NEK2 promotes the migration, invasion, proliferation of ESCC and mediates ESCC immunotherapy.

Purpose: Esophageal squamous cell carcinoma (ESCC) is a disease with a high incidence rate and high mortality worldwide. The Never in Mitosis A (NIMA) family member NIMA-related kinase 2 (NEK2) plays an important role in mitosis. However, the role of NEK2 in the pathogenesis of ESCC remains unclear. Patients and methods: The expression and function of NEK2 in TCGA and GEO data sets were analyzed by bioinformatics. We verified the expression of NEK2 in ESCC tissues and cell lines by Western blotting and immunohistochemical methods and further explored the relationship between tumor stage and NEK2 expression. The differences in NEK2 expression and survival in patients with EC were verified by bioinformatics analysis. ESCC cell lines with stable knockdown of NEK2 were established by lentivirus-mediated shRNA delivery. The effects of NEK2 on ESCC cells were analyzed on the cytological level with assays including CCK-8, EdU, cell scratch, Transwell migration and invasion, colony formation, flow cytometry and apoptosis assays. Tumor growth was measured in a mouse xenograft model. Results: We found that NEK2 is highly expressed in ESCC tissues and ESCC cells and that the high expression of NEK2 is associated with poor tumor healing. Knockdown of the NEK2 gene inhibits the migration, proliferation, invasion and cell cycle of ESCC cells. Biologic analysis shows that NEK2 is involved in biological processes such as progression and apoptosis of esophageal cancer, and is related to E2F.Mechanistically, NEK2 knockdown decreases the expression levels of E2F1 and IGF2. NEK2 competes with the transcription factor E2F1 to bind CDC20, resulting in decreased degradation and increased expression of E2F1. IGF2 expression is also increased, which promotes the expression of thymidylate synthase, further promoting the drug resistance of ESCC cells. NEK2 is associated with immune infiltration in esophageal cancer. Conclusion: NEK2 is highly expressed in ESCC and can promote the migration, proliferation and invasion of ESCC cells. NEK2 mediates ESCC immunotherapy.

Effects of S-ketamine added to patient-controlled analgesia on early postoperative pain and recovery in patients undergoing thoracoscopic lung surgery: A randomized double-blinded controlled trial.

STUDY OBJECTIVE: To investigate whether the addition of S-ketamine to patient-controlled hydromorphone analgesia decreases postoperative moderate-to-severe pain and improves the quality of recovery (QoR) in patients undergoing thoracoscopic lung surgery. DESIGN: Single-center prospective randomized double-blinded controlled trial. SETTING: Tertiary university hospital. PATIENTS: 242 patients undergoing thoracoscopic lung surgery. INTERVENTIONS: Patients were randomized to receive intravenous patient-controlled analgesia (IV-PCA) with hydromorphone alone or hydromorphone combined with S-ketamine (0.5 mg/kg/48 h, 1 mg/kg/48 h, or 2 mg/kg/48 h). MEASUREMENTS: Primary outcome was proportion of patients with moderate-to-severe pain. (numerical rating scale [NRS] pain scores ≥4 when coughing) within 2 days after surgery. Postoperative QoR scores and other prespecified outcomes were also recorded. MAIN RESULTS: Of 242 enrolled patients, 220 were included in the final analysis. The results demonstrated that the incidence of postoperative moderate-to-severe pain was significantly different between the hydromorphone group and combined S-ketamine group (absolute difference, 27.9%; 95% confidence interval [CI], 11.7% to 42.1%; P < 0.001). Patients who received S-ketamine had lower NRS pain scores at rest and when coughing on postoperative day 1 (POD1; median difference 1 and 1, P < 0.001) and postoperative day 2 (POD2; median difference 1 and 1, P < 0.001). The QoR-15 scores were higher in the combined S-ketamine group on POD1 (mean difference 6, P < 0.001) and POD2 (mean difference 6, P < 0.001) than in the hydromorphone group. A higher dose of S-ketamine was associated with deeper sedation. No differences were detected in the other safety outcomes. CONCLUSIONS: Addition of S-ketamine to IV-PCA hydromorphone significantly reduced the incidence of postoperative moderate-to-severe pain and improved the QoR in patients undergoing thoracoscopic lung surgery. TRIAL REGISTRATION: Chinese Clinical Trail Register (identifier: ChiCTR2200058890).

