Rare SMARCA4-deficient thoracic tumor: Insights into molecular characterization and optimal therapeutics methods.

INTRODUCTIONS: The 2021 WHO Classification of Thoracic Tumors recognized SMARCA4-deficient undifferentiated thoracic tumors (SMARCA4-dUT) as a distinct entity that shows a striking overlap in demographic and molecular profiles with SMARCA4-deficient non-small lung cancer (SMARCA4-dNSCLC). The implications of SMARCA4 deficiency based on immunohistochemistry remain unclear. We aimed to investigate molecular characteristics of SMARCA4-deficient thoracic tumors (SDTT) and explore optimal therapeutics. METHODS: From June.15, 2018, to Nov.15, 2023, a large cohort including patients diagnosed with SMARCA4-deficient (N = 196) and SMARCA4-intact (N = 438) thoracic tumors confirmed by immunohistochemistry at SYSUCC were screened. Clinicopathologic and molecular characteristics were identified and compared. External SRRSH cohort (N = 34) was combined into a pooled cohort to compare clinical outcome of first-line therapy efficacy. RESULTS: SDTT is male predominance with smoking history, high tumor burden, and adrenal metastases. The relationship between SMARCA4 mutation and protein expression is not completely parallel. The majority of SMARCA4-deficient patients harbor truncating (Class-I) SMARCA4 mutations, whereas class-II alterations and wild-type also exist. Compared with SMARCA4-intact thoracic tumors, patients with SDTT displayed a higher tumor mutation burden (TMB) and associated with a shorter median OS (16.8 months vs. Not reached; P < 0.001). Notably, SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in these differences. SDTT is generally resistant to chemotherapy, while sensitive to chemoimmunotherapy (median PFS: 7.5 vs. 3.5 months, P < 0.001). In particular, patients with SMARCA4 deficient thoracic tumors treated with paclitaxel-based chemoimmunotherapy achieved a longer median PFS than those with pemetrexed-based chemoimmunotherapy (10.0 vs. 7.3 months, P = 0.028). CONCLUSIONS: SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in its characteristics of higher TMB and poor prognosis. Chemoimmunotherapy serves as the optimal option in the current treatment regimen. Paclitaxel-based chemoimmunotherapy performed better than those with pemetrexed-based chemoimmunotherapy.

Full-Space Electric Field in Mo-Decorated Zn2In2S5 Polarization Photocatalyst for Oriented Charge Flow and Efficient Hydrogen Production.

Integration of photocatalytic hydrogen (H2) evolution with oxidative organic synthesis presents a highly attractive strategy for the simultaneous production of clean H2 fuel and high-value chemicals. However, the sluggish dynamics of photogenerated charge carriers across the photocatalysts result in low photoconversion efficiency, hindering the wide applications of such a technology. Herein, this work overcomes this limitation by inducing the full-space electric field via charge polarization engineering on a Mo cluster-decorated Zn2In2S5 (Mo-Zn2In2S5) photocatalyst. Specifically, this full-space electric field arises from a cascade of the bulk electric field (BEF) and local surface electric field (LSEF), triggering the oriented migration of photogenerated electrons from [Zn-S] regions to [In-S] regions and eventually to Mo cluster sites, ensuring efficient separation of bulk and surface charge carriers. Moreover, the surface Mo clusters induce a tip enhancement effect to optimize charge transfer behavior by augmenting electrons and proton concentration around the active sites on the basal plane of Zn2In2S5. Notably, the optimized Mo1.5-Zn2In2S5 catalyst achieves exceptional H2 and benzaldehyde production rates of 34.35 and 45.31 mmol gcat -1 h-1, respectively, outperforming pristine ZnIn2S4 by 3.83- and 4.15-fold. These findings mark a significant stride in steering charge flow for enhanced photocatalytic performance.

Instance-level 6D pose estimation based on multi-task parameter sharing for robotic grasping.

