Nlrp6 protects from corticosterone-induced NSPC ferroptosis by modulating RIG-1/MAVS-mediated mitophagy.

Hippocampal neural stem/progenitor cells (NSPCs) are highly vulnerable to different stress stimuli, resulting in adult neurogenesis decline and eventual cognitive defects. Our previous study demonstrated that NOD-like receptor family pyrin domain-containing 6 (Nlrp6) highly expressed in NSPCs played a critical role in sustaining hippocampal neurogenesis to resist stress-induced depression, but the underlying mechnistms are still unclear. Here, we found that Nlrp6 depletion led to cognitive defects and hippocampal NSPC loss in mice. RNA-sequencing analysis of the primary NSPCs revealed that Nlrp6 deficiency altered gene expression profiles of mitochondrial energy generation and ferroptotic process. Upon siNlrp6 transfection, as well as corticosterone (CORT) exposure, downregulation of Nlrp6 suppressed retinoic acid-inducible gene I (RIG-1)/mitochondrial antiviral signaling proteins (MAVS)-mediated autophagy, but drove NSPC ferroptotic death. More interesting, short chain fatty acids (SCFAs) upregulated Nlrp6 expression and promoted RIG-1/MAVS-mediated mitophagy, preventing CORT-induced NSPC ferroptosis. Our study further demonstrates that Nlrp6 should be a sensor for RIG-1/MAVS-mediated mitophagy and play a critical role in maintain mitochondrial homeostasis of hippocampal NSPCs. These results suggests that Nlrp6 should be a potential drug target to combat neurodegenerative diseases relative with chronic stress.

A Bioinspired Injectable, Adhesive, and Self-Healing Hydrogel with Dual Hybrid Network for Neural Regeneration after Spinal Cord Injury.

Hydrogel-based regenerated scaffolds show promise as a platform for neural regeneration following spinal cord injury (SCI). Nevertheless, the persistent problem of poor mechanical strength and limited integration with the host tissue still exists. In this study, a bioinspired hydrogel with highly sophisticated features for neural regeneration after SCI is developed. The hydrogel is composed of dihydroxyphenylalanine (DOPA)-grafted chitosan and a designer peptide, offering a unique set of qualities such as being injectable, having self-healing abilities, and adhering to tissues. Compared to conventional hydrogels, this hydrogel ensures a significant promotion of immune response modulation and axon regrowth while featuring synapse formation of various neurotransmitters and myelin regeneration. Subsequently, functional recoveries are enhanced, including motor function, sensory function, and particularly bladder defect repair. These positive findings demonstrate that the hydrogel has great potential as a strategy for repairing SCI. Moreover, the versatility of this strategy goes beyond neural regeneration and holds promise for tissue regeneration in other contexts. Overall, this proposed hydrogel represents an innovative and multifaceted tool for engineering structures in the biomedical field.

Cooperative assembly of a designer peptide and silk fibroin into hybrid nanofiber gels for neural regeneration after spinal cord injury.

Local reconstruction of a permissive environment with biomaterials is a promising strategy to treat spinal cord injury (SCI). We reported a hybrid hydrogel fabricated from a small functional self-assembling peptide (F-SAP) and large silk fibroin (SF). The diffusion of SF micelles into F-SAP solution was driven by the dynamic synergy between osmotic pressure and F-SAP/SF electrostatic interactions, resulting in the rearrangement of SF micelles and the formation of rod-like filaments with axes nearly perpendicular to F-SAP nanofibers. Spectroscopy analysis, including circular dichroism, Raman and fluorescence, indicated conformation changes of SF from random coil to ß sheet, which contributed to enhanced mechanical properties of the resultant hybrid hydrogel. Furthermore, the F-SAP/SF hybrid hydrogel coupled with controlled release of NT-3 provided a permissive environment for neural regeneration by providing nanofibrous substrates for regenerating axons, inflammatory modulation and remyelination, consequently resulting in improved locomotion and electrophysiological properties. This hydrogel could be used as a long-term stent in vivo for the treatment of SCI.

