Centimeter-Sized Single Crystals of Tetrahedral Manganese (II) Halide Hybrids for Wide-Color Gamut Backlighting Displays.

Phosphors with narrow-band green emissions and high photoluminescent quantum efficiency (PLQY) are significantly required for backlighting displays with wider color gamut. In this work, two centimeter-sized manganese (II) halide single crystals TMG2 MnCl4 and TMG2 MnBr4 (TMG = 1,1,3,3-tetramethylguanidine) are synthesized, exhibiting bright narrow-band green emissions with high PLQYs up to 62% and 90%, respectively. The narrow-band green light emission is located at 520 nm with a full-width at half-maximum (FWHM) of only 57 nm. The photoluminescence mechanisms of two single crystals are elaborated. Two white-light-emitting diodes for backlighting displays (BD-WLEDs) based on them are fabricated, exhibiting the widest color gamut of 122% National Television Standards Committee (NTSC), and a luminous efficacy reached ≈93 lm W-1 with excellent luminescence stability at high temperatures. These properties indicate the potential applications of tetrahedral manganese (II) hybrids in wide-color gamut backlighting displays.

One-Dimensional Organic-Inorganic Lead Bromide Hybrids with Excitation-Dependent White-Light Emission Templated by Pyridinium Derivatives.

Organic-inorganic hybrid metal halides have attracted widespread attention due to their excellent tunability and versatility. Here, we have selected pyridinium derivatives with different substituent groups or substitution positions as the organic templating cations and obtained six 1D chain-like structures. They are divided into three types: type I (single chain), type II (double chain), and type III (triple chain), with tunable optical band gaps and emission properties. Among them, only (2,4-LD)PbBr3 (2,4-LD = 2,4-lutidine) shows an exciton-dependent emission phenomenon, ranging from strong yellow-white to weak red-white light. By comparing its photoluminescence spectrum with that of its bromate (2,4-LD)Br, it is found that the strong yellow-white emission at 534 nm mainly came from the organic component. Furthermore, through a comparison of the fluorescence spectra and lifetimes of (2,4-LD)PbBr3 and (2-MP)PbBr3 (2-MP = 2-methylpyridine) with similar structures at different temperatures, we confirm that the tunable emission of (2,4-LD)PbBr3 comes from different photoluminescent sources corresponding to organic cations and self-trapped excitons. Density functional theory calculations further reveal that (2,4-LD)PbBr3 has a stronger interaction between organic and inorganic components compared to (2-MP)PbBr3. This work highlights the importance of organic templating cations in hybrid metal halides and the new functionalities associated with them.

Identification and quantification of immune infiltration landscape on therapy and prognosis in left- and right-sided colon cancer.

BACKGROUND: The left-sided and right-sided colon cancer (LCCs and RCCs, respectively) have unique molecular features and clinical heterogeneity. This study aimed to identify the characteristics of immune cell infiltration (ICI) subtypes for evaluating prognosis and therapeutic benefits. METHODS: The independent gene datasets, corresponding somatic mutation and clinical information were collected from The Cancer Genome Atlas and Gene Expression Omnibus. The ICI contents were evaluated by "ESTIMATE" and "CIBERSORT." We performed two computational algorithms to identify the ICI landscape related to prognosis and found the unique infiltration characteristics. Next, principal component analysis was conducted to construct ICI score based on three ICI patterns. We analyzed the correlation between ICI score and tumor mutation burden (TMB), and stratified patients into prognostic-related high- and low- ICI score groups (HSG and LSG, respectively). The role of ICI scores in the prediction of therapeutic benefits was investigated by "pRRophetic" and verified by Immunophenoscores (IPS) (TCIA database) and an independent immunotherapy cohort (IMvigor210). The key genes were preliminary screened by weighted gene co-expression network analysis based on ICI scores. And they were further identified at various levels, including single cell, protein and immunotherapy response. The predictive ability of ICI score for prognosis was also verified in IMvigor210 cohort. RESULTS: The ICI features with a better prognosis were marked by high plasma cells, dendritic cells and mast cells, low memory CD4+ T cells, M0 macrophages, M1 macrophages, as well as M2 macrophages. A high ICI score was characterized by an increased TMB and genomic instability related signaling pathways. The prognosis, sensitivities of targeted inhibitors and immunotherapy, IPS and expression of immune checkpoints were significantly different in HSG and LSG. The genes identified by ICI scores and various levels included CA2 and TSPAN1. CONCLUSION: The identification of ICI subtypes and ICI scores will help gain insights into the heterogeneity in LCC and RCC, and identify patients probably benefiting from treatments. ICI scores and the key genes could serve as an effective biomarker to predict prognosis and the sensitivity of immunotherapy.

