Synthesis of α-Diimine Complex Enabling Rapidly Covalent Attachment to Silica Supports and Application of Homo-/Heterogeneous Catalysts in Ethylene Polymerization.

For covalent attachment-supported α-diimine catalysts, on the basis of ensuring the thermal stability and activity of the catalysts, the important problem is that the active group on the catalyst can quickly react with the support, anchoring it firmly on the support, shortening the loading time, reducing the negative impact of the support on the active centers, and further improving the polymer morphology, which makes them suitable for use in industrial polymerization temperatures. Herein, we synthesized a α-diimine nickel(II) catalyst bearing four hydroxyl substituents. The hydroxyl substituents enable the catalyst to be immobilized firmly on silica support by covalent linkage in 5-10 min. Compared with the toluene solvent system, the homogeneous catalysts show high activity and thermal stability in hexane solvent at the same conditions. Compared with homogeneous catalysts, heterogeneous catalysis leads to improvements in catalyst lifetime, polymer morphology control, catalytic activity, and the molecular weight of polyethylene (up to 679 kg/mol). The silica-supported catalysts resulted in higher melting temperatures as well as lower branching densities in polyethylenes. Even at 70 °C, the polyethylene prepared by S-CatA-2 still exhibits dispersed particle morphology, and there is no phenomenon of reactor fouling, which is suitable for industrial polymerization processes.

Pleural effusion as an indicator for the poor prognosis of COVID-19 patients.

BACKGROUND: Coronavirus Disease 19 (COVID-19) is a global health concern that has become a pandemic over the past few months. This study aims at understanding the clinical manifestations of COVID-19 patients with pleural effusion. METHODS: COVID-19 patients were retrospectively enrolled from the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Pharyngeal swabs from patients were tested using real-time polymerase chain reaction. Patients with COVID-19 were divided into two groups based on their computed tomography (CT) scans for the presence of pleural effusion at admission. We compared the clinical features, laboratory findings, scans and clinical outcomes between the two groups. RESULTS: Pleural effusion was observed in 9.19% of the patients. Patients with pleural effusion were more likely to be severe or critical cases. Moreover, patients with pleural effusion were associated with increased mortality. Of the 799 discharged patients, patients with pleural effusion had longer hospital stays and duration of viral shedding since the onset of symptoms as compared with that for patients without pleural effusion. After discharge, 217 patients visited for a follow-up CT re-examination at the Union Hospital. The CT scans showed that patients with pleural effusion required a longer time to resolve the lung inflammation after the onset of COVID-19 as compared with the time required by patients without pleural effusion. CONCLUSION: This population of patients requires special attention and pleural effusion may be an indicator of poor prognosis in COVID-19 patients.

Diarrhea Is Associated With Prolonged Symptoms and Viral Carriage in Corona Virus Disease 2019.

BACKGROUND & AIMS: We compared clinical, laboratory, radiological, and outcome features of patients with SARS-CoV-2 infection (COVID-19) with pneumonia, with vs without diarrhea. METHODS: We performed a retrospective, single-center analysis of 84 patients with SARS-CoV-2 pneumonia in Wuhan Union Hospital, China, from January 19 through February 7, 2020. Cases were confirmed by real-time reverse-transcriptase PCR of nasal and pharyngeal swab specimens for SARS-CoV-2 RNA. Blood samples were analyzed for white blood cell count, lymphocyte count, alanine aminotransferase, creatine kinase, lactate dehydrogenase, D-dimer, C-reactive protein, and in some cases, immunoglobulins, complement, lymphocyte subsets, and cytokines. Virus RNA was detected in stool samples by real-time PCR. RESULTS: Of the 84 patients with SARS-CoV-2 pneumonia, 26 (31%) had diarrhea. The duration of fever and dyspnea in patients with diarrhea was significantly longer than those without diarrhea (all P < .05). Stool samples from a higher proportion of patients with diarrhea tested positive for virus RNA (69%) than from patients without diarrhea (17%) (P < .001). As of February 19, a lower proportion of patients with diarrhea had a negative result from the latest throat swab for SARS-CoV-2 (77%) than patients without diarrhea (97%) (P = .010), during these patients' hospitalization. Of 76 patients with a negative result from their latest throat swab test during hospitalization, a significantly higher proportion of patients with diarrhea had a positive result from the retest for SARS-CoV-2 in stool (45%) than patients without diarrhea (20%) (P = .039). CONCLUSIONS: At a single center in Wuhan, China, 31% of patients with SARS-CoV-2 pneumonia had diarrhea. A significantly higher proportion of patients with diarrhea have virus RNA in stool than patients without diarrhea. Elimination of SARS-CoV-2 from stool takes longer than elimination from the nose and throat.

