Oncogenic HPV-induced high expression of ESM1 predicts poor prognosis and regulates aerobic glycolysis in cervical cancer.

The impact of endothelial cell-specific molecule 1 (ESM1) on the initiation and progression of diverse cancers has been extensively studied, yet its regulatory mechanisms in relation to cervical cancer remain insufficiently understood. Through bioinformatics analysis, we revealed that ESM1 was highly expressed in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and correlated with dismal clinicopathological features. The activation of ESM1 is facilitated by the presence of oncogenic HPV E6 and E7. HPV E6 and E7 enhance the expression of ESM1 by diminishing the levels of miR-205-5p, which specifically targets the 3' untranslated region of ESM1 mRNA. In addition, we demonstrated that ESM1 facilitates aerobic glycolysis of cervical cancer cells via the Akt/mTOR pathway. Suppression of ESM1 led to a reduction in the expression of HIF-1α and multiple glycolytic enzymes. Taken together, our findings provide insights into the mechanisms by which HPV infections regulate oncogenes, thereby contributing to cervical carcinogenesis.

Peptidyl-prolyl isomerase F as a prognostic biomarker associated with immune infiltrates and mitophagy in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is among the most prevalent malignancies worldwide, with unfavorable treatment outcomes. Peptidyl-prolyl isomerase F (PPIF) is known to influence the malignancy traits of tumor progression by modulating the bioenergetics and mitochondrial permeability in cancer cells; however, its role in LUAD remains unclear. Our study seeks to investigate the clinical significance, tumor proliferation, and immune regulatory functions of PPIF in LUAD. Methods: The expression of PPIF in LUAD tissues and cells was assessed using bioinformatics analysis, immunohistochemistry (IHC), and Western blotting. Survival curve analysis was conducted to examine the prognostic association between PPIF expression and LUAD. The immunomodulatory role of PPIF in LUAD was assessed through the analysis of PPIF expression and immune cell infiltration. A series of gain- and loss-of-function experiments were conducted on PPIF to investigate its biological functions in LUAD both in vitro and in vivo. The mechanisms underlying PPIF's effects on LUAD were delineated through functional enrichment analysis and Western blotting assays. Results: PPIF exhibited overexpression in LUAD tissues compared to normal controls. Survival curve analysis revealed that patients with LUAD exhibiting higher PPIF expression demonstrated decreased overall survival and a shorter progression-free interval. PPIF was implicated in modulating immune cell infiltration, particularly in regulating the T helper 1-T helper 2 cell balance. Functionally, PPIF was discovered to promote tumor cell proliferation and advance cell-cycle progression. Furthermore, PPIF could impede mitophagy by targeting the FOXO3a/PINK1-Parkin signaling pathway. Conclusions: The findings of this study indicate that the prognosis-related gene PPIF may have a significant role in the regulation of LUAD cell proliferation, tumor-associated immune cell infiltration, and mitophagy, and thus PPIF may be a promising therapeutic target of LUAD.

Assessing the use of PEC and jf methods for strengthening the evaluation of new heat exchangers.

The new type of heat exchanger uses the micro heat pipe as the main heat transfer material. Compared with the traditional heat exchanger of the same kind, the performance of the new type of heat exchanger has significantly improved. By studying the evaluation method of strengthening the performance of the heat exchanger, the performance of the heat exchanger can be further optimized. Most of the current literature study the heat transfer coefficient of the heat exchanger, but there are many influencing factors. Therefore, the evaluation lacks accuracy, and there is no clear research description of fin strengthening performance of the heat exchanger. In this paper, the PEC and jf methods were used in evaluating the enhanced performance of a new type of heat exchanger. Multiple performance indexes were used as evaluation factors and the characteristics of flow and heat transfer were analyzed by studying the working medium, heat transfer coefficient and pressure drop in the heat exchanger. The study, therefore, proposed an optimization direction and the results proved that PEC and jf methods can be used to evaluate the performance of the new heat exchanger efficiently, and the two conclusions were similar. The fins were more capable to improve the performance of heat exchanger when Re >31000.

Occurrence of Anthracnose Caused by Colletotrichum fructicola on Ficus hirta in Southern China.

