Pan-cancer analysis for the prognostic and immunological role of CD47: interact with TNFRSF9 inducing CD8 + T cell exhaustion.

PURPOSE: The research endeavors to explore the implications of CD47 in cancer immunotherapy effectiveness. Specifically, there is a gap in comprehending the influence of CD47 on the tumor immune microenvironment, particularly in relation to CD8 + T cells. Our study aims to elucidate the prognostic and immunological relevance of CD47 to enhance insights into its prospective utilities in immunotherapeutic interventions. METHODS: Differential gene expression analysis, prognosis assessment, immunological infiltration evaluation, pathway enrichment analysis, and correlation investigation were performed utilizing a combination of R packages, computational algorithms, diverse datasets, and patient cohorts. Validation of the concept was achieved through the utilization of single-cell sequencing technology. RESULTS: CD47 demonstrated ubiquitous expression across various cancer types and was notably associated with unfavorable prognostic outcomes in pan-cancer assessments. Immunological investigations unveiled a robust correlation between CD47 expression and T-cell infiltration rather than T-cell exclusion across multiple cancer types. Specifically, the CD47-high group exhibited a poorer prognosis for the cytotoxic CD8 + T cell Top group compared to the CD47-low group, suggesting a potential impairment of CD8 + T cell functionality by CD47. The exploration of mechanism identified enrichment of CD47-associated differentially expressed genes in the CD8 + T cell exhausted pathway in multiple cancer contexts. Further analyses focusing on the CD8 TCR Downstream Pathway and gene correlation patterns underscored the significant involvement of TNFRSF9 in mediating these effects. CONCLUSION: A robust association exists between CD47 and the exhaustion of CD8 + T cells, potentially enabling immune evasion by cancer cells and thereby contributing to adverse prognostic outcomes. Consequently, genes such as CD47 and those linked to T-cell exhaustion, notably TNFRSF9, present as promising dual antigenic targets, providing critical insights into the field of immunotherapy.

Early patient-reported outcomes after robotic-assisted versus video-assisted thoracoscopic lobectomy.

BACKGROUND: Robotic-assisted thoracoscopic surgery (RATS) can achieve traditional clinical outcomes comparable to those of video-assisted thoracoscopic surgery (VATS). However, patient-reported outcomes (PROs) during the early period after RATS and VATS remain unclear. This study aimed to utilize longitudinal electronic PRO (ePRO) assessments to evaluate symptom burden and functional status between these approaches from patients' perspective. METHODS: This study comprised patients who underwent lobectomy via RATS or VATS for non-small cell lung cancer. We collected multiple-time-point PROs data from the prospective longitudinal study via an ePRO system. Symptom severity and function status were assessed using the perioperative symptom assessment for patients undergoing lung surgery and were analyzed between groups using linear mixed-effects models. RESULTS: Of the 164 patients, 42 underwent RATS and 122 underwent VATS. After propensity score matching (PSM), 42 RATS and 84 VATS exhibited similar baseline characteristics. During the 7-day postoperative period, participants underwent RATS reported milder pain (p = 0.014), coughing (p < 0.001), drowsiness (p = 0.001), and distress (p = 0.045) compared with those underwent VATS. Moreover, participants in RATS group showed less functional interference with walking (p < 0.001) and general activity (p < 0.001). RATS exhibited a shorter postoperative hospitalization (p = 0.021) but higher hospital cost (p < 0.001). Meanwhile, short-term clinical outcomes of operative time, dissected lymph node stations, chest tube drainage, and postoperative complication rates were comparable. CONCLUSION: PROs are important metrics for assessing patients' recovery after lobectomy. Compared with VATS, RATS may induce less symptom burden and better functional status for patients in the early postoperative period.

Rational Lithium Salt Molecule Tuning for Fast Charging/Discharging Lithium Metal Battery.