White Light-Emitting Diodes Based on One-Dimensional Organic-Inorganic Hybrid Metal Chloride with Dual Emission.

White-light emissive organic-inorganic hybrid metal halides (MHs) have shown promising potential applications in solid-state lighting. As one-dimensional (1D) MHs for white-light emission remain rare and the key role of halogen regulation in 1D hybrid MHs for broadband emission (BE) has not been well established yet, herein, we report a family of 1D hybrid MHs TMGPbX3 (TMG = 1,1,3,3-tetramethylguanidine, X = Cl-, Br-, or I-) to systematically explore the influence of halogen on crystal structures and photoluminescence (PL) properties in 1D organic-inorganic hybrid MHs. Under ultraviolet excitation, TMGPbBr3 and TMGPbI3 exhibit BE originating from self-trapped excitons (STEs), while TMGPbCl3 manifests the special blue-white dual emission, which is contributed by STEs in inorganic frameworks and free excitons (FEs) in the organic component. Different emission mechanisms of three 1D MHs are well demonstrated and compared. With a PL quantum yield (PLQY) up to 11.67%, a white light-emitting diode (WLED) based on TMGPbCl3 was fabricated to show its valuable application in solid-state lighting.

Comprehensive analysis of prognostic immune-related genes and drug sensitivity in cervical cancer.

BACKGROUND: Cervical cancer (CC) is the leading cause of cancer-related death in women. A limited number of studies have investigated whether immune-prognostic features can be used to predict the prognosis of CC. This study aimed to develop an improved prognostic risk scoring model (PRSM) for CC based on immune-related genes (IRGs) to predict survival and determine the key prognostic IRGs. METHODS: We downloaded the gene expression profiles and clinical data of CC patients from the TCGA and GEO databases. The ESTIMATE algorithm was used to calculate the score for both immune and stromal cells. Differentially expressed genes (DEGs) in different subpopulations were analyzed by "Limma". A weighted gene co-expression network analysis (WGCNA) was used to establish a DEG co-expression module related to the immune score. Immune-related gene pairs (IRGPs) were constructed, and univariate- and Lasso-Cox regression analyses were used to analyze prognosis and establish a PRSM. A log-rank test was used to verify the accuracy and consistency of the scoring model. Identification of the predicted key IRG was ensured by the application of functional enrichment, DisNor, protein-protein interactions (PPIs) and heatmap. Finally, we extracted the key prognostic immune-related genes from the gene expression data, validated the key genes by immunohistochemistry and analyzed the correlation between their expression and drug sensitivity. RESULTS: A new PRSM was developed based on 22 IRGPs. The prognosis of the low-risk group in the model group (P < 0.001) and validation group (P = 0.039) was significantly better than that in the high-risk group. Furthermore, M1 and M2 macrophages were highly expressed in the low-risk group. Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway were significantly enriched in the low-risk group. Three representative genes (CD80, CD28, and LCP2) were markers of CC prognosis. CD80 and CD28 may more prominent represent important indicators to improve patient prognosis. These key genes was positively correlated with drug sensitivity. Finally, we found that differences in the sensitivity to JNK inhibitors could be distinguished based on the use and risk grouping of this PRSM. CONCLUSIONS: The prognostic model based on the IRGs and key genes have potential clinical significance for predicting the prognosis of CC patients, providing a foundation for clinical prognosis judgment and individualized treatment.