Ficus hirta Vahl. is a Moraceae plant, named for its palm-like leaves. It is a widely used traditional medicinal material with definite curative effect. At the same time, it is also a commonly used soup material among the folk in South China. In March 2022, a serious leaf spot disease with symptoms similar to anthracnose was observed on F. hirta in several plantations in Qinzhou and Zhanjiang City of China, with an incidence of 32~65%. The early symptoms of infected leaves were small, round, yellow spots that further expanded into larger, brown, irregular, necrotic lesions surrounded by dark brown edges, which eventually led to leaf wilt. Twenty symptomatic leaves were collected from three plantations with a total area of about 10 hm2. Fragments (2×2 mm) from the 20 infected leaves were surface sterilized, plated on potato dextrose agar (PDA) and incubated at 28°C. After 3 days, isolates with similar cultural morphology were obtained and three representative isolates (WZMT-1, WZMT-3 and WZMT-8) were randomly selected for following study. The colonies by single-spore purification on PDA were initially cottony, pale white and became grayish green with age. The conidia were hyaline, abundant, cylindrical, with rounded ends, 14.4~18.2 µm×4.6~6.0 µm (av. 16.2 µm×5.4 µm, n=100). Conidiogenous cells hyaline, cylindrical or ampulliform, 6.2~22.7 µm × 2.7~5.0 µm (av. 12.9 µm×3.8 µm, n=50). Appressoria were brown to dark brown, ovoid to clavate, elliptical or irregular, 7.9~13.4 µm × 5.6~9.2 µm (av. 10.6 µm×7.9 µm, n=50). The morphology of the fungus resembled Colletotrichum fructicola (Prihastuti et al. 2009). For molecular identification, the internal transcribed spacer (ITS) regions, glyceraldehyde-3-phosphatedehydrogenase (GAPDH), actin (ACT), beta-tubulin 2 (TUB2), calmodulin (CAL), partial manganese superoxide dismutase (sod2), partial Apn2-Mat1-2 intergenic spacer and partial mating type (Mat1-2) (ApMat) genes were amplified from genomic DNA for the isolates using the primers described by Silva et al. (2012) and Weir et al. (2012). The sequences of the above seven loci of the three isolates (accession nos. OQ121661 to OQ121663 and OQ133400 to OQ133417) were obtained and showed over 99% identity with the existing sequences of ex-type culture ICMP 18581 of Colletotrichum fructicola (Weir et al. 2012). A multilocus phylogenetic analysis of the seven loci concatenated sequences using the maximum likelihood method revealed that the isolates belong to C. fructicola. To confirm pathogenicity, five 3-month-old potted plants were used for inoculation with each representative isolate. Tested plants were sprayed with 10 ml of a conidial suspension (1 × 108 conidia/ml) , and the controls plants were sprayed with sterile water. All the plants were incubated in a growth chamber at 26 ± 2°C with 95% relative humidity. After 10 days, typical lesions like those observed on the field plants appeared on all inoculated plants, while the control remained healthy. The same fungal pathogen was reisolated and the identity was confirmed by morphological characterization and molecular analysis, confirming Koch's postulates. The pathogen has been reported as the causal agent of anthracnose on a wide range of plant hosts worldwide (Marquez-Zequera et al. 2018; Horfer et al. 2021; Jiang et al. 2022; Li et al. 2023). To our knowledge, this is the first report of anthracnose on F. hirta caused by C. fructicola in southern China.

Cyclin O promotes lung cancer progression and cetuximab resistance via cell cycle regulation and CDK13 interaction.

Background: Cyclin O (CCNO) is a novel cyclin family protein containing a cyclin-like domain, which plays a role in cell cycle regulation. Recent research suggests that inhibition of CCNO leads to cell apoptosis in gastric cancer, cervical squamous cell carcinoma, and post-operative lung cancer. Methods: The protein expression and signal transduction were detected by Western blot (WB) and immunohistochemistry (IHC). Overexpression or lacking CCNO stable cell lines were transfected with lentiviruses and selected with puromycin. The tumor behaviors of lung adenocarcinoma (LUAD) cells were assessed: cell proliferation by 5-Ethynyl-2'-deoxyuridine (EdU) staining and Cell Counting Kit-8 (CCK8) assay, cell cycle and by flow cytometry analysis, and migration and invasion using wound healing and Transwell system. Co-immunoprecipitation was used to detect protein-protein interactions. Xenograft models for evaluating tumor growth and anti-tumor drug efficacy. Results: A higher expression of CCNO was observed in LUAD cancer tissues and predicted the overall survival of LUAD patients. Moreover, CCNO expression was negatively correlated with cancer cell proliferation, migration, and invasion. Co-immunoprecipitation and western blot indicated that CCNO interacted with CDK13 to promote cancer cell proliferation signaling activation. Furthermore, CCNO promoted tumor cell growth and cetuximab resistance in vivo, and a CDK13 inhibitor effectively inhibited the oncological effect of CCNO. Conclusions: The current study suggests that CCNO may be a driver in the development of LUAD and that its function is related to CDK13 interaction that promotes proliferation signaling activation.

