Inhibition of urethral stricture by a catheter loaded with nanoparticle/ pirfenidone complexes.

Background: Urethral strictures are common injurious conditions of the urinary system. Reducing and preventing urethral strictures has become a hot and challenging topic for urological surgeons and related researchers. In this study, we developed a catheter loaded with nanoparticle/pirfenidone (NP/PFD) complexes and evaluated its effectiveness at inhibiting urethral stricture in rabbits, providing more references for the clinical prevention and reduction of urethral stenosis. Methods: Twelve adult male New Zealand rabbits were selected and divided into the following four groups in a ratio of 1:1:1:1 using the random number table method: Group A, sham; Group B, urethral stricture (US); Group C, US + unmodified catheter; and Group D, US + NP/PFD catheter. On the 30th day after modelling, retrograde urethrography was performed to evaluate urethral stricture formation, and histopathological examination was performed on the tissues of the corresponding surgical site. Meanwhile, changes in the expression level of Transforming growth factor ß1 (TGF-ß1) in the tissues were detected by immunohistochemistry. Results: The NP/PFD complexes adhered uniformly to the catheter surface. They remained on the surface of the catheter after insertion into the urethra. In addition, the NP/PFD complexes spread into the urethral epithelium 2 weeks after surgery. Ultimately, urethral strictures were significantly reduced with the placement of the NP/PFD complex catheter. Conclusion: Our catheter loaded with NP/PFD complexes effectively delivered PFD to the urethral epithelium through continuous local delivery, thereby reducing fibrosis and stricture after urethral injury, which may be associated with the inhibition of TGF-ß1 expression.

Identification of lysosomal genes associated with prognosis in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, representing 40% of all cases of this tumor. Despite immense improvements in understanding the molecular basis, diagnosis, and treatment of LUAD, its recurrence rate is still high. Methods: RNA-seq data from The Cancer Genome Atlas (TCGA) LUAD cohort were download from Genomic Data Commons Portal. The GSE13213 dataset from Gene Expression Omnibus (GEO) was used for external validation. Differential prognostic lysosome-related genes (LRGs) were identified by overlapping survival-related genes obtained via univariate Cox regression analysis with differentially expressed genes (DEGs). The prognostic model was built using Kaplan-Meier curves and least absolute shrinkage and selection operator (LASSO) analyses. In addition, univariate and multivariate Cox analyses were employed to identify independent prognostic factors. The responses of patients to immune checkpoint inhibitors (ICIs) were further predicted. The pRRophetic package and rank-sum test were used to compute the half maximal inhibitory concentrations (IC50) of 56 chemotherapeutic drugs and their differential effects in the low- and high-risk groups. Moreover, quantitative real-time polymerase chain reaction, Western blot, and human protein atlas (HPA) database were used to verify the expression of the four prognostic biomarkers in LUAD. Results: Of the nine candidate differential prognostic LRGs, GATA2, TFAP2A, LMBRD1, and KRT8 were selected as prognostic biomarkers. The prediction of the risk model was validated to be reliable. Cox independent prognostic analysis revealed that risk score and stage were independent prognostic factors in LUAD. Furthermore, the nomogram and calibration curves of the independent prognostic factors performed well. Differential analysis of ICIs revealed CD276, ICOS, PDCD1LG2, CD27, TNFRSF18, TNFSF9, ENTPD1, and NT5E to be expressed differently in the low- and high-risk groups. The IC50 values of 12 chemotherapeutic drugs, including epothilone.B, JNK.inhibitor.VIII, and AKT.inhibitor.VIII, significantly differed between the two risk groups. KRT8 and TFAP2A were highly expressed, while GATA2 and LMBRD1 were poorly expressed in LUAD cell lines. In addition, KRT8 and TFAP2A were highly expressed, while GATA2 and LMBRD1 were poorly expressed in tumor tissues. Conclusions: Four key prognostic biomarkers-GATA2, TFAP2A, LMBRD1, and KRT8-were used to construct a significant prognostic model for LUAD patients.

