Microsurgical Anatomy of the Common Tendinous Ring and Its Surgical Implications.

BACKGROUND AND OBJECTIVES: The common tendinous ring (CTR), also known as the common annular tendon or annulus of Zinn, is a critical anatomic structure located at the convergence of the orbital apex, superior orbital fissure (SOF), optic canal, and the anterior aspect of the lateral sellar compartment. It plays a vital role in both neurosurgical and neuro-ophthalmological interventions. The aim of this study was to delineate the complex 3-dimensional (3D) topography of the CTR and explore its implications for surgical procedures. METHODS: Ten formalin-fixed skull base specimens from adult Chinese cadavers were meticulously dissected to investigate the morphology of the CTR, focusing particularly on its relationship with the 4 extraocular rectus tendons, the optic strut, the SOF, and the optic canal. Additional skull base specimens were subjected to 3D surface scanning, computed tomography, and histopathological examinations to deepen our understanding of the CTR's structural complexities. RESULTS: The CTR establishes a spatial, 3D tendinous assembly, encompassing 4 rectus tendons, 2 tendinous connections, and a singular common tendinous root. These components interlink to form a distinctive dual-ring configuration, featuring the optic foramen and the oculomotor foramen. The posterior part of the superior rectus tendon demarcates the common boundary between these 2 foramina. The oculomotor foramen itself serves as the central sector of the SOF. Precise incisions of the medial and lateral tendinous connections and fusions are essential for safely opening the CTR. CONCLUSION: The structural composition, interconnections, and dual-ring configuration of the CTR are crucial for precise and safe surgery of orbital apex and adjacent regions.

Effect of Preoperative Serum Lactate Dehydrogenase-to-Albumin Ratio on the Survival of Oral Cancer: A Retrospective Study.

Background: Several studies have investigated the relationship between serum lactate dehydrogenase-to-albumin ratio (LAR) and the prognosis of cancers. However, no studies have explored the association between serum LAR and the survival of oral cancer (OC). This study was aimed to determine the association of serum LAR with the overall survival (OS) of OC. Methods: One hundred and ninety patients with OC were included in this study between January 2018 and December 2019. Log rank test and Kaplan-Meier method were used to compare the survival rate of OC between the low LAR group and the high LAR group. The association between serum LAR and the survival of OC patients was determined via univariate and multivariate Cox regression analyses. Results: Kaplan-Meier analysis and Log rank test indicated that the OS rate in low LAR group was significantly higher than that in high LAR group (P < 0.05). Univariate cox analysis showed that TNM III-IV stage, serum LDH > 162 U/L, and serum LAR > 3.79 were significantly associated with the OS of OC patients. Multivariate Cox analysis suggested that the TNM III-IV stage (HR, 2.317; 95% CI, 1.423-3.774, P = 0.001) and serum LAR > 3.79 (HR, 5.138; 95% CI, 2.245-11.756, P = 0.000) were independently related with poor OS of OC patients. Conclusion: High serum LAR (>3.79) is an independent predictor of adverse prognosis in OC patients. LAR could be used as a promising marker for predicting the OS of OC patients.

DSG2 and c-MYC Interact to Regulate the Expression of ADAM17 and Promote the Development of Cervical Cancer.