Tumor-associated macrophages: A promising target for a cancer immunotherapeutic strategy.

Macrophages, a type of myeloid immune cell, play essential roles in fighting against pathogenic invasion and activating T cell-mediated adaptive immune responses. As a major constituent of the tumor microenvironment (TME), macrophages play a complex role in tumorigenesis and tumor progression. They can inhibit tumor growth by releasing proinflammatory cytokines and exerting cytotoxic activities but principally contribute to tumor progression by promoting tumor proliferation, angiogenesis, and metastasis. The tumor-promoting hallmarks of macrophages have aroused widespread interest in targeting tumor-associated macrophages (TAMs) for cancer immunotherapy. Increasing preclinical and clinical studies suggest that TAMs are a promising target for cancer immunotherapy. To date, TAM-targeted therapeutic strategies have mainly been divided into two kinds: inhibiting pro-tumor TAMs and activating anti-tumor TAMs. We reviewed the heterogeneous and plastic characteristics of macrophages in the TME and the feasible strategies to target TAMs in cancer immunotherapy and summarized the complementary effect of TAM-targeted therapy with traditional treatments or other immunotherapies.

Enantioselective Toxicity in Adult Zebrafish ( Danio rerio) Induced by Chiral PCB91 through Multiple Pathways.

This study aimed to further investigate the toxic mechanism of chiral polychlorinated biphenyl (PCB) 91 in adult zebrafish ( Danio rerio) exposed to racemic (rac-), (+)-, or (-)-PCB91 for 63 days. The enantioselective mortalities of adult zebrafish exposed to rac-/(+)-/(-)-PCB91 were 95.86, 50.08, and 81.50%, respectively. Tubular necrosis and cellular hypertrophy occurred in the kidneys of (-)-PCB91-treated groups, whereas demyelination and immune cell infiltration occurred in brains of the rac-, (+)-, and (-)-PCB91-treated groups. Additionally, exposure to chiral PCB91 enantioselectively induced neurotoxicity, apoptosis, and inflammation in brain tissues owing to perturbations of gene expression, protein content and sphingolipid levels. The high mortality after rac-/(+)-PCB91 exposure might be due to toxic effects on brain tissue, while the high mortality after (-)-PCB91 exposure might be due to toxic effects on kidney as well as brain tissues. Thus, our findings offer an important reference for elucidating the enantioselective toxicological mechanism of chiral PCBs in aquatic organisms.

[Clinical outcomes of allogeneic hematopoietic stem cell transplantation patients with co-activation of cytomegalovirus and Epstein-Barr virus].

