Design, synthesis, and activity evaluation of 2-iminobenzimidazoles as c-Myc inhibitors for treating multiple myeloma.

Multiple myeloma (MM) is a plasma cell malignancy that remains incurable and poses a significant threat to global public health. The multifunctional transcription factor c-Myc plays a crucial role in various cellular processes and is closely associated with MM progression. As part of the basic-helix-loop-helix-leucine zipper (bHLHZip) family, c-Myc forms heterodimers with its obligate partner Max, binds to the Enhancer-box (E-box) of DNA, and ultimately co-regulates gene expression. Therefore, impeding the capacity for heterodimerization to bind to DNA represents a favored strategy in thwarting c-Myc transcription. In this study, we first synthesized a series of novel 2-iminobenzimidazole derivatives and further estimated their potential anti-MM activity. Notably, among all the derivatives, 5b and 5d demonstrated remarkable inhibitory activity against RPMI-8226 and U266 cells, with IC50 values of 0.85 µM and 0.97 µM for compound 5b, and 0.96 µM and 0.89 µM for compound 5d. Western blot and dual-luciferase reporter assays demonstrated that compounds 5b and 5d effectively suppressed both c-Myc protein expression and transcriptional activity of the c-Myc promoter in RPMI-8226 and U266 cells. Furthermore, these compounds induced apoptosis and G1 cell cycle arrest in the aforementioned MM cells. Molecular docking studies revealed that 5b and 5d exhibited strong binding affinity to the interface between c-Myc/Max and E-box of DNA. Taken together, our findings suggest that further investigations are warranted for potential therapeutic applications of 5b and 5d for c-Myc-related diseases.

A Narrative Review of Diabetic Macroangiopathy: From Molecular Mechanism to Therapeutic Approaches.

Diabetic macroangiopathy, a prevalent and severe complication of diabetes mellitus, significantly contributes to the increased morbidity and mortality rates among affected individuals. This complex disorder involves multifaceted molecular mechanisms that lead to the dysfunction and damage of large blood vessels, including atherosclerosis (AS) and peripheral arterial disease. Understanding the intricate pathways underlying the development and progression of diabetic macroangiopathy is crucial for the development of effective therapeutic interventions. This review aims to shed light on the molecular mechanism implicated in the pathogenesis of diabetic macroangiopathy. We delve into the intricate interplay of chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulated angiogenesis, all of which contribute to the vascular complications observed in this disorder. By exploring the molecular mechanism involved in the disease we provide insight into potential therapeutic targets and strategies. Moreover, we discuss the current therapeutic approaches used for treating diabetic macroangiopathy, including glycemic control, lipid-lowering agents, and vascular interventions.

Effects of Balsa Fish Skin Gelatin, Lentinula edodes Mushrooms, Soy Protein Isolate, and Starch on the Sensory Quality and Characterization of Physicochemical and Antioxidant Properties of New Sausage.

Sausages are loved by people for their unique texture, satisfying chewiness, and pleasant flavor. However, in the production of sausages, red meat and a large amount of fat are mainly used, and long-term consumption will increase the risk of diseases such as obesity, heart disease, hypertension, and cancer. Our previous studies have shown that the intake of red meat and fat can be reduced through the replacement of lean meat and fat in sausages by Lentinula edodes and Pleaurotus eryngii mushrooms, but this will lead to the deterioration of the gel of sausage products and seriously affect the sensory quality of sausages. In this study, the response surface method was used to optimize the amount of balsa fish skin gelatin, soy protein isolate, and starch added to, and the proportion of Lentinula edodes mushrooms replacing lean meat in, the new sausage, with Pleaurotus eryngii mushrooms replacing fat. The results show that Lentinula edodes mushrooms replaced 36.1% of the lean meat, and the addition of 0.96% balsa fish skin gelatin, 10.61% starch, and 9.94% soy protein isolate resulted in the highest sensory score and the sensory quality being the closest to that of traditional sausages. Compared with the control group, this novel sausage exhibits characteristics such as lower fat and saturated fatty acid content, reduced energy levels, and higher levels of amino acids (aspartic acid, glutamic acid, cysteine, methionine, and proline) and polyunsaturated fatty acids. The total phenolic content of the novel sausage is 12.52 times higher than that of the control. In comparison with the control group, the novel sausage demonstrates a 65.58% increase in DPPH radical scavenging activity and a 3.88-fold improvement in ABTS+ radical scavenging activity. These findings highlight the outstanding antioxidant performance of the novel sausage. This study provides new ideas for improving the sensory quality of new sausages, promoting the healthy development of the sausage industry, and promoting the high-value utilization of edible mushrooms.