Purpose: To explore the effect of DSG2 on the growth of cervical cancer cells and its possible regulatory mechanism. Methods: The expression levels and survival prognosis of DSG2 and ADAM17 in cervical squamous cell carcinoma tissues and adjacent normal tissues were analyzed by bioinformatics. CCK-8 assay, colony formation assay and Transwell assay were used to detect the effects of DSG2 on the proliferative activity, colony formation ability and migration ability of SiHa and Hela cells. The effect of DSG 2 on the level of ADAM17 transcription and translation was detected by qPCR and Western blot experiments. The interaction between DSG2 and c-MYC was detected by immunocoprecipitation. c-MYC inhibitors were used in HeLa cells overexpressing DSG2 to analyze the effects of DSG2 and c-MYC on proliferation, colony formation and migration of Hela cells, as well as the regulation of ADAM17 expression. Results: DSG2 was highly expressed in cervical squamous cell carcinoma compared with normal tissues (P<0.05), and high DSG2 expression suggested poor overall survival (P<0.05). After DSG2 knockdown, the proliferative activity, colony formation and migration ability of SiHa and Hela cells were significantly decreased (P<0.05). Compared with adjacent normal tissues, ADAM17 was highly expressed in cervical squamous cell carcinoma (P<0.05), and high ADAM17 expression suggested poor overall survival in cervical cancer patients (P<0.05). The results of immunocoprecipitation showed the interaction between DSG2 and c-MYC. Compared with DSG2 overexpression group, DSG2 overexpression combined with c-MYC inhibition group significantly decreased cell proliferation, migration and ADAM17 expression (P < 0.05). Conclusion: DSG2 is highly expressed in cervical cancer, and inhibition of DSG2 expression can reduce the proliferation and migration ability of cervical cancer cells, which may be related to the regulation of ADAM17 expression through c-MYC interaction.

Highly Selective Ionic Gel-Based Gas Sensor for Halogenated Volatile Organic Compound Detection: Effect of Dipole-Dipole Interaction.

Halogenated volatile organic compounds (abbreviated as X-VOCs) are a class of hazardous gas pollutants that are difficult to detect due to their thermal stability, chemical inertness, and poisoning effect on gas sensors at high temperatures. In this work, room-temperature detection of X-VOCs is achieved using a surface acoustic wave (SAW) gas sensor coated with a 1-ethyl-3-methylimidazolium bis(trifluoromethylsufonyl)imide (EMIM-TFSI)-based ionic gel film. We experimentally verify that the high selectivity of the ionic gel-based SAW gas sensor for X-VOCs is due to the presence of halogen atoms in these gas molecules. Meanwhile, the sensor has very little response to common organic gases such as ethanol, isopropanol, and acetone, reflecting a low cross-sensitivity to nonhalogenated VOCs. This unique advantage shows potential applications in selective detection of X-VOCs and is validated by comparison with a commercial metal oxide semiconductor (MOS) sensor. Furthermore, the internal sensing mechanism is explored by the density functional theory (DFT) method. The simulation results demonstrate that the X-VOC molecules are highly polarized by the inductive effect of halogen atom substitution, which is beneficial for being adsorbed by the EMIM-TFSI ionic liquid via dipole-dipole interaction.

PG545 Prevents Osteoarthritis Development by Regulating PI3K/AKT/mTOR Signaling and Activating Chondrocyte Autophagy.

INTRODUCTION: Osteoarthritis (OA) is a degenerative disease common in the elderly and is characterized by joint pain, swelling, and restricted movement. In recent years, heparanase has been reported to play an important role in the development of osteoarthritic cartilage. PG545 is a heparan sulfate mimetic with heparanase inhibitory activity. In this study, the therapeutic effects and possible mechanisms of PG545 were investigated in a chondrocyte injury model induced by interleukin-1ß (IL -1ß). METHODS: Following treatment with PG545 or the autophagy inhibitor 3-methyladenine (3-MA), chondrocyte viability was detected using Cell Counting Kit-8 and fluorescein diacetate/propidium iodide double staining. The apoptosis rate of chondrocytes was determined by flow cytometry. Expression of light chain 3 and P62 was monitored by immunofluorescence labeling. Western blot, lentivirus infection with red fluorescent protein and green fluorescent protein, and quantitative real-time polymerase chain reaction were used to determine the expression levels of chondrocyte markers, apoptosis-related factors, autophagy proteins, and key proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. The expression and activity of stress-specific enzymes such as malondialdehyde, superoxide dismutase, and catalase (CAT) were investigated. Chondrocytes with ATG5 knockdown were used to investigate the relationship between the therapeutic effect of PG545 and autophagy. The therapeutic effect of PG545 was verified in vivo. RESULTS: PG545 had a significant protective effect on chondrocytes by reducing oxidative stress, apoptosis, and degradation of chondrocytes and increasing chondrocyte proliferation. PG545 was effective in inducing autophagy in IL-1ß-treated cells, while 3-MA attenuated the effect. The PI3K/Akt/mTOR pathway may be involved in the promotion of autophagy and OA treatment by PG545. CONCLUSION: PG545 was able to restore impaired autophagy and autophagic flux via the PI3K/Akt/mTOR pathway, thereby delaying the progression of OA, suggesting that PG545 may be a novel therapeutic approach for OA.