A portable analog front-end system for label-free sensing of proteins using nanowell array impedance sensors.

Proteins are useful biomarkers for a wide range of applications such as cancer detection, discovery of vaccines, and determining exposure to viruses and pathogens. Here, we present a low-noise front-end analog circuit interface towards development of a portable readout system for the label-free sensing of proteins using Nanowell array impedance sensing with a form factor of approximately 35cm2. The electronic interface consists of a low-noise lock-in amplifier enabling reliable detection of changes in impedance as low as 0.1% and thus detection of proteins down to the picoMolar level. The sensitivity of our system is comparable to that of a commercial bench-top impedance spectroscope when using the same sensors. The aim of this work is to demonstrate the potential of using impedance sensing as a portable, low-cost, and reliable method of detecting proteins, thus inching us closer to a Point-of-Care (POC) personalized health monitoring system. We have demonstrated the utility of our system to detect antibodies at various concentrations and protein (45 pM IL-6) in PBS, however, our system has the capability to be used for assaying various biomarkers including proteins, cytokines, virus molecules and antibodies in a portable setting.

Regulations of LINC0196/miR-584-5p/miR-34a-5p/TRIM59 on Progression of Pediatric Neuroblastoma.

This work was to study the regulatory mechanism of large intergenic non-coding RNA 0196 (LINC0196), miR-584-5p, miR-34a-5p, and tripartite motif 59 (TRIM59) on neuroblastoma. The interaction among the four was analyzed to provide a research basis for the clinical treatment of neuroblastoma at the molecular level. The human neuroblastoma SK-N-SH cells were collected and cultured. According to the transfection methods, the cells were divided into control group (without any treatment), si-LINC0196 group (si-LINC0196 transfection), si-LINC0196-NC group (si-LINC0196 vector transfection), miR-584-5p group (miR-584-5p mimic transfection), miR-584-5p-NC group (miR-584-5p inhibitor transfection), miR-34a-5p group (miR-34a-5p mimic transfection), and miR-34a-5p-NC group (miR-34a-5p inhibitor transfection). The proliferation, migration, and apoptosis of SK-N-SH cells in each group were compared. The effects of LINC0196, miR-584-5p, miR-34a-5p, and TRIM59 were evaluated. The expressions of LINC0196 and TRIM59 in SK-N-SH cells in si-LINC0196, miR-584-5p, and miR-34a-5p groups were up-regulated. miR-584-5p and miR-34a-5p in si-LINC0196-NC, miR-584-5p-NC, and miR-34a-5p-NC groups decreased significantly (P < 0.05). The proliferation rate, migration rate, and invasiveness of SK-N-SH cells in miR-584-5p and miR-34a-5p groups were lower than those in si-LINC0196-NC, miR-584-5p-NC, and miR-34a-5p-NC groups, while the apoptosis rate increased (P < 0.05). After miR-584-5p and miR-34a-5p transfections, the relative activities of WT-LINC0196 and WT-TRIM59 dual luciferase were greatly inhibited (P < 0.05). LINC0196 could regulate TRIM59 by regulating miR-584-5p and miR-34a-5p, thereby indirectly regulating cell proliferation, apoptosis, migration, and invasion of SK-N-SH cells.

Electrical Impedance Analysis for Lung Cancer: A Prospective, Multicenter, Blind Validation Study.