MAFF confers vulnerability to cisplatin-based and ionizing radiation treatments by modulating ferroptosis and cell cycle progression in lung adenocarcinoma.

AIMS: Lung cancer is the leading cause of cancer mortality and lung adenocarcinoma (LUAD) accounts for more than half of all lung cancer cases. Tumor elimination is mostly hindered by drug resistance and the mechanisms remain to be explored in LUAD. METHODS: CRISPR screens in cell and murine models and single-cell RNA sequencing were conducted, which identified MAF bZIP transcription factor F (MAFF) as a critical factor regulating tumor growth and treatment resistance in LUAD. RNA and ChIP sequencing analyses were performed for transcriptional target expression and specific binding sites of MAFF. Functions of MAFF in inhibiting tumor growth and promoting cisplatin or irradiation efficacy were investigated using cellular and xenograft models. RESULTS: Patients with lung adenocarcinoma and reduced MAFF expression had worse clinical outcomes. MAFF inhibited tumor cell proliferation by regulating the expression of SLC7A11, CDK6, and CDKN2C, promoting ferroptosis and preventing cell cycle progression from G1 to S. MAFF also conferred tumor cells vulnerable to cisplatin-based or ionizing radiation treatments. MAFF reduction was a final event in the acquisition of cisplatin resistance of LUAD cells. The intracellular cAMP/PKA/CREB1 pathway upregulated MAFF in response to cisplatin-based or ionizing radiation treatments. CONCLUSIONS: MAFF suppresses tumor growth, and pharmacological agonists targeting MAFF may improve cisplatin or irradiation therapies for lung adenocarcinoma patients.

Discovery of Palbociclib as a potent c-Myc G4 stabilizer for lung cancer treatment using molecular docking, molecular dynamics simulation, and in vitro activity evaluation.

Despite significant progress in lung cancer treatment, this disease remains a prevalent and serious global malignancy, leading to high rates of illness and death. Urgent research is needed to discover new or alternative therapies that can improve clinical outcomes for lung cancer patients. In our study, we successfully demonstrated the effectiveness of Palbociclib, a CDK4/6 inhibitor, in suppressing the growth of lung cancer cells. The IC50 values obtained were 11.00 µM and 11.74 µM for H1299 and A549 cells, respectively. Furthermore, our findings indicate that Palbociclib may possess strong c-Myc G4 stabilizing properties by significantly reducing both protein and mRNA expression levels of c-Myc. Additionally, Palbociclib induces apoptosis and causes cell cycle arrest at the G2/M phase in two cells. Through circular dichroism (CD), molecular docking, and molecular dynamics (MD) simulation, we have provided evidence that Palbociclib enhances the structural stability of c-Myc G4 while exhibiting a high binding affinity to its ligand's binding site on c-Myc G4. These results suggest that Palbociclib holds promise as a novel c-Myc G4 stabilizer for treating cancers associated with abnormal c-Myc activity; further optimization and development are warranted.

Chinese herbal medicine and active ingredients for diabetic cardiomyopathy: molecular mechanisms regulating endoplasmic reticulum stress.

