioma patients: a meta-analysis.

BACKGROUND: In recent years, cyclooxygenase-2 (COX-2) has been identified as a cancer stem cell (CSC) marker in gliomas. Nevertheless, the clinical and prognostic significance of COX-2 in glioma patients remains controversial. OBJECTIVE: To evaluate the correlation of COX-2 with the prognosis in glioma patients. METHODS: Eligible studies on this subject were included, and pooled odd ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Publication bias was assessed through funnel plots, and heterogeneity and sensitivity were analyzed as well. RESULTS: In the present study, 11 articles with a total of 641 patients were included. The high expression of COX-2 in glioma patients was negatively associated with overall survival (OS) (n = 11; HR = 2.26; 95%CI = 1.79-2.86), and the subgroup analysis showed no differences in OS between Asian (n = 5; HR = 2.16; 95%CI = 1.57-2.97) and non-Asian (n = 6; HR = 2.39; 95%CI = 1.69-3.38) glioma patients. The Begg funnel plots test indicated that there was no evident risk of publication bias in the meta-analysis. CONCLUSION: The present study suggests that COX-2 could be recommended as a useful pathological and prognostic biomarker in the clinical practice.

INTRODUçãO: Nos últimos anos, a ciclooxigenase-2 (COX-2) foi identificada como um marcador de células-tronco cancerígenas (CSC) em gliomas. No entanto, o significado clínico e prognóstico da COX-2 em pacientes com glioma permanece controverso. OBJETIVO: Avaliar a correlação da COX-2 com o prognóstico em pacientes com glioma. MéTODOS: Estudos elegíveis sobre este assunto foram incluídos e foram estimados odds ratios (ORs) e hazard ratios (HRs) com intervalos de confiança de 95% (IC 95%). O viés de publicação foi avaliado por meio de gráficos de funil, e a heterogeneidade e a sensibilidade também foram analisadas. RESULTADOS: No presente estudo foram incluídos 11 artigos com um total de 641 pacientes. A alta expressão de COX-2 em pacientes com glioma foi negativamente associada à sobrevida global (OS) (n = 11; HR = 2,26; IC 95% = 1,79-2,86), e a análise de subgrupo não mostrou diferenças na OS entre asiáticos (n = 5; HR = 2,16; IC 95% = 1,57­2,97) e não asiáticos (n = 6; HR = 2,39; IC 95% = 1,69­3,38) pacientes com glioma. O teste de gráficos de funil de Begg indicou que não havia risco evidente de viés de publicação na metanálise. CONCLUSãO: O presente estudo sugere que a COX-2 pode ser recomendada como um biomarcador patológico e prognóstico útil na prática clínica.

Clinicopathological and prognostic significance of COX-2 in glioma patients: a meta-analysis / Significância clinicopatológica e prognóstica da COX-2 em pacientes com glioma: uma metanálise

Abstract Background In recent years, cyclooxygenase-2 (COX-2) has been identified as a cancer stem cell (CSC) marker in gliomas. Nevertheless, the clinical and prognostic significance of COX-2 in glioma patients remains controversial. Objective To evaluate the correlation of COX-2 with the prognosis in glioma patients. Methods Eligible studies on this subject were included, and pooled odd ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Publication bias was assessed through funnel plots, and heterogeneity and sensitivity were analyzed as well. Results In the present study, 11 articles with a total of 641 patients were included. The high expression of COX-2 in glioma patients was negatively associated with overall survival (OS) (n = 11; HR = 2.26; 95%CI = 1.79-2.86), and the subgroup analysis showed no differences in OS between Asian (n = 5; HR = 2.16; 95%CI = 1.57-2.97) and non-Asian (n = 6; HR = 2.39; 95%CI = 1.69-3.38) glioma patients. The Begg funnel plots test indicated that there was no evident risk of publication bias in the meta-analysis. Conclusion The present study suggests that COX-2 could be recommended as a useful pathological and prognostic biomarker in the clinical practice.