Metabolomics approach for predicting response to neoadjuvant chemotherapy for colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a clinically heterogeneous disease, which necessitates a variety of treatments and leads to different outcomes. Only some CRC patients will benefit from neoadjuvant chemotherapy (NACT). OBJECTIVES: An accurate prediction of response to NACT in CRC patients would greatly facilitate optimal personalized management, which could improve their long-term survival and clinical outcomes. METHODS: In this study, plasma metabolite profiling was performed to identify potential biomarker candidates that can predict response to NACT for CRC. Metabolic profiles of plasma from non-response (n = 30) and response (n = 27) patients to NACT were studied using UHPLC-quadruple time-of-flight)/mass spectrometry analyses and statistical analysis methods. RESULTS: The concentrations of nine metabolites were significantly different when comparing response to NACT. The area under the receiver operating characteristic curve value of the potential biomarkers was up to 0.83 discriminating the non-response and response group to NACT, superior to the clinical parameters (carcinoembryonic antigen and carbohydrate antigen 199). CONCLUSION: These results show promise for larger studies that could result in more personalized treatment protocols for CRC patients.

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/ß-catenin signaling.

BACKGROUND: With more than 600,000 mortalities each year, colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. Recently, mechanisms involving noncoding RNAs have been implicated in the development of CRC. METHODS: We examined expression levels of lncRNA CRNDE and miR-181a-5p in 64 cases of CRC tissues and cell lines by qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of CRNDE and miR-181a-5p on proliferation and chemoresistance of CRC cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of CRNDE in CRC cells. RESULTS: In this study, we found that the expression levels of the CRNDE were upregulated in CRC clinical tissue samples. We identified microRNA miR-181a-5p as an inhibitory target of CRNDE. Both CRNDE knockdown and miR-181a-5p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that ß-catenin and TCF4 were inhibitory targets of miR-181a-5p, and that Wnt/ß-catenin signaling was inhibited by both CRNDE knockdown and miR-181a-5p overexpression. Significantly, we found that the repression of cell proliferation, the reduction of chemoresistance, and the inhibition of Wnt/ß-catenin signaling induced by CRNDE knockdown would require the increased expression of miR-181a-5p. CONCLUSIONS: Our study demonstrated that the lncRNA CRNDE could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-181a-5p and the activity of Wnt/ß-catenin signaling.

Ruthenium-Amine Conjugated Organometallic Materials for Multistate Near-IR Electrochromism and Information Storage.

Monometallic and dimetallic complexes with the ruthenium-amine conjugated structural unit have been prepared. These complexes display consecutive redox waves with low potentials and rich and intense absorptions in the near-infrared region. The electrochemical and spectroscopic properties can be modulated using substituents or auxiliary ligands with different electronic natures. Through simple functionalization, electropolymerized or monolayer thin films of these complexes have been prepared. These films display multistate near-infrared electrochromism with good contrast ratios and long optical retention times. In addition, flip-flop and flip-flap-flop memories have been demonstrated on the basis of these thin films.

Three-state near-infrared electrochromism at the molecular scale.

Self-assembled monolayer films of a cyclometalated ruthenium complex with a redox-active amine substituent and three carboxylic acid groups have been prepared on ITO electrode surfaces. The obtained thin films show three-state electrochromic switching with low electrochemical potential inputs and high near-infrared absorbance outputs. Thanks to the long retention time of each oxidation states, these films have been used to demonstrate surface-confined flip-flop memory functions with high ON/OFF ratios at the molecular scale.

A Molecular Platform for Multistate Near-Infrared Electrochromism and Flip-Flop, Flip-Flap-Flop, and Ternary Memory.