Background: Diabetic cardiomyopathy (DCM) is one of the serious microvascular complications of diabetes mellitus. It is often associated with clinical manifestations such as arrhythmias and heart failure, and significantly reduces the quality of life and years of survival of patients. Endoplasmic reticulum stress (ERS) is the removal of unfolded and misfolded proteins and is an important mechanism for the maintenance of cellular homeostasis. ERS plays an important role in the pathogenesis of DCM by causing cardiomyocyte apoptosis, insulin resistance, calcium imbalance, myocardial hypertrophy and fibrosis. Targeting ERS is a new direction in the treatment of DCM. A large number of studies have shown that Chinese herbal medicine and active ingredients can significantly improve the clinical outcome of DCM patients through intervention in ERS and effects on myocardial structure and function, which has become one of the hot research directions. Purpose: The aim of this review is to elucidate and summarize the roles and mechanisms of Chinese herbal medicine and active ingredients that have the potential to modulate endoplasmic reticulum stress, thereby contributing to better management of DCM. Methods: Databases such as PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data Knowledge Service Platform were used to search, analyze, and collect literature, in order to review the mechanisms by which phytochemicals inhibit the progression of DCM by targeting the ERS and its key signaling pathways. Keywords used included "diabetic cardiomyopathy" and "endoplasmic reticulum stress." Results: This review found that Chinese herbs and their active ingredients can regulate ERS through IRE1, ATF6, and PERK pathways to reduce cardiomyocyte apoptosis, ameliorate myocardial fibrosis, and attenuate myocardial hypertrophy for the treatment of DCM. Conclusion: A comprehensive source of information on potential ERS inhibitors is provided in this review. The analysis of the literature suggests that Chinese herbal medicine and its active ingredients can be used as potential drug candidates for the treatment of DCM. In short, we cannot ignore the role of traditional Chinese medicine in regulating ERS and treating DCM, and look forward to more research and new drugs to come.

Opioid-Free Versus Opioid-Based Anesthesia on Postoperative Pain After Thoracoscopic Surgery: The Use of Intravenous and Epidural Esketamine.

BACKGROUND: The effectiveness and safety of opioid-free anesthesia (OFA) regimens in distinct types of surgeries remain controversial. In this study, we investigated whether OFA could reduce the occurrence of chronic postoperative pain in patients receiving video-assisted thoracoscopic surgery (VATS). METHODS: We conducted a 2-center, randomized, controlled trial from September 2021 to January 2022. A total of 162 lung tumor patients scheduled to undergo VATS were randomly divided into an opioid-based anesthesia (OA) group and an OFA group. The OA group received general anesthesia combined with thoracic epidural block using morphine, while the OFA group received general anesthesia combined with thoracic epidural block using esketamine. Patient-controlled epidural analgesia (PCEA) was used after surgery (ropivacaine and morphine for the OA group versus ropivacaine and esketamine for the OFA group). The primary end point was chronic pain rates at 3 months after VATS, which were analyzed using a logistic regression model. The secondary end points were chronic pain rates at 6 months, acute pain rates at 24 hours and 48 hours postoperatively, postoperative side effects, and perioperative variables. RESULTS: The final analysis included 159 patients. Acute postoperative pain at 24 hours occurred in 0 of the 79 (0%) patients in the OA group and 10 of the 80 (17.5%) patients in the OFA group (odds ratio, 52.14; 95% confidence interval [CI], 6.47-420.10; P < .001). Acute postoperative pain at 48 hours occurred in 3 of the 79 (3.8%) patients in the OA group and 2 of the 80 (2.5%) patients in the OFA group (odds ratio, 2.07; 95% CI, 0.99-4.32; P = .053). In this study, none of the patients had moderate or severe pain in either group at 3 and 6 months postsurgically. Mild chronic postoperative pain at 3 months occurred in 27 of the 79 (34.2%) patients in the OA group and 14 of the 80 (17.5%) patients in the OFA group (odds ratio, 3.52; 95% CI, 1.49-8.31; P = .004). At 6 months, mild chronic pain still occurred in 23 of the 79 (29.1%) patients in the OA group and 9 of the 80 (11.3%) patients in the OFA group (odds ratio, 5.55; 95% CI, 2.01-15.33; P = .001). In addition, the OFA group included fewer patients with side effects, including nausea, vomiting, and pruritus, within 48 hours after surgery. CONCLUSIONS: Replacement of opioids by esketamine, intraoperatively as intravenous injection and epidural infusion and postoperatively as epidural infusion, reduces the incidence of mild chronic postoperative pain and side effects in patients after VATS.