Ultra-rapid Idylla™ EGFR mutation screening followed by next-generation sequencing: An integrated solution to molecular diagnosis of non-small cell lung cancer.

Background: Rapid profiling of the EGFR mutations is crucial to help clinicians choose the optimal treatment for patients with advanced/metastatic Non-Small Cell Lung Cancer (NSCLC). Unfortunately, current diagnostic techniques, including ARMS-PCR and NGS, generally require several days to deliver final results. This diagnostic delay may lead to treatment delays for patients who are worsening rapidly. Methods: This study introduced the ultra-rapid Idylla™ system for rapid, sensitive and specific identification of the EGFR mutations among Chinese NSCLC patients. Idylla™ EGFR Assay, an integrated cartridge running on the Idylla™ system, which can detect 51 EGFR mutations directly from Formalin-Fixed, Paraffin-Embedded (FFPE) samples within 2.5 hours, was used in this study. The sensitivity and specificity of the Idylla™ system were evaluated in comparison with ARMS-PCR or NGS using 95 clinical samples. Results: The Idylla™ system achieved a sensitivity of 97.6%, a specificity of 100%, and an overall concordance of 97.9% for 95 retrospective samples. When compared to ARMS-PCR, the Idylla™ system demonstrated high accuracy with an overall agreement of 97.1% (34/35), a sensitivity of 95.2% (20/21) (95% CI, 76.2% - 99.9%), and an estimated specificity of 100% (12/12) (95% CI, 76.8% - 100%) for 35 prospective samples. Conclusions: This Idylla system provides a rapid, accurate and simple approach for screening EGFR mutations, which can guide Tyrosine Kinase Inhibitors (TKI) treatment for NSCLC patients in a timely manner.

Hollow-core fiber with stable propagation delay between -150°C and +60°C.

Optical fibers with a low thermal coefficient of delay (TCD) have been developed for frequency and timing transmission/distribution. However, their temperature sensitivity changes as a function of temperature and, to date, no study of such fibers has demonstrated improved performance over extended temperature ranges, especially at sub-zero temperatures. Here, we show that a hollow core fiber (HCF) with a thin acrylate coating can have a TCD within ±2.0 ps/km/°C over a broad temperature range from -150°C to +60°C. In addition, this thinly coated HCF can be fully insensitive to temperature around -134°C, making it of interest, e.g., for laser stabilization close to cryogenic temperatures.

Corrigendum: Negatively regulated by miR-29c-3p, MTFR1 promotes the progression and glycolysis in lung adenocarcinoma via the AMPK/mTOR signalling pathway.

[This corrects the article DOI: 10.3389/fcell.2021.771824.].

Low-loss microwave photonics links using hollow core fibres.

There are a host of applications in communications, sensing, and science, in which analogue signal transmission is preferred over today's dominant digital transmission. In some of these applications, the advantage is in lower cost, while in others, it lies in superior performance. However, especially for longer analogue photonics links (up to 10 s of km), the performance is strongly limited by the impairments arising from using standard single-mode fibres (SSMF). Firstly, the three key metrics of analogue links (loss, noise figure, and dynamic range) tend to improve with received power, but this is limited by stimulated Brillouin scattering in SSMF. Further degradation is due to the chromatic dispersion of SSMF, which induces radio-frequency (RF) signal fading, increases even-order distortions, and causes phase-to-intensity-noise conversion. Further distortions still, are caused by the Kerr nonlinearity of SSMF. We propose to address all of these shortcomings by replacing SSMFs with hollow-core optical fibres, which have simultaneously six times lower chromatic dispersion and several orders of magnitude lower nonlinearity (Brillouin, Kerr). We demonstrate the advantages in this application using a 7.7 km long hollow-core fibre sample, significantly surpassing the performance of an SSMF link in virtually every metric, including 15 dB higher link gain and 6 dB lower noise figure.

Acupuncture for neuropathic pain: A meta-analysis of randomized control trials.