A diruthenium complex with a redox-active amine bridge has been designed, synthesized, and studied by single-crystal X-ray analysis and DFT and TDDFT calculations. It shows three well-separated redox processes with exclusive near-infrared (NIR) absorbance at each redox state. The electropolymerized film of a related vinyl-functionalized complex displays multistate NIR electrochromism with low operational potential, good contrast ratio, and long retention time. Flip-flop, flip-flap-flop, and ternary memories have been realized by using the obtained film (ca. 15-20 nm thick) with three electrochemical inputs and three NIR optical outputs that each displays three levels of signal intensity.

Expression and clinicopathological significance of Mel-18 mRNA in colorectal cancer.

Mel-18 is a member of the polycomb group (PcG) of proteins, which are chromatin regulatory factors that play an important role in oncogenesis. This study was designed to investigate the clinical and prognostic significance of Mel-18 in colorectal cancer (CRC) patients. For this purpose, expression of Mel-18 mRNA was evaluated in 82 primary CRC and paired noncancerous mucosa samples by qRT-PCR and Western blotting. We found that overall Mel-18 mRNA expression in the CRC tissue was significantly lower than in the noncancerous mucosal tissue (p = 0.007, Wilcoxon matched-pairs signed-ranks test). Mel-18 was conversely correlated with the pathological classifications (p = 0.003 for T, p < 0.001 for N, and p = 0.015 for M classifications, respectively) and clinical AJCC stage (p < 0.001). Furthermore, CRC patients with a higher level of Mel-18 showed prolonged disease-free survivals (DFS) (p < 0.001). In multivariate analysis, the diminished Mel-18 expression may be a risk factor for the patients' 3-year DFS (HR = 1.895; 95 % CI 1.032, 3.477; p = 0.039). It was therefore concluded that the lower Mel-18 expression might contribute to the CRC development/progression.

Prognostic significance of lymph node status in patients with metastatic colorectal carcinoma treated with lymphadenectomy.

BACKGROUND AND OBJECTIVES: To test prognostic significance of lymph node status in patients with metastatic colorectal carcinoma (mCRC). METHODS: Four hundred ninety six patients diagnosed with synchronous mCRC and treated with lymphadenectomy between 1995 and 2008 were identified and divided into groups pN0, pN1, and pN2 (140 (28.2%) in pN0, 223 (45.0%) in pN1, and 133 (26.8%) in pN2 group) according to their lymph node status. The Kaplan-Meier and Cox regression analyses were used to test associations and independent predictor status of lymph node involvement. RESULTS: The Cox proportional hazards regression showed pN as significantly associated with disease-specific survival (DSS) both in univariate (HR = 1.609, 95% CI 1.411 to 1.835, P < 0.001) and multivariate (HR = 1.630, 95% CI 1.422 to 1.868, P < 0.001) analyses. The Kaplan-Meier analysis demonstrated that patients with pN2 and pN1 had a significantly worse DSS compared with patients with pN0 tumors (respectively, 17.273 ± 1.020 and 27.145 ± 1.715 vs. 34.992 ± 2.143 months; P < 0.001). In accuracy analyses based on AUC values, nodal status demonstrated the highest accuracy (65.1%) out of all the variables. CONCLUSIONS: Our findings indicate that optimal TNM staging for mCRC should incorporate lymph node status to provide a more effective and predictive model.

A combined experimental and computational study of linear ruthenium(II) coordination oligomers with end-capping organic redox sites: insight into the light absorption and charge delocalization.

Two series of linear ruthenium coordination oligomers, [(Ntpy)Ru(n)(tppz)(n-1)(tpy)](2n+) (mono-Ntpy series, n = 1-3) and [(Ntpy)2Ru(n)(tppz)(n-1)](2n+) (bis-Ntpy series, n = 1-3) have been prepared, where Ntpy is the capping ligand 4'-di-p-anisylamino-2,2':6',2''-terpyridine, tppz is tetra-2-pyridylpyrazine, and tpy is 2,2':6',2''-terpyridine. The electrochemical measurements evidence oxidation events from both the amine segments and the metal centers and reduction waves from tppz and the capping ligands. Both series complexes display much enhanced light absorption with respect to model complexes without terminal amine units. Density functional theory (DFT) calculations have been performed on both series and time-dependent DFT (TD-DFT) calculations have been performed on the bis-Ntpy-series compounds (n = 1-4) to characterize their electronic structures and excited states and predict the electronic properties of long-chain polymers. Upon one-electron oxidation, the mono-Ntpy-series monoruthenium and diruthenium complexes display N(+)-localized transitions and metal-to-nitrogen charge-transfer (MNCT) transitions in the near-infrared (NIR) region. DFT and TD-DFT computations on the one-electron-oxidized forms of the mono-Ntpy-series compounds (n = 1-4) provide insight into the nature of the MNCT transitions and the degree of charge delocalization.