Hyperuricemia promotes the progression of atherosclerosis by activating endothelial cell pyroptosis via the ROS/NLRP3 pathway.

Hyperuricemia closely correlates with the development of atherosclerosis, but little is known of the mechanism by which atherosclerosis progression occurs in hyperuricemia. Atherosclerosis appears to involve pyroptosis, an emerging mechanism of proinflammatory regulated cell death. This study tested the hypothesis that pyroptosis underlies the relationship between hyperuricemia and atherosclerosis, using ApoE-/- mice (a model of atherosclerosis), human umbilical vein endothelial cells (HUVECs), and human atherosclerotic arterial samples. We found that hyperuricemia can aggravate the aortic atherosclerotic plaque-load in ApoE-/- mice and promote endothelial cell pyroptosis. Additionally, hyperuricemia can increase the levels of serum inflammatory factors (including IL-1ß and IL-18). Exposure to lipopolysaccharide plus a high concentration of soluble uric acid (≥12 mg/dL) induced cell pyroptosis in HUVECs, as evidenced by increased expression of pyroptosis-related proteins and elevated release of lactate dehydrogenase (a marker of tissue damage). Further, MCC950, a selective nucleotide-binding oligomerization domain (NOD)-like receptor 3 (NLRP3) inflammasome inhibitor, and N-acetyl- l-cysteine, an antioxidant, attenuated HUVEC pyroptosis by inhibiting activation of the NLRP3 inflammasome and production of intracellular reactive oxygen species (ROS). Finally, we detected significantly higher expression of pyroptosis-associated proteins in carotid specimens from patients with hyperuricemia. Collectively, our findings suggest that hyperuricemia can aggravate endothelial cell pyroptosis in aortic atherosclerotic plaques, promoting the development of atherosclerosis. Additionally, a high concentration of soluble uric acid can trigger the activation stage of the NLRP3 inflammasome, mediating endothelial cell pyroptosis, and this process is regulated by the cellular ROS level.

Genomic characteristics and prognosis of lung cancer patients with MSI-H: A cohort study.

BACKGROUND: Microsatellite instability (MSI) is the first pan-cancer biomarker approved to guide immune checkpoint inhibitor therapy for MSI-high (MSI-H) solid tumors. In lung cancer, the MSI-H frequency is very low, and the genetic characteristics and prognosis of lung cancer with MSI-H were rarely reported. METHODS: Next-generation sequencing and immunohistochemistry were used detect MSI status, tumor mutation burden (TMB) and PD-L1 expression. RESULTS: Among 12,484 lung cancer patients screened, 66 were found with MSI-H, the proportion was as low as 0.5%. Compared with Microsatellite stability (MSS), TMB was higher in MSI-H lung cancer patients, while PD-L1 expression showed no considerable difference between MSI-H and MSS. After propensity score matching, compared with MSS, the most common companion mutations in MSI-H were TP53, BRCA2, TGFBR2, PTEN and KMT2C. In MSI-H lung adenocarcinoma with EGFR mutation, TGFBR2 and ERBB2 had higher mutation frequency than in MSS. CONCLUSION: The current study reveals the genetic characteristics of MSI-H lung cancer, which advanced our understanding of MSI-H lung cancer.