The electrolytes for lithium metal batteries (LMBs) are plagued by a low Li+ transference number (T+) of conventional lithium salts and inability to form a stable solid electrolyte interphase (SEI). Here, we synthesized a self-folded lithium salt, lithium 2-[2-(2-methoxy ethoxy)ethoxy]ethanesulfonyl(trifluoromethanesulfonyl) imide (LiETFSI), and comparatively studied with its structure analogue, lithium 1,1,1-trifluoro-N-[2-[2-(2-methoxyethoxy)ethoxy)]ethyl]methanesulfonamide (LiFEA). The special anion chemistry imparts the following new characteristics: i) In both LiFEA and LiETFSI, the ethylene oxide moiety efficiently captures Li+, resulting in a self-folded structure and high T+ around 0.8. ii) For LiFEA, a Li-N bond (2.069 Å) is revealed by single crystal X-ray diffraction, indicating that the FEA anion possesses a high donor number (DN) and thus an intensive interphase "self-cleaning" function for an ultra-thin and compact SEI. iii) Starting from LiFEA, an electron-withdrawing sulfone group is introduced near the N atom. The distance of Li-N is tuned from 2.069 Šin LiFEA to 4.367 Šin LiETFSI. This alteration enhances ionic separation, achieves a more balanced DN, and tunes the self-cleaning intensity for a reinforced SEI. Consequently, the fast charging/discharging capability of LMBs is progressively improved. This rationally tuned anion chemistry reshapes the interactions among Li+, anions, and solvents, presenting new prospects for advanced LMBs.

Disruption of the rice ALS1 localized in chloroplast causes seedling-lethal albino phenotype.

Chloroplasts are the organelles responsible for photosynthesis and regulate normal plant growth. Although translation elongation factors play important roles in chloroplast development, functional studies of chloroplast translation elongation factors in higher plants remain very sparse. Here, we obtained a rice mutant exhibiting seedling-lethal albino phenotype and named it albino and lethal seedling 1 (als1). Consistently, low content of photosynthetic pigments, malformed chloroplasts and defective photosynthesis were observed in als1 mutant leaves. Map-based cloning experiment showed that als1 mutant had a T base insertion in Os02g0595700, causing a frame shift and premature stop codon. ALS1 encoded a GTP-binding protein EF-Tu, which acts as a translation elongation factor in chloroplast protein translation. ALS1 was found to be expressed throughout plant with highest expression level in young leaves. Moreover, ALS1 was located in chloroplast, whereas the truncated als1 could not normally be located in chloroplast. Additionally, the ALS1 mutation significantly influenced the expression of downstream genes, such as genes relevant to chlorophyll biosynthesis, photosynthesis as well as chloroplast development. These results show that ALS1 acts as a key regulator of chloroplast development and plant growth.

KD_ConvNeXt: knowledge distillation-based image classification of lung tumor surgical specimen sections.

Introduction: Lung cancer is currently among the most prevalent and lethal cancers in the world in terms of incidence and fatality rates. In clinical practice, identifying the specific subtypes of lung cancer is essential in diagnosing and treating lung lesions. Methods: This paper aims to collect histopathological section images of lung tumor surgical specimens to construct a clinical dataset for researching and addressing the classification problem of specific subtypes of lung tumors. Our method proposes a teacher-student network architecture based on a knowledge distillation mechanism for the specific subtype classification of lung tumor histopathological section images to assist clinical applications, namely KD_ConvNeXt. The proposed approach enables the student network (ConvNeXt) to extract knowledge from the intermediate feature layers of the teacher network (Swin Transformer), improving the feature extraction and fitting capabilities of ConvNeXt. Meanwhile, Swin Transformer provides soft labels containing information about the distribution of images in various categories, making the model focused more on the information carried by types with smaller sample sizes while training. Results: This work has designed many experiments on a clinical lung tumor image dataset, and the KD_ConvNeXt achieved a superior classification accuracy of 85.64% and an F1-score of 0.7717 compared with other advanced image classification methods.

Pretreatment radiomic biomarker for immunotherapy responder prediction in stage IB-IV NSCLC (LCDigital-IO Study): a multicenter retrospective study.

