Neuroinvasive virus facilitates viral replication by employing lipid droplets to reduce arachidonic acid-induced ferroptosis.

Lipids have been previously implicated in the lifecycle of neuroinvasive viruses. However, the role of lipids in programmed cell death and the relationship between programmed cell death and lipid droplets (LDs) in neuroinvasive virus infection remains unclear. Here, we found that the infection of neuroinvasive virus, such as rabies virus and encephalomyocarditis virus could enhance the LD formation in N2a cells, and decreasing LDs production by targeting diacylglycerol acyltransferase could suppress viral replication. The lipidomics analysis revealed that arachidonic acid (AA) was significantly increased after reducing LD formation by restricting diacylglycerol acyltransferase, and AA was further demonstrated to induce ferroptosis to inhibit neuroinvasive virus replication. Moreover, lipid peroxidation and viral replication inhibition could be significantly alleviated by a ferroptosis inhibitor, ferrostatin-1, indicating that AA affected neuroinvasive virus replication mainly through inducing ferroptosis. Furthermore, AA was demonstrated to activate the acyl-CoA synthetase long-chain family member 4-lysophosphatidylcholine acyltransferase 3-cytochrome P450 oxidoreductase axis to induce ferroptosis. Our findings highlight novel cross-talks among viral infection, LDs, and ferroptosis for the first time, providing a potential target for antiviral drug development.

Restraint Stress, Foot Shock and Corticosterone Differentially Alter Autophagy in the Rat Hippocampus, Basolateral Amygdala and Prefrontal Cortex.

Autophagy is a conserved lysosomal degradation process that has recently been found to be associated with stress-related psychological diseases. However, previous studies have yielded inconsistent results regarding the effects of various stress patterns on autophagy in different brain regions. This discrepancy may arise from differences in autophagy flux across nuclei, the type of stress experienced, and the timing of autophagy assessment after stress exposure. In this study, we assessed autophagy flux in the rat hippocampus (HPC), medial prefrontal cortex (mPFC), and basal lateral amygdala (BLA) by quantifying protein levels of p-ULK1, LC3-I, LC3-II, and p62 via Western blot analysis at 15 min, 30 min, and 60 min following various stress paradigms: restraint stress, foot shock, single corticosterone injection, and chronic corticosterone treatment. We found that: (1) hippocampal autophagy decreased within 1 h of restraint stress, foot shock, and corticosterone injection, except for a transient increase at 30 min after restraint stress; (2) autophagy increased 1 h after restraint stress and corticosterone injection but decreased 1 h after foot shock in mPFC; (3) In BLA, autophagy increased 1 h after foot shock and corticosterone injection but decreased 1 h after restraint stress; (4) Chronic corticosterone increased autophagy in mPFC and BLA but had no effects in HPC. These findings suggest that stress regulates autophagy in a brain region- and stressor-specific manner within 1 h after stress exposure, which may contribute to the development of stress-related psychological disorders.

Predicting dissolved oxygen level using Young's double-slit experiment optimizer-based weighting model.

Accurate prediction of the dissolved oxygen level (DOL) is important for enhancing environmental conditions and facilitating water resource management. However, the irregularity and volatility inherent in DOL pose significant challenges to achieving precise forecasts. A single model usually suffers from low prediction accuracy, narrow application range, and difficult data acquisition. This study proposes a new weighted model that avoids these problems, which could increase the prediction accuracy of the DOL. The weighting constructs of the proposed model (PWM) included eight neural networks and one statistical method and utilized Young's double-slit experimental optimizer as an intelligent weighting tool. To evaluate the effectiveness of PWM, simulations were conducted using real-world data acquired from the Tualatin River Basin in Oregon, United States. Empirical findings unequivocally demonstrated that PWM outperforms both the statistical model and the individual machine learning models, and has the lowest mean absolute percentage error among all the weighted models. Based on two real datasets, the PWM can averagely obtain the mean absolute percentage errors of 1.0216%, 1.4630%, and 1.7087% for one-, two-, and three-step predictions, respectively. This study shows that the PWM can effectively integrate the distinctive merits of deep learning methods, neural networks, and statistical models, thereby increasing forecasting accuracy and providing indispensable technical support for the sustainable development of regional water environments.