A fluorescent probe for protein tyrosine kinase 7 detection in serum and cell imaging.

Tyrosine protein kinase 7 (PTK7) is overexpressed in breast cancer, which is considered as a cancer marker for breast cancer diagnosis. Therefore, a simple fluorescent probe for PTK7 detection and cell imaging was developed. In the developed probe, Fe3O4 magnetic nanoparticles were used as the fluorescent separator, and the fluorescence of carbon dots were used as the detection signal. The probe was worked by control the configurations of the aptamer of PTK7, the aptamer would be open chains by recognition of PTK7, which bond with carbon dots and show fluorescent signal. Based on the remarkably high affinity and selectivity of aptamer for PTK7, the excellent fluorescence property of carbon dots and the outstanding magnetism of Fe3O4 magnetic nanoparticles, the developed probe showed satisfied results for PTK7 detection in serum and MCF-7 cell imaging. The probe detected PTK7 in the range of 0.2-200 ng mL-1 with a detection limit of 0.0347 ng mL-1, and successfully imaged the cancer cell expressed PTK7. The results indicate that the nano-fluorescent probe has great potential for clinical applications.

The comparison of Lobe-Specific or Systematic Mediastinal Lymph Node Dissection for Early-Stage Lung Adenocarcinoma With Consolidation Tumor Ratio Over 0.5.

INTRODUCTION: Surgery is the most effective treatment for early-stage lung cancer. This study will propose a personalized plan for mediastinal lymph node dissection in early-stage lung adenocarcinoma to reduce the risk of surgery and improve the quality of life. METHODS: This study retrospectively analyzed the patients underwent lobectomy and lymph node dissection in the Department of Thoracic Surgery, Zhongshan Hospital, Fudan University. Clinical stage I lung adenocarcinoma patients with solid component ratio (CTR) between 0.5 and 1 were included. Patients were divided into systematic (S-MLND) and lobe-specific (L-MLND) mediastinal lymph node dissection groups. The days of hospitalization, the presence or absence of complications, the recurrence-free survival rate, and the overall survival rate were calculated to evaluate the postoperative quality and operation risk of the patients. RESULTS: 210 patients (138 L-MLND and 72 S-MLND) were included. 2 lymph node metastases appeared in the S-MLND group while none in the L-MLND group (P = .049). No differences were shown in age, tumor site, size, solid component, degree of tumor invasion, and stage. The proportion of patients with severe postoperative cough and the length of hospital stay in the L-MLND group decreased. The 5-year OS of the entire cohort was 98.1%, 98.6% in L-MLND, compared with 97.2% in S-MLND; RFS was 94.8%, 95.7% in L-MLND, compared with 93.0% in S-MLND. CONCLUSION: For cIA lung adenocarcinoma, according to the Thin-slice CT within 1 month before the operation, if the main lesion was less than 3 cm and CTR over 0.5, L-MLND is as effective as S-MLND.

Dual-emissive ratiometric fluorescent nanosensor based on multi-nanomaterials for Ag+ determination in lake water.

In this study, a sensitive ratiometric fluorescent nanosensor was constructed using a facile one-pot method by encapsulating carbon dots (CDs) and cadmium telluride quantum dots (CdTe QDs) into the pore cavities of a metal-organic framework (ZIF-8). In this nanosensor (CD/CdTe QD@ZIF-8), the fluorescence attributed to CdTe QDs was quenched by silver ions (Ag+), and the fluorescence intensity of CDs did not change. The introduction of ZIF-8 into the system can not only adsorb Ag+ but also easily separate CDs and CdTe QDs from the matrix. The developed CD/CdTe QD@ZIF-8 composite used as a ratiometric fluorescent probe exhibited high sensitivity and selectivity towards Ag+. The working linear range was 0.1-20 µM with a limit of detection (LOD) of 1.49 nM. Finally, the proposed nanosensor was applied to determine Ag+ in lake water with satisfactory results.