Hypothesis: Patients with cancer have different impedances or conductances than patients with benign normal tissue; thus, we can apply electrical impedance analysis (EIA) to identify patients with cancer. Method: To evaluate EIA's efficacy and safety profile in diagnosing pulmonary lesions, we conducted a prospective, multicenter study among patients with pulmonary lesions recruited from 4 clinical centers (Zhongshan Hospital Ethics Committee, Approval No. 2015-16R and 2017-035(3). They underwent EIA to obtain an Algorithm Composite Score or 'Prolung Index,' PI. The classification threshold of 29 was first tested in an analytical validation set of 144 patients and independently validated in a clinical validation set of 418 patients. The subject's final diagnosis depended on histology and a 2-year follow-up. Results: In total, 418 patients completed the entire protocol for clinical validation, with 186 true positives, 145 true negatives, 52 false positives, and 35 false negatives. The sensitivity, specificity, and diagnostic yield were 84% (95% CI 79.3%-89.0%), 74% (95% CI 67.4%-79.8%), and 79% (95%CI 75.3%-83.1%), respectively, and did not differ according to age, sex, smoking history, body mass index, or lesion types. The sensitivity of small lesions was comparable to that of large lesions (p = 0.13). Four hundred eighty-four patients who underwent the analysis received a safety evaluation. No adverse events were considered to be related to the test. Conclusion: Electrical impedance analysis is a safe and efficient tool for risk stratification of pulmonary lesions, especially for patients with a suspicious lung lesion.

Stent-in-stent technique under fluoroscopy for removal of embedded esophageal stent: a retrospective case series.

Background: Treatment of complications after esophageal stent placement and methods for removal of stents need to be improved. The purpose of this study was to evaluate the safety and efficacy of stent-in-stent (SIS) removal of esophageal stent under fluoroscopy. Methods: This study analyzed the clinical data of consecutive patients undergoing esophageal stent removal by the SIS technique under fluoroscopy. The procedure was performed under local anesthesia on conscious sedated patients. Under fluoroscopy, a second esophageal stent was released within the lumen of the first esophageal stent. The second stent was larger than the first, with both ends protruding 1-2 cm beyond the ends of the first stent. Four weeks later, both esophageal stents were removed by the SIS technique under fluoroscopy. All procedures were performed by the same interventional radiologist (with >10 years of experience). Results: A total of 25 patients were treated by the SIS removal technique. In 23 patients, the first esophageal stent was easily removed by the SIS technique; in the other 2 patients, stent fracture occurred, and some residual nitinol wire had to be removed endoscopically. No serious complications occurred in any patient. Conclusions: The SIS removal technique appears to be a safe and effective method for removal of embedded esophageal metallic stents.

Inversion technique under fluoroscopy for removal of self-expanding nitinol esophageal stent after long-term placement: review of 107 consecutive cases.

BACKGROUND: Removal of self-expanding esophageal metal stents that have been implanted for a long time can be difficult and risky. PURPOSE: In this paper, we describe the use of the "inversion technique" under fluoroscopy for removal of self-expandable nitinol esophageal stents that have been placed for long periods and evaluate the effectiveness and safety of the method. METHODS: Retrospective analysis of patients who underwent removal of self-expanding nitinol esophageal stents by the inversion technique under fluoroscopy at our center. Demographic characteristics, type of esophageal stents, stent retention time, reasons for stent removal, and related complications were collected from the case records and analyzed. RESULTS: A total of 112 metal esophageal stents (62 fully covered esophageal stents and 50 partially covered esophageal stents) were extracted from the 107 patients included in the study. Indications for stent implantation were malignant esophageal stenosis (27 patients), benign esophageal stenosis (42 patients), and esophageal fistula (38 patients). Median duration of stent retention was 77 days (29-727 days). All stents were removed successfully without major complications such as esophageal rupture, massive hemorrhage, asphyxia, or cardiorespiratory arrest. CONCLUSION: Inversion technique under fluoroscopy appears to be a safe, effective, and quick procedure for removal of self-expanding nitinol esophageal stent after long-term placement.

Sequential treatment of severe airway stenosis caused by esophageal cancer by using airway stent implantation and arterial infusion chemotherapy.