Background: Neuropathic pain (NP) is expected to increase due to the high risk of global population aging. Acupuncture has a definite clinical effect on NP. Therefore, a systematic review and meta-analysis were conducted to evaluate the effect on pain intensity and safety of acupuncture in patients with NP. Methods: An encompassing search of specific authoritative databases in English, from their inception to 2022, was performed. The databases were as follows: Scopus, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations, and Daily. All the randomized controlled trials regarding the acupuncture treatment of NP will be included. Methodological quality assessment of the included trials was assessed based on the risk of bias from the Cochrane handbook. A meta-analysis was performed for the main outcomes. In addition, sensitivity analysis, subgroup analysis, and funnel plot were also carried out. Results: A total of 16 studies with 1,021 patients with NP were evaluated in a systematic review. According to the results of the overall meta-analysis in eight RCTs with 338 participants, the acupuncture group was better than the control group in improving changes in pain intensity (SMD -0.59, 95% CI: -0.95 to -0.23, P = 0.001). In subgroup analysis, five trials indicated that acupuncture was more effective in improving changes in pain intensity than sham acupuncture (SMD -0.54, 95% CI: -0.95 to -0.13, P = 0.01), two trials evaluated the effect on changes in pain intensity in the comparison of acupuncture and conventional treatments, no significant difference existed (SMD -0.61, 95% CI: -1.83 to 0.61, P = 0.33), and one trial compared acupuncture with blank control evaluating the effect of changes in pain intensity with a significant difference. Eleven studies mentioned the safety conditions and acupuncture-induced AEs were mild and reversible. Both the sensitivity analysis and funnel plot analysis showed that the meta-analysis was stable and irreversible without publication bias. The GRADE was rated as "very low." Conclusion: The acupuncture group had higher effectiveness than sham intervention or blank control for changes in pain intensity, but there is no significant difference between acupuncture and conventional treatments in treating NP. The acupuncture-induced adverse events were mild and reversible. However, the interpretation of our results should be performed cautiously due to the low methodological quality of selected publications. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022306461.

Acupuncture combined with balloon dilation for post-stroke cricopharyngeal achalasia: A meta-analysis of randomized controlled trials.

Background: The purpose of this study was to systematically evaluate the effectiveness of acupuncture combined with balloon dilatation in patients with post-stroke cricopharyngeal achalasia (CPA) according to the effective rate, videofluoroscopy swallowing study (VFSS) score and standardized swallowing function assessment scale (SSA) score through Meta-analysis. Methods: English and Chinese language literature published before July 24,2022 were searched in ten electronic databases. The identified articles were screened, data were extracted, and the methodological quality of the included trials was assessed. Using RevMan 5.4.1 software to perform Meta-analysis. Results: 10 studies with 517 patients with post-stroke CPA were included. Meta-analysis showed that the effective rate of the experience group was higher than that of the control group [OR = 0.62; 95% CI (2.32, 13.05); I 2 = 0%; p = 0.0001]. Compared to the control group, the SSA score was lower in the experience group [MD = -4.22; 95% CI (-4.57, -3.87); I 2 = 42%; p < 0.00001]. In terms of VFSS scores, the experience group showed greater efficacy differences than control group [MD = 1.53; 95% CI (1.32, 1.75); I 2 = 0%; p < 0.00001]. The subgroup analysis of VFSS score based on the average course of disease (<1 month vs. ≥1 month) showed no significant difference. The subgroup analysis based on average age (>60 years vs. ≤60 years) showed the VFSS score of the experience group was significantly higher than that of the control group, and the effect may be better in the subgroup older than 60 years. The subgroup analysis based on the treatment course (>30 days vs. ≤30 days) showed the VFSS score of the experience group was significantly higher than that of the control group, and the effect may be better in the subgroup the treatment course>30 days. Conclusion: Acupuncture combined with balloon dilatation may be an effective method for treating post-stroke CPA. Compared with balloon dilatation, acupuncture combined with balloon can significantly improve the swallowing function of patients, and it is also effective for patients of different courses, ages, and treatment course, while patients over 60 years old and the treatment course over 30 days may have better clinical outcomes.

Negatively Regulated by miR-29c-3p, MTFR1 Promotes the Progression and Glycolysis in Lung Adenocarcinoma via the AMPK/mTOR Signalling Pathway.