Biomarkers and experimental models for cancer immunology investigation.

The rapid advancement of tumor immunotherapies poses challenges for the tools used in cancer immunology research, highlighting the need for highly effective biomarkers and reproducible experimental models. Current immunotherapy biomarkers encompass surface protein markers such as PD-L1, genetic features such as microsatellite instability, tumor-infiltrating lymphocytes, and biomarkers in liquid biopsy such as circulating tumor DNAs. Experimental models, ranging from 3D in vitro cultures (spheroids, submerged models, air-liquid interface models, organ-on-a-chips) to advanced 3D bioprinting techniques, have emerged as valuable platforms for cancer immunology investigations and immunotherapy biomarker research. By preserving native immune components or coculturing with exogenous immune cells, these models replicate the tumor microenvironment in vitro. Animal models like syngeneic models, genetically engineered models, and patient-derived xenografts provide opportunities to study in vivo tumor-immune interactions. Humanized animal models further enable the simulation of the human-specific tumor microenvironment. Here, we provide a comprehensive overview of the advantages, limitations, and prospects of different biomarkers and experimental models, specifically focusing on the role of biomarkers in predicting immunotherapy outcomes and the ability of experimental models to replicate the tumor microenvironment. By integrating cutting-edge biomarkers and experimental models, this review serves as a valuable resource for accessing the forefront of cancer immunology investigation.

Erratum: Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/ß-catenin signaling: Erratum.

[This corrects the article DOI: 10.7150/thno.30726.].

Kinetics, mechanism, and application of sodium persulfate activated by sodium hydroxide for removing 1,2-dichloroethane from groundwater.

1,2-Dichloroethane (1,2-DCA) is a common compound found in groundwater contaminated with organics. This compound is difficult to remove from groundwater and has the potential to inflict significant harm on human health and the environment. This study used sodium persulfate (Na2S2O8) activated by sodium hydroxide (NaOH) to remove 1,2-DCA from aqueous solutions. Density functional theory was employed to calculate the potential energy surface of the reactants, intermediates, transient states, and products to thoroughly analyze the degradation pathways. The computations were performed in combination with in situ remediation of a 1,2-DCA plume from a point source to verify the industrial applicability of the technology. The results showed the 1,2-DCA removal efficiency was impacted considerably by the Na2S2O8 dosage and the dosing sequence of Na2S2O8 and NaOH, with the mean removal ratio reaching 96.24%. A free radical reaction was the main pathway of 1,2-DCA degradation; superoxide radical (O2•-) existed stably and played a key role in the reaction, and the main transformation proceeded via a vinyl chloride intermediate. The maximum removal of 1,2-DCA reached 91.79% in the in situ remediation. The developed technology exhibits important advantages in enabling flexible control over chemical dosages, long durations of effective activity, and rapid full-cycle remediation.

Rapid detection of hepatitis B virus DNA level based on interval-point data fusion of infrared spectra.

Hepatitis B is an infectious disease cause by the hepatitis B virus (HBV). In recent years, HBV-DNA level clinically gets more attention for its detailed information than other serological markers. Unfortunately, common clinical method for HBV-DNA level detection is limited for its hours consuming. This study combined infrared spectroscopy with machine learning to investigate the feasibility of near-infrared (NIR) and mid-infrared (MIR) spectra for rapid detection of HBV-DNA level. Based on partial least squares-discriminant analysis (PLS-DA) modeling method, the optimal NIR and MIR models and traditional data fusion models were constructed, respectively. Considering inequal weight between interval and point data in machine learning, interval-point data fusion method was used to compare with other traditional date fusion methods. The results of the study illustrate that interval-point data fusion of NIR and MIR spectra combined with PLS-DA modeling can provide a rapid method for HBV-DNA level detection.

An SOI-Structured Piezoresistive Differential Pressure Sensor with High Performance.