Resumo Introdução Nos últimos anos, a ciclooxigenase-2 (COX-2) foi identificada como um marcador de células-tronco cancerígenas (CSC) em gliomas. No entanto, o significado clínico e prognóstico da COX-2 em pacientes com glioma permanece controverso. Objetivo Avaliar a correlação da COX-2 com o prognóstico em pacientes com glioma. Métodos Estudos elegíveis sobre este assunto foram incluídos e foram estimadosodds ratios (ORs) ehazard ratios (HRs) com intervalos de confiança de 95% (IC 95%). O viés de publicação foi avaliado por meio de gráficos de funil, e a heterogeneidade e a sensibilidade também foram analisadas. Resultados No presente estudo foram incluídos 11 artigos com um total de 641 pacientes. A alta expressão de COX-2 em pacientes com glioma foi negativamente associada à sobrevida global (OS) (n = 11; HR = 2,26; IC 95% = 1,79-2,86), e a análise de subgrupo não mostrou diferenças na OS entre asiáticos (n = 5; HR = 2,16; IC 95% = 1,57-2,97) e não asiáticos (n = 6; HR = 2,39; IC 95% = 1,69-3,38) pacientes com glioma. O teste de gráficos de funil de Begg indicou que não havia risco evidente de viés de publicação na metanálise. Conclusão O presente estudo sugere que a COX-2 pode ser recomendada como um biomarcador patológico e prognóstico útil na prática clínica.

Water deficit affects inter-kingdom microbial connections in plant rhizosphere.

The frequency and severity of drought are increasing due to anthropogenic climate change and are already limiting cropping system productivity in many regions around the world. Few microbial groups within plant microbiomes can potentially contribute towards the fitness and productivity of their hosts under abiotic stress events including water deficits. However, microbial communities are complex and integrative work considering the multiple co-existing groups of organisms is needed to better understand how the entire microbiome responds to environmental stresses. We hypothesize that water deficit stress will differentially shape bacterial, fungal, and protistan microbiome composition and influence inter-kingdom microbial interactions in the rhizospheres of corn and sugar beet. We used amplicon sequencing to profile bacterial, fungal, and protistan communities in corn and sugar beet rhizospheres grown under irrigated and water deficit conditions. The water deficit treatment had a stronger influence than host species on bacterial composition, whereas the opposite was true for protists. These results indicate that different microbial kingdoms have variable responses to environmental stress and host factors. Water deficit also influenced intra- and inter-kingdom microbial associations, wherein the protist taxa formed a separate cluster under water deficit conditions. Our findings help elucidate the influence of environmental and host drivers of bacterial, fungal, and protistan community assembly and co-occurrence in agricultural rhizosphere environments.

A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus.

Atrial fibrillation (AF) represents the most common type of sustained cardiac arrhythmia in humans and confers a significantly increased risk for thromboembolic stroke, congestive heart failure and premature death. Aggregating evidence emphasizes the predominant genetic defects underpinning AF and an increasing number of deleterious variations in more than 50 genes have been involved in the pathogenesis of AF. Nevertheless, the genetic basis underlying AF remains incompletely understood. In the current research, by whole-exome sequencing and Sanger sequencing analysis in a family with autosomal-dominant AF and congenital patent ductus arteriosus (PDA), a novel heterozygous variation in the PRRX1 gene encoding a homeobox transcription factor critical for cardiovascular development, NM_022716.4:c.373G>T;p.(Glu125*), was identified to be in co-segregation with AF and PDA in the whole family. The truncating variation was not detected in 306 unrelated healthy individuals employed as controls. Quantitative biological measurements with a reporter gene analysis system revealed that the Glu125*-mutant PRRX1 protein failed to transactivate its downstream target genes SHOX2 and ISL1, two genes that have been causally linked to AF. Conclusively, the present study firstly links PRRX1 loss-of-function variation to AF and PDA, suggesting that AF and PDA share a common abnormal developmental basis in a proportion of cases.

Analgesia with 5' extracellular nucleotidase-mediated electroacupuncture for neuropathic pain.