Six-dimensional pose estimation task predicts its 3D rotation matrix and 3D translation matrix in the world coordinate system by inputting the color image or depth image of the target object. Existing methods usually use deep neural networks to directly predict or regress object poses based on keypoint methods. The prediction results usually have deviations depending on whether the surface shape of the object is prominent or not and the size of the object. To solve this problem, we propose the six-dimensional pose estimation based on multi-task parameter sharing (PMP) framework to incorporate object category information into the pose estimation network through the form of an object classification auxiliary task. First, we extract the image features and point cloud features of the target object separately, and fuse them point by point; then, we share the confidence of each keypoint in pose estimation task and the knowledge of the classification task, get the key points with higher confidence, and predict the object pose; finally, the obtained object pose is passed through an iterative optimization network to obtain the final pose. The experimental results on the LineMOD dataset show that the proposed method can improve the accuracy of pose estimation and narrow the gap in the prediction accuracy of objects with different shapes. We also tested on a new dataset of small-scale objects, which contains object RGBD images and accurate 3D point cloud information. The proposed method is applied to the grasping experiment on the UR5 robotic arm, which satisfies the real-time pose estimation results during the grasping process.

Prioritization of organic contaminants in China's groundwater based on national-scale monitoring data and their persistence, bioaccumulation, and toxicity.

There has been increasing concern regarding the adverse environmental and health effects of organic pollutants. A list of priority control organic pollutants (PCOPs) can provide regulatory frameworks for the use and monitoring of organic compounds in the environment. In this study, 20,010 groundwater samples were collected from 15 "first level" groundwater resource zones in China. Fifty (50) organic compounds were analyzed based on their prevalence, occurrence, and physicochemical properties (persistence, bioaccumulation, and toxicity). Results showed that 16 PCOPs, including 12 pesticides, 3 aromatic hydrocarbons (AHs), and 1 phthalate ester, were recognized. Pesticides and AHs accounted for 75 % and 18.75 % of the high-priority pollutants, respectively. There were significant differences in PCOPs between confined and phreatic groundwater. Higher concentrations of pesticides were mainly detected in phreatic groundwater. PCOPs detected in samples from the 15 groundwater resource zones were mainly pesticides and AHs. The groundwater data indicate that the organic compounds detected in the Yellow River Basin (YRB), Yangtze River Basin (YZB), Liaohe River Basin (LRB), and Songhua River Basin (SRB) are mainly categorized as Q1 (high priority) and Q2 (medium priority) pollutants based on the contaminants ranking system in China. The findings from this study offer a snapshot of the wide distribution of PCOPs in the surveyed regions, and are expected to establishing treatment and prevention measures at both the regional and national levels in China.

Genomic and transcriptomic profiling of combined small-cell lung cancer through microdissection: unveiling the transformational pathway of mixed subtype.

BACKGROUND: Combined small-cell lung carcinoma (cSCLC) represents a rare subtype of SCLC, the mechanisms governing the evolution of cancer genomes and their impact on the tumor immune microenvironment (TIME) within distinct components of cSCLC remain elusive. METHODS: Here, we conducted whole-exome and RNA sequencing on 32 samples from 16 cSCLC cases. RESULTS: We found striking similarities between two components of cSCLC-LCC/LCNEC (SCLC combined with large-cell carcinoma/neuroendocrine) in terms of tumor mutation burden (TMB), tumor neoantigen burden (TNB), clonality structure, chromosomal instability (CIN), and low levels of immune cell infiltration. In contrast, the two components of cSCLC-ADC/SCC (SCLC combined with adenocarcinoma/squamous-cell carcinoma) exhibited a high level of tumor heterogeneity. Our investigation revealed that cSCLC originated from a monoclonal source, with two potential transformation modes: from SCLC to SCC (mode 1) and from ADC to SCLC (mode 2). Therefore, cSCLC might represent an intermediate state, potentially evolving into another histological tumor morphology through interactions between tumor and TIME surrounding it. Intriguingly, RB1 inactivation emerged as a factor influencing TIME heterogeneity in cSCLC, possibly through neoantigen depletion. CONCLUSIONS: Together, these findings delved into the clonal origin and TIME heterogeneity of different components in cSCLC, shedding new light on the evolutionary processes underlying this enigmatic subtype.

Two-stream Graph Convolutional Networks with Task-specific Loss for Dual-task Gait Analysis.