This paper presents a piezoresistive differential pressure sensor based on a silicon-on-insulator (SOI) structure for low pressure detection from 0 to 30 kPa. In the design phase, the stress distribution on the sensing membrane surface is simulated, and the doping concentration and geometry of the piezoresistor are evaluated. By optimizing the process, the realization of the pressure sensing diaphragm with a controllable thickness is achieved, and good ohmic contact is ensured. To obtain higher sensitivity and high temperature stability, an SOI structure with a 1.5 µm ultra-thin monocrystalline silicon layer is used in device manufacturing. The device diaphragm size is 700 µm × 700 µm × 2.1 µm. The experimental results show that the fabricated piezoresistive pressure sensor has a high sensitivity of 2.255 mV/V/kPa and a sensing resolution of less than 100 Pa at room temperature. The sensor has a temperature coefficient of sensitivity (TCS) of -0.221 %FS/°C and a temperature coefficient of offset (TCO) of -0.209 %FS/°C at operating temperatures ranging from 20 °C to 160 °C. The reported piezoresistive microelectromechanical systems (MEMS) pressure sensors are fabricated on 8-inch wafers using standard CMOS-compatible processes, which provides a volume solution for embedded integrated precision detection applications of air pressure, offering better insights for high-temperature and miniaturized low-pressure sensor research.

Bimorph Dual-Electrode ScAlN PMUT with Two Terminal Connections.

This paper presents a novel bimorph Piezoelectric Micromachined Ultrasonic Transducer (PMUT) fabricated with 8-inch standard CMOS-compatible processes. The bimorph structure consists of two layers of 20% scandium-doped aluminum nitride (Sc0.2Al0.8N) thin films, which are sandwiched among three molybdenum (Mo) layers. All three Mo layers are segmented to form the outer ring and inner plate electrodes. Both top and bottom electrodes on the outer ring are electrically linked to the center inner plate electrodes. Likewise, the top and bottom center plate electrodes are electrically connected to the outer ring in the same fashion. This electrical configuration maximizes the effective area of the given PMUT design and improves efficiency during the electromechanical coupling process. In addition, the proposed bimorph structure further simplifies the device's electrical layout with only two-terminal connections as reported in many conventional unimorph PMUTs. The mechanical and acoustic measurements are conducted to verify the device's performance improvement. The dynamic mechanical displacement and acoustic output under a low driving voltage (1 Vpp) are more than twice that reported from conventional unimorph devices with a similar resonant frequency. Moreover, the pulse-echo experiments indicate an improved receiving voltage of 10 mV in comparison with the unimorph counterpart (4.8 mV). The validation of device advancement in the electromechanical coupling effect by using highly doped ScAlN thin film, the realization of the proposed bimorph PMUT on an 8-inch wafer paves the path to production of next generation, high-performance piezoelectric MEMS.

Early warning and diagnostic visualization of Sclerotinia infected tomato based on hyperspectral imaging.

This research explored the feasibility of early warning and diagnostic visualization of Sclerotinia infected tomato by using hyperspectral imaging technology. Healthy tomato plants and tomato plants with Sclerotinia sclerotiorum were cultivated, and hyperspectral images at 400-1000 nm were collected from healthy and infected tomato leaves at 1, 3, 5, and 7 days of incubation. After preprocessing the spectra with first derivative (FD), second derivative (SD), standard normal variant (SNV), and multiplicative scatter correction (MSC) partial least squares discriminant analysis (PLS-DA) and support vector machine (SVM) were used to construct tomato sclerotinia identification model and select the best preprocessing method. On this basis, two band screening methods, competitive adaptive reweighted sampling (CARS) and successive projections algorithm (SPA), were introduced to reduce data redundancy and improve the model's prediction accuracy. The results showed that the accuracy of the validation sets and operation speed of the CARS-PLS and CARS-SVM models were 87.88% and 1.8 s, and 87.95% and 1.78 s, respectively. The experiment was based on the SNV-CARS-SVM prediction model combined with image processing, spectral extraction, and visualization analysis methods to create diagnostic visualization software, which opens a new avenue to the implementation of online monitoring and early warning system for sclerotinia infected tomato.

Nondestructive Wafer Level MEMS Piezoelectric Device Thickness Detection.