BACKGROUND: The predictive efficacy of current biomarker of immune checkpoint inhibitors (ICIs) is not sufficient. This study investigated the causality between radiomic biomarkers and immunotherapy response status in patients with stage IB-IV non-small cell lung cancer (NSCLC), including its biological context for ICIs treatment response prediction. METHODS: CT images from 319 patients with pretreatment NSCLC receiving immunotherapy between January 2015 and November 2021 were retrospectively collected and composed a discovery (n=214), independent validation (n=54), and external test cohort (n=51). A set of 851 features was extracted from tumorous and peritumoral volumes of interest (VOIs). The reference standard is the durable clinical benefit (DCB, sustained disease control for more than 6 months assessed via radiological evaluation). The predictive value of combined radiomic signature (CRS) for pathological response was subsequently assessed in another cohort of 98 patients with resectable NSCLC receiving ICIs preoperatively. The association between radiomic features and tumor immune landscape on the online data set (n=60) was also examined. A model combining clinical predictor and radiomic signatures was constructed to improve performance further. RESULTS: CRS discriminated DCB and non-DCB patients well in the training and validation cohorts with an area under the curve (AUC) of 0.82, 95% CI: 0.75 to 0.88, and 0.75, 95% CI: 0.64 to 0.87, respectively. In this study, the predictive value of CRS was better than programmed cell death ligand-1 (PD-L1) expression (AUC of PD-L1 subset: 0.59, 95% CI: 0.50 to 0.69) or clinical model (AUC: 0.66, 95% CI: 0.51 to 0.81). After combining the clinical signature with CRS, the predictive performance improved further with an AUC of 0.837, 0.790 and 0.781 in training, validation and D2 cohorts, respectively. When predicting pathological response, CRS divided patients into a major pathological response (MPR) and non-MPR group (AUC: 0.76, 95% CI: 0.67 to 0.81). Moreover, CRS showed a promising stratification ability on overall survival (HR: 0.49, 95% CI: 0.27 to 0.89; p=0.020) and progression-free survival (HR: 0.43, 95% CI: 0.26 to 0.74; p=0.002). CONCLUSION: By analyzing both tumorous and peritumoral regions of CT images in a radiomic strategy, we developed a non-invasive biomarker for distinguishing responders of ICIs therapy and stratifying their survival outcome efficiently, which may support the clinical decisions on the use of ICIs in advanced as well as patients with resectable NSCLC.

Evaluation of combined pathological responses in primary tumor and lymph nodes following neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

BACKGROUND: Inconsistent pathological responses of tumor and lymph nodes (LNs) were frequently observed in non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. However, there is a lack of studies to report the prognostic significance and the relevant clinicopathological factors of tumor-nodal inconsistent responses after neoadjuvant immunotherapy or chemoimmunotherapy. Therefore, this study aimed to depict the inconsistent pathological combined tumor-nodal responses in NSCLC patients after neoadjuvant chemoimmunotherapy as well as the underlying clinical significance. METHODS: A total of 81 node-positive NSCLC patients who underwent neoadjuvant chemoimmunotherapy were eligible for inclusion. Demographic, radiologic, and pathological features of patients were recorded. Patients with pathological complete response of both tumor (ypT(pCR)) and LNs (ypN0) were classified into the combined good responder group and the relevant clinicopathological features were evaluated. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. RESULTS: The ypN0 and ypT(pCR) rates were 74.1 % and 42.0 %, respectively. A significant correlation was observed between ypT(pCR) and ypN0 (P = 0.003), but inconsistent responses remained. The combined responses of the primary tumor and LNs demonstrated a significant association with the prognosis outcome (P = 0.005). Notably,patients who received at least twice of their infusions of immune checkpoint inhibitors after 15:30 had a worse prognosis (P = 0.015). CONCLUSION: A significant but not absolute correlation was observed between good tumor response and good nodal response in NSCLC patients after neoadjuvant chemoimmunotherapy, but inconsistent responses were also found. The combination of tumor and nodal responses is significantly associated with prognosis and combined good responder can be used as a reliable prognosis predictor.

Biomimetic Hydrogel Applications and Challenges in Bone, Cartilage, and Nerve Repair.