Dual-task gait systems can be utilized to assess elderly patients for cognitive decline. Although numerous research studies have been conducted to estimate cognitive scores, this field still faces two significant challenges. Firstly, it is crucial to fully utilize dual-task cost representations for diagnosis. Secondly, the design of optimal strategies for effectively extracting dual-task cost representations remains a challenge. To address these issues, in this paper, we propose a deep learning-based framework that implements a spatio-temporal graph convolutional neural network (ST-GCN) with single-task and dual-task pathways for cognitive impairment detection in gait. We also introduce a novel loss, termed task-specific loss, to ensure that single-task and dual-task representations are distinguishable from each other. Furthermore, dual-task cost representations are calculated as the difference between dual-task and single-task representations, which are resilient to individual differences and contribute to the robustness of the framework. These representations provide a comprehensive view of single-task and dual-task gait information to generate task predictions. The proposed framework outperforms existing approaches with a sensitivity of 0.969 and a specificity of 0.940 for cognitive impairment detection.

Adaptive Graph Convolutional Networks for Medical Image Segmentation.

Medical image segmentation is very essential for computer-aided diagnosis in the field of medical imaging. In the last decade, Deep Learning-based frameworks (e.g., UNet) have been widely used in medical applications such as image segmentation tasks. Recently, numerous Transformer-based frameworks are presented for the image segmentation tasks as their design can utilize long-range dependencies. Transformer's design has a weak inductive bias since it does not take advantage of local relationships between pixels and lacks scale invariance. Consequently, Transformers require large datasets for convergence whereas the availability of massive medical datasets is challenging. In this paper, we present a graph-based approach replacing Transformer design to capture long-range dependencies and reduce computational cost. Our proposed framework achieves competitive performance using publicly available dataset Synapse.

Case report: Leptomeningeal metastasis of advanced nasopharyngeal carcinoma treated with chemoimmunotherapy.

Leptomeningeal metastasis (LM) of nasopharyngeal carcinoma (NPC) is rare and associated with a poor prognosis. Immune checkpoint inhibitors (ICIs) have been the standard first-line treatment for metastatic NPC, but their effect on meningeal metastasis of NPC needs further investigation. A 38-year-old man complained of bilateral neck masses and sought medical care. He was diagnosed with nasopharyngeal undifferentiated non-keratinizing carcinoma with bilateral cervical lymph node metastasis and multiple bone metastasis, stage cT4N2M1 IVb. Then, the patient received first-line anti-PD-1 antibody tislelizumab combined with gemcitabine and cisplatin and achieved partial response. After seven cycles of first-line chemoimmunotherapy, the patient subsequently developed neurological symptoms, including unsteady walking, slurred speech, coughing on drinking, and unconsciousness. MRI showed leptomeningeal linear enhancement, and cerebrospinal fluid (CSF) analysis indicated Epstein-Barr virus (EBV) infection and squamous cell carcinoma cytology, suggesting the diagnosis of leptomeningeal metastasis. After the definite diagnosis of LM, the patient's condition deteriorated rapidly, leading to his death from brain herniation. We reported the first case of advanced NPC with pathologically confirmed leptomeningeal metastasis after receiving first-line chemoimmunotherapy. Considering the poor prognosis of LM, it is suggested to perform MRI and CSF examination when patients have neurological symptoms. Although immunotherapy significantly improved survival outcomes of advanced NPC patients, it seemed not effective in the setting of LM. The effect of other treatment options, such as radiation therapy and intrathecal therapy, requires further verification.

Genetic Diversity Analysis of the Red Swamp Crayfish Procambarus clarkii in Three Cultured Populations Based on Microsatellite Markers.

With the increasing scale of crayfish breeding, the self-propagation and "catch large and keep small" breeding patterns have led to serious degradation of the fry, so the selection and breeding of high-quality fry is very important. Selecting a population with a high genetic diversity as the base population for breeding can greatly improve the breeding efficiency. Fifteen microsatellite loci were used to understand the genetic structure and diversity of three Procambarus clarkii populations in Chongming, Shanghai; Gaoyou, Jiangsu; and Xuancheng, Anhui. The results indicated that the three populations were diverse and the number of alleles, observed heterozygosity, expected heterozygosity, Shannon information index, and polymorphic information content ranged from 4.8 to 6.2, 0.5567 to 0.6257, 0.6166 to 0.7086, 1.1292 to 1.3987, and 0.5446 to 0.6452, respectively. The Xuancheng population had the highest genetic diversity. The genetic differentiation coefficient and gene flow of the three populations were between 0.0553 and 0.1068 and 2.0908 and 4.2708, respectively, and there was extensive genetic exchange between the Chongming and Xuancheng populations. Analyses of molecular variance indicated that the genetic variation was mainly within the population (91.51%) and inter-population genetic variation accounted for 8.49%. The unweighted pair group method with an arithmetic mean clustering map was utilised based on the genetic distance between groups, and the results showed that the Gaoyou group was grouped alone, while the Chongming and Xuancheng groups were clustered together. The structural results indicated that the Chongming and Xuancheng groups had the same origin, although the Xuancheng group possessed a more complex genetic structure. This study indicated that all three populations had a high genetic diversity, with the Xuancheng population exhibiting the highest diversity. The results of the study provide a reference for the selection of base populations in breeding programs and confirm that the Xuancheng population in Anhui has a better genetic background. The selection of the Xuancheng population as one of the base populations for genetic breeding will be more efficient to accumulate superior traits.