The purpose of this clinical study was to investigate the efficacy and safety of airway stent implantation and transarterial infusion chemotherapy in the sequential treatment of severe airway stenosis caused by esophageal cancer. Data of patients with advanced esophageal cancer complicated by severe airway stenosis treated with airway stent implantation and transarterial infusion chemotherapy were retrospectively analyzed. Furthermore, dyspnea, clinical efficacy, adverse reactions, and survival of patients were evaluated. 71 patients were included in this study. There were 28 patients with grade III dyspnea and 43 patients with grade IV dyspnea before airway stent implantation, and 34 patients with grade I dyspnea, 35 patients with grade II dyspnea and 2 patients with grade III dyspnea after airway stent implantation. After airway stent implantation and 1-3 courses of transarterial infusion chemotherapy, 11, 41 and 19 patients had complete response, partial response and stable response respectively. Total disease control rate (DCR) and objective response rate (ORR) were 100.0% and 73.2%, respectively. During the follow-up, 32 patients died of organ failure, 24 patients died of tumor-related respiratory failure, and 10 patients died of gastrointestinal bleeding. The median survival time of all patients was 8 months, and the 1-year survival rate was 40.8%. Airway stent implantation combined with arterial infusion chemotherapy is safe and effective for sequential treatment of esophageal cancer with severe airway stenosis.

Safety and efficacy of large balloon dilatation under fluoroscopy.

The maximum diameter of the balloon used for balloon dilatation(BD) of esophagogastric anastomotic stricture (EAS) is generally 20 millimeters. This study aimed to evaluate the safety and efficacy of BD under fluoroscopy, using balloons with a diameter of 25-30 millimeters. We retrospectively analyzed the data of patients with benign EAS treated by large BD (balloon diameter, 25-30 mm) under fluoroscopy. The Cox proportional hazards model (PHM) was used to identify the factors associated with stricture-free survival. The results show that a total of 127 patients were included in this study, and 204 BDs were performed. The technical success rate was 96.6%, and the clinical success rate was 99.2%. The incidence of serious adverse events was 3.4% (7/204). One patient died of massive hemorrhage during BD, and nine patients were lost to follow-up. For the remaining 117 patients, the median stricture-free survival period was 14.9 months. In multivariable analysis using the Cox PHM, only balloon diameter was significantly associated with stricture-free survival. The stricture-free survival period tended to increase as balloon diameter increased. Large BD under fluoroscopy appears to be safe and effective for the treatment of benign EAS after esophagectomy.

Maritimibacter alexandrii sp. nov., a New Member of Rhodobacteraceae Isolated from Marine Phycosphere.

Marine phycosphere hosts cross-kingdom algae-bacteria interactions playing a variety of crucial roles in aquatic ecosystems especially for the prevention and control of harmful algal blooms (HABs). During the investigation of structural composition of phycosphere microbiota (PM) of diverse marine HAB dinoflagellates, a Gram-negative, strictly aerobic, non-motile and rod-shaped bacterium designated LZ-17T was isolated from the phycosphere of highly toxic Alexandrium catenella LZT09. The 16S rRNA gene sequence analysis and the multilocus sequence analysis (MLSA) based on five protein-coding housekeeping genes (atpD, gyrB, mutL, topA and rpoD) indicated that strain LZ-17T was affiliated to the genus Maritimibacter within the family Rhodobacteraceae, and closely related to Maritimibacter alkaliphilus HTCC2654T (99.1%), 'Maritimibacter harenae' DP07T (97.9%) and M. lacisalsi X12M-4T (95.7%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain LZ-17T and the type strain of M. alkaliphilus were 96.9% and 74.7%. However, strain LZ-17T could be clearly distinguished from its closest by the phenotypical and phenotypical characteristics. Strain LZ-17T contained Q-10 as its major isoprenoid quinone, and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), C16:0 and C16:0 2-OH as the predominant fatty acids (>10%). The major polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylcholine. The DNA G + C content was 64.3 mol%. Based on the polyphasic taxonomic characterization, strain LZ-17T represents a novel species of the genus Maritimibacter, for which the name Maritimibacter alexandrii sp. nov. is proposed, with the type strain LZ-17T (=CCTCC 2019005T = KCTC 72193T).