OBJECTIVE: To evaluate the impact of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) co-activation on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. METHODS: We retrospectively analyzed 330 consecutive allo-HSCT patients at First Affiliated Hospital of Soochow University from December 2011 to August 2013. CMV and EBV DNA were regularly monitored by quantitative polymerase chain reaction (PCR) from the engraftment of granuloCyte within one year after transplantation. The incidences of viremia and clinical outcomes were analyzed by χ(2) test and Kaplan-Meier analysis. RESULTS: After a median follow-up period of 16 (7-25) months, a total of 113 (34.2%) patients were identified with CMV viremia (CMV+) alone, 82 (24.8%) with EBV viremia (EBV+) alone and 32 (9.7%) with CMV and EBV co-activation (CMV/EBV+). The proportion of patients undergoing HLA mismatched transplantation and ones with acute graft-versus-host disease (aGVHD) in CMV/EBV+ group was significantly higher than CMV+ group or EBV+ group (78.1% (25/32) vs 58.5% (48/82) or 50.4% (57/113), P = 0.047,0.008; 56.3% (18/32) vs 32.9% (27/82) or 34.5% (39/113) , P = 0.022, 0.026) . The incidence of post-transplant lymphoproliferative disorder (PTLD) was similar to EBV+ group (12.5% (4/32) vs 11.0% (9/82) , P = 0.802) and so did the incidence of CMV disease when compared with CMV+ group (9.4% (3/32) vs 7.1% (8/113) , P = 0.665). The 2-year overall survival (OS) of CMV+, EBV+ and CMV/EBV+ groups was 68.7%, 61.5% and 62.4% respectively. And no significant difference existed between CMV/EBV+ and the other two groups (P = 0.598, 0.717). However, the 6-month non-relapse mortality (NRM) of CMV/EBV+ group was significantly higher than that of CMV+ or EBV+ group (18.7% vs 8.9%, P = 0.036; 18.7% vs 8.1%, P = 0.032). CONCLUSIONS: HLA mismatch transplants and aGVHD are frequent in CMV and EBV co-activation group. When compared with EBV+ or CMV+ patients, the CMV/EBV+ patients have similar incidence of PTLD or CMV disease and 2-year OS.However, the 6-month NRM is significantly higher in CMV/EBV+ group. It suggests that CMV and EBV co-activation is a risk factor for early mortality of allo-HSCT patients.

[In situ investigation to three dimensional structures of Chinese medicines seeds].

This paper is aimed to microscopic identification of traditional Chinese medicines (TCMs) using an in situ imaging method. In this study, two kinds of Zingiberaceae seeds, Amomi Rotundus Fructus and Alpiniae Katsumadai Semen, were investigated by synchrotron radiation in-line X-ray phase-contrast computed tomography (IXPCT) imaging method. The results showed that the microstructures of these Zingiberaceae seeds could be clearly obtained from the virtual slices information in different observing angles. It proves that IXPCT is an effective imaging method, which can provide the imaging information for the microscopic identification of the intact TCMs in situ and non-destructively.

[Research on ECG de-noising method based on ensemble empirical mode decomposition and wavelet transform using improved threshold function].

A de-noising method for electrocardiogram (ECG) based on ensemble empirical mode decomposition (EEMD) and wavelet threshold de-noising theory is proposed in our school. We decomposed noised ECG signals with the proposed method using the EEMD and calculated a series of intrinsic mode functions (IMFs). Then we selected IMFs and reconstructed them to realize the de-noising for ECG. The processed ECG signals were filtered again with wavelet transform using improved threshold function. In the experiments, MIT-BIH ECG database was used for evaluating the performance of the proposed method, contrasting with de-noising method based on EEMD and wavelet transform with improved threshold function alone in parameters of signal to noise ratio (SNR) and mean square error (MSE). The results showed that the ECG waveforms de-noised with the proposed method were smooth and the amplitudes of ECG features did not attenuate. In conclusion, the method discussed in this paper can realize the ECG denoising and meanwhile keep the characteristics of original ECG signal.

[De-noising method research of ballistocardiogram signal].