Comparison of hexaminolevulinate (HAL) -guided versus white light transurethral resection for NMIBC: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: We systematically reviewed the effectiveness of hexaminolevulinic acid (HAL) after traditional light cystoscopy vs. only white light cystoscopy (WLC) on nonmuscle-invasive bladder cancer (NMIBC) clinical outcomes. METHODS: Systematic literature searches of PubMed, Embase, Web of Science, and the Cochrane database and reference lists were performed. A total of 12 randomized controlled trials (RCTs) of HAL fluorescent cystoscopy (FC) and WLC vs. white light cystoscopy alone for the diagnosis of initial or recurrent bladder cancer that reported bladder cancer recurrence, progression, recurrence-free survival (RFS), and other effects were selected for review. RESULTS: Our results included 2,775 patients identified for analysis and showed that the HAL group had a lower recurrence rate than the white light cystoscopy group with a statistically significant difference (RR=0.77, 95% CI 0.69-0.85. P < 0.05), and this advantage still existed for patients receiving intravesical chemotherapy. There was also a statistically significant difference in favour of fluorescent cystoscopy in recurrence-free survival and progression rate (HR=0.79, 95% CI 0.67-0.92. P < 0.05, RR = 0.63, 95% CI 0.43-0.94. P < 0.05, respectively). The time to first recurrence was not significantly different from that in the WLC group (SMD=0.73, 95% CI, -0.39-1.85. P = 0.2). And the HAL group did not have a significantly reduced residual tumor rate (RR=0.59, 95% CI 0.23-1.51. P = 0.27). CONCLUSIONS: Fluorescent cystoscopy was associated with a reduced risk of bladder cancer recurrence and reduced progression rate; it also has advantages for RFS. However, there was no significant difference in the rate of residual tumor and the time of first recurrence. More studies are needed to better understand the effects of the photosensitizer used on NMIBC patients.

Identifying the key genes of Epstein-Barr virus-regulated tumour immune microenvironment of gastric carcinomas.

The Epstein-Barr virus (EBV) is involved in the carcinogenesis of gastric cancer (GC) upon infection of normal cell and induces a highly variable composition of the tumour microenvironment (TME). However, systematic bioinformatics analysis of key genes associated with EBV regulation of immune infiltration is still lacking. In the present study, the TCGA and GEO databases were recruited to analyse the association between EBV infection and the profile of immune infiltration in GC. The weighted gene co-expression analysis (WGCNA) was applied to shed light on the key gene modules associated with EBV-associated immune infiltration in GC. 204 GC tissues were used to analysed the expression of key hub genes by using the immunohistochemical method. Real-time PCR was used to evaluate the association between the expression of EBV latent/lytic genes and key immune infiltration genes. Our results suggested that EBV infection changed the TME of GC mainly regulates the TIICs. The top three hub genes of blue (GBP1, IRF1, and LAP3) and brown (BIN2, ITGAL, and LILRB1) modules as representative genes were associated with EBV infection and GC immune infiltration. Furthermore, EBV-encoded LMP1 expression is account for the overexpression of GBP1 and IRF1. EBV infection significantly changes the TME of GC, and the activation of key immune genes was more dependent on the invasiveness of the whole EBV virion instead of single EBV latent/lytic gene expression.

Radiomics Signature of Epicardial Adipose Tissue for Predicting Postoperative Atrial Fibrillation after Off-Pump Coronary Artery Bypass Surgery.