Tissue engineering and regenerative medicine is a highly sought-after field for researchers aiming to compensate and repair defective tissues. However, the design and development of suitable scaffold materials with bioactivity for application in tissue repair and regeneration has been a great challenge. In recent years, biomimetic hydrogels have shown great possibilities for use in tissue engineering, where they can tune mechanical properties and biological properties through functional chemical modifications. Also, biomimetic hydrogels provide three-dimensional (3D) network spatial structures that can imitate normal tissue microenvironments and integrate cells, scaffolds, and bioactive substances for tissue repair and regeneration. Despite the growing interest in various hydrogels for biomedical use in previous decades, there are still many aspects of biomimetic hydrogels that need to be understood for biomedical and clinical trial applications. This review systematically describes the preparation of biomimetic hydrogels and their characteristics, and it details the use of biomimetic hydrogels in bone, cartilage, and nerve tissue repair. In addition, this review outlines the application of biomimetic hydrogels in bone, cartilage, and neural tissues regarding drug delivery. In particular, the advantages and shortcomings of biomimetic hydrogels in biomaterial tissue engineering are highlighted, and future research directions are proposed.

Radiation-sensitive genetic prognostic model identifies individuals at risk for radiation resistance in head and neck squamous cell carcinoma.

BACKGROUND: The advantages of radiotherapy for head and neck squamous cell carcinoma (HNSCC) depend on the radiation sensitivity of the patient. Here, we established and verified radiological factor-related gene signature and built a prognostic risk model to predict whether radiotherapy would be beneficial. METHODS: Data from The Cancer Genome Atlas, Gene Expression Omnibus, and RadAtlas databases were subjected to LASSO regression, univariate COX regression, and multivariate COX regression analyses to integrate genomic and clinical information from patients with HNSCC. HNSCC radiation-related prognostic genes were identified, and patients classified into high- and low-risk groups, based on risk scores. Variations in radiation sensitivity according to immunological microenvironment, functional pathways, and immunotherapy response were investigated. Finally, the expression of HNSCC radiation-related genes was verified by qRT-PCR. RESULTS: We built a clinical risk prediction model comprising a 15-gene signature and used it to divide patients into two groups based on their susceptibility to radiation: radiation-sensitive and radiation-resistant. Overall survival was significantly greater in the radiation-sensitive than the radiation-resistant group. Further, our model was an independent predictor of radiotherapy response, outperforming other clinical parameters, and could be combined with tumor mutational burden, to identify the target population with good predictive value for prognosis at 1, 2, and 3 years. Additionally, the radiation-resistant group was more vulnerable to low levels of immune infiltration, which are significantly associated with DNA damage repair, hypoxia, and cell cycle regulation. Tumor Immune Dysfunction and Exclusion scores also suggested that the resistant group would respond less favorably to immunotherapy. CONCLUSIONS: Our prognostic model based on a radiation-related gene signature has potential for application as a tool for risk stratification of radiation therapy for patients with HNSCC, helping to identify candidates for radiation therapy and overcome radiation resistance.

Self-assembling peptide RADA16: a promising scaffold for tissue engineering and regenerative medicine.

RADA16 is a peptide-based biomaterial whose acidic aqueous solution spontaneously forms an extracellular matrix-like 3D structure within seconds upon contact with physiological pH body fluids. Meanwhile, its good biocompatibility, low immunogenicity, nontoxic degradation products and ease of modification make it an ideal scaffold for tissue engineering. RADA16 is a good delivery vehicle for cells, drugs and factors. Its shear thinning and thixotropic properties allow it to fill tissue voids by injection and not to swell. However, the weaker mechanical properties and poor hydrophilicity are troubling limitations of RADA16. To compensate for this limitation, various functional groups and polymers have been designed to modify RADA16, thus contributing to its scope and progress in the field of tissue engineering.

Correlation of event-related potentials N170 with dysfunctional attitudes in patients with major depressive disorder.