Arterial Infusion Chemotherapy for Neoplastic Esophagogastric Anastomotic Strictures After Esophagectomy.

BACKGROUND: Neoplastic esophagogastric anastomotic strictures after resection of esophageal cancer is a very difficult problem in clinical practice. We aim at to investigate the safety and feasibility of arterial infusion chemotherapy in treatment of neoplastic esophagogastric anastomotic strictures after esophagectomy. METHODS: From October 2014 to December 2019, 50 patients with Neoplastic esophagogastric anastomotic strictures after resection of esophageal cancer were assessed retrospectively. Preoperative dysphagia was grade III in 34 cases and grade IV in 16 cases. Thirty-eight patients had different degrees of dyspnea before surgery Twenty-five patients had intolerable (grade IV) dyspnea and airway stenting was undertaken before surgery. Thirteen patients had tolerable dyspnea that did not require airway stenting, and preoperative dyspnea was grade III. RESULTS: All patients were successfully treated with arterial infusion chemotherapy, no paraplegia or death occurred. The dysphagia grade of 50 patients after AIC was compared: one case had grade I, 40 cases had grade II, and nine cases had grade III. Thirteen patients had tolerable dyspnea that did not necessitate airway stenting. Dyspnea was classified as grade I in five cases and grade II in eight cases. After 1-3 courses of AIC, 50 patients were followed up for a complete response (eight cases), partial response (28) and stable disease (14 cases). Total objective effective rate (complete response+ partial response) and disease control rate(complete response + partial response + stable disease)were 72.0% and 100.0%, respectively. The median duration of follow-up was 8.5 months. One-year survival was 46.0%. CONCLUSION: Arterial infusion chemotherapy is safe and efficacious treatment for Neoplastic esophagogastric anastomotic strictures after esophagectomy.

MicroRNA-499 serves as a sensitizer for lung cancer cells to radiotherapy by inhibition of CK2α-mediated phosphorylation of p65.

The present study aimed to define the tumor-suppressive role of microRNA-499 (miR-499) in lung cancer cells and its underlying mechanism. First, qRT-PCR analysis revealed poor expression of miR-499 in clinical samples and cell lines of lung cancer. Next, we performed loss- and gain-of-function experiments for the expression of miR-499 in lung cancer cells exposed to irradiation (IR) to determine the effect of miR-499 expression on cell viability and apoptosis as well as tumor growth. Results showed that overexpression of miR-499 inhibited cell viability, enhanced the radiosensitivity of lung cancer cells, and promoted cell apoptosis under IR. Furthermore, CK2α was verified to be a target of miR-499, and miR-499 was identified to repress p65 phosphorylation by downregulating CK2α expression, which ultimately diminished the survival rate of lung cancer cells under IR. Collectively, the key findings of the study illustrate the tumor-inhibiting function of miR-499 and confirmed that miR-499-mediated CK2α inhibition and altered p65 phosphorylation enhances the sensitivity of lung cancer cells to IR.

Clinical Evaluation of Transarterial Infusion Chemotherapy for Advanced Esophageal Cancer.