Controlling the directional excitation of surface plasmon polaritons using tunable non-Hermitian metasurfaces.

In this work, we propose an efficient approach to controlling the directional excitation of surface plasmon polaritons (SPPs) by dynamically modulating the real-part perturbation in a passive parity-time symmetric metasurface. This non-Hermitian system can experience two exceptional points that can induce two unidirectional excitation states of SPPs along opposite directions. Empowered by its superior modulation depth, the energy ratio and energy intensities of two excited SPP states can be effectively manipulated by this non-Hermitian metasurface. To demonstrate these findings, we design and numerically verify non-Hermitian metasurfaces integrated with an Sb2Se3 phase-change material. Our work provides a promising platform for the controllable engineering of SPP excitations, holding significant potential for the development of new plasmonic devices, including on-chip SPP sources, routers and sorters, and integrated optical circuits.

STK11/LKB1-Deficient Phenotype Rather Than Mutation Diminishes Immunotherapy Efficacy and Represents STING/Type I Interferon/CD8+ T-Cell Dysfunction in NSCLC.

INTRODUCTION: Conflicting findings have been reported regarding the association between STK11/LKB1 mutations and immune checkpoint inhibitor (ICB) efficacy in NSCLC. It has been reported that tumors could exhibit impaired STK11/LKB1 function even without STK11 mutations. We hypothesized that STK11 phenotype rather than mutation may better stratify ICB outcomes. METHODS: Selected functional STK11 events and LKB1 protein data were leveraged to establish a transcriptomics-based classifier of STK11 phenotype (STK11-deficient [-def] or -proficient [-prof]). We analyzed in-house and Genentech/Roche's data of three randomized trials of programmed cell death protein-1 or programmed death-ligand 1 (PD-L1) inhibition in NSCLC (ORIENT-11, n = 171; OAK, n = 699; POPLAR, n = 192) and The Cancer Genome Atlas-NSCLC cohort. RESULTS: Tissue STK11 mutation did not affect ICB outcomes. However, the survival benefit of ICB versus chemotherapy were lost or reversed in STK11-def tumors (hazard ratios for death, 95% confidence interval: OAK [0.97, 0.69-1.35]; POPLAR [1.61, 0.88-2.97]; ORIENT-11 [1.07, 0.50-2.29]), while remaining in STK11-prof tumors (hazard ratios for death, 95% confidence interval: OAK [0.81, 0.66-0.99]; POPLAR [0.66, 0.46-0.95]; ORIENT-11 [0.59, 0.37-0.92]). In tumors differentially classified by phenotype and mutation status, STK11-wild-type/def tumors had significantly worse ICB outcomes than STK11-mutated (STK11-MUT)/prof tumors (p < 0.05). The deleterious impact of STK11 deficiency was independent of STK11/KRAS/KEAP1 status or PD-L1 expression. The STING/interferon-I signaling, which was previously shown to be suppressed in STK11-MUT models, was perturbed in patients with STK11-def tumors rather than those with STK11-MUT tumors. Surprisingly, whereas high CD8+ T-cell infiltration was significantly associated with prolonged survival with ICB in STK11-prof tumors (p < 0.05 for 3 trials), it predicted an opposite trend toward worse ICB outcomes in STK11-def tumors across three trials. This suggested an association between STK11 deficiency and CD8+ T-cell dysfunction, which might not be reversed by programmed cell death protein 1 or PD-L1 blockade. CONCLUSIONS: STK11 phenotype rather than mutation status can accurately identify patients with ICB-refractory NSCLC and reflect immune suppression. It can help refine stratification algorithms for future clinical research and also provide a reliable resource aiding basic and translational studies in identifying therapeutic targets.