BACKGROUND: Cognitive impairment frequently accompanies first-episode major depressive disorder (MDD) in patients. Early detection and intervention for cognitive impairment can enhance the quality of life for individuals with depressive disorders. Impaired emotion recognition may serve as an initial manifestation of cognitive impairment in these patients. This study examines the characteristics of event-related potentials N170 and dysfunctional attitudinal questionnaire total scores, as well as each factor and their correlation, revealing characteristic electroencephalogram (EEG) changes associated with cognitive impairment in first-episode MDD patients. METHOD: A total of 88 patients experiencing first-episode MDD and 29 healthy volunteers from the same period participated in the study. They underwent event-related potential N170 measures to assess mood recognition function, the 17-item Hamilton depression scale (HAMD-17) to evaluate the severity of depressive disorder, and the Dysfunctional Attitudes Scales(DAS) to appraise cognitive function. RESULT: The dysfunctional attitude questionnaire's total score and each factor score were higher in the MDD group compared to the healthy control (HC) group. The MDD group exhibited lower amplitudes than the HC group at CZ, PZ, POZ, P7, PO7, P8, and PO8 electrode points. A correlation was identified between the P7 and PO7 electrode points of the event-related potential N170 and cognitive function. LIMITATION: This study solely considered neutral face emotional stimuli and did not account for depressive disorder subtypes. CONCLUSION: Differences were observed between the MDD and HC groups in cognitive function and N170 amplitude in the central brain region (CZ, PZ, POZ), left posterior temporal region (P7), left occipitotemporal region (PO7), right posterior temporal region (P8), and right occipitotemporal region (PO8). Additionally, a correlation was found between N170 latency in the left posterior temporal region of the brain (P7) and the left occipitotemporal region (PO7) with cognitive function.

A homologous and molecular dual-targeted biomimetic nanocarrier for EGFR-related non-small cell lung cancer therapy.

The abnormal activation of epidermal growth factor receptor (EGFR) drives the development of non-small cell lung cancer (NSCLC). The EGFR-targeting tyrosine kinase inhibitor osimertinib is frequently used to clinically treat NSCLC and exhibits marked efficacy in patients with NSCLC who have an EGFR mutation. However, free osimertinib administration exhibits an inadequate response in vivo, with only ∼3% patients demonstrating a complete clinical response. Consequently, we designed a biomimetic nanoparticle (CMNP@Osi) comprising a polymeric nanoparticle core and tumor cell-derived membrane-coated shell that combines membrane-mediated homologous and molecular targeting for targeted drug delivery, thereby supporting a dual-target strategy for enhancing osimertinib efficacy. After intravenous injection, CMNP@Osi accumulates at tumor sites and displays enhanced uptake into cancer cells based on homologous targeting. Osimertinib is subsequently released into the cytoplasm, where it suppresses the phosphorylation of upstream EGFR and the downstream AKT signaling pathway and inhibits the proliferation of NSCLC cells. Thus, this dual-targeting strategy using a biomimetic nanocarrier can enhance molecular-targeted drug delivery and improve clinical efficacy.

Metabolomics and transcriptomics strategies to reveal the mechanism of diversity of maize kernel color and quality.

BACKGROUND: Maize has many kernel colors, from white to dark black. However, research on the color and nutritional quality of the different varieties is limited. The color of the maize grain is an important characteristic. Colored maize is rich in nutrients, which have received attention for their role in diet-related chronic diseases and have different degrees of anti-stress protection for animal and human health. METHODS: A comprehensive metabolome (LC-MS/MS) and transcriptome analysis was performed in this study to compare different colored maize varieties from the perspective of multiple recombination in order to study the nutritional value of maize with different colors and the molecular mechanism of color formation. RESULTS: Maize kernels with diverse colors contain different types of health-promoting compounds, highlighting that different maize varieties can be used as functional foods according to human needs. Among them, red-purple and purple-black maize contain more flavonoids than white and yellow kernels. Purple-black kernels have a high content of amino acids and nucleotides, while red-purple kernels significantly accumulate sugar alcohols and lipids. CONCLUSION: Our study can provide insights for improving people's diets and provide a theoretical basis for the study of food structure for chronic diseases.

Early and Persistent Dysphagia Relief Predicts Tumor Response in Esophageal Squamous Cell Carcinoma Patients Treated with Immunochemotherapy.