Cuproptosis in lung cancer: mechanisms and therapeutic potential.

Cuproptosis, a recently identified form of cell death that differs from other forms, is induced by the disruption of the binding of copper to mitochondrial respiratory acylation components. Inducing cell cuproptosis and targeting cell copper death pathways are considered potential directions for treating tumor diseases. We have provided a detailed introduction to the metabolic process of copper. In addition, this study attempts to clarify and summarize the relationships between cuproptosis and therapeutic targets and signaling pathways of lung cancer. This review aims to summarize the theoretical achievements for translating the results of lung cancer and cuproptosis experiments into clinical treatment.

Identification of a polycomb group-related gene signature for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma.

Background: Several studies have reported the role of polycomb group (PcG) genes in human cancers; however, their role in lung adenocarcinoma (LUAD) is unknown. Methods: Firstly, consensus clustering analysis was used to identify PcG patterns among the 633 LUAD samples in the training dataset. The PcG patterns were then compared in terms of the overall survival (OS), signaling pathway activation, and immune cell infiltration. The PcG-related gene score (PcGScore) was developed using Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) algorithm to estimate the prognostic value and treatment sensitivity of LUAD. Finally, the prognostic ability of the model was validated using a validation dataset. Results: Two PcG patterns were obtained by consensus clustering analysis, and the two patterns showed significant differences in prognosis, immune cell infiltration, and signaling pathways. Both the univariate and multivariate Cox regression analyses confirmed that the PcGScore was a reliable and independent predictor of LUAD (P<0.001). The high- and low-PCGScore groups showed significant differences in the prognosis, clinical outcomes, genetic variation, immune cell infiltration, and immunotherapeutic and chemotherapeutic effects. Lastly, the PcGScore demonstrated exceptional accuracy in predicting the OS of the LUAD patients in a validation dataset (P<0.001). Conclusions: The study indicated that the PcGScore could serve as a novel biomarker to predict prognosis, clinical outcomes, and treatment sensitivity for LUAD patients.

Cancellous bone should not be exposed during medialized rotator cuff repair based on bone-to-tendon healing in a rat mode.

PURPOSE: To compare the biological bone-to-tendon healing using three different medialized bone bed preparation techniques (i.e. cortical bone exposure, cancellous bone exposure, and no cartilage removal) in a rat model of medialized rotator cuff repair. METHODS: Twenty-one male Sprague-Dawley rats with 42 shoulders were subjected to bilateral supraspinatus tenotomy from the greater tuberosity. The rotator cuff was repaired using medialized anchoring with the cortical bone exposed, the cancellous bone exposed, or no cartilage removed. Four and three rats in each group were killed for biomechanical testing and histological evaluation, respectively, at postoperative 6 weeks. RESULTS: All rats survived until the end of the study, but one infected shoulder in the cancellous bone exposure group was excluded from further analysis. Compared with the cortical bone exposure and no cartilage removal groups, the rotator cuff healing of the cancellous bone exposure group showed significantly lower maximum load (cancellous bone exposure group: 26.2 ± 2.3 N, cortical bone exposure group: 37.6 ± 7.9 N, no cartilage removal group: 34.6 ± 7.2 N, P = 0.005 and 0.029) and less stiffness (cancellous bone exposure group: 10.5 ± 2.4 N/mm, cortical bone exposure group: 17.4 ± 6.7 N, no cartilage removal group: 16.0 ± 3.9 N, P = 0.015 and 0.050) at postoperative 6 weeks. In all three groups, the repaired supraspinatus tendon healed towards the original insertion rather than the medialized insertion. The cancellous bone exposure group showed inferior fibrocartilage formation and insertion healing. CONCLUSIONS: The medialized bone-to-tendon repair strategy does not guarantee complete histological healing, and the removal of excessive bony structure impairs bone-to-tendon healing. This study concludes that surgeons should not expose the cancellous bone during the medialized rotator cuff repair.

Shedding light on macrophage immunotherapy in lung cancer.