Enhance PD/A biofilm formation via a novel biochar/tourmaline modified-biocarriers to treat low-strength contaminated surface water: Initial adhesion and high-substrate microenvironment.

In this work, a novel polyurethane carrier modified with biochar and tourmaline/zeolite powder at ratio of 1:1 and 1:2 was developed to promote the formation of biofilms and the synergy of overall bacterial activity for Partial Denitrification/Anammox to treat low-nitrogen contaminated surface water. Based on the batch experiment, the modified biocarrier, BTP2 (biochar: tourmaline = 2: 1), exhibited the highest total nitrogen removal efficiency (83.63%) under influent total nitrogen of 15 mg/L and COD/NO3- of 3. The dense biofilm was formed in inner side of biocarrier owing to the increased surface roughness and various functional groups suggested by scanning electron microscopy and Fourier-transform infrared analysis. The EPS content increased from 200.15 to 220.26 mg/g VSS in BTP2 system. Besides, the rapid NH4+ capture and organics release of the modified carrier fueled the growth of anammox and denitrification bacteria, with the activity of 2.13 ± 0.52 mg N/gVSS/h and 6.70 ± 0.52 mg N/gVSS/h (BTP2). High-throughput sequencing unraveled the increased abundances of Candidatus_Competibacter (0.82%), Thauera (0.60%) and Candidatus_Brocadia (0.55%) which was responsible for the synergy of incomplete reduction of NO3- to NO2- and NH4+ oxidation. Overall, this study provided a valid and simple-control guide for biofilm formation towards rapid enrichment and great collaboration of Anammox and denitrification bacteria.

Fine particles removal of pyrolysis gasification flue gas from rural domestic waste: Laboratory research, molecular dynamics simulation, and applications.

Chinese rural domestic waste has increased considerably with the modernization of agriculture and urbanization. Pyrolysis gasification is a common high-temperature waste treatment method. However, this method is usually accompanied by a large amount of particle emission. In this study, a rural domestic waste pyrolysis gasification station in Gansu Province, Northwest China, was selected for research. The particle emission characteristics of this station were analyzed, and the results showed that the original particle removal technologies were inefficient in fine particles. Hence, a new method of fine particle treatment, i.e., Cloud-Air-Purifying (CAP) technology, was explored herein. In CAP, fine particles grow in size via heterogeneous condensation in a supersaturated water vapor environment and are then collected efficiently using a supergravity field. A laboratory-scale pyrolysis gasifier and CAP equipment were built. Moreover, the CAP removal efficiency for particles generated from four typical rural domestic waste categories was studied. The results showed that CAP technology considerably increased the efficiency of fine particle removal. However, the removal efficiency for particles released owing to the incineration of wood was only ∼75%. This was because the tar substances formed during wood pyrolysis were attached to the surface of escaping particles, which led to a decrease in their hydrophilicity and particle condensation growth. To address this issue, the improvement in particle hydrophilicity using different surfactants was studied via molecular dynamic simulations. When the increase in water molecule adsorption, surface polarity, and the solid-liquid interaction energy for different surfactants were compared, alkylphenol ethoxylate (OP10) proved to be the most effective surfactant. Finally, the improved CAP technology combined with OP10 was applied to the on-site pyrolysis gasification flue gas treatment. Long term monitoring of the proposed technology revealed that particle removal efficiency remained >94%, exhibiting excellent fine particle removal. The successful application of the proposed technology demonstrates its potential for further application.

Ensemble system for short term carbon dioxide emissions forecasting based on multi-objective tangent search algorithm.