HIF-1α switches the functionality of TGF-ß signaling via changing the partners of smads to drive glucose metabolic reprogramming in non-small cell lung cancer.

BACKGROUND: Most cancer cells have fundamentally different metabolic characteristics, particularly much higher glycolysis rates than normal tissues, which support the increased demand for biosynthesis and promote tumor progression. We found that transforming growth factor (TGF)-ß plays a dual function in regulating glycolysis and cell proliferation in non-small cell lung cancer. METHODS: We used the PET/MRI imaging system to observe the glucose metabolism of subcutaneous tumors in nude mice. Energy metabolism of non-small cell lung cancer cell lines detected by the Seahorse XFe96 cell outflow analyzer. Co-immunoprecipitation assays were used to detect the binding of Smads and HIF-1α. Western blotting and qRT-PCR were used to detect the regulatory effects of TGF-ß and HIF-1α on c-MYC, PKM1/2, and cell cycle-related genes. RESULTS: We discovered that TGF-ß could inhibit glycolysis under normoxia while significantly promoting tumor cells' glycolysis under hypoxia in vitro and in vivo. The binding of hypoxia-inducible factor (HIF)-1α to the MH2 domain of phosphorylated Smad3 switched TGF-ß function to glycolysis by changing Smad partners under hypoxia. The Smad-p107-E2F4/5 complex that initially inhibited c-Myc expression was transformed into a Smad-HIF-1α complex that promoted the expression of c-Myc. The increased expression of c-Myc promoted alternative splicing of PKM to PKM2, resulting in the metabolic reprogramming of tumor cells. In addition, the TGF-ß/Smad signal lost its effect on cell cycle regulatory protein p15/p21. Furthermore, high expression of c-Myc inhibited p15/p21 and promoted the proliferation of tumor cells under hypoxia. CONCLUSIONS: Our results indicated that HIF-1α functions as a critical factor in the dual role of TGF-ß in tumor cells, and may be used as a biomarker or therapeutic target for TGF-ß mediated cancer progression.

Rhodium-Catalyzed C-H Annulation of Free Anilines with Vinylene Carbonate as a Bifunctional Synthon.

Chemical transformation with vinylene carbonate as an emerging synthetic unit has recently attracted considerable attention. This report is a novel conversion pattern with vinylene carbonate, in which such a vibrant reagent unprecedentedly acts as a difunctional coupling partner to complete the C-H annulation of free anilines. From commercially available substrates, this protocol leads to the rapid construction of synthetically versatile 2-methylquinoline derivatives (43 examples) with excellent functionality tolerance.

Rhodium-Catalyzed Dehydrogenative Annulation of N-Arylmethanimines with Vinylene Carbonate for Synthesizing Quinolines.

Here we report a novel Rh-catalyzed C-H/C-H alkenylation of N-arylmethanimines with vinylene carbonate acting as a vinylene unit. Forty examples of C3,C4-nonsubstituted quinolines were achieved from commercially available starting materials. This identified process features an exceedingly simple system, a lower loading of catalyst, and the capacity for postfunctionalization with bioactive molecules.

Harvesting Solar Energy by Flowerlike Carbon Cloth Nanocomposites for Simultaneous Generation of Clean Water and Electricity.

Harvesting solar energy for photothermal conversion in an efficient manner for steam-electricity cogeneration is particularly opportune in the context of comprehensive solar utilization to address the challenge of a global shortage of fresh water. However, the fragile solar thermal devices and the single-energy utilization pattern greatly hinder extensive solar energy exploitation and practical application. Herein, a flexible carbon cloth nanocomposite with a biomimetic pelargonium hortorum-petal-like surface that embraces all desirable chemical and physical properties, that is, enhanced light acquisition, excellent photothermal property, and operational durability, for high-performance solar-driven interfacial water evaporation distillation is reported. Combined with the two-dimensional water channel, the solar evaporator shows a solar-to-steam conversion efficiency of 93% under the simulated solar illumination of 1 kW m-2. More strikingly, the solar steam generation-induced electricity based on the practical consideration toward more infusive solar thermal application is proposed. Such integrative steam-electricity generators presented here provide an attractive method to produce on-site electricity and fresh water in an individualized mode in various resource-constrained areas.

Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets.

BACKGROUND: Generally, cancer cells undergo metabolic reprogramming to adapt to energetic and biosynthetic requirements that support their uncontrolled proliferation. However, the mutual relationship between two critical metabolic pathways, glycolysis and oxidative phosphorylation (OXPHOS), remains poorly defined. METHODS: We developed a "double-score" system to quantify glycolysis and OXPHOS in 9668 patients across 33 tumor types from The Cancer Genome Atlas and classified them into four metabolic subtypes. Multi-omics bioinformatical analyses was conducted to detect metabolism-related molecular features. RESULTS: Compared with patients with low glycolysis and high OXPHOS (LGHO), those with high glycolysis and low OXPHOS (HGLO) were consistently associated with worse prognosis. We identified common dysregulated molecular features between different metabolic subgroups across multiple cancers, including gene, miRNA, transcription factor, methylation, and somatic alteration, as well as investigated their mutual interfering relationships. CONCLUSION: Overall, this work provides a comprehensive atlas of metabolic heterogeneity on a pan-cancer scale and identified several potential drivers of metabolic rewiring, suggesting corresponding prognostic and therapeutic utility.

Enhanced Steam Temperature Enabled by a Simple Three-Tier Solar Evaporation Device.

Interfacial water evaporation technology by using solar energy provides one of the promising pathways for freshwater shortage management. However, current research mainly focuses on the improvement of evaporation efficiency by macro or microregulations, ignoring the steam temperature, which is a manifestation of the quality of water. Herein not only is a high-rate solar evaporation achieved but also steam temperature is enhanced by a simple three-tier (wet absorber-air gap-dry absorber) device. In a routine interfacial evaporation test, the evaporator achieves a stable evaporation rate up to 2.15 kg m-2 h-1 under one sun, demonstrating a competitive evaporation rate compared with other reports. With the three-tier device, the steam temperature can increase 33.7%, 41.13%, and 47% without dry absorber under one sun, two sun, and three sun illumination, respectively. At the same time, the steam temperature can be as high as 95.5 °C under three sun intensities. This work provides the possibility of using a simple three-tier device for high-temperature steam generation without extra energy input, which contributes to an idea for future research on the production high-quality water.

Zinc-catalyzed C-H alkenylation of quinoline N-oxides with ynones: a new strategy towards quinoline-enol scaffolds.

A zinc-catalyzed C-H alkenylation of quinoline N-oxides with ynones has been developed to rapidly assemble a broad collection of valuable quinoline-enol organic architectures. Uncommonly, this novel reaction involves C-H functionalization, and N-O, C-C and C[triple bond, length as m-dash]C bond cleavage in one operation, and leads exclusively to the formation of an enol rather than a keto product. Application of the enols generated was highlighted by further derivative transformation and preparation of a series of "BODIPY" analogues with high quantum yields (up to 86%).

Solid Components in the Mediastinal Window of Computed Tomography Define a Distinct Subtype of Subsolid Nodules in Clinical Stage I Lung Cancers.