The search for therapeutic options for lung cancer continues to advance, with rapid advances in the search for therapies to improve patient prognosis. At present, systemic chemotherapy, immune checkpoint inhibitor therapy, antiangiogenic therapy, and targeted therapy for driver gene positivity are available in the clinic. Common clinical treatments fail to achieve desired outcomes due to immunosuppression of the tumor microenvironment (TME). Tumor immune evasion is mediated by cytokines, chemokines, immune cells, and other cells such as vascular endothelial cells within the tumor immune microenvironment. Tumor-associated macrophages (TAMs) are important immune cells in the TME, inducing tumor angiogenesis, encouraging tumor cell proliferation and migration, and suppressing antitumor immune responses. Thus, TAM targeting becomes the key to lung cancer immunotherapy. This review focuses on macrophage phenotype, polarization mechanism, role in lung cancer, and advances in macrophage centric immunotherapies.

A cuproptosis-related lncRNAs risk model to predict prognosis and guide immunotherapy for lung adenocarcinoma.

Background: Cuproptosis, one of the newest forms of cell death induction, is attracting mounting attention. However, the role of cuproptosis in lung cancer is currently unclear. In this study, we constructed a prognostic signature utilizing cuproptosis-related long noncoding RNAs (CRL) in lung adenocarcinoma (LUAD) and researched its clinical and molecular function. Methods: RNA-related and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed CRLs were screened using the 'limma' package of R software. We used coexpression analysis and univariate Cox analysis to further identify prognostic CRLs. Applying least absolute shrinkage and selection operator (LASSO) regression and Cox regression models, a prognostic risk model based on 16 prognostic CRLs was constructed. To validate prognostic CRL function in LUAD, vitro experiments were conducted to explore the expression of GLIS2-AS1, LINC01230, and LINC00592 in LUAD. Subsequently, according to a formula, patients in the training, test, and overall groups were split into high- and low-risk groups. Kaplan-Meier and receiver operating characteristic (ROC) analyses were applied to assess the predictability of the risk model. Finally, the associations between risk signature and immunity-related analysis, somatic mutation, principal component analysis (PCA), enriched molecular pathways, and drug sensitivity was investigated. Results: A cuproptosis-related long noncoding RNAs (lncRNAs) signature was constructed. Using quantitative polymerase chain reaction (qPCR) trial, we verified that the expressions of GLIS2-AS1, LINC01230, and LINC00592 in LUAD cell lines and tissues were consistent with the above screening results. Based on this signature, a total of 471 LUAD samples from TCGA data set were split into two risk groups based on the computed risk score. The risk model showed a better capacity in predicting prognosis than traditional clinicopathological features. Moreover, significant differences were found in immune cell infiltration, drug sensitivity, and immune checkpoint expression between the two risk groups. Conclusions: The CRLs signature was shown to be a prospective biomarker to forecast prognosis in patients with LUAD and presents new insights for personalized treatment of LUAD.

ADCY9 functions as a novel cancer suppressor gene in lung adenocarcinoma.

Background: The process of lucubrating into lung adenocarcinoma (LUAD) is of profound clinical and practical significance in improving the prognosis of LUAD patients. Multiple biomarkers are reportedly involved in the proliferation or metastasis of adenocarcinoma. However, whether the ADCY9 gene influences the development of LUAD remains unknown. Therefore, we aimed to elucidate the relationship between the expression of ADCY9 and the proliferation and migration of LUAD. Methods: The ADCY9 gene was filtered via a survival analysis of LUAD acquired from the Gene Expression Omnibus (GEO). Then, we conducted a validation analysis and ADCY9-microRNA, microRNA-lncRNA, and ADCY9-lncRNA targeting relationship analysis through the data obtained from The Cancer Genome Atlas (TCGA) dataset. The survival curve, correlation, and prognostic analysis were implemented through bioinformatics methods. Both protein and mRNA expression levels of LUAD cell lines and LUAD patient samples (80 pairs) were detected using western blot assays and quantitative real-time polymerase chain reaction (qRT-PCR). An immunohistochemistry assay was performed to display the correlation between the expression level of the ADCY9 gene and prognosis in LUAD patients (2012-2013; n=115). Overexpression of cell lines SPCA1 and A549 were used for a series of cell function assays. Results: Compared with the expression level in adjacent normal tissues, ADCY9 expression was downregulated in LUAD tissues. Based on the result of the survival curve analysis, high expression of ADCY9 may lead to a better prognosis and may be seen as an independent predictor for LUAD patients. High expression of ADCY9-related microRNA hsa-miR-7-5p may lead to a worse prognosis, and high expression of hsa-miR-7-5p-related lncRNAs may lead to the opposite effects. Overexpression of ADCY9 restrained the proliferation, invasion, and migration abilities of SPCA1, A549 cells. Conclusions: Results indicate that the ADCY9 gene acts as a tumor suppressor to restrain the proliferation, migration, and invasion in LUAD and can lead to a better survival or prognosis in LUAD patients.