Ballistocardiogram (BCG) signal is a physiological signal, reflecting heart mechanical status. It can be measured without any electrodes touching subject's body surface and can realize physiological monitoring ubiquitously. However, BCG signal is so weak that it would often be interferred by superimposed noises. For measuring BCG signal effectively, we proposed an approach using joint time-frequency distribution and empirical mode decomposition (EMD) for BCG signal denoising. We set up an adaptive optimal kernel for BCG signal and extracted BCG signals components using it. Then we de-noised the BCG signal by combing empirical mode decomposition with it. Simulation results showed that the proposed method overcome the shortcomings of empirical mode decomposition for the signals with identical frequency content at different times, realized the filtering for BCG signal and also reconstructed the characteristics of BCG.

A bibliometric review of unilateral neglect: Trends, frontiers, and frameworks.

BACKGROUND: Owing to the adverse effects of unilateral neglect (UN) on rehabilitation outcomes, fall risk, and activities of daily living, this field has gradually got considerable interest. Notwithstanding, there is presently an absence of efficient portrayals of the entire research field; hence, the motivation behind this study was to dissect and evaluate the literature published in the field of UN following stroke and other nonprogressive brain injuries to identify hotspots and trends for future research. MATERIALS AND METHODS: Original articles and reviews related to UN from 1970 to 2022 were retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. CiteSpace, VOSviewer, and Bibliometrix software were used to observe publication fields, countries, and authors. RESULTS: A total of 1,202 publications were incorporated, consisting of 92% of original articles, with an overall fluctuating upward trend in the number of publications. Italy, the United Kingdom, and the United States made critical contributions, with Neuropsychologia being the most persuasive academic journal, and Bartolomeo P. ranked first in both the quantity of publications and co-citations. Keywords were divided into four clusters, and burst keyword detection demonstrated that networks and virtual reality might additionally emerge as frontiers of future development and warrant additional attention. CONCLUSIONS: UN is an emerging field, and this study presents the first bibliometric analysis to provide a comprehensive overview of research in the field. The insights and guidance garnered from our research on frontiers, trends, and popular topics could prove highly valuable in facilitating the rapid development of this field while informing future research directions.

Preparation of VC nanoliposomes by high pressure homogenization: Process optimization and evaluation of efficacy, transdermal absorption, and stability.

Vitamin C (VC) possesses antioxidant and whitening effects. However, its effectiveness is hindered by challenges such as instability, impaired solubility, and limited bioavailability hinder. In this study, VC was encapsulated in nanoliposomes by primary emulsification and high-pressure homogenization. The VC nanoliposomes were comprehensively characterized for their microscopic morphology, particle size, polydispersity index (PDI), and encapsulation efficiency (EE). Orthogonal experiments were designed to optimize the optimal preparation process, and the antioxidant activity, whitening efficacy, transdermal absorption, and stability of VC nanoliposomes were evaluated based on this optimized process. The findings demonstrated the high reproducibility of the optimal process, with particle size, PDI, and EE values of 113.502 ± 4.360 nm, 0.104 ± 0.010, and 56.09 ± 1.01 %, respectively. Differential scanning calorimetry analysis showed effective encapsulation of VC nanoliposomes with better thermal stability than aqueous VC solution. Besides, the VC nanoliposomes demonstrated excellent antioxidant and whitening effects in efficacy experiments, stronger skin permeability in transdermal experiments and fluorescence tracking. Furthermore, storage stability tests indicated that the VC in nanoliposomes remained relatively stable after 60 days of storage. These findings highlighted the potential use of VC nanoliposomes in a wide range of applications for the cosmetic market, especially in the development of ingredients for skin care products.

Synthesis of High-Molecular-Weight Polypropylene Elastomer by Propylene Polymerization Using α-Diimine Nickel Catalysts.