BACKGROUND: We aimed to validate the clinicopathologic characteristics and prognostic value of the presence of solid components in the mediastinal window of computed tomography scan in clinical stage I pulmonary subsolid nodules (SSNs). METHODS: We retrospectively evaluated patients with pulmonary SSNs resected between 2011 and 2016. We classified SSNs into heterogeneous ground-glass nodules (HGGNs) (solid component detected only in lung window) and part-solid nodules (PSNs) (solid component detected both in lung/mediastinal windows). RESULTS: A total of 487 patients (216 PSNs) were included. PSNs were associated with higher frequencies of micropapillary or solid pathologic patterns (18.1% vs. 3.3%; P < .001), epidermal growth factor receptor gene mutation (39.4% vs. 32.8%), and other types of gene mutations (2.3% vs. 1.1%; P = .043). Logistic regression analysis revealed that male sex (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.20-5.57; P = .016) and higher consolidation tumor ratio (CTR) (OR, 110.04; 95% CI, 8.56-1414.39; P < .001) remained independent for invasive adenocarcinomas with poor differentiation. Receiver operating characteristic analyses revealed that solid component size in the mediastinal window (area under the curve [AUC], 0.731; 95% CI, 0.653-0.808; P < .0001) showed a better predictive ability to poor differentiation compared with solid component size in the lung window and CTR. The 5-year recurrence-free survival (RFS) rate of PSNs was worse than that of HGGNs (94.6% vs. 99.1%; P = .019). Multivariate Cox regression revealed that positive lymph node status (hazard ratio, 22.99; 95% CI, 4.52-116.86; P < .001) indicated worse RFS for PSNs. CONCLUSION: SSNs with solid components in mediastinal window demonstrated clinicopathologic and prognostic features different from those without in clinical stage I lung cancer. Solid components in mediastinal window was a strong predictor of poor differentiation.

Prognostic Impact of Radiological Consolidation Tumor Ratio in Clinical Stage IA Pulmonary Ground Glass Opacities.

OBJECTIVES: Our study aimed to validate pathologic findings of ground-glass nodules (GGOs) of different consolidation tumor ratios (CTRs), and to explore whether GGOs could be stratified according to CTR with an increment of 0.25 based on its prognostic role. METHODS: We retrospectively evaluated patients with clinical stage IA GGOs who underwent curative resection between 2011 and 2016. The patients were divided into 4 groups according to CTR step by 0.25. Cumulative survival rates were calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were conducted to obtain the risk factors on relapse-free survival (RFS). The surv_function of the R package survminer was used to determine the optimal cutoff value. Receiver operating characteristic (ROC) analysis was generated to validate optimal cutoff points of factors. RESULTS: A total of 862 patients (608 women; median age, 59y) were included, with 442 patients in group A (CTR ≤ 0.25), 210 patients in group B (0.25

Identification of immune-related gene signature predicting survival in the tumor microenvironment of lung adenocarcinoma.

The tumor microenvironment (TME) plays an essential role in the occurrence and progression of malignancy. The potential prognostic TME-related biomarkers of lung adenocarcinoma (LUAD) remained unclear, which were investigated in this research. The RNA-sequencing profiles and corresponding clinical parameters were extracted from TCGA and GEO databases, based on which the stromal and immune scores were calculated through the ESTIMATE algorithm. Overlapping differentially expressed genes between stromal and immune score group were analyzed by the LASSO and Random Forrest algorithms and validated in cases from our center. And a prognostic 8-gene signature was constructed using Cox regression. The infiltration of 22 hematopoietic cell phenotypes was assessed by the CIBERSORT algorithms. We found that female, elder patients, and solid predominant subtype had obviously higher stromal and immune scores. And patients with early stage LUAD received a prominently higher immune score. A high stromal or immune score meant a good prognosis. Subsequently, eight TME-related prognostic genes (ATAD5, CYP4F3, CYP4F12, ESPNL, FXYD2, GPX2, NLGN4Y, and SERPINC1) were identified by both LASSO regression and Radom Forest algorithms. High 8-gene signature group exhibited worse overall survival. Furthermore, B cell naïve, plasma cells, T cell follicular helper, and macrophages M1 were prominently more in high signature group. Nevertheless, fewer T cells CD4 memory resting, monocytes, and dendritic cell resting were identified in the high signature group. The composition of the tumor microenvironment significantly affected the prognosis of LUAD patients. We provided a new strategy for the exploration of prognostic TME-related biomarkers and immunotherapy.