Background: Postoperative new atrial fibrillation (POAF) is a commonly observed complication after off-pump coronary artery bypass surgery (OPCABG), and models based on radiomics features of epicardial adipose tissue (EAT) on non-enhanced computer tomography (CT) to predict the occurrence of POAF after OPCABG remains unclear. This study aims to establish and validate models based on radiomics signature to predict POAF after OPCABG. Methods: Clinical characteristics, radiomics signature and features of non-enhanced CT images of 96 patients who underwent OPCABG were collected. The participants were divided into a training and a validation cohort randomly, with a ratio of 7:3. Clinical characteristics and EAT CT features with statistical significance in the multivariate logistic regression analysis were utilized to build the clinical model. The least absolute shrinkage and selection operator (LASSO) algorithm was used to identify significant radiomics features to establish the radiomics model. The combined model was constructed by integrating the clinical and radiomics models. Results: The area under the curve (AUC) of the clinical model in the training and validation cohorts were 0.761 (95% CI: 0.634-0.888) and 0.797 (95% CI: 0.587-1.000), respectively. The radiomics model showed better discrimination ability than the clinical model, with AUC of 0.884 (95% CI: 0.806-0.961) and 0.891 (95% CI: 0.772-1.000) respectively for the training and the validation cohort. The combined model performed best and exhibited the best predictive ability among the three models, with AUC of 0.922 (95% CI: 0.853-0.990) in the training cohort and 0.913 (95% CI: 0.798-1.000) in the validation cohort. The calibration curve demonstrated strong concordance between the predicted and actual observations in both cohorts. Furthermore, the Hosmer-Lemeshow test yielded p value of 0.241 and 0.277 for the training and validation cohorts, respectively, indicating satisfactory calibration. Conclusions: The superior performance of the combined model suggests that integrating of clinical characteristics, radiomics signature and features on non-enhanced CT images of EAT may enhance the accuracy of predicting POAF after OPCABG.

Preoperative pulmonary vascular resistance and neutrophil-to-lymphocyte ratio predict the demand of extracorporeal membrane oxygenation after pulmonary endarterectomy.

BACKGROUND: Acute respiratory and circulatory collapse might occasionally happen after pulmonary endarterectomy (PEA). We aimed to investigate the utilization of extracorporeal membrane oxygenation (ECMO) after PEA and potential risk factors. METHODS: Demographic characteristics, clinical and surgical data were collected for all patients who underwent PEA from December 2016 to June 2022. All factors were compared between patients in the ECMO group and those in the other group. The most characteristic risk factors were obtained by least absolute shrinkage and selection operator regression and support vector machine machine learning, and receiver operating characteristics (ROC) Curve analysis was performed to verify the diagnostic value of the obtained risk factors. RESULTS: A total of 117 patients underwent PEA, and 8 (6.8%) of them received ECMO treatment intraoperatively or postoperatively. There were significant differences between the two groups in terms of cardiac function, pulmonary vascular resistance (PVR), preoperative inflammation and cardiopulmonary bypass time. The PVR and neutrophil-to-lymphocyte ratio (N/L ratio) were the most characteristic risk factors with an area under the ROC curve of 0.847 (95% confidence interval [CI] = 0.7517-0.9420, p = .005) and 0.896 (95% CI = 0.803-0.989, p = .001), respectively. The ECMO group had higher PVR (1549.4 ± 600.7 vs. 952.9 ± 466.9 dyn.s.cm-5 , p = .004) and N/L ratio (6.3 ± 5.6 vs. 2.4 ± 1.7, p = .001). CONCLUSIONS: PVR and N/L ratio can correctly predict who is likely to receive ECMO treatment after PEA. Therefore, addressing the preoperative inflammatory status might be beneficial but further research is needed.

Association Between Nadir Hematocrit and Severe Acute Kidney Injury After Off-Pump Coronary Artery Bypass Graft Surgery: A Retrospective Cohort Study Based on the MIMIC-IV Database.