BACKGROUND: Acupuncture is a treatment for neuropathic pain, but its mechanism remains unclear. Previous studies showed that analgesia was induced in rats with neuropathic pain when their spinal cord adenosine content increased after electroacupuncture (EA); however, the mechanism behind this electroacupuncture-induced increase has not been clarified. OBJECTIVE: This study aimed to determine the role that ecto-5'-nucleotidase plays in EA-induced analgesia for neuropathic pain. METHODS: We performed electroacupuncture at the Zusanli acupoint on the seventh day after establishing a rat model of neuropathic pain induced through chronic constriction injuries. We observed the mechanical withdrawal threshold and thermal pain threshold and detected the expression of ecto-5'-nucleotidase in the spinal cord using Western blot. Chronic constriction injury rat models were intraperitoneally injected with α,ß-methyleneadenosine 5'-diphosphate, an ecto-5'-nucleotidase inhibitor, 30 min before electroacupuncture. The adenosine content of the spinal cord was detected using high-performance liquid chromatography. Lastly, the adenosine A1 receptor agonist N6-cyclopentyladenosine was intrathecally injected into the lumbar swelling of the rats, and the mechanical withdrawal and thermal pain thresholds were reevaluated. RESULTS: Analgesia and increased ecto-5'-nucleotidase expression and adenosine content in the spinal cord were observed 1 h after electroacupuncture. α,ß-methyleneadenosine 5'-diphosphate was able to inhibit upregulation of adenosine content and electroacupuncture-induced analgesia. After administration of N6-cyclopentyladenosine, electroacupuncture-induced analgesia was restored. CONCLUSIONS: Our results suggest that electroacupuncture at Zusanli can produce analgesia in chronic constriction injury rat models, possibly via the increased ecto-5'-nucleotidase expression induced through electroacupuncture, thus leading to increased adenosine expression in the spinal cord.

Family Environment, Heritage Language Profiles, and Socioemotional Well-being of Mexican-origin Adolescents with First Generation Immigrant Parents.

Although Mexican-origin youth with first-generation immigrant parents are relatively good at retaining their heritage language of Spanish, limited research has been conducted on their Spanish language development during adolescence. From three-wave longitudinal data across six years (Nwave1 = 604, Mage.wave1 = 12.91, 54% female), distinct groups of adolescents with consistently high, improved, declined, and consistently low Spanish proficiencies were identified. Family relationship quality was more predictive of adolescents' Spanish proficiency than family language environment. The benefits of Spanish proficiency were consistent across adolescents' ethnic identity, resilience, and life meaning. More research and practical attention to parent-adolescent relationships is needed to capitalize on the continued plasticity of adolescents' Spanish language development and to promote consequent positive outcomes.

The Phenotypic, Psychological, and Social Interplays of Skin Color and Developmental Outcomes among Mexican-origin Adolescents: Dismantling Systems of Racism and Oppression during Adolescence: Dismantling Systems of Racism and Oppression during Adolescence.

Mexican-origin children from immigrant families are impacted by various systemic oppressions in life. The study seeks to examine how adolescents' developmental outcomes are associated with specific phenotypic, psychological, and social features of skin color, as manifested by skin tone, skin color satisfaction, and foreigner stress. By taking a holistic approach, we examine both positive and negative adjustment outcomes, including delinquency, resilience, and effortful control. Participants were 604 Mexican-origin adolescents aged between 11.08 and 15.29 (Mage = 12.91, SD = 0.92) with at least one immigrant parent. The findings highlight the harm of foreigner stress and the benefit of skin color satisfaction in Mexican-origin adolescents' development of delinquency, resilience, and effortful control, especially for those with a darker skin color.

Outbreak of the South American tomato leafminer, Tuta absoluta, in the Chinese mainland: geographic and potential host range expansion.

BACKGROUND: In 2017 Tuta absoluta was identified as an invasive species in China. Due to its rapid geographic expansion and the severe crop damage it causes, T. absoluta poses a serious threat to China's tomato production industry. To determine its geographic distribution and host range, intensive surveys and routine monitoring were conducted across the Chinese mainland between 2018 and 2019. The population colonization coefficient (PCC; ratio of colonized sites and prefectures) and population occurrence index (POI; ratio of infested host species and PCCs) were calculated. RESULTS: In northwestern China, T. absoluta populations established in Xinjiang exhibited a medium PCC value (~0.03). In southwestern China, populations in Yunnan and its five neighboring provinces exhibited high (~0.50 in Yunnan and Guizhou), or low (<0.02 in Guangxi, Sichuan, Hunan, and Chongqing) PCC values. In the Chinese mainland, infestations of four crop plant species (tomato, eggplant, potato, and Chinese lantern) and two wild plant species (black nightshade and Dutch eggplant) were identified; tomatoes were infested in every colonized province. Chinese lantern and Dutch eggplant are potentially novel hosts. Yunnan, Guizhou, and Xinjiang experienced the most serious damage (POI). In southwestern China, observed damage significantly decreased with increased distance from the first discovery site of T. absoluta to the farthest county of an infested province increased. CONCLUSION: T. absoluta populations are well-established and could potentially spread to other regions of China. The present study helps to inform the establishment of better pest management guidelines and strategies in China and tomato-producing regions worldwide. © 2021 Society of Chemical Industry.