Background: Lung adenocarcinoma (LUAD) is the major form of lung cancer that presents a major peril to public health. Owing to the high rates of morbidity, mortality and chemoresistance, it is necessary to develop more effective therapeutic targets of LUAD. Mitochondrial fission regulator 1 (MTFR1) affects the occurrence and development of some diseases by regulating mitochondrial dynamics and is dysregulated in LUAD. However, the functions and molecular mechanisms of MTFR1 in LUAD have not been investigated. Methods: Immunohistochemical (IHC) analysis, real-time quantitative polymerase chain reaction (RT-qPCR), bioinformatic analysis and western blot (WB) were performed to assess the expression of MTFR1 at both protein and mRNA levels. The biological functions of MTFR1 in LUAD cells were assessed based on various in vivo and in vitro experiments. The dual-luciferase reporter assay and some rescue experiments were performed to evaluate the underlying mechanism of MTFR1 in LUAD. Results: MTFR1 was upregulated in LUAD cells and tissues and correlated with dismal clinicopathologic features and a worse prognosis of patients with LUAD. Functionally, MTFR1 overexpression stimulated the proliferation, invasion, migration and glycolytic capacity and impeded the apoptosis of LUAD cells; however, opposite results were obtained when MTFR1 expression was knocked down. MTFR1, which was directly targeted by miR-29c-3p, may exert its biological functions through the AMPK/mTOR signalling pathway. Conclusion: MTFR1 promotes the progression of LUAD. Therefore, targeting MTFR1 can offer an effective therapeutic strategy for LUAD treatment.

Thinly coated hollow core fiber for improved thermal phase-stability performance.

The optical phase accumulated when light propagates through an optical fiber changes with temperature. It has been shown by various authors that this thermal phase sensitivity is significantly smaller in hollow core fibers (HCFs) than in standard single-mode fibers (SSMFs). However, there have been considerable differences in the level of sensitivity reduction claimed, with factors in the range ×3 to ×20 improvement for HCFs relative to SSMFs reported. Here we show experimentally that this large variation is likely attributable to the influence of fiber coating, which is exacerbated in HCFs with a relatively thin silica glass outer wall (e.g., the wall thickness is typically just 20 µm in a 125 µm diameter HCF). Further, we show that the coating also causes the optical phase stability to suffer from relaxation effects, which have not been previously discussed in the HCF literature, to the best of our knowledge. In addition to demonstrating these relaxation effects experimentally, we analyze them through numerical simulations. Our results strongly suggest that they originate from the viscoelastic properties of the coating. To minimize the adverse effects of the coating, we have fabricated a HCF with a relatively thick wall (∼50µm) and a very thin coating (10 µm). This results in an almost 30-fold reduction in HCF thermal phase sensitivity relative to SSMFs - a significantly lower sensitivity than in previous reports. Moreover, our thinly coated HCF exhibits no discernable relaxation effects while maintaining good mechanical properties.

Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. The role of molecular alterations and the immune microenvironment in ESCC development has not been fully elucidated. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. Nine gene expression datasets from the Gene Expression Omnibus (GEO) database were analysed to identify robust differentially expressed genes (DEGs) using the robust rank aggregation (RRA) algorithm. Functional enrichment analyses showed that the 152 robust DEGs are involved in multiple processes in the tumor microenvironment (TME). Immune cell infiltration analysis based on the 9 normalized GEO microarray datasets was conducted with the CIBERSORT algorithm. The changes in macrophages between ESCC and normal tissues were particularly obvious. In ESCC tissues, M0 and M1 macrophages were increased dramatically, while M2 macrophages were decreased. A robust DEG-based protein-protein interaction (PPI) network was used for hub gene selection with the CytoHubba plugin in Cytoscape. Nine hub genes (CDA, CXCL1, IGFBP3, MMP3, MMP11, PLAU, SERPINE1, SPP1 and VCAN) had high diagnostic efficiency for ESCC according to receiver operating characteristic (ROC) curve analysis. The expression of all hub genes except MMP3 and PLAU was significantly related to macrophage infiltration. Univariate and multivariate regression analyses showed that a 7-gene signature constructed from the robust DEGs was useful for predicting ESCC prognosis. Our results might facilitate the exploration of potential targeted TME therapies and prognostic evaluation in ESCC.

Dietary supplements and herbal medicine for COVID-19: A systematic review of randomized control trials.