Background: Most esophageal cancer patients are diagnosed at an advanced stage when there are few effective treatments. Transarterial infusion chemotherapy is a local chemotherapy method wherein chemotherapeutic drugs are directly injected into tumor vessels. Methods: Transarterial infusion chemotherapy was performed on advanced esophageal cancer patients once a month, and each patient underwent 1-3 treatments. The clinical results, complications, and effectiveness rates of each treatment episode were recorded and analyzed. Results: Transarterial infusion chemotherapy was successfully performed in all patients, and no severe complications such as paraplegia or death were noted. Complete response, partial response, and stable disease were noted in 17.3% (13/75), 77.3% (58/75), and 5.3% (4/75) of cases after transarterial infusion chemotherapy, respectively. The total treatment efficacy (complete response + partial response) was 94.7%. All cases exhibited improvement in clinical stage, with a marked decrease in dysphagia. Subsequent treatments were administered to 13 patients, including radical radiation in 7 and chemotherapy in 6. During follow-up, death was caused by progressive carcinoma in 20, tumor-related pneumatic infection and respiratory failure in 11, and gastrointestinal hemorrhage in 17. The median survival time was 15 months and the 1-year survival rate was 58.1%. Conclusions: Transarterial infusion chemotherapy may be safely and effectively used for treatment of advanced esophageal cancer.

Montmorillonite-supported nanoscale zero-valent iron for thiamethoxam removal: response surface optimization and degradation pathway.

As a highly efficient insecticide, thiamethoxam was widely used in the world. However, it was bioaccumulative and toxic to aquatic organisms that must be removed from water. In this work, nanoscale zero-valent iron particles loaded on montmorillonite (nZVI/Mt) were successfully synthesized for effective removal of thiamethoxam. The properties of nZVI/Mt for the removal of thiamethoxam were investigated, and the reaction conditions were optimized through response surface methodology. Furthermore, the degradation products were analyzed by liquid chromatography-mass spectrometry (LC/MS). The results demonstrated that the reaction activity of nZVI was enhanced because the agglomeration and oxidation of nZVI particles were effectively inhibited by using montmorillonite as a support. The significance of the effects of each factor on the removal of thiamethoxam was determined to be in the order of pH Ëƒ temperature Ëƒ reaction time Ëƒ nZVI/Mt dosage. The optimal conditions were as follows: a dosage of nZVI/Mt of 2 g/L, a reaction time of 2 h, a reaction temperature of 35 °C, and a solution pH of 3. The removal efficiency of thiamethoxam (C0 = 20 mg/L) was observed to be as high as 94.29% under the optimal conditions, which was close to the value of 94.47% that was predicted using the mathematical model, indicating that the model could accurately predict the removal efficiency of thiamethoxam. The degradation mechanism involved the -NO2 group on the thiamethoxam molecule was reduced and eliminated by nZVI/Mt.

Self-Expandable Metallic Stent Implantation Combined With Bronchial Artery Infusion Chemoembolization in the Treatment of Lung Cancer With Complete Atelectasis.

BACKGROUND: Atelectasis is a common complication of lung cancer, and there are few reports about the treatment methods. This study retrospectively analyzed the safety and effectiveness of endotracheal metal stent implantation combined with arterial infusion chemoembolization in the treatment of non-small cell lung cancer with complete atelectasis. METHODS: The clinical data of patients with non-small cell lung cancer and complete atelectasis treated by self-expandable metallic stent implantation combined with arterial infusion chemotherapy were retrospectively analyzed. The clinical efficacy was evaluated and postoperative adverse reactions were observed. Progression-free survival and overall survival were analyzed by Kaplan-Meier method. RESULTS: In all, 42 endotracheal metallic stents were implanted in 42 patients under fluoroscopy. 5-7 days after stent implantation, CT showed that 24 patients (57.1%) had complete lung recruitment, and that 13 (31.0%) had partial lung recruitment. The technical success rate was 100%, and the clinical success rate was 88.1% (37/42). 5-7 days after stent implantation, bronchial artery infusion chemoembolization was performed in all patients. The median progression-free survival and overall survival were 6 months (95% CI: 2.04-9.66) and 10 months (95% CI: 7.22-12.79), respectively. CONCLUSION: Self-expandable metallic stent implantation combined with arterial infusion chemoembolization may be an effective and safe strategy in the treatment of lung cancer with atelectasis clinically.