BACKGROUND: In this prospective study, we aimed to investigate the role of patient-reported dysphagia relief in predicting pathological tumor responses to neoadjuvant immunochemotherapy (NAIC) in locally advanced esophageal squamous cell carcinoma (ESCC) patients. METHODS: This study was designed as a multi-center, prospective study including ESCC patients who received NAIC in the discovery and validation cohorts. The patients' responses to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-OES 18 and QLQ-C30 were collected at multiple time points. Subsequent time point-intensive esophageal cancer-specific dysphagia trajectories were depicted using growth mixture modeling (GMM) analysis. Furthermore, univariate and multivariate binary logistic regression was used to assess the independent predictors for pathological tumor responses. RESULTS: A total of 120 patients from the discovery cohort and 42 patients from the validation cohort were included in the analysis. In the discovery cohort, 19 (22.9%) of the 83 patients achieved pCR status. In the independent validation cohort, 24 patients underwent surgery, and 9 (37.5%) patients achieved pCR status. Trajectory analysis showed that, in the pCR group, the beginning of rapid declines in the slope occurred on days 3, 6, and 9. Further multivariate analysis showed that the degree of dysphagia relief (△dysphagia%) was the only significant independent predictor for pCR status (OR = 3.267, 95% CI 1.66-6.428, P < 0.001). The AUC value for △dysphagia% was 0.961 (95% CI: 0.922-0.999, P < 0.001). CONCLUSION: The current study demonstrated that a longitudinal patient-reported outcome (PRO) was an easily obtained, cost-effective, and noninvasive tool for predicting tumor responses to neoadjuvant immunochemotherapy.

Nanoscale Treatment of Intervertebral Disc Degeneration: Mesenchymal Stem Cell Exosome Transplantation.

A common surgical disease, intervertebral disc degeneration (IVDD), is increasing at an alarming rate in younger individuals. Repairing damaged intervertebral discs (IVDs) and promoting IVD tissue regeneration at the molecular level are important research goals.Exosomes are extracellular vesicles (EVs) secreted by cells and can be derived from most body fluids. Mesenchymal stem cell-derived exosomes (MSC-exos) have characteristics similar to those of the parental MSCs. These EVs can shuttle various macromolecular substances, such as proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs) and regulate the activity of recipient cells through intercellular communication. Reducing inflammation and apoptosis can significantly promote IVD regeneration to facilitate the repair of the IVD. Compared with MSCs, exosomes are more convenient to store and transport, and the use of exosomes can prevent the risk of rejection with cell transplantation. Furthermore, MSC-exo-mediated treatment may be safer and more effective than MSC transplantation. In this review, we summarize the use of bone marrow mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (AMSCs), nucleus pulposus mesenchymal stem cells (NPMSCs), and stem cells from other sources for tissue engineering and use in IVDD. Here, we aim to describe the role of exosomes in inhibiting IVDD, their potential therapeutic effects, the results of the most recent research, and their clinical application prospects to provide an overview for researchers seeking to explore new treatment strategies and improve the efficacy of IVDD treatment.

Silk fibroin-based biomaterials for disc tissue engineering.

Low back pain is the major cause of disability worldwide, and intervertebral disc degeneration (IVDD) is one of the most important causes of low back pain. Currently, there is no method to treat IVDD that can reverse or regenerate intervertebral disc (IVD) tissue, but the recent development of disc tissue engineering (DTE) offers a new means of addressing these disadvantages. Among numerous biomaterials for tissue engineering, silk fibroin (SF) is widely used due to its easy availability and excellent physical/chemical properties. SF is usually used in combination with other materials to construct biological scaffolds or bioactive substance delivery systems, or it can be used alone. The present article first briefly outlines the anatomical and physiological features of IVD, the associated etiology and current treatment modalities of IVDD, and the current status of DTE. Then, it highlights the characteristics of SF biomaterials and their latest research advances in DTE and discusses the prospects and challenges in the application of SF in DTE, with a view to facilitating the clinical process of developing interventions related to IVD-derived low back pain caused by IVDD.