Two Novel Two-Dimensional Organic-Inorganic Hybrid Lead Halides with Broadband Emission for White-Light-Emitting Diodes.

Low-dimensional organic-inorganic metal halides (LOMHs) recently have attracted much attention due to their tunable crystal structures and excellent photoelectric properties. The configuration and arrangement of organic cations in LOMHs have significant effect on the structure of inorganic frameworks and luminescence properties. In this work, we systematically explored the "spatial effect" and "hydrogen bonding effect" of organic cations on the structure and properties of LOMHs, by synthesizing three LOMHs including (N-AD)PbCl4, (N-AD)2Pb2Br7, and (N-AD)4Pb3I12 (N-AD: N-acetylethylenediamine, C4H10N2O). Specifically, (110)-oriented two-dimensional (N-AD)PbCl4 and (N-AD)2Pb2Br7 with manifest blue-white emissions, originating from the free excitons (FEs) and self-trapped excitons (STEs), respectively. The UV-pumped light-emitting diode (LED)-based on (N-AD)2Pb2Br7 was prepared, and the highest color rendering index (CRI) and correlated color temperature (CCT) were up to 80 and 4484 K, respectively. This proves its potential application in solid-state lighting.

Identification and Validation in a Novel Quantification System of Ferroptosis Patterns for the Prediction of Prognosis and Immunotherapy Response in Left- and Right-Sided Colon Cancer.

Background: This study aimed to establish a novel quantification system of ferroptosis patterns and comprehensively analyze the relationship between ferroptosis score (FS) and the immune cell infiltration (ICI) characterization, tumor mutation burden (TMB), prognosis, and therapeutic sensitivity in left-sided and right-sided colon cancers (LCCs and RCCs, respectively). Methods: We comprehensively evaluated the ferroptosis patterns in 444 LCCs and RCCs based on 59 ferroptosis-related genes (FRGs). The FS was constructed to quantify ferroptosis patterns by using principal component analysis algorithms. Next, the prognostic value and therapeutic sensitivities were evaluated using multiple methods. Finally, we performed weighted gene co-expression network analysis (WGCNA) to identify the key FRGs. The IMvigor210 cohort, TCGA-COAD proteomics cohort, and Immunophenoscores were used to verify the predictive abilities of FS and the key FRGs. Results: Two ferroptosis clusters were determined. Ferroptosis cluster B demonstrated a high degree of congenital ICI and stromal-related signal enrichment with a poor prognosis. The prognosis, response of targeted inhibitors, and immunotherapy were significantly different between high and low FS groups (HSG and LSG, respectively). HSG was characterized by high TMB and microsatellite instability-high subtype with poor prognosis. Meanwhile, LSG was more likely to benefit from immunotherapy. ALOX5 was identified as a key FRG based on FS. Patients with high protein levels of ALOX5 had poorer prognoses. Conclusion: This work revealed that the evaluation of ferroptosis subtypes will contribute to gaining insight into the heterogeneity in LCCs and RCCs. The quantification for ferroptosis patterns played a non-negligible role in predicting ICI characterization, prognosis, and individualized immunotherapy strategies.

Exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer: Multi-omics and ctDNA sequencing collaboration.