The α-diimine late transition metal catalyst represents a new strategy for the synthesis of atactic polypropylene elastomer. Taking into account the properties of the material, enhancing the molecular weight of polypropylene at an elevated temperature through modifying the catalyst structure, and further increasing the activity of α-diimine catalyst for propylene polymerization, are urgent problems to be solved. In this work, two α-diimine nickel(II) catalysts with multiple hydroxymethyl phenyl substituents were synthesized and used for propylene homopolymerization. The maximum catalytic activity was 5.40 × 105 gPP/molNi·h, and the activity was still maintained above 105 gPP/molNi·h at 50 °C. The large steric hindrance of catalysts inhibited the chain-walking and chain-transfer reactions, resulting in polypropylene with high molecular weights (407~1101 kg/mol) and low 1,3-enchainment content (3.57~16.96%) in toluene. The low tensile strength (0.3~1.0 MPa), high elongation at break (218~403%) and strain recovery properties (S.R. ~50%, 10 tension cycles) of the resulting polypropylenes, as well as the visible light transmittance of approximately 90%, indicate the characteristics of the transparent elastomer.

Efficacy and safety of different cycles of neoadjuvant immunotherapy in resectable non-small cell lung cancer: A systematic review and meta-analysis.

Background: There is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell lung cancer (NSCLC). We carried out a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy with different treatment cycles in order to provide valuable information for clinical decision-making. Methods: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were systematically searched before May 2023. The included studies were categorized based on different treatment cycles of neoadjuvant immunotherapy to assess their respective efficacy and safety in patients with resectable NSCLC. Results: Incorporating data from 29 studies with 1331 patients, we found major pathological response rates of 43 % (95%CI, 34-52 %) with two cycles and 33 % (95%CI, 22-45 %) with three cycles of neoadjuvant immunotherapy. Radiological response rates were 39 % (95%CI, 28-50 %) and 56 % (95%CI, 44-68 %) for two and three cycles, respectively, with higher incidence rates of severe adverse events (SAEs) in the three-cycle group (32 %; 95%CI, 21-50 %). Despite similar rates of R0 resection between two and three cycles, the latter showed a slightly higher surgical delay rate (1 % vs. 7 %). Neoadjuvant treatment modes significantly affected outcomes, with the combination of immunotherapy and chemotherapy demonstrating superiority in improving pathological and radiological response rates, while the incidence of SAEs in patients receiving combination therapy remained within an acceptable range (23 %; 95%CI, 15-35 %). However, regardless of the treatment mode administered, an increase in the number of treatment cycles did not result in substantial improvement in pathological response rates. Conclusion: There are clear advantages of combining immunotherapy and chemotherapy in neoadjuvant settings. Increasing the number of cycles of neoadjuvant immunotherapy from two to three primarily may not substantially improve the overall efficacy, while increasing the risk of adverse events. Further analysis of the outcomes of four cycles of neoadjuvant immunotherapy is necessary.

Multi-level thresholding image segmentation for rubber tree secant using improved Otsu's method and snake optimizer.

The main disease that decreases the manufacturing of natural rubber is tapping panel dryness (TPD). To solve this problem faced by a large number of rubber trees, it is recommended to observe TPD images and make early diagnosis. Multi-level thresholding image segmentation can extract regions of interest from TPD images for improving the diagnosis process and increasing the efficiency. In this study, we investigate TPD image properties and enhance Otsu's approach. For a multi-level thresholding problem, we combine the snake optimizer with the improved Otsu's method and propose SO-Otsu. SO-Otsu is compared with five other methods: fruit fly optimization algorithm, sparrow search algorithm, grey wolf optimizer, whale optimization algorithm, Harris hawks optimization and the original Otsu's method. The performance of the SO-Otsu is measured using detail review and indicator reviews. According to experimental findings, SO-Otsu performs better than the competition in terms of running duration, detail effect and degree of fidelity. SO-Otsu is an efficient image segmentation method for TPD images.

The Function of Hydrotalcite as a Support Material in the Alcohol-Assisted Catalytic CO2 Hydrogenation Reaction.