Mitochondrial ROS-dependent CD4+PD-1+T cells are pathological expansion in patients with primary immune thrombocytopenia.

OBJECTIVE: Aberrant-activated T cells, especially CD4+T cells, play a crucial part in the pathogenetic progress of immune thrombocytopenia (ITP). PD-1-mediated signals play a negative part in the activation of CD4+T cells. However, knowledge is limited on the pathogenic characteristics and function of CD4+PD-1+T cells in ITP. MATERIALS AND METHODS: The frequency and phenotype including cell activation, apoptosis, and cytokine production of CD4+PD-1+T cells were evaluated by flow cytometry. PD-1 Ligation Assay was performed to assess the function of PD-1 pathway in CD4+T cells. Mitochondrial reactive oxygen species (mtROS) were detected by MitoSOX Red probe. RESULTS: Compared with healthy controls (HC), the frequencies of CD4+PD-1+T cells were significantly increased in ITP patients. However, these cells are not exhausted despite PD-1 expression. Besides retaining cytokine-producing potential, these CD4+PD-1+T cells also had a possible B-cell helper function including expressing ICOS, CD84, and CD40L. Moreover, the CD4+PD-1+T cell subset contained higher levels of mitochondrial ROS than CD4+PD-1-T cell subset in patients with ITP. And mtROS inhibition could reduce the secretion of the inflammatory cytokines and regulate the function of CD4+PD-1+T cells. Upon in-vitro T cell receptor (TCR) stimulation of CD4+T cells in the presence of plate-bound PD-L1 fusion protein (PD-L1-Ig), CD4+T cells from ITP patients appeared resistant to such PD-1-mediated inhibition of interferon (IFN)-γ secretion. CONCLUSIONS: The CD4+PD-1+T cells were more abundant in patients with ITP. Additionally, this CD4+PD-1+T cell subset may be a potential etiology of ITP and a potential immune therapeutic target for ITP patients in the future.

Bibliometric Analysis of Global Research on Tumor Dormancy.

Tumor dormancy continues to be a research hotspot with numerous pressing problems that need to be solved. The goal of this study is to perform a bibliometric analysis of pertinent articles published in the twenty-first century. We concentrate on significant keywords, nations, authors, affiliations, journals, and literature in the field of tumor dormancy, which will help researchers to review the results that have been achieved and better understand the directions of future research. We retrieved research articles on tumor dormancy from the Web of Science Core Collection. This study made use of the visualization tools VOSviewer, CiteSpace, and Scimago Graphica, as visualization helps us to uncover the intrinsic connections between information. Research on tumor dormancy has been growing in the 21st century, especially from 2015 to the present. The United States is a leader in many aspects of this research area, such as in the number of publications, the number of partners, the most productive institutions, and the authors working in this field. Harvard University is the institution with the highest number of publications, and Aguirre-Ghiso, Julio A. is the author with the highest number of publications and citations. The keywords that emerged after 2017 were "early dissemination", "inhibition", "mechanism", "bone metastasis", and "promotion". We believe that research on tumor dormancy mechanisms and therapy has been, and will continue to be, a major area of interest. The exploration of the tumor dormancy microenvironment and immunotherapeutic treatments for tumor dormancy is likely to represent the most popular future research topics.

IL-27 enhances peripheral B cell glycolysis of rheumatoid arthritis patients via activating mTOR signaling.

Our previous study found that increased serum IL-27 could promote rheumatoid arthritis (RA) B cell dysfunction via activating mTOR signaling pathway. This study aimed to explore the effects of IL-27 on B cell metabolism and clarify the mechanisms via which IL-27 enhancing glycolysis to induce B cells hyperactivation. Peripheral CD19+ B cells were purified from healthy controls (HC) and RA patients and then cultured with or without anti-CD40/CpG and glycolysis inhibitor 2-deoxy-D-glucose (2-DG) or mTOR inhibitor rapamycin. Furthermore, the isolated CD19+ B cells were treated by HC serum or RA serum in the presence and absence of recombinant human IL-27 or anti-IL-27 neutralizing antibodies or 2-DG or rapamycin. The B cell glycolysis level, proliferation, differentiation and inflammatory actions were detected by qPCR, flow cytometry or ELISA. We found that the glycolysis in RA B cells was increased significantly compared with HC B cells. Glycolysis inhibition downregulated the proliferation, differentiation, and inflammatory actions of RA B cells. RA serum and IL-27 promoted B cell glycolysis, which could be obviously rescued by anti-IL-27 antibodies or mTOR inhibitor rapamycin. Our results suggest that the enhanced cellular glycolysis of RA B cells induced by IL-27 may contribute to B cells hyperactivation through activating the mTOR signaling pathway.