This paper introduces a novel nondestructive wafer scale thin film thickness measurement method by detecting the reflected picosecond ultrasonic wave transmitting between different interfacial layers. Unlike other traditional approaches used for thickness inspection, this method is highly efficient in wafer scale, and even works for opaque material. As a demonstration, we took scandium doped aluminum nitride (AlScN) thin film and related piezoelectric stacking layers (e.g. Molybedenum/AlScN/Molybdenum) as the case study to explain the advantages of this approach. In our experiments, a laser with a wavelength of 515 nm was used to first measure the thickness of (1) a single Molybdenum (Mo) electrode layer in the range of 100-300 nm, and (2) a single AlScN piezoelectric layer in the range of 600-1000 nm. Then, (3) the combined stacking layers were measured. Finally, (4) the thickness of a standard piezoelectric composite structure (Mo/AlScN/Mo) was characterized based on the conclusions and derivation extracted from the aforementioned sets of experiments. This type of standard piezoelectric composite has been widely adopted in a variety of Micro-electromechanical systems (MEMS) devices such as the Piezoelectric Micromachined Ultrasonic Transducer (PMUT), the Film Bulk Acoustic Resonator (FBAR), the Surface Acoustic Wave (SAW) and more. A comparison between measurement data from both in-line and off-line (using Scanning Electron Microscope) methods was conducted. The result from such in situ 8-inch wafer scale measurements was in a good agreement with the SEM data.

Estimation of chemical oxygen demand in different water systems by near-infrared spectroscopy.

To monitor environmental water pollution effectively and meet human water needs, it is crucial to develop a fast, simple, and accurate method for monitoring chemical oxygen demand (COD) in various water systems. In this study, COD prediction models for different water systems were developed by combining near-infrared (NIR) spectroscopy with partial least squares regression (PLSR). Samples of wastewater, surface water, and seawater were collected from Guangzhou, Guangdong Province, China. Three pretreatment methods were used to preprocess the spectra in order to improve the accuracy and minimalism of the model. We investigate the performance of two variable selection algorithms, namely, binary gray wolf optimization (BGWO) and competitive adaptive reweighting sampling (CARS). The results show that both BGWO and CARS improved the performance of the model in terms of higher accuracy and less wavelength input; both of the combined model performances were better than that of PLSR alone, and CARS-PLSR achieved the best results. Using CARS-PLSR, surface water, wastewater, and seawater model inputs were reduced by 96 %, 96 %, and 82 % as compared to the PLSR results, respectively, and the testing sets R2 reached 0.860, 0.815, and 0.692, respectively. The spectral variable selection algorithm could identify the important spectral variables between COD content and NIR spectra in three water systems, thereby improving the accuracy and simplicity of the PLSR model for COD prediction. Our results have important practical value for predicting COD content in different water systems by NIR spectroscopy.

MiR-4739 inhibits the malignant behavior of esophageal squamous cell carcinoma cells via the homeobox C10/vascular endothelial growth factor A/phosphatidylinositol 3-kinase/AKT pathway.

Esophageal cancer is a lethal disease, and emerging evidence has shown that microRNAs are involved in its development, progression, and clinical outcome. MicroRNAs are potential biomarkers for esophageal squamous cell carcinoma (ESCC), and may be useful in advanced RNA therapy for ESCC. This study was conducted to evaluate the molecular mechanism of miR-4739 in ESCC. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to measure RNA and protein levels. Transwell assay, Cell Counting Kit-8 assay, cytometry analysis, and human umbilical vein endothelial cell tube formation assay were conducted to determine the molecular function of miR-4739 in ESCC. Potential targets of miR-4739 were predicted using bioinformatics tools and confirmed in ESCC cells using a luciferase reporter and RNA pulldown assay. Finally, we performed immunohistochemistry to evaluate the effects of administering agomir-4739 to a mouse model of ESCC. MiR-4739 expression was downregulated in ESCC tissues and cells. MiR-4739 overexpression inhibited cell proliferation, migration, and invasion, and promoted apoptosis of ESCC cells. Furthermore, vascular endothelial growth factor A expression was downregulated by miR-4739 mimics in ESCC cells. MiR-4739 negatively regulated homeobox C10 expression. Additionally, agomir-4739 inhibited tumor growth and angiogenesis in vivo. We demonstrated that miR-4739 overexpression exerted an inhibitory effect on ESCC cells by preventing the expression of homeobox C10 via the vascular endothelial growth factor A/phosphatidylinositol 3-kinase/AKT pathway, indicating the potential of this microRNA as a treatment target in ESCC.