Carbon emissions play a crucial role in inducing global warming and climate change. Accurate and stable carbon emissions forecasting is beneficial for formulating emissions reduction schemes and achieving carbon neutrality as early as possible. Although previous studies have concentrated on employing one or several methods for carbon emissions forecasting, the improvement in forecasting performance is limited because they ignore the importance of objectively selecting the models and the necessity of interval forecasting. In this paper, a novel ensemble prediction system, composed of data decomposition, model selection, phase space reconstruction, ensemble point prediction, and interval prediction, is proposed to conduct both point and interval predictions, which has been proven to be effective in prompting carbon emissions forecasting accuracy and stability. According to the empirical results, the mean MAPE results of our proposed forecasting strategy in point prediction are 1.1102% (in Dataset A) and 1.1382% (in Dataset B), and the mean CWC values in the interval forecasting are 0.3512 and 0.1572, respectively. Thus, the proposed forecasting system improves the forecasting performance relative to other models considerably, which can provide meaningful references for policymakers.

Regulation of cyp26a1 on Th17 cells in mouse peri-implantation.

Cytochrome P450 26A1 (cyp26a1) is expressed in the mouse uterus during peri-implantation. The repression of this protein is closely associated with a reduction in implantation sites, suggesting a specific role for cyp26a1 in pregnancy and prompting questions concerning how a metabolic enzyme can generate this distinct outcome. To explore the effective downstream targets of cyp26a1 and confirm if its role in peri-implantation depends on its metabolic substrate RA (retinoic acid), we characterized the changes in the peripheral blood, spleen and uterine implantation sites using the cyp26a1 gene vaccine constructed before. Flow cytometry results showed a significant increase in CD4(+) RORγt(+) Th17 cells in both the peripheral blood and spleen in the experimental group. The expression of RORγt and IL-17 presented the Th17 cells reduction in uterus followed by the suppression of cyp26a1 expression. For greater certainty, cyp26a1 antibody blocking model and RNA interference model were constructed to determine the precise target immune cell group. High performance liquid chromatography results showed a significant increase in uterine at-RA followed by the immunization of cyp26a1 gene vaccine. Both the ascertain by measuring RARα protein levels in peri-implantation uterus after gene vaccine immunization and researches using the specific agonist and antagonist against RARα suggested that RARα may be the main RA receptor for signal transduction. These results provided more evidence for the signal messenger role of RA in cyp26a1 regulation from the other side. Here, we showed that the cyp26a1-regulated Th17 cells are dependent on at-RA signalling, which is delivered through RARα in mouse peri-implantation.

Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application.

Lung cancer poses a global threat to human health, while common cancer treatments (chemotherapy and targeted therapies) have limited efficacy. Immunotherapy offers hope of sustained remission for many patients with lung cancer, but a significant proportion of patients fail to respond to treatment owing to immune resistance. There is extensive evidence to suggest the immunosuppressive microenvironment as the cause of this treatment failure. Numerous studies have suggested that the adenosine (ADO) pathway plays an important role in the formation of an immunosuppressive microenvironment and may be a key factor in the development of immune resistance in EGFR-mutant cell lung cancer. Inhibition of this pathway may therefore be a potential target to achieve effective reversal of ADO pathway-mediated immune resistance. Recently, an increasing number of clinical trials have begun to address the broad prospects of using the ADO pathway as an immunotherapeutic strategy. However, few researchers have summarized the theoretical basis and clinical rationale of the ADO pathway and immune checkpoint dual blockade in a systematic and detailed manner, particularly in lung cancer. As such, a timely review of the potential value of the ADO pathway in combination with immunotherapy strategies for lung cancer is warranted. This comprehensive review first describes the role of ADO in the formation of a lung tumor-induced immunosuppressive microenvironment, discusses the key mechanisms of ADO inhibitors in reversing lung immunosuppression, and highlights recent evidence from preclinical and clinical studies of ADO inhibitors combined with immune checkpoint blockers to improve the lung cancer immunosuppressive microenvironment.

Copper Phenylacetylide and TiO2 Modification for an Efficient Visible-Light-Driven Oxidative Coupling of Amines.