BACKGROUND We aimed to evaluate the association between postoperative nadir hematocrit (Hct) and severe acute kidney injury (AKI) in patients undergoing off-pump coronary artery bypass graft (OPCABG) surgery. MATERIAL AND METHODS Data of patients who received OPCABG were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. A generalized additive model was applied to explore the relationship between nadir Hct and severe AKI. Patients were divided into 4 groups by quartiles of postoperative nadir Hct, with the lowest group (Hct <25%) as reference. We conducted multivariate logistic regression models to calculate adjusted odds ratios (OR) and 95% CI and evaluate trend among the 4 groups. RESULTS In total, 1783 OPCABG patients were included. A nonlinear association between nadir Hct and severe AKI was identified. After adjusting for potential confounders, nadir Hct was negatively associated with risk of severe AKI when Hct was less than 31%; there was no statistical significance between highest Hct group (Hct ≥31%) and control group (Hct <25%; P>0.05). Tests for trend were significant (P<0.05). Subgroup analyses showed each 1% increase in postoperative nadir Hct was associated with a 23% decrease in risk of severe AKI (OR, 0.77; P=0.002) in lower BMI group (<30 kg/m²). CONCLUSIONS The association between postoperative nadir Hct and severe AKI in patients after OPCABG was nonlinear. Lower nadir Hct may be associated with increased risk of severe AKI when Hct values are less than 31%. However, no statistical significance was found between the highest Hct group and control group.

Retraction Notice to: Knockdown of KCNQ1OT1 Suppresses Cell Invasion and Sensitizes Osteosarcoma Cells to CDDP by Upregulating DNMT1-Mediated Kcnq1 Expression.

[This retracts the article DOI: 10.1016/j.omtn.2019.06.010.].

Various Subtypes of EGFR Mutations in Patients With NSCLC Define Genetic, Immunologic Diversity and Possess Different Prognostic Biomarkers.

Based on data analysis of 9649 Chinese primary NSCLC patients, we calculated the exact proportion of EGFR subtypes in NSCLC and evaluated the TMB level, PD-L1 expression level and tumor immune microenvironment among different EGFR mutation subtypes. Postoperative follow-up data for 98 patients were collected and analyzed. The results showed that several uncommon EGFR mutation subtypes have a higher proportion of TMB-high or strong positive PD-L1 expression than the total EGFR mutation group. In addition, different subtypes have different characteristics related to the immune microenvironment, such as G719 mutations being associated with more CD8+ T cell infiltration into tumors; except for EGFR 19del, CD8+ T cell infiltration into tumors of other EGFR mutation subtypes were similar to that of wildtype EGFR. Moreover, follow-up results revealed that components of the immune microenvironment have prognostic value for NSCLC patients, with different prognostic biomarkers for NSCLC patients with and without EGFR mutations. These results suggest that patients with different EGFR mutations need to be treated differently. The prognosis of NSCLC patients may be assessed through components of tumor immune microenvironment, and ICIs treatment may be considered for those with some uncommon EGFR mutation subtypes.

Affibody Modified G-quadruplex DNA Micelles Incorporating Polymeric 5-Fluorodeoxyuridine for Targeted Delivery of Curcumin to Enhance Synergetic Therapy of HER2 Positive Gastric Cancer.

Combination chemotherapy is emerging as an important strategy for cancer treatment with decreased side effects. However, chemotherapeutic drugs with different solubility are not easy to realize co-delivery in traditional nanocarriers. Herein, an affibody modified G-quadruplex DNA micellar prodrug (affi-F/GQs) of hydrophilic 5-fluorodeoxyuridine (FUdR) by integrating polymeric FUdRs into DNA strands is developed for the first time. To achieve synergistic efficacy with hydrophobic drugs, curcumin (Cur) is co-loaded into affi-F/GQs micelles to prepare the dual drug-loaded DNA micelles (Cur@affi-F/GQs), in which affibody is employed as a targeting moiety to facilitate HER2 receptor-mediated uptake. Cur@affi-F/GQs have a small size of approximately 130 nm and exhibit excellent stability. The system co-delivers FUdR and Cur in a ratiometric manner, and the drug loading rates are 21.1% and 5.6%, respectively. Compared with the physical combination of FUdR and Cur, Cur@affi-F/GQs show higher cytotoxicity and greater synergistic effect on HER2 positive gastric cancer N87 cells. Surprisingly, Cur@affi-F/GQs significantly enhance the expression and activity of apoptosis-associated proteins in Bcl-2/Bax-caspase 8, 9-caspase 3 apoptotic pathway, which is the main factor in the death of tumor cells induced by FUdR. Overall, this nanoencapsulation is a promising candidate for the targeted co-delivery of drugs with significant differences in solubility.