The traditional CO2 hydrogenation reaction in gas phase always requires harsh reaction conditions to activate CO2 , resulting in huge energy consumption. However, with the assistance of 1-butanol solvent, catalytic CO2 hydrogenation can be proceeded at a mild condition of 170 °C and 30 bars. To further improve the catalytic performance of the widely studied Cu-ZnO-ZrO2 catalyst (CZZ), the catalysts were modified by incorporating hydrotalcite (HTC) as a support material. The addition of HTC significantly improved the copper dispersion and surface area of the catalyst. The performance of CZZ-HTC catalysts was investigated at varying weight percentages of HTC, and all showed higher space-time yield of methanol (STYMeOH ) compared to the commercial catalyst. Notably, CZZ-6HTC exhibited the highest methanol selectivity, further highlighting the beneficial role of HTC as a support material.

Early Mobilization for Critically Ill Patients.

Advances in the field of critical care medicine have helped improve the survival rate of these ill patients. Several studies have demonstrated the potential benefits of early mobilization as an important component of critical care rehabilitation. However, there have been some inconsistent results. Moreover, the lack of standardized mobilization protocols and the associated safety concerns are a barrier to the implementation of early mobilization in critically ill patients. Therefore, determining the appropriate modalities of implementation of early mobilization is a key imperative to leverage its potential in these patients. In this paper, we review the contemporary literature to summarize the strategies for early mobilization of critically ill patients, assess the implementation and validity based on the International Classification of Functioning, Disability and Health, as well as discuss the safety aspects of early mobilization.

microRNA-29b-3p/sirtuin-1/peroxisome proliferator-activated receptor γ suppress osteogenic differentiation.

Osteoporosis is described as an age-associated impairment of bone formation. microRNA (miR)-29b-3p was thought to be linked to osteoblast differentiation; however, the underlying molecular pathways are yet unknown. The study's goal was to look into the involvement of miR-29b-3p in osteoporosis and the pathophysiological mechanisms. A murine model of estrogen deficiency-induced bone loss was established to simulate postmenopausal osteoporosis. Reverse transcription-quantitative PCR (RT-qPCR) was performed to assess the level of miR-29b-3p of bone tissue. Additionally, miR-29b-3p/sirtuin-1 (SIRT1)/peroxisome proliferator-activated receptor γ (PPARγ) axis in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was examined. Osteogenesis-related markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2), were assessed at protein and molecular levels. ALP staining and Alizarin Red staining were used to detect ALP activity and calcium deposition. The ovariectomy group was shown to express miR-29b-3p at higher levels in vitro, and miR-29b-3p mimics suppressed osteogenic differentiation and protein/mRNA expression levels of osteogenesis-related markers in vivo. SIRT1 was identified as a target of miR-29b-3p using luciferase reporter assays. Overexpression of SIRT1 reduced the inhibition of osteogenic differentiation by miR-29b-3p. Rosiglitazone, an activator of PPARγ signaling, was able to reverse the downregulation of the osteogenic differentiation of BMSCs and the protein expression of PPARγ caused by miR-29b-3p inhibitors. The results revealed that osteogenesis was suppressed by miR-29b-3p, which blocks the SIRT1/PPARγ axis. These results suggested that postmenopausal osteoporosis could be treated by targeting miR-29b-3p SIRT1/PPARγ.

C1q+ tumor-associated macrophages contribute to immunosuppression through fatty acid metabolic reprogramming in malignant pleural effusion.