BACKGROUND: The world is currently struggling with the Coronavirus disease 2019 (COVID-19) pandemic. Dietary supplements (DSs) and herbal medicine provide a potentially convenient and accessible method for its recovery, but direct evidence is limited. OBJECTIVE: This study aims to investigate the effectiveness of DSs and herbs in patients with COVID-19. METHODS: A systematic literature search was conducted in multiple electronic English and Chinese databases. Randomized controlled trials (RCTs) involving DSs or herbal medicine interventions on patients with COVID-19 from November 2019 to February 2021 were included. Data was extracted, summarized and critically examined. RESULTS: Out of 9402 records identified in the initial search, twelve RCTs were included in this review. Risk of bias of these RCTs was deemed high. Most of the trials were of low methodologic quality. Nine studies showed herbal supplements were beneficial to the recovery of COVID-19 patients; zinc sulfate could shorten the duration of loss of smell but not total recovery from COVID-19. No severe adverse events were reported. CONCLUSION: Herbal supplements may help patients with COVID-19, zinc sulfate is likely to shorten the duration of olfactory dysfunction. DS therapy and herbal medicine appear to be safe and effective adjuvant therapies for patients with COVID-19. These results must be interpreted with caution due to the overall low quality of the included trials. More well-designed RCTs are needed in the future.

Effects of Tai Chi on Patients with Mild Cognitive Impairment: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

DESIGN: Randomized controlled trials (RCTs) from multiple databases from inception to December 2020 published in English were searched. Two researchers independently performed eligible study screening and data extraction. The methodological quality was assessed with the Jadad score. Meta-analysis of RCTs on TC in the treatment of MCI was performed with RevMan Version 5.4.1. RESULTS: Seven RCTs with 1265 participants were included. For most RCTs, the overall reporting of methodological quality was high. Results of the meta-analysis indicate that TC improved MCI patients' cognitive function significantly, including overall cognitive function (MD = -2.24, 95% CI -3.51 to -0.97, P = 0.0005), memory and learning (SMD = 0.83, 95% CI 0.22 to 1.45, P = 0.008), visuospatial ability (MD = 3.15, 95% CI 0.74 to 5.56, P = 0.01), executive functions (MD = 0.32, 95% CI 0.03 to 0.61, P = 0.03), and physical activity (MD = 18.78, 95% CI 10.80 to 26.76, P < 0.00001). However, no significant benefit was found for TC on psychological activity (MD = 0.17, 95% CI -0.62 to 0.96, P = 0.36) and biomarker improvement. CONCLUSION: The meta-analysis confirmed the clinical therapeutic effect of TC for MCI. More rigorous and long-term follow-up RCTs should be conducted in the future.

Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma.

BACKGROUND: Lung cancer is a malignant tumor with the highest morbidity and mortality rates worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Overall, current treatments of LUAD are not satisfactory; therefore, novel targets need to be explored. Let-7b-3p is an important member of the let-7 family of microRNAs (miRNAs), and has not been studied separately in LUAD. This study aimed to investigate the role and molecular mechanism of let-7b-3p in LUAD. METHODS: Herein, let-7b-3p expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) assays. MTT, colony formation assay, flow cytometry analysis, wound-healing, Transwell and in vivo experiments were conducted to assess let-7b-3p's function in LUAD. The downstream target TFIIB-related factor 2 (BRF2) was predicted using bioinformatics analyses and confirmed by dual-luciferase reporter assay and rescue experiments. Additionally, BRF2 was found to affect the MAPK/ERK pathway through transcriptome sequencing analysis and western blot (WB) assay. RESULTS: Let-7b-3p is downregulated in LUAD cells and tissue samples and low let-7b-3p expression is correlated with a poor prognosis in LUAD patients. Let-7b-3p suppresses the proliferation and metastasis of LUAD cells both in vivo and in vitro by directly targeting the BRF2-mediated MAPK/ERK pathway. CONCLUSIONS: Let-7b-3p inhibits the development of LUAD and is an ideal novel therapeutic target for the treatment of LUAD.