PTBP3 mediates TGF-ß-induced EMT and metastasis of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is associated with a poor prognosis due to early metastasis to distant organs. TGF-ß potently induces epithelial-to-mesenchymal transition (EMT) and promotes invasion and metastasis of cancers. However, the mechanisms underlying this alteration are largely unknown. PTBP3 plays a critical role in RNA splicing and transcriptional regulation. Although accumulating evidence has revealed that PTBP3 exhibits a pro-oncogenic role in several cancers, whether and how PTBP3 mediates TGF-ß-induced EMT and metastasis in LUAD remains unknown. The expression levels and prognostic value of PTBP3 were analyzed in human LUAD tissues and matched normal tissues. siRNAs and lentivirus-mediated vectors were used to transfect LUAD cell lines. Various in vitro experiments including western blot, qRT-PCR, a luciferase reporter assay, chromatin immunoprecipitation (ChIP), transwell migration and invasion assay and in vivo metastasis experiment were performed to determine the roles of PTBP3 in TGF-ß-induced EMT and metastasis. PTBP3 expression was significantly upregulated in patients with LUAD, and high expression of PTBP3 indicated a poor prognosis. Intriguingly, we found that PTBP3 expression level in LUAD cell lines was significantly increased by exogenous TGF-ß1 in a Smad-dependent manner. Mechanistically, p-Smad3 was recruited to the PTBP3 promoter and activated its transcription. In turn, PTBP3 knockdown abolished TGF-ß1-mediated EMT through the inhibition of Smad2/3 expression. Furthermore, PTBP3 overexpression increased lung and liver metastasis of LUAD cells in vivo. PTBP3 is indispensable to TGF-ß-induced EMT and metastasis of LUAD cells and is a novel potential therapeutic target for the treatment of LUAD.

Feasibility evaluation of the transapical saddle-shaped valved stent for transcatheter mitral valve implantation.

BACKGROUND AND AIMS OF STUDY: Transcatheter mitral valve implantation (TMVI) is a promising and minimally invasive treatment for high-risk mitral regurgitation. We aimed to investigate the feasibility of a novel self-expanding valved stent for TMVI via apical access. METHODS: We designed a novel self-expanding mitral valve stent system consisting of an atrial flange and saddle-shaped ventricular body connected by two opposing anchors and two opposing extensions. During valve deployment, each anchor was controlled by a recurrent string. TMVI was performed in 10 pigs using the valve prosthesis through apical access to verify technical feasibility. Echocardiography and ventricular angiography were used to assess hemodynamic data and valve function. Surviving pigs were killed 4 weeks later to confirm stent deployment. RESULTS: Ten animals underwent TMVI using the novel mitral valve stent. Optimal valve deployment and accurate anatomical adjustments were obtained in nine animals. Implantation failed in one case, and the animal died 1 day later due to stent mismatch. After stent implantation, the hemodynamic parameters of the other animals were stable, and valve function was normal. The mean pressure across the mitral valve and left ventricular outflow tract were 2.98 ± 0.91 mmHg and 3.42 ± 0.66 mmHg, respectively. Macroscopic evaluation confirmed the stable and secure positioning of the stents. No obvious valve displacement, embolism, or paravalvular leakage was observed 4 weeks postvalve implantation. CONCLUSIONS: This study demonstrated that the novel mitral valve is technically feasible in animals. However, the long-term feasibility and durability of this valved stent must be improved and verified.

Effects of Preserving the Pulmonary Vagus Nerve Branches on Cough After Pneumonectomy During Video-Assisted Thoracic Surgery.