Introduction: This study aimed to identified the key genes and sequencing metrics for predicting prognosis and efficacy of neoadjuvant chemotherapy (nCT) in rectal cancer (RC) based on genomic DNA sequencing in samples with different origin and multi-omics association database. Methods: We collected 16 RC patients and obtained DNA sequencing data from cancer tissues and plasma cell-free DNA before and after nCT. Various gene variations were analyzed, including single nucleotide variants (SNV), copy number variation (CNV), tumor mutation burden (TMB), copy number instability (CNI) and mutant-allele tumor heterogeneity (MATH). We also identified genes by which CNV level can differentiate the response to nCT. The Cancer Genome Atlas database and the Clinical Proteomic Tumor Analysis Consortium database were used to further evaluate the specific role of therapeutic relevant genes and screen out the key genes in multi-omics levels. After the intersection of the screened genes from differential expression analysis, survival analysis and principal components analysis dimensionality reduction cluster analysis, the key genes were finally identified. Results: The genes CNV level of principal component genes in baseline blood and cancer tissues could significantly distinguish the two groups of patients. The CNV of HSP90AA1, EGFR, SRC, MTOR, etc. were relatively gained in the better group compared with the poor group in baseline blood. The CNI and TMB was significantly different between the two groups. The increased expression of HSP90AA1, EGFR, and SRC was associated with increased sensitivity to multiple chemotherapeutic drugs. The nCT predictive score obtained by therapeutic relevant genes could be a potential prognostic indicator, and the combination with TMB could further refine prognostic prediction for patients. After a series of analysis in multi-omics association database, EGFR and HSP90AA1 with significant differences in multiple aspects were identified as the key predictive genes related to prognosis and the sensitivity of nCT. Discussion: This work revealed that effective combined application and analysis in multi-omics data are critical to search for predictive biomarkers. The key genes EGFR and HSP90AA1 could serve as an effective biomarker to predict prognose and neoadjuvant chemosensitivity.

Low-Dimensional Metal Halide Perovskite Crystal Materials: Structure Strategies and Luminescence Applications.

Replacing methylammonium (MA+ ), formamidine (FA+ ), and/or cesium (Cs+ ) in 3D metal halide perovskites by larger organic cations have built a series of low-dimensional metal halide perovskites (LDMHPs) in which the inorganic metal halide octahedra arranging in the forms of 2D layers, 1D chains, and 0D points. These LDMHPs exhibit significantly different optoelectronic properties from 3D metal halide perovskites (MHPs) due to their unique quantum confinement effects and large exciton binding energies. In particular, LDMHPs often have excellent broadband luminescence from self-trapped excitons. Chemical composition, hydrogen bonding, and external factors (temperature and pressure etc.) determine structures and influence photoelectric properties of LDMHPs greatly, and especially it seems that there is no definite regulation to predict the structure and photoelectric properties when a random cation, metal, and halide is chosen to design a LDMHP. Therefore, this review discusses the construction strategies of the recent reported LDMHPs and their application progress in the luminescence field for a better understanding of these factors and a prospect for LDMHPs' development in the future.