Infection pattern and immunological characteristics of Epstein-Barr virus latent infection in cervical squamous cell carcinoma.

Previous studies reported the association between Epstein-Barr virus (EBV) and cervical squamous cell carcinoma (CSCC), but its infection pattern and clinical significance unclear. This study aimed to comprehensively investigate the infection pattern, clinicopathology, outcomes, and immunology of this entity in central China. We evaluated a total of 104 untreated CSCC tumor tissue specimens using in situ hybridization for EBV-encoded small RNAs (EBERs), and by employing flowcytometry fluorescence hybridization for human papillomavirus (HPV) genotyping. The expression of EBV latency proteins and immune biomarkers was evaluated and quantified by immunohistochemistry. EBERs transcripts were detected in 21 (20.2%) cases overall (in malignant epithelial cells of 13 cases and in lymphocytes of 8 cases). EBV belonged to latency type I infection in CSCC. The high-risk (HR)-HPV was detected in all of EBV-positive CSCC, and the difference of detection rate of HR-HPV was significant when compared with EBV-negative CSCC (p = 0.001). The specific clinicopathology with increased frequency of advanced clinical stages, tumor-positive lymph nodes, neural invasion, and increased infiltration depth (all p value < 0.05) were observed in cases with EBV. However, EBV infection was found to have no impact on prognosis of patients with CSCC. Increased densities of forkhead box P3 (FoxP3)+-tumor infiltrating lymphocytes (TILs) (p = 0.005) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)+-TILs (p = 0.017) and higher expression of programmed cell death-1 (PD-1) (p = 0.002) and programmed cell death-1 ligand 1 (PD-L1) (p = 0.040) were associated with EBV latent infection in CSCC, and these immunological changes were more likely to be associated with the infection in lymphocytes rather than tumor cells. Moreover, in patients with HPV-positive CSCC, similar significant differences were still found. In conclusions, EBV-positive CSCC may have specific infection pattern and clinicopathology and can exhibit an immunosuppressive microenvironment dominated by Treg cells aggregation and immune checkpoint activation.

Classification of Tumor Immune Microenvironment According to Programmed Death-Ligand 1 Expression and Immune Infiltration Predicts Response to Immunotherapy Plus Chemotherapy in Advanced Patients With NSCLC.

INTRODUCTION: According to mechanisms of adaptive immune resistance, tumor immune microenvironment (TIME) is classified into four types: (1) programmed death-ligand 1 (PD-L1)-negative and tumor-infiltrating lymphocyte (TIL)-negative (type I); (2) PD-L1-positive and TIL-positive (type II); (3) PD-L1-negative and TIL-positive (type III); and (4) PD-L1-positive and TIL-negative (type IV). However, the relationship between the TIME classification model and immunotherapy efficacy has not been validated by any large-scale randomized controlled clinical trial among patients with advanced NSCLC. METHODS: On the basis of RNA-sequencing and immunohistochemistry data from the ORIENT-11 study, we optimized the TIME classification model and evaluated its predictive value for the efficacy of immunotherapy plus chemotherapy. RESULTS: PD-L1 mRNA expression and immune score calculated by the ESTIMATE method were the strongest predictors for the efficacy of immunotherapy plus chemotherapy. Therefore, they were determined as the optimized definition of the TIME classification system. When compared between combination therapy and chemotherapy alone, only the type II subpopulation with high immune score and high PD-L1 mRNA expression was significantly associated with improved progression-free survival (PFS) (hazard ratio = 0.12, 95% confidence interval: 0.06-0.25, p < 0.001) and overall survival (hazard ratio = 0.27, 95% confidence interval: 0.13-0.55, p < 0.001). In the combination group, the type II subpopulation had a much longer survival time, not even reaching the median PFS or overall survival, but the other three subpopulations were susceptible to having similar PFS. In the chemotherapy group, there was no marked association between survival outcomes and TIME subtypes. CONCLUSIONS: Only patients with both high PD-L1 expression and high immune infiltration could benefit from chemotherapy plus immunotherapy in first-line treatment of advanced NSCLC. For patients lacking either PD-L1 expression or immune infiltration, chemotherapy alone might be a better treatment option to avoid unnecessary toxicities and financial burdens.