Background: Cough is one of the most common complications of early-stage non-small cell lung cancer (NSCLC) after video-assisted thoracoscopic surgery (VATS). The vagus nerve plays an important role in pulmonary inflammation and the cough reflex. In this study, we attempted to reduce the incidence of postoperative chronic cough and other complications by preserving the pulmonary vagus nerve branches. Patients and Methods: This study was a randomized controlled double-blinded trial of subjects and observers. A total of 158 NSCLC patients were enrolled. We randomly assigned 79 patients to Group A (pulmonary branch of vagus nerve preservation group) and 79 cases to Group B (conventional surgical treatment group). In the final analysis, 72 patients from Group A and 69 patients from Group B were included. The main outcome measure of the study was the occurrence of CAP or other postoperative complications within five weeks. This trial was registered with ClinicalTrials.gov (number NCT03921828). Results: There was no significant difference in preoperative general clinical data between the two groups. No death during the perioperative period occurred in either of the two groups. There was no significant difference between the two groups in operation time, intraoperative bleeding, number of lymph nodes sent for examination, number of cases transferred to ICU after operation, postoperative catheterization time, or postoperative hospital stay (P>0.05). There was no significant difference in other pulmonary and cardiovascular complications between the two groups, including pulmonary infection (2.78% vs. 8.70%, P = 0.129), atelectasis (1.39% vs. 0%, P = 0.326), pleural effusion (2.78% vs. 1.45%, P = 0.585), persistent pulmonary leakage (2.78% vs. 2.90%, P = 0.965), arrhythmia (2.78% vs. 1.45%, P = 0.585), and heart failure (0% vs. 1.45%, P = 0.305). The incidence of CAP in Group A was significantly lower than that in Group B (13.89% vs. 30.43%, P = 0.018). The LCQ-MC scores in Group A were significantly higher than those in Group B at two and five weeks after operation (P<0.05). Univariate and multivariate analysis showed that the risk factors for postoperative CAP were surgical side (right lung), surgical lung lobe (upper lobe), preservation of pulmonary branch of the vagus nerve during operation, and duration of anesthesia. Conclusions: Preserving the pulmonary vagus nerve branches during VATS in patients with stage IA1-2 NSCLC can reduce the incidence of postoperative CAP.

GDF11 alleviates neointimal hyperplasia in a rat model of artery injury by regulating endothelial NLRP3 inflammasome activation and rapid re-endothelialization.

BACKGROUND: Neointimal hyperplasia induced by interventional surgery can lead to progressive obliteration of the vascular lumen, which has become a major factor affecting prognosis. The rate of re-endothelialization is known to be inversely related to neointima formation. Growth differentiation factor 11 (GDF11) is a secreted protein with anti-inflammatory, antioxidant, and antiaging properties. Recent reports have indicated that GDF11 can improve vascular remodeling by maintaining the differentiated phenotypes of vascular smooth muscle cells. However, it is not known whether and how GDF11 promotes re-endothelialization in vascular injury. The present study was performed to clarify the influence of GDF11 on re-endothelialization after vascular injury. METHODS: An adult Sprague-Dawley rat model of common carotid artery balloon dilatation injury was surgically established. A recombinant adenovirus carrying GDF11 was delivered into the common carotid artery to overexpress GDF11. Vascular re-endothelialization and neointima formation were assessed in harvested carotid arteries through histomolecular analysis. CCK-8 analysis, LDH release and Western blotting were performed to investigate the effects of GDF11 on endothelial NLRP3 inflammasome activation and relevant signaling pathways in vitro. RESULTS: GDF11 significantly enhanced re-endothelialization and reduced neointima formation in rats with balloon-dilatation injury by suppressing the activation of the NLRP3 inflammasome. Administration of an endoplasmic reticulum stress (ER stress) inhibitor, 4PBA, attenuated endothelial NLRP3 inflammasome activation induced by lysophosphatidylcholine. In addition, upregulation of LOX-1 expression involved elevated ER stress and could result in endothelial NLRP3 inflammasome activation. Moreover, GDF11 significantly inhibited NLRP3 inflammasome-mediated endothelial cell pyroptosis by negatively regulating LOX-1-dependent ER stress. CONCLUSIONS: We conclude that GDF11 improves re-endothelialization and can attenuate vascular remodeling by reducing endothelial NLRP3 inflammasome activation. These findings shed light on new treatment strategies to promote re-endothelialization based on GDF11 as a future target.