Sustainably released nanoparticle-based rhynchophylline limits pulmonary fibrosis by inhibiting the TEK-PI3K/AKT signaling pathway.

Background: Pulmonary fibrosis (PF) is a rapidly progressing and irreversible disease, and the currently available types of clinical drugs are limited and inefficient. In our previous study, we observed that Rhynchophylline (Rhy) hindered tendon adhesion and stimulated the healing of injured tendon structures. Considering the similar mechanisms between adhesion formation and PF, we explored the roles of Rhy in PF. Methods: The cytotoxicity of Rhy was tested by a Cell Counting Kit-8 (CCK-8) assay. The degree of PF was evaluated by Western blot (WB), Masson and hematoxylin-eosin (HE) staining, and hydroxyproline quantification. The Rhy-loaded nanoparticles were prepared through an emulsification sonication technique and characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The release of the Rhy-loaded nanoparticles was tested using the absorbance value of the supernatant. Transcriptome sequencing was performed to determine the downstream target and pathway of Rhy, which was then verified by WB. Results: In vitro, Rhy decreased Transforming Growth Factor Beta 1 (TGF-ß1)-induced abnormal overexpression of fibronectin (FN), collagen I (Col I), α-smooth muscle actin (α-SMA) in a dose-dependent manner in human lung fibroblast (HFL1) cells. In vivo, we confirmed (through Masson staining) that the intraperitoneal injection of Rhy reduced collagen deposition and the fibrotic area in a dose-dependent manner. Our results indicated that the Rhy-loaded nanoparticles intratracheal spray intuitively narrowed collagen deposition, shrank collagen deposition and the fibrotic area (Masson and HE staining), and reduced the expression of fibrosis-related markers (WB). Meanwhile, the lung index value and hydroxyproline content were markedly lower than the bleomycin (BLM)-treated group. By transcriptional sequencing analysis, we identified Receptor Tyrosine Kinase (TEK)-Phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/AKT) as the downstream target and pathway of Rhy. It was also observed that Rhy could reverse the TGF-ß1-induced TEK and phosphorylated AKT (p-AKT) elevated expression. Conclusions: Our findings indicate that Rhy constrained PF progression by inhibiting TEK-PI3K/AKT signaling pathway. Hence, this sustainable release system of Rhy is a highly effective therapy to limit PF and should be developed.

Recent progress and applications of poly(beta amino esters)-based biomaterials.

Poly(beta-amino esters, PBAEs) are a promising class of cationic polymers synthesized from diacrylates and amines via Michael addition. Recently, PBAEs have been widely developed for drug delivery, immunotherapy, gene therapy, antibacterial, tissue engineering and other applications due to their convenient synthesis, good bio-compatibility and degradation properties. Herein, we mainly summarize the recent progress in the PBAEs synthesis and their applications. The amine groups of PBAEs could be protonated in low pH environment, exhibiting proton sponge and pH-sensitive abilities. Furthermore, the positive PBAEs can interact with negative genes via electrostatic interactions for efficient delivery of nucleic acids. Moreover, positive PBAEs could also directly kill bacteria by disrupting their membranes at high doses. Finally, PBAEs can augment the immune responses, and improve the bioactivity of hydrogels in tissue engineering.