The selective oxidation of amines to imines under mild conditions has attracted much attention. Our study reveals that copper phenylacetylide (PhC2Cu) could serve as an efficient photocatalyst for imine synthesis under visible-light irradiation (>400 nm). Utilizing benzylamine as a model reactant, PhC2Cu achieves an imine yield of 50.4%, which is 5 times higher than that of P25 under the same conditions and comparable to the yield obtained by the 3 wt % Au/P25 photocatalyst (55.4%). Further loading 3.9 nm TiO2 onto PhC2Cu through tetrabutyl titanate hydrolysis increases the imine yield to 84.7%, with a Ti:Cu atomic ratio of 3.65%. Control experiments, photoluminescence (PL) spectra, optical pump terahertz probe (OPTP) spectra, and electron spin resonance (ESR) tests confirm that the optimized TiO2 modification promotes the separation of excited carriers and electron transfer in PhC2Cu and facilitates the activation of surface oxygen, thereby enhancing the formation of superoxide radicals, a key active oxygen species in the reaction system. This work presents a promising strategy for efficient imine synthesis via amine coupling and expands the application field of PhC2Cu-based photocatalysts.

Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancer.

BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. RESULTS: A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Advanced diseases and metastases to other organs would be fit for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. CONCLUSION: ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.

Efficacy of Xianling Gubao capsule vs. its combination therapy in the treatment of primary osteoporosis: A network meta-analysis of randomized controlled trials.

Objective: This study aimed to evaluate the efficacy of the Xianling Gubao (XLGB) capsule alone and its combination therapy in primary osteoporosis (POP). Methods: Databases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and SinoMed were searched from their inception to January 16, 2024, for randomized controlled trials (RCTs) investigating the XLGB treatment for POP. A network meta-analysis (NMA) was performed to evaluate the efficacy and safety of multiple interventions in the treatment of POP. The Cochrane risk-of-bias tool was used to assess the quality of RCTs included in the meta-analysis. Software Stata (version 15.0) was used for statistical analysis. The surface under the cumulative ranking curve (SUCRA) method was used to present the findings from this NMA numerically and graphically by ranking multiple interventions. Results: A total of 107 RCTs were included in the meta-analysis, involving 10,032 participants and 21 interventions. Meta-analysis showed that XLGB + calcium (Ca) + calcitonin (99.9 %) was the most desirable treatment option for improving clinical efficacy. XLGB + Ca + bisphosphonate (BP) was most effective for improving bone mineral density (BMD) at the lumbar spine, femoral neck BMD, and serum bone Gla protein (BGP). SUCRA values for improving these three outcome measures by XLGB + Ca + BP were 87.4 %, 77.2 %, and 84.3 %, respectively. XLGB + calcitonin was the optimal option in terms of safety evaluation and improving visual analogue scale (VAS), with the SUCRA values being 89.6 % and 94.9 %, respectively. Conclusions: The XLGB combination therapy is a desirable option for treating POP as it can effectively improve the therapeutic effects, BMD, and serum BGP, as well as relieve pain in patients with POP.

Lymph node dissection in small-sized pulmonary metastasectomy: Impact on the long-term survival.

INTRODUCTION: Pulmonary metastasectomy has been clarified in improving long-term survival in most primary malignancies with pulmonary metastasis, while the role of additional lymph node dissection remained controversial. We aimed to investigate the prognosis of lymph node involvement and identify the role of lymph node dissection during pulmonary metastasectomy in a real-world cohort. METHODS: We identified patients diagnosed with pulmonary metastases with ≤3 cm in size and received pulmonary metastasectomy between 2004 and 2017 in the Surveillance, Epidemiology, and End Results database. We compared the survival via Kaplan-Meier analysis and propensity score matching method, and the multivariable analysis was conducted by cox regression analysis. RESULTS: A total of 3452 patients were included, of which 2268(65.7%) received lymph node dissection, and the incidence of node-positive was 11.3%(256/2268). In total, the median overall survival was 62.8 months(interquartile range, 28.6-118.9 months), and the lymph node involvement was referred to an impaired survival compared to node-negative diseases(5-year overall survival rate, 58.0% versus 38.6%), with comparable survival between N1 and N2 diseases(P = 0.774). Lymph node dissection was associated with improved survival(HR = 0.80; 95%CI, 0.71-0.90; P < 0.001), and the survival benefits remained regardless of age, sex, the number of metastases, and surgical procedures, even in those with node-negative diseases. At least eight LNDs might lead to a significant improvement in survival, and additional survival benefits might be limited with additional dissected lymph nodes. CONCLUSIONS: Lymph node involvement was associated with impaired survival, and lymph node dissection during pulmonary metastasectomy could improve long-term survival and more accurate staging.