Rapid Assessment of Surface Markers on Cancer Cells Using Immuno-Magnetic Separation and Multi-frequency Impedance Cytometry for Targeted Therapy.

The rapid qualitative assessment of surface markers on cancer cells can allow for point-of-care prediction of patient response to various cancer drugs. Preclinical studies targeting cells with an antibody to "activated" matriptase conjugated to a potent toxin show promise as a selective treatment for a variety of solid tumors. In this paper, we implemented a novel technique for electrical detection of proteins on surfaces of cancer cells using multi-frequency microfluidic impedance cytometry. The biosensor, consists of two gold microelectrodes on a glass substrate embedded in a PDMS microfluidic channel, is used in conjugation with immuno-magnetic separation of cancer cells, and is capable of differentiating between bare magnetic beads, cancer cells and bead-cell aggregates based on their various impedance and frequency responses. We demonstrated proof-of-concept based on detection of "activated" matriptase proteins on the surface of cultured Mantle cells.

Molecular and Immune Characteristics for Lung Adenocarcinoma Patients With ERLIN2 Overexpression.

Background: Endoplasmic reticulum lipid raft-associated protein 2 (ERLIN2) is protein contained in the membrane of the endoplasmic reticulum. In lung adenocarcinoma (LUAD), the molecular function of ERLIN2 and the correlation between ERLIN2 and tumor-infiltrating immune cells have been unclear. The aim of our study was to determine the role of ERLIN2 in LUAD development to provide a better understanding of the molecular pathogenesis of this disease and identify new therapeutic targets for its treatment. Methods: Immunohistochemistry, Western blotting, and real-time quantitative polymerase chain reaction were used to detect protein and mRNA levels of ERLIN2 in LUAD and adjacent normal tissues. Using the A549, H1299 cell line, ERLIN2-short hairpin RNA was applied to silence ERLIN2 to determine its role in LUAD cell proliferation and invasion. Based on mRNA expression of ERLIN2 from the Cancer Genome Atlas (TCGA) database, we identified ERLIN2-related protein-coding genes and analyzed the Kyoto Encyclopedia of Genes and Genomes pathway to explore its potential biological functions and determined the correlation between ERLIN2 and tumor-infiltrating immune cells. Results: ERLIN2 was abnormally expressed in a variety of tumor tissues and is highly expressed in LUAD. This overexpression was associated with histological grade (P = 0.044), TNM stage (P = 0.01), and lymph node metastasis (P = 0.038). Patient overall survival was poorer with ERLIN2 overexpression. Downregulation of ERLIN2 inhibited LUAD cell proliferation and invasion in vitro. Based on mRNA expression of ERLIN2 from the TCGA database, 13 ERLIN2-related genes and 10 pathways were identified and showed a correlation between ERLIN2 and naive B cells and neutrophils. Conclusion: ERLIN2 could serve as a potential diagnostic and prognostic biomarker for LUAD and has demonstrated to be correlated with immune infiltrates, which suggests that it may represent a new therapeutic target for LUAD.

Toward point-of-care assessment of patient response: a portable tool for rapidly assessing cancer drug efficacy using multifrequency impedance cytometry and supervised machine learning.

We present a novel method to rapidly assess drug efficacy in targeted cancer therapy, where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor cells. We have fabricated and characterized a device capable of rapidly assessing tumor cell sensitivity to drugs using multifrequency impedance spectroscopy in combination with supervised machine learning for enhanced classification accuracy. Currently commercially available devices for the automated analysis of cell viability are based on staining, which fundamentally limits the subsequent characterization of these cells as well as downstream molecular analysis. Our approach requires as little as 20 µL of volume and avoids staining allowing for further downstream molecular analysis. To the best of our knowledge, this manuscript presents the first comprehensive attempt to using high-dimensional data and supervised machine learning, particularly phase change spectra obtained from multi-frequency impedance cytometry as features for the support vector machine classifier, to assess viability of cells without staining or labelling.