A bio-orthogonally functionalized chitosan scaffold with esterase-activatable release for nerve regeneration.

Developing nerve conduits with biological cues is a promising approach for repairing peripheral nerve injuries. Although most biological cues incorporated into conduits generally exert their biological functions at the surface, they could not be released into the on-demand regeneration sites under physiological conditions. Herein, we firstly report a bio-orthogonally functionalized chitosan scaffold with esterase-activatable release for peripheral nerve regeneration. In this study, biological cues are not only selectively conjugated into nerve conduits by bio-orthogonal reaction, but also precisely released in on-demand regeneration sites via esterase-activatable cleavage for peripheral nerve repair. Moreover, this nerve scaffold with esterase-activatable release could promote Schwann cells proliferation. In a rat sciatic nerve defect model, the bio-orthogonally functionalized scaffold with esterase-activatable release significantly increased sciatic nerve function recovery and improved target muscles weight. This strategy of incorporating esterase-activatable bioactive cues into peripheral nerve conduits offers great potential in preclinical studies.

Novel immunogenic cell death-related risk signature to predict prognosis and immune microenvironment in lung adenocarcinoma.

PURPOSE: Immunogenic cell death (ICD) is a type of regulated cell death (RCD) which was discovered to activate adaptive immunity. To date, the effect of ICD on lung adenocarcinoma (LUAD) remains unclear. In this research, we will study the role of ICD-related genes (ICDG) in LUAD. METHODS: RNA sequencing and clinical data were gathered from TCGA-LUAD cohorts and GEO database. Using unsupervised cluster analysis, three clusters were identified with distinctive immune characteristics and significant overall survival based on 18 ICDG. Using LASSO Cox regression, three genes were identified and used to construct the prognosis signature. The association between the 3-ICDG risk signature and immune microenvironment analysis, somatic mutation, and enriched molecular pathways was investigated. RESULTS: Consensus clustering separated the LUAD samples into three clusters (ICDcluster A, B and C), and ICDcluster B had the best prognosis. Different TME cell infiltration characteristics and biological behavior were found in three ICD clusters. Prognostic risk model was contrasted based on the 3 best prognostic ICD-related genes. Subsequently, vitro experiments verified the above analysis results. The high-risk group showed a poor prognosis and enrichment of cancer promoting signal pathway. Multivariate analysis indicated that this 3-ICDG prognostic model might be an accurate prediction parameter for LUAD. Moreover, conducting immune related analysis, we found that the 3-ICDG risk signature was characterized by an immune-active subtype on account of the high infiltration of immune-active cells. CONCLUSION: This study expands our cognition of ICD in LUAD microenvironment, excavated prognostic biomarkers, and provided potential value for guiding immunotherapy and chemotherapy.

Absorbable suture knots on the supraspinatus tendon prevent adverse effects of nonabsorbable suture knots in a rat model.

PURPOSE: To compare the absorbable and nonabsorbable suture knots on the tendon on bone-to-tendon healing during the early phase in a rat rotator cuff tear (RCT) model. METHODS: Fifty-two male Sprague-Dawley rats (10 weeks old; mean weight, 380 g) were used in this study, and 51 of them were randomly assigned into three groups: absorbable suture group (ASG, n = 22), nonabsorbable suture group (NSG, n = 22), and sham surgery group (SSG, n = 7), and the remaining rat was used to take surgical pictures. Bilateral supraspinatus tendon tears were created and repaired immediately in ASG and NSG. Three rats from ASG and NSG were killed for Western blot and histological evaluation at 3 days, 1 week, and 4 weeks after surgery. At 4 weeks, four rats from each group were killed for biomechanical test, and three rats from SSG were used for histological evaluation. RESULTS: Absorbable suture knots on the tendon completely degraded at 4 weeks. However, nonabsorbable suture knots remained intact between the tendon and articular side. ASG showed a stronger inflammatory reaction at 3 days and 1 week, but a weaker reaction at 4 weeks as confirmed by gross observation and Western blot. Besides, ASG showed superior biomechanical properties in terms of maximum load to failure and stiffness at 4 weeks. Modified Bonar score revealed superior maturity for tissue healing in ASG to that in NSG at 4 weeks. Furthermore, inferior bone-to-tendon interface and weakest link formation were observed in NSG on histologic images. CONCLUSION: Absorbable suture knots on the tendon contributed to better mechanical properties compared with the nonabsorbable one after rotator cuff repair.