Rapid enrichment of AnAOB with a novel vermiculite/tourmaline modification technology for enhanced DEAMOX process.

The DEnitrifying AMmonium OXidation (DEAMOX) has been proven to be a promising process treating contaminated surface water containing ammonia and nitrate, while the enrichment of the slow-growing anammox bacteria (AnAOB) remains a challenge. In this study, a novel polyurethane-adhesion vermiculite/tourmaline (VTP) modified carrier was developed to achieve effective enrichment of AnAOB. The results demonstrated that the VTP-1 (vermiculite: tourmaline = 1:1) system exhibited the greatest performance with the total nitrogen removal efficiency reaching 87.6% and anammox contributing 63% to nitrogen removal. Scanning electron microscope analysis revealed the superior biofilm structure of the VTP-1 carrier, providing attachment for AnAOB. The addition of VTP-1 promoted the secretion of EPS (extracellular polymeric substances) by microorganisms, which increased to 85.34 mg/g VSS, contributing to the aggregation of anammox cells. The favorable substrate microenvironment created by NH4+ adsorption and NO2- supply via partial denitrification process facilitated the growth of AnAOB. The relative abundance of Candidatus Brocadia and Thauera increased from 0.04% to 0.3%-1.03% and 2.06% in the VTP-1 system, respectively. This study sheds new light on the anammox biofilm formation and provides a valid approach to initiate the DEAMOX process for low nitrogen polluted water treatment.

Effects of tea residues-fermented feed on production performance, egg quality, antioxidant capacity, caecal microbiota, and ammonia emissions of laying hens.

This study was to assess the effects of tea residues-fermented feed (TR-fermented feed) on production performance, egg quality, serum antioxidant capacity, caecal microbiota, and ammonia emissions of laying hens. A total of 1,296 Lohmann laying hens have randomly distributed four groups with six parallels and fed with diets TR-fermented feed at the rates of 0 (control), 1, 3, and 5%. The inclusion of 1% (TR)-fermented feed resulted in a significant increase in egg-laying rate and average egg weight of birds, and a reduction in the feed-to-egg ratio when compared to the control group (p < 0.05). The addition of 1 and 3% of (TR)-fermented feed significantly improved the Haugh unit of eggs (p < 0.05). The eggshell thickness was observed to increase by almost one-fold upon the inclusion of 3 and 5% (TR)-fermented feed in the basal diet (p < 0.05). The supplementation of 3% (TR)-fermented feed significantly increased the content of methionine, tyrosine, proline, essential amino acids (EAA), alpha linoleic acid (C18:3n6), docosanoic acid (C22:0), docosahexaenoic acid (C22:6n3), twenty-three carbonic acids (C23:0), ditetradecenoic acid (C24:1) and total omega-3 polyunsaturated fatty acids (∑ω-3 PUFA) in the eggs (p < 0.05). The addition of a certain amount of (TR)-fermented feed can enhance the activity of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in chicken serum, and reduce the level of malondialdehyde (MDA) (p < 0.05). The ammonia concentration in the hen house of laying hens in the treatment groups decreased significantly (p < 0.05). Bacteroidetes and Firmicutes, the main phyla in the cecal bacterial community, were differentially abundant in each group, comprising greater than 55 and 33%, respectively. Collectively, this research indicates that (TR)-fermented feed supplementation improves the performance of laying hens and reduces ammonia emissions and can be used in industry-scale layer production.

Complete pathological response and negative postoperative ctDNA were not predictive of discontinuation of adjuvant crizotinib therapy in a patient with locally advanced MET ex14 skipping mutation-positive non-small cell lung cancer: a case report.