Clinicopathological analysis of retroperitoneal solitary fibrous tumours: a study of 31 cases.

A solitary fibrous tumour (SFT) is a mesenchymal tumour that exhibits fibroblast differentiation and rarely occurs in the retroperitoneum. The main purpose of this study was to explore the clinical manifestation, histopathological features and biological behaviour of retroperitoneal SFT. From 2011 to 2020, 31 patients were hospitalized and diagnosed with retroperitoneal SFTs. We summarized and analysed the morphological features, immunophenotype, treatment and prognosis. Patients (13 M; 18 F) ranged in age from 25 to 79 years with a mean age of 53.6 years. The main symptoms included an abdominal mass (48.4%) and abdominal discomfort (25.8%). The mean maximum diameter of the tumours was 12.9 cm (range, 4-40 cm). Histopathologically, there were 17 classic cases and 14 hemangiopericytoma-like cases. The tumour cells were positive for STAT6 (96.8%), CD34 (96.8%), CD99 (93.5%) and BCL-2 (90.3%). All patients were treated with complete surgical excision, and 3 of the patients also received chemotherapy. After a median follow up period of 44 months (range, 6 to 107 months), 2 patients died. Patients in the high- or intermediate-risk group were prone to metastasis and/or recurrence. The sites of metastases and/or recurrences involved the liver, bone and pelvis. The Ki-67 labelling index in the high-intermediate risk group (median, 10%) was significantly higher than that in the low-risk group (median, 3%). The retroperitoneal SFT demonstrates an indolent clinical course, and patients from the high- or intermediate-risk group require close follow-up. A Ki-67 labelling index ≥10% may be used as an important reference for prognosis.

Ferredoxin 1 is downregulated by the accumulation of abscisic acid in an ABI5-dependent manner to facilitate rice stripe virus infection in Nicotiana benthamiana and rice.

Ferredoxin 1 (FD1) accepts and distributes electrons in the electron transfer chain of plants. Its expression is universally downregulated by viruses and its roles in plant immunity have been brought into focus over the past decade. However, the mechanism by which viruses regulate FD1 remains to be defined. In a previous report, we found that the expression of Nicotiana benthamiana FD1 (NbFD1) was downregulated following infection with potato virus X (PVX) and that NbFD1 regulates callose deposition at plasmodesmata to play a role in defense against PVX infection. We now report that NbFD1 is downregulated by rice stripe virus (RSV) infection and that silencing of NbFD1 also facilitates RSV infection, while viral infection was inhibited in a transgenic line overexpressing NbFD1, indicating that NbFD1 also functions in defense against RSV infection. Next, a RSV-derived small interfering RNA was identified that contributes to the downregulation of FD1 transcripts. Further analysis showed that the abscisic acid (ABA) which accumulates in RSV-infected plants also represses NbFD1 transcription. It does this by stimulating expression of ABA insensitive 5 (ABI5), which binds the ABA response element motifs in the NbFD1 promoter, resulting in negative regulation. Regulation of FD1 by ABA was also confirmed in RSV-infected plants of the natural host rice. The results therefore suggest a mechanism by which virus regulates chloroplast-related genes to suppress their defense roles.

The genomic landscape of young and old lung cancer patients highlights age-dependent mutation frequencies and clinical actionability in young patients.