Inhibition of Ureteral Stricture by Pirfenidone-Loaded Nanoparticle-Coated Ureteral Stents with Slow-Release Pirfenidone.

Introduction: Ureteral stricture caused by iatrogenic ureteral injury induced ureteral injury is more common and challenging to recover quickly. The effective prevention of ureteral stricture due to iatrogenic ureteral injury-induced ureteral damage is a current challenge for urologists. The purpose of this study was to evaluate the effectiveness of nanoparticle/pirfenidone complex-coated ureteral stents with slow-release pirfenidone for the prevention of ureteral stricture in rabbits. In this study, we developed a nanoparticle/pirfenidone complex-coated ureteral stent to deliver pirfenidone into the injured ureter to inhibit ureteral stricture. Methods: Twelve New Zealand rabbits were divided into four groups: Sham, US, US+ Unmodified ureteral stent, and US+NP/PFD ureteral stent; we constructed an irreversible electroporation model of ureteral injury in rabbits and placed unmodified ureteral stents and nanoparticle/pirfenidone complex-coated ureteral stents into the ureter. Two weeks later, we euthanized the rabbits and removed their bilateral kidneys and ureters. We evaluated the effect of ureteral stent prophylaxis by gross specimen observation, section staining, and Western Blot. Results: We found that the nanoparticle/pirfenidone complexes could adhere uniformly to the surface of the ureteral stent. After placement into the ureter, the nanoparticle/pirfenidone complexes were able to remain on the surface of the ureteral stent. We found nanoparticle/pirfenidone complexes could diffuse in the ureteral epithelial tissue two weeks after the order. The study showed that nanoparticle/pirfenidone complex-coated ureteral stents placed into the ureter showed significantly less stenosis due to fibrosis than in US control rabbits and rabbits treated with unmodified ureteral stents. Conclusion: We used a novel platform based on nanoparticle/pirfenidone complex-coated ureteral stents for local and sustained delivery of pirfenidone, which can effectively deliver pirfenidone to the tissue and can slowly control the release of pirfenidone. Therefore, combining ureteral stents with nanoparticle/pirfenidone complexes was an effective measure to prevent ureteral stricture.

Analysis of prognostic model based on immunotherapy related genes in lung adenocarcinoma.

Lung cancer is one of the most common malignant tumors, and ranks high in the list of mortality due to cancers. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Despite progress in the diagnosis and treatment of lung cancer, the prognosis of these patients remains dismal. Therefore, it is crucial to identify the predictors and treatment targets of lung cancer to provide appropriate treatments and improve patient prognosis. In this study, the gene modules related to immunotherapy were screened by weighted gene co-expression network analysis (WGCNA). Using unsupervised clustering, patients in The Cancer Genome Atlas (TCGA) were divided into three clusters based on the gene expression. Next, gene clustering was performed on the prognosis-related differential genes, and a six-gene prognosis model (comprising PLK1, HMMR, ANLN, SLC2A1, SFTPB, and CYP4B1) was constructed using least absolute shrinkage and selection operator (LASSO) analysis. Patients with LUAD were divided into two groups: high-risk and low-risk. Significant differences were found in the survival, immune cell infiltration, Tumor mutational burden (TMB), immune checkpoints, and immune microenvironment between the high- and low-risk groups. Finally, the accuracy of the prognostic model was verified in the Gene Expression Omnibus (GEO) dataset in patients with LUAD (GSE30219, GSE31210, GSE50081, GSE72094).