Neoadjuvant targeted therapy is an alternative treatment for locally advanced non-small cell lung cancer (NSCLC) patients with driver gene mutation. MET ex14 mutation is considered a driver gene, and crizotinib is the first oral tyrosine kinase inhibitor (TKI) for metastatic MET ex14 mutation-positive NSCLC patients. Here, we reported a case of a locally advanced NSCLC patient harboring MET ex14 mutation who achieved pathological complete response following neoadjuvant crizotinib therapy but developed rapid metastasis due to discontinuation of short-term postoperative adjuvant crizotinib therapy. Although no driver gene mutation was found via next-generation sequencing (NGS) with blood samples before discontinuation of adjuvant crizotinib, the patient was given crizotinib rechallenge. Fortunately, the patient achieved durable complete response. This suggested that neither pathological complete response nor negative circulating tumor DNA (ctDNA) could be an effective predictor for discontinuation of adjuvant targeted therapy. This case report demonstrated the potential of crizotinib as neoadjuvant therapy in MET ex14 mutation-positive NSCLC patients as well as the importance of long-term postoperative therapy even with negative ctDNA in blood.

Lobe-specific lymph node dissection in early-stage non-small-cell lung cancer: An overview.

Lymph node dissection is a vital part of surgical treatment for early-stage non-small cell lung cancer (NSCLC). Lobectomy with systematic lymph node dissection (SLND) still remains the gold standard surgical treatment for early-stage NSCLC patients. However, an increasing number of studies have demonstrated that lobe-specific lymph node dissection (L-SLND) can be used as an alternative therapy for SLND in carefully selected patients with early-stage NSCLC. However, there are no currently available evidences of review summarizing the role of L-SLDN in treating early-stage NSCLC. Therefore, we performed this literature review by summarizing the existing literatures on the lymph node drainage pattern, definition, scope and role of L-SLND in patients with early-stage NSCLC, aiming to provide evidence for the application of L-SLND in patients with early-stage NSCLC.

A novel intergenic (between REG3A and CTNNA2-AS1)-ALK fusion responds to alectinib in lung adenocarcinoma.

OBJECTIVES: The wide implementation of next generation sequencing (NGS) technology has led to the identification of a greater number of uncommon partners of anaplastic lymphoma kinase (ALK) fusion. The clinical significance of the intergenic-ALK fusion was deemed limited due to the ambiguous functional partner. Herein, we reported a case of lung adenocarcinoma harboring a novel intergenic (between REG3A and CTNNA2-AS1)-ALK fusion which is sensitive to alectinib. MATERIALS AND METHODS: Hematoxylin-eosin staining (HE), immunohistochemistry (IHC), and DNA-based next-generation sequencing (NGS) based on a 168-gene panel were performed on the biopsy sample. RESULTS: A 50-year-old Chinese male patient diagnosed with stage IVA adenocarcinoma of the upper lobe of the right lung. A novel ALK fusion, resulting from the intergenic region between REG3A and CTNNA2-AS1 fusing with intron 19 of ALK, was unveiled by NGS analysis. Furthermore, positive expression of ALK was confirmed through IHC analysis. The patient was administered alectinib at a dose of 600 mg twice daily as first-line therapy, and partial response was assessed. To date, the progression-free survival (PFS) has exceeded 14 months without any observed serious toxicities. CONCLUSION: To the best of our knowledge, this represents the inaugural report of a patient harboring a novel intergenic-ALK fusion with a breakpoint situated between REG3A and CTNNA2-AS1, who exhibited favorable response to alectinib. This case warrants further investigation and offers valuable insights into the response of this novel intergenic-ALK fusion to alectinib.

Identification of tumor microenvironment-based genes associated with acquired resistance to EGFR Tyrosine Kinase Inhibitor in Lung Adenocarcinoma.