BACKGROUND: Although immune checkpoint blockade (ICB) therapy has shown remarkable benefits in cancers, a subset of patients with cancer exhibits unresponsiveness or develop acquired resistance due to the existence of abundant immunosuppressive cells. Tumor-associated macrophages (TAMs), as the dominant immunosuppressive population, impede the antitumor immune response; however, the underlying mechanisms have not been fully elucidated yet. METHODS: Single-cell RNA sequencing analysis was performed to portray macrophage landscape and revealed the underlying mechanism of component 1q (C1q)+ TAMs. Malignant pleural effusion (MPE) of human and mouse was used to explore the phenotypes and functions of C1q+ TAMs. RESULTS: C1q+ TAMs highly expressed multiple inhibitory molecules and their high infiltration was significantly correlated with poor prognosis. C1q+ TAMs promote MPE immunosuppression through impairing the antitumor effects of CD8+ T cells. Mechanistically, C1q+ TAMs enhance fatty acid binding protein 5 (FABP5)-mediated fatty acid metabolism, which activate transcription factor peroxisome proliferator-activated receptor-gamma, increasing the gene expression of inhibitory molecules. A high-fat diet increases the expression of inhibitory molecules in C1q+ TAMs and the immunosuppression of MPE microenvironment, whereas a low-fat diet ameliorates these effects. Moreover, FABP5 inhibition represses the expression of inhibitory molecules in TAMs and tumor progression, while enhancing the efficacy of ICB therapy in MPE and lung cancer. CONCLUSIONS: C1q+ TAMs impede antitumor effects of CD8+ T cells promoting MPE immunosuppression. Targeting C1q+ TAMs effectively alleviates the immunosuppression and enhances the efficacy of ICB therapy. C1q+ TAMs subset has great potential to be a therapeutic target for cancer immunotherapy.

Promising immunotherapeutic targets in lung cancer based on single-cell RNA sequencing.

Immunotherapy has made great strides in the treatment of lung cancer, but a significant proportion of patients still do not respond to treatment. Therefore, the identification of novel targets is crucial to improving the response to immunotherapy. The tumor microenvironment (TME) is a complex niche composed of diverse pro-tumor molecules and cell populations, making the function and mechanism of a unique cell subset difficult to understand. However, the advent of single-cell RNA sequencing (scRNA-seq) technology has made it possible to identify cellular markers and understand their potential functions and mechanisms in the TME. In this review, we highlight recent advances emerging from scRNA-seq studies in lung cancer, with a particular focus on stromal cells. We elucidate the cellular developmental trajectory, phenotypic remodeling, and cell interactions during tumor progression. Our review proposes predictive biomarkers and novel targets for lung cancer immunotherapy based on cellular markers identified through scRNA-seq. The identification of novel targets could help improve the response to immunotherapy. The use of scRNA-seq technology could provide new strategies to understand the TME and develop personalized immunotherapy for lung cancer patients.

Silencing of circCRIM1 Drives IGF2BP1-Mediated NSCLC Immune Evasion.

OBJECTIVES: Circular RNAs (circRNAs) have been found to have significant impacts on non-small cell lung cancer (NSCLC) progression through various mechanisms. However, the mechanism of circRNAs modulating tumor immune evasion in NSCLC has yet to be well-revealed. MATERIALS AND METHODS: Through analyzing the expression profiles of circRNAs in NSCLC tissues, RNA FISH, pull-down assay, mass spectrometry analysis, and RIP, circCRIM1 was identified, and its interaction with IGF2BP1 was confirmed. The effects of circCRIM1 on modulating tumor immune evasion were explored via co-culture in vitro and in tumor xenograft models. Subsequently, we evaluated the regulatory effects of circCRIM1 on IGF2BP1 and screened its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circCRIM1 could regulate the stability of target mRNA. RESULTS: circCRIM1 was downregulated in NSCLC, and its expression was positively correlated with favorable prognoses. Furthermore, circCRIM1 was more stable than its linear transcript and was mainly localized in the cytoplasm. Mechanistically, circCRIM1 destabilized HLA-F mRNA via competitive binding to IGF2BP1. Importantly, the overexpression of circCRIM1 suppressed the immune evasion of NSCLC and promoted the expressions of Granzyme B, IFN-γ, and TNF-α of CD8+ T and NK cell in vitro co-culture assays and tumor xenograft models. CONCLUSIONS: This study identifies circCRIM1 as a new tumor suppressor that inhibits tumor immune evasion through a competitive combination with IGF2BP1 to destabilize HLA-F mRNA.