Histone acetylation modification regulator-mediated tumor microenvironment infiltration characteristics and prognostic model of lung adenocarcinoma patients.

Background: The incidence rate of lung adenocarcinoma (LUAD) is rapidly increasing. Recent studies have reported that histone acetylation modification plays an important role in the occurrence and development of tumors. However, the potential role of modification of histone acetylation modification in the development of tumor immune microenvironment is still unclear. Methods: In this study, we comprehensively evaluated the acetylation modification patterns of LUAD samples obtained from various different databases based on 36 histone modification regulators, and constructed a prognostic model based on The Cancer Genome Atlas (TCGA) LUAD cohort using the Cox regression method. The close relationship between histone acetylation and tumor immune characteristics was further studied, including immune infiltration, immune escape and immunotherapy. Finally, we combined three cohort (GSE30219, GSE72094 and GSE50081) from Gene Expression Omnibus (GEO) database to verify the above results. Results: We analyzed the expression, mutation and interaction of 36 histone acetylation regulated genes. After Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO), 5 genes (KAT2B, SIRT2, HDAC5, KAT8, HDAC2) were screened to establish the prognosis model and calculate the risk score. Then, patients in the TCGA cohort were divided into high- and low-risk groups based on the risk scores. Further analysis indicated that patients in the high-risk group exhibited significantly reduced overall survival (OS) compared with those in the low-risk group. The high- and low-risk groups exhibited significant differences in terms of tumor immune characteristics, such as immune infiltration, immune escape and immunotherapy. The high-risk group had lower immune score, less immune cell infiltration and higher clinical stage. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. In addition, drugs sensitive for this classification were identified. Finally, the efficacy of the prognostic model was validated by cohort (GSE30219, GSE72094 and GSE50081) from GEO database. Conclusions: Our study provided a robust signature for predicting changing prognosis of patients with LUAD. Thus, it appears to be a potentially useful prognostic tool. Moreover, the important relationship between histone acetylation and tumor immune microenvironment was revealed.

Chitosan degradation products promote healing of burn wounds of rat skin.

Burns can impair the barrier function of the skin, and small burns can also cause high mortality. The WHO has described that over 180,000 people die of burns worldwide each year. Thus, the treatment of burn wounds is a major clinical challenge. Chitooligosaccharides (COS) are alkaline amino oligosaccharides with small molecular weights obtained by enzyme or chemical degradation of chitosan. With the characteristics of biocompatibility, water solubility and degradability, it has attracted increasing attention in the fields of biomedicine. In the present study, we used COS to treat deep second-degree burn wounds of rat skin and found that COS was able to promote wound healing. We also revealed that COS could promote fibroblast proliferation. Transcriptome sequencing analysis was performed on COS-treated fibroblasts to identify the underlying mechanisms. The results showed that COS was able to promote wound healing through regulation of the mitogen-activated protein kinase (MAPK) pathway and growth factor Hepatocyte Growth Factor (HGF). Our results provide a potential drug for burn wound therapy and the related molecular mechanism.

Characteristic of Molecular Subtypes in Lung Squamous Cell Carcinoma Based on Autophagy-Related Genes and Tumor Microenvironment Infiltration.