Background: The tumor microenvironment evidently affects treatment response and clinical outcome. This study aims to construct a tumor microenvironment-based crosstalk between immunotherapy and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in lung adenocarcinoma. Methods: We used ESTIMATE algorithm to calculate stromal and immune scores. Differentially expressed genes (DEGs) were extracted based on the comprehensive analysis of immune score groups and EGFR-TKI resistance samples. The independent prognostic value of the five selected genes was assessed by univariate/multivariate Cox regression analysis, survival analysis and the receiver operating characteristic (ROC) curve. Correlation analysis was performed using Spearman's rho value through TIMER 2.0. Results: The Kaplan-Meier survival curve show that patients with higher immune scores have significantly better overall survival. We identified 1328 DEGs from immune score groups and 806 DEGs from the EGFR-TKI resistance cohort GSE123066. A total of 19 co-regulated genes were found, and the Cox regression model produced a significant statistical prognosis for five genes (CENPF, CYSLTR1, GLDN, PIGR and SCGB3A1). Multivariate Cox regression analysis showed that the selected five gene signatures could be used as independent prognostic indicators. Furthermore, GSEA and correlation analysis demonstrated that CENPF was positively correlated to the signalling pathway which related to EGFR-TKI resistance and the well-known bypass gene. Conclusion: Our findings indicate that CENPF, CYSLTR1, GLDN, PIGR and SCGB3A1 are independent prognostic biomarkers associated with acquired EGFR-TKI resistance and tumor immune cell infiltration in lung adenocarcinoma, and CENPF may be a potential target that can improve immunotherapy efficacy and overcome the acquired EGFR-TKI resistance.

Wedge Resection vs. Stereotactic Body Radiation Therapy for Clinical Stage I Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background: Whether wedge resection or stereotactic body radiation therapy (SBRT) has better effectiveness in treatment of clinical stage I non-small cell lung cancer (NSCLC) patients remains unclear. Here we conducted the first meta-analysis to directly compare the survival outcomes of clinical stage I NSCLCs treated with wedge resection and SBRT. Methods: We systematically searched studies from PubMed, Embase, and Corchrane Library up to October 1, 2021. Data for analysis mainly included overall survival (OS) and disease-free survival (DFS), which were obtained directly from the text results or calculated from the Kaplan-Meier survival curve. We used the standard random-effect model test (DerSimonian and Laird method) to analyze the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). The Q-test and I 2-test were used to assess heterogeneity. The stability of pooled HRs was examined by sensitivity analysis. Results: Six retrospective studies with a total of 11,813 clinical stage I NSCLCs who received wedge resection or SBRT were included. The results showed that patients receiving wedge resection had a significantly better OS (HR = 1.20, 95% CI = [1.07, 1.34], P = 0.002) than those with SBRT, but no significant difference of DFS (HR 1.53, 95% CI = [0.83-2.83], P = 0.17) was observed. There was no significant heterogeneity during our analysis, but there may be potential publication bias among these studies. Conclusions: Our meta-analysis showed that clinical stage I NSCLCs treated with wedge resection had superior OS than those treated with SBRT. However, more prospective clinical trials should be well-designed to evaluate the optimal treatment modality of early-stage NSCLCs.

Systemic Immune-Inflammation Index Is a Prognostic Factor for Breast Cancer Patients After Curative Resection.

BACKGROUND: The preoperative systemic immune-inflammation index (SII) is correlated with prognosis in several malignancies. The aim of this study was to investigate the prognosis value of SII in patients with resected breast cancer. MATERIALS AND METHODS: A total of 784 breast cancer patients who underwent surgical resection were consecutively investigated. The optimal cutoff value of SII was evaluated using the receiver operating characteristic (ROC) curve. The collection of SII with clinicopathological characteristic and prognosis was further evaluated. RESULTS: The optimal cutoff value for SII in the prediction of survival was 514 according to ROC curve analysis. A high SII was significantly correlated with younger age (P = 0.037), PR status (P < 0.001), and HER2 status (P = 0.035). Univariate analysis revealed that SII (P < 0.001), T-stage (P < 0.001), lymph node involvement post-surgery (P = 0.024), and histological grade (P < 0.001) were significantly related to DFS, and SII (P < 0.001), T-stage (P = 0.003), lymph node involvement post-surgery (P = 0.006), and histological grade (P < 0.001) were significantly associated with OS. In multivariate analysis, a high SII was an independent worse prognostic factor for DFS (HR, 4.530; 95% CI, 3.279-6.258; P < 0.001) and OS (HR, 3.825; 95% CI, 2.594-5.640; P < 0.001) in all the enrolled patients. Furthermore, subgroup analysis of molecular subtype revealed that SII was significantly associated with prognosis in all subtypes. CONCLUSION: Preoperative SII is a simple and useful prognostic factor for predicting long-term outcomes for breast cancer patients undergoing surgery.