FcγRIIIA activation-mediated up-regulation of glycolysis alters MDSCs modulation in CD4+ T cell subsets of Sjögren syndrome.

Our and other researchers' previous studies found that myeloid-derived suppressor cells (MDSCs) were increased, and these MDSCs, supposed to play immunosuppressive roles, showed significant pro-inflammatory effects in Sjögren's syndrome (SS). However, the key factors and potential mechanisms leading MDSCs to be inflammatory remain unclear. In this study, we found that MDSCs from SS patients were positively correlated with the percentages of Th17 cells, disease activity and serum autoantibodies, and showed higher levels of Fc gamma receptor (FcγR) IIIA and glycolysis. Most importantly, SS MDSCs or heat-aggregated IgG (HAIG)-treated MDSCs down-regulated Th1/Th2 ratio and up-regulated Th17/Treg ratio, which could be obviously rescued by IgG monomer or glycolysis inhibitor 2-DG. As well, the levels of FcγRIV and glycolysis in MDSCs and the ratio of Th17/Treg were increased, and the ratio of Th1/Th2 was decreased in SS-like NOD mice. Our study indicated that MDSCs showed pro-inflammatory phenotypes by disturbing CD4+ T-cell balances in SS. The pro-inflammatory effects of MDSCs might be directly linked to the enhanced glycolysis mediated by FcγRIIIA activation.

Tunable dual quasi-bound states in continuum and electromagnetically induced transparency enabled by the broken material symmetry in all-dielectric compound gratings.

Dual quasi-bound states in continuum (quasi-BICs) enabled by the broken geometric symmetry offer an effective way to design high-quality photonic devices, yet challenged by tunable functionalities. Here we employ the material asymmetry originating from the tunable material property of phase-change materials to design quasi-BICs in all-dielectric compound gratings. We find the even and odd quasi-BICs are modulated by the geometric and material asymmetries, respectively, and this effect is ensured by two different types of structural symmetries in the compound structure. Particularly, tunable electromagnetically induced transparency (EIT) can be achieved by modulating the material asymmetry. Furthermore, we systematically design the compound gratings consisting of the phase-change material of Sb2Se3 to demonstrate tunable dual quasi-BICs and EITs. Analytical calculations and numerical simulations are performed to verify these findings. Our work provides a promising way to enhance the flexibility of realizing quasi-BICs, which may boost tunable applications in nanodevices assisted by quasi-BICs.

Dynamin-Related Protein 1 Binding Partners MiD49 and MiD51 Increased Mitochondrial Fission In Vitro and Atherosclerosis in High-Fat-Diet-Fed ApoE-/- Mice.

Novel components of the mitochondrial fission machinery, mitochondrial dynamics proteins of 49 kDa (MiD49) and 51 kDa (MiD51), have been recently described, and their potential therapeutic targets for treating cardiovascular disease have been shown, including acute myocardial infarction (AMI), anthracycline cardiomyopathy and pulmonary arterial hypertension (PAH). Here, we examined the role of MiD49 and MiD51 in atherosclerosis. MiD49/51 expression was increased in the aortic valve endothelial cells (ECs) of high-fat diet-induced atherosclerosis in ApoE-/-mice and IL-8-induced human umbilical vein endothelial cells (HUVECs), which accelerated dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Silencing MiD49/51 reduced atherosclerotic plaque size, increased collagen content, and decreased the IL-8-induced adhesion and proliferation of HUVECs. MiD51 upregulation resulted from decreased microRNA (miR)-107 expression and increased hypoxia-inducible factor-1a (HIF-1a) expression. Treatment with miR-107 mimics decreased atherosclerotic plaque size by reducing HIF-1α and MiD51 production. Both MiD49 and MiD51 were involved in atherosclerotic plaque formation through Drp1-mediated mitochondrial fission, and the involvement of MiD51 in this process was the result of decreased miR-107 expression and increased HIF-1α expression. The miR-107-HIF-1α-MiD51 pathway might provide new therapeutic targets for atherosclerosis.