Background: Recently, a large number of studies have sought personalized treatment for lung squamous cell carcinoma (LUSC) by dividing patients into different molecular subtypes. Autophagy plays an important role in maintaining the tumor microenvironment and immune-related biological processes. However, the molecular subtypes mediated by autophagy in LUSC are not clear. Methods: Based on 490 LUSC samples, we systematically analyzed the molecular subtype modification patterns mediated by autophagy-related genes. The ssGSEA and CIBERSORT algorithm were utilized to quantify the relative abundance of TME cell infiltration. Principal component analysis was used to construct autophagy prognostic score (APS) model. Results: We identified three autophagy subtypes in LUSC, and their clinical outcomes and TME cell infiltration had significant heterogeneity. Cluster A was rich in immune cell infiltration. The enrichment of EMT stromal pathways and immune checkpoint molecules were significantly enhanced, which may lead to its immunosuppression. Cluster B was characterized by relative immunosuppression and relative stromal activation. Cluster C was activated in biological processes related to repair. Patients with high APS were significantly positively correlated with TME stromal activity and poor survival. Meanwhile, high APS showed an advantage in response to anti-PD1 and anti-CTLA4 immunotherapy. Conclusion: This study explored the autophagy molecular subtypes in LUSC. We also discovered the heterogeneity of TME cell infiltration driven by autophagy-related genes. The established APS model is of great significance for evaluating the prognosis of LUSC patients, the infiltration of TME cells, and the effect of immunotherapy.

Chloride Intracellular Channel 1 is a Potential Biomarker for Breast Cancer.

Purpose: Multiple reports have demonstrated that highly expressed chloride intracellular channel 1 (CLIC1) exists in a range of malignant tumors and is involved in proliferation, invasion, and migration of cancer cells. There are few studies on CLIC1 and breast cancer (BC). The purpose of this research was to evaluate the expression level of CLIC1 in BC and its impact on prognosis of BC patients. Patients and Methods: Differences in CLIC1 expression levels in 25 pairs of BC and corresponding paracancerous specimens were tested by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB). Immunohistochemistry (IHC) was performed to discuss the relevance between CLIC1 expression in BC tissue chips and clinicopathological parameters of BC patients. The effect of CLIC1 expression on patient prognosis was evaluated by Kaplan-Meier survival curve and Cox regression analysis. Receiver operating characteristic (ROC) curve assessed the diagnostic performance of CLIC1 for BC. Results: The experimental results of qRT-PCR and WB demonstrated that CLIC1 was highly expressed in BC tissues. IHC results showed that overexpression of CLIC1 was strictly correlated with tumor size, TNM classification, pathological grade, lymph node metastasis and Ki67. Patients with lower CLIC1 expression had longer overall survival (OS) and progression-free survival (PFS). Cox regression analysis and ROC curve confirmed that CLIC1 could independently influence the prognosis of BC patients and might have diagnostic efficiency. Conclusion: Overexpressed CLIC1 is closely related to the progression of BC and the poor prognosis of the patients, suggesting that it may act as a potential biological diagnostic index for BC.

Platelet-Membrane-Encapsulated Carvedilol with Improved Targeting Ability for Relieving Myocardial Ischemia-Reperfusion Injury.

In recent years, cell membrane drug delivery systems have received increasing attention. However, drug-loaded membrane delivery systems targeting therapy in myocardial ischemia-reperfusion injury (MIRI) have been relatively rarely studied. The purpose of this study was to explore the protective effect of platelet-membrane-encapsulated Carvedilol on MIRI. We extracted platelets from the blood of adult SD rats and prepared platelet membrane vesicles (PMVs). Carvedilol, a nonselective ß-blocker, was encapsulated into the PMVs. In order to determine the best encapsulation rate and drug-loading rate, three different concentrations of Carvedilol in low, medium, and high amounts were fused to the PMVs in different volume ratios (drugs/PMVs at 2:1, 1:1, 1:2, and 4:1) for determining the optimum concentration and volume ratio. By comparing other delivery methods, including abdominal injection and intravenous administration, the efficacy of PMVs-encapsulated drug-targeted delivery treatment was observed. The PMVs have the ability to target ischemic-damaged myocardial tissue, and the concentration and volume ratio at the optimum encapsulation rate and the drug-loading rate are 0.5 mg and 1:1. We verified that PMVs@Carvedilol had better therapeutic effects compared to other treatment groups, and immunofluorescence observation showed a significant improvement in the apoptosis indicators and infarction area of myocardial cells. Targeted administration of PMVs@Carvedilol may be a promising treatment for myocardial reperfusion injury, as it significantly improves postinjury cardiac function and increases drug utilization compared to other delivery methods.