Spontaneous Rupture of Esophageal Diverticulum-A Case Report and Literature Review.

The spontaneous rupture of the esophageal diverticulum is a rare condition that occurs without any warning signs. Its incidence is low, but the mortality rate is high. This paper reports a case of spontaneous esophageal diverticulum rupture and analyzes it along with 13 other cases to explore its prevention and treatment measures. When patients suffer from chronic swallowing difficulties and chest pain or vomiting that cannot be explained after meals, they should be suspected to have a possible spontaneous rupture of the esophageal diverticulum, which is critical to the patient's prognosis.

Music therapy effect on anxiety reduction among patients with cancer: A meta-analysis.

Introduction: The study aimed to investigate the effect of music therapy on anxiety alleviation among cancer patients. Methods: A comprehensive literature research was performed in four electronic databases (PubMed, Embase, Cochrane Library, and Web of Science). Fifteen randomized controlled trials (RCTs) were included. The risk of bias for the RCTs was evaluated by the Cochrane Risk of Bias tool. Anxiety levels were extracted to synthesize the combined effect by using meta-analysis. All analyses were performed using R version 4.0.4. Results: In total, 15 RCTs met the inclusion criteria involving 1320 cancer patients (662 patients in the experimental group and 658 patients in the controlled group). The majority of interventions were performed with recorded music lasting for 15-60 minutes. Compared with standard care, music intervention had a moderate superiority of anxiety alleviation (SMD: -0.54, 95% CI: [-0.92, -0.16]). Discussion: Music intervention could reduce cancer-related anxiety moderately. Nevertheless, the result should be interpreted with caution as high heterogeneity in this pooled study. Well-designed trials with higher quality were still warranted in the future.

CircRNA-DOPEY2 enhances the chemosensitivity of esophageal cancer cells by inhibiting CPEB4-mediated Mcl-1 translation.

BACKGROUND: Cisplatin-based chemotherapy is a mainstay systematic therapy for advanced esophageal squamous cell carcinoma (ESCC), and cisplatin resistance, which is not uncommon, is the major barrier to improving patient outcomes. Circular RNAs (circRNAs) are novel noncoding RNAs that are implicated in cancer progression, but their involvement in modulating cisplatin responsiveness in ESCC remains unknown. METHODS: Bioinformatics analysis was used to profile and identify the circRNAs involved in cisplatin responsiveness in ESCC. The chemosensitive role of cDOPEY2 was confirmed both in vitro and in vivo. The molecular mechanism of cDOPEY2 was investigated by mass spectrometry, immunoprecipitation, and ubiquitination analyses. RESULTS: We report that a novel circRNA (cDOPYE2, hsa_circ_0008078) was markedly downregulated in cisplatin-resistant ESCC cells (ESCC-CR) compared with parental chemosensitive cells. Re-expression of cDOPEY2 substantially enhanced the cell-killing ability of cisplatin by augmenting the apoptotic process in ESCC-CR cells, which was achieved by decreasing the abundance of the antiapoptotic protein Mcl-1. Mechanistically, we showed that cDOPEY2 acted as a protein scaffold to enhance the interaction between the cytoplasmic polyadenylation element binding protein (CPEB4) and the E3 ligase TRIM25, which in turn facilitated the ubiquitination and degradation of CPEB4. The increased Mcl-1 expression in ESCC-CR cells was dependent on the binding of CPEB4 to its untranslated mRNA, and depletion of CPEB4 mediated by cDOPEY2 reversed this effect. Rescue experiments confirmed that the critical role of cDOPEY2 in maintaining cisplatin sensitivity was dependent on the depletion of CEPB4 and its downstream target Mcl-1. Clinical and in vivo data further corroborated the significant relevance of cDOPEY2 to cisplatin responsiveness in ESCC. CONCLUSIONS: We provide evidence that cDOPEY2 inhibits CPEB4-mediated Mcl-1 translation by promoting the ubiquitination and degradation of CPEB4 to alleviate cisplatin resistance, indicating that cDOPEY2 may serve as a valuable biomarker and potential therapeutic target in ESCC.