Oncogenic role of abnormal spindle­like microcephaly­associated protein in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common malignant cancer worldwide. It is urgent to explore its underlying molecular mechanism and identify novel diagnostic biomarkers. Abnormal spindle­like microcephaly (ASPM) has recently received considerable attention due to its function in tumor progression. However, its role in LUAD is unclear. The present study aimed to explore the clinical role of ASPM in LUAD. Seven pairs of LUAD and adjacent normal tissues were collected to identify potential LUAD biomarkers using transcriptome sequencing. The association between ASPM expression and LUAD progression was evaluated using bioinformatics analysis and data obtained from clinical specimens. Using small interfering RNA technology, the function of ASPM was analyzed in the LUAD H1299 and A549 cell lines. Transcriptional profiling of ASPM­deficient H1299 cells was then performed to determine the downstream targets of ASPM. Using databases and clinical specimens, it was revealed that ASPM expression was frequently elevated in LUAD tissues, and this upregulation was highly associated with LUAD progression. ASPM served as an oncogenic regulator of LUAD cell proliferation and metastasis. Mechanistically, ASPM facilitated epithelial­mesenchymal transition (EMT) via the PI3K/AKT signaling pathway and 740 Y­P, an activator of this pathway, restored the migratory ability of ASPM­knockdown LUAD cells. The current study identified ASPM as an independent prognostic biomarker of LUAD that served an important oncogenic role in regulating LUAD cell metastasis by promoting EMT via the PI3K/AKT signaling pathway. Targeting ASPM may therefore be a therapeutic strategy for treating LUAD.

Mex3a interacts with LAMA2 to promote lung adenocarcinoma metastasis via PI3K/AKT pathway.

Lung adenocarcinoma (LUAD) is the main subtype of lung cancer. In this study, we found that RBP Mex3a was significantly upregulated in LUAD tissues and elevated Mex3a expression was associated with poor LUAD prognosis and metastasis. Furthermore, we demonstrated that Mex3a knockdown significantly inhibited LUAD cell migration and invasion in vitro and metastasis in nude mice. Transcriptome sequencing indicated that Mex3a affected gene expression linked to ECM-receptor interactions, including laminin subunit alpha 2(LAMA2). RNA immunoprecipitation (RIP) assay revealed Mex3a directly bound to LAMA2 mRNA and Mex3a increased the instability of LAMA2 mRNA in LUAD cells. Furthermore, we discovered that LAMA2 was surprisingly downregulated in LUAD and inhibited LUAD metastasis. LAMA2 knockdown partially reverse the decrease of cell migration and invasion caused by Mex3a knockdown. In addition, we found that both Mex3a and LAMA2 could influence PI3K-AKT pathway, which are downstream effectors of the ECM-receptor pathway. Moreover, the reduced activation of PI3K-AKT pathway in caused by Mex3a depletion was rescued by LAMA2 knockdown. In conclusion, we demonstrated that Mex3a downregulates LAMA2 expression to exert a prometastatic role in LUAD. Our study revealed the prognostic and prometastatic effects of Mex3a in LUAD, suggesting that Mex3a can serve as a prognostic biomarker and a target for metastatic therapy.

Tuina for cervical vertigo: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: Cervical vertigo (CV), one of the most common causes of vertigo, makes patients feel dizzy, which seriously affects patients' lives. As a traditional Chinese bone-setting manipulation, Tuina is widely used to treat CV. This article aims to evaluate the effectiveness and safety of Tuina for CV. METHODS: Nine databases were searched. Methodological quality was evaluated with the Cochrane Collaboration's tool. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to determine confidence in the effect estimates. Stata 12.0 software was used to carry out the meta-analysis, and a trial sequential analysis (TSA) was performed with TSA 0.9. RESULTS: Nine randomized controlled trials (RCTs) were included. Low-quality evidence suggested that Tuina showed a significantly higher effectiveness rate compared to massage therapy (risk ratio (RR) = 1.11, 95% confidence intervals (CI): 1.05 to 1.17, p < 0.0001) and cervical traction (RR = 1.37, 95% CI: 1.09 to 1.72, p = 0.007; I2 = 0%, p = 0.826). Two trials reported that Tuina was better than acupuncture (RR = 1.40, 95% CI: 1.07 to 1.83) or betahistine mesilate (RR = 1.17, 95% CI: 0.99 to 1.37) based on an improved effectiveness rate. Low-quality evidence showed that Tuina was superior to massage therapy in improving scores on the evaluation scale for cervical vertigo (ESCV) (weighted mean differences (WMD) = 2.52, 95% CI: 1.11 to 3.94, p < 0.0001). Adverse events were tolerable. TSA revealed that an improved effectiveness rate was indicated. CONCLUSION: Tuina might improve the effectiveness rate and ESCV scores in patients with CV. However, the level of all the available evidence was low, and larger-scale and well-designed RCTs should be encouraged.