The aim of the study was to investigate age-dependent tendency of genomic alterations in lung cancer, and also to examine mutational profiles and its association with clinical treatment outcomes in young adenocarcinoma patients. By studying 7858 lung cancer samples using targeted-gene sequencing, we investigated genomic differences and clinical on-treatment time (OTT) to different therapies between young (≤ 45 years) and old (> 45 years) patients. The age-dependent trend test for genomic alterations in all patients revealed steady increases in tumor mutation burden and alterations in a number of genes with age, including KRAS, MET, CDKN2A, PIK3CA and MDM2, while the frequencies of ALK, ROS1 and RET fusions and ERBB2 mutations were decreasing. The highest rate of EGFR alterations was observed in the 45 ~ 50 years age group. Comparisons of young and old adenocarcinoma patients found that young patients were characterized by a higher prevalence of ALK, ROS1 and RET fusions, and ERBB2 exon-20 insertions and EGFR exon-19 deletions. Actionable mutations were highly prevalent in young adenocarcinoma patients, with 88% of patients harboring at least one actionable genetic alteration. First-line therapies in EGFR-positive patients (n = 979) by EGFR tyrosine kinase inhibitors or chemotherapy resulted in similar OTT between young and old patients. Somatic interaction analyses implied that young EGFR-positive patients were more likely to also have PIK3CA, MET, TP53 and RB1 mutations than old patients. Lung cancer in young patients, and especially those with adenocarcinoma, exhibited different clinical features and genomic attributes compared to old patients, which should be considered for therapeutic decision-making purposes.

Gas Sensor Based on Surface Enhanced Raman Scattering.

In order to address problems of safety and identification in gas detection, an optical detection method based on surface enhanced Raman scattering (SERS) was studied to detect ethanol vapor. A SERS device of silver nanoparticles modified polyvinylpyrrolidone (PVP) was realized by freeze-drying method. This SERS device was placed in a micro transparent cavity in order to inject ethanol vapor of 4% and obtain Raman signals by confocal Raman spectrometer. We compared different types of SERS devices and found that the modification of polyvinylpyrrolidone improves adsorption of ethanol molecules on surfaces of silver nanoparticle, and finally we provide the mechanism by theory and experiment. Finite Difference Time Domain(FDTD) simulation shows that single layer close-packed Ag nanoparticles have strong local electric field in a wide spectral range. In this study, we provide a case for safety and fingerprint recognition of ethanol vapor at room temperature and atmospheric pressure.

The prospect of immunotherapy combined with chemotherapy in patients with advanced non-small cell lung cancer: a narrative review.

OBJECTIVE: Based on a thorough analysis of monotherapy (pembrolizumab) and chemoimmunotherapy, the immunomodulatory effects of chemotherapy agents are emphasized. BACKGROUND: The combination of chemotherapy and immune checkpoint inhibitors should and is already being regarded as a new standard strategy for the first-line treatment of advanced NSCLC. As some scientists hold, chemoimmunotherapy is the beginning of a new era of lung cancer therapy. Scientists of this field are trying to make the perfect blend, that is, to explore the perfect condition for combination therapy. However, first, we should fully understand the specific role of chemotherapy agents in combination therapy and its specific mechanism. However, our current consideration of this aspect is not comprehensive enough. Based on a full understanding of the mechanisms and roles of these partner treatments, can the perfect blend or a more appropriate combination strategy of cancer immunotherapy be established? METHODS: Search and discuss the literature of pembrolizumab in the treatment of non-small cell lung cancer, as well as previous studies on the immune regulatory function of chemotherapeutic agents, to analyze the mechanism of chemotherapeutic agents in combination immunotherapy. CONCLUSION: Here, we carefully analyzed the details of clinical trials of pembrolizumab in the treatment of NSCLC, and reviewed literature in this field. Therefore, we aim to put forward that chemoimmunotherapy is not a simple model of one plus another. Accordingly, we believe that the more likely role of chemotherapeutics in combination therapy with pembrolizumab is an immunomodulator. Based on this perspective, we propose that more attention and efforts should be devoted to understanding and exploring the immunomodulatory function of chemotherapy agents.