Prognostic Immune-Related Analysis Based on Differentially Expressed Genes in Left- and Right-Sided Colon Adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) can be divided into left-sided and right-sided COAD (LCCs and RCCs, respectively). They have unique characteristics in various biological aspects, particularly immune invasion and prognosis. The purpose of our study was to develop a prognostic risk scoring model (PRSM) based on differentially expressed immune-related genes (IRGs) between LCCs and RCCs, therefore the prognostic key IRGs could be identified. METHODS: The gene sets and clinical information of COAD patients were derived from TCGA and GEO databases. The comparison of differentially expressed genes (DEGs) of LCCs and RCCs were conducted with appliance of "Limma" analysis. The establishment about co-expression modules of DEGs related with immune score was conducted by weighted gene co-expression network analysis (WGCNA). Furthermore, we screened the module genes and completed construction of gene pairs. The analysis of the prognosis and the establishment of PRSM were performed with univariate- and lasso-Cox regression. We employed the PRSM in the model group and verification group for the purpose of risk group assignment and PRSM accuracy verification. Finally, the identification of the prognostic key IRGs was guaranteed by the adoption of functional enrichment, "DisNor" and protein-protein interaction (PPI). RESULTS: A total of 215 genes were screened out by differential expression analysis and WGCNA. A PRSM with 16 immune-related gene pairs (IRGPs) was established upon the genes pairing. Furthermore, we confirmed that the risk score was an independent factor for survival by univariate- and multivariate-Cox regression. The prognosis of high-risk group in model group (P < 0.001) and validation group (P = 0.014) was significantly worse than that in low-risk group. Treg cells (P < 0.001) and macrophage M0 (P = 0.015) were highly expressed in the high-risk group. The functional analysis indicated that there was significant up-regulation with regard of lymphocyte and cytokine related terms in low-risk group. Finally, we identified five prognostic key IRGs associated with better prognosis through PPI and prognostic analysis, including IL2RB, TRIM22, CIITA, CXCL13, and CXCR6. CONCLUSION: Through the analysis and screening of the DEGs between LCCs and RCCs, we constructed a PRSM which could predicate prognosis of LCCs and RCCs, and five prognostic key IRGs were identified as well. Therefore, the basis for identifying the benefits of immunotherapy and immunomodulatory was built.

Deubiquitinating Enzymes Orchestrate the Cancer Stem Cell-Immunosuppressive Niche Dialogue: New Perspectives and Therapeutic Potential.

Cancer stem cells (CSCs) are sparks for igniting tumor recurrence and the instigators of low response to immunotherapy and drug resistance. As one of the important components of tumor microenvironment, the tumor associated immune microenvironment (TAIM) is driving force for the heterogeneity, plasticity and evolution of CSCs. CSCs create the inhibitory TAIM (ITAIM) mainly through four stemness-related signals (SRSs), including Notch-nuclear factor-κB axis, Hedgehog, Wnt and signal transducer and activator of transcription. Ubiquitination and deubiquitination in proteins related to the specific stemness of the CSCs have a profound impact on the regulation of ITAIM. In regulating the balance between ubiquitination and deubiquitination, it is crucial for deubiquitinating enzymes (DUBs) to cleave ubiquitin chains from substrates. Ubiquitin-specific peptidases (USPs) comprise the largest family of DUBs. Growing evidence suggests that they play novel functions in contribution of ITAIM, including regulating tumor immunogenicity, activating stem cell factors, upregulating the SRSs, stabilizing anti-inflammatory receptors, and regulating anti-inflammatory cytokines. These overactive or abnormal signaling may dampen antitumor immune responses. The inhibition of USPs could play a regulatory role in SRSs and reversing ITAIM, and also have great potential in improving immune killing ability against tumor cells, including CSCs. In this review, we focus on the USPs involved in CSCs signaling pathways and regulating ITAIM, which are promising therapeutic targets in antitumor therapy.

Identification and Validation of Immune-Related Gene for Predicting Prognosis and Therapeutic Response in Ovarian Cancer.

Ovarian cancer (OC) is a devastating malignancy with a poor prognosis. The complex tumor immune microenvironment results in only a small number of patients benefiting from immunotherapy. To explore the different factors that lead to immune invasion and determine prognosis and response to immune checkpoint inhibitors (ICIs), we established a prognostic risk scoring model (PRSM) with differential expression of immune-related genes (IRGs) to identify key prognostic IRGs. Patients were divided into high-risk and low-risk groups according to their immune and stromal scores. We used a bioinformatics method to identify four key IRGs that had differences in expression between the two groups and affected prognosis. We evaluated the sensitivity of treatment from three aspects, namely chemotherapy, targeted inhibitors (TIs), and immunotherapy, to evaluate the value of prediction models and key prognostic IRGs in the clinical treatment of OC. Univariate and multivariate Cox regression analyses revealed that these four key IRGs were independent prognostic factors of overall survival in OC patients. In the high-risk group comprising four genes, macrophage M0 cells, macrophage M2 cells, and regulatory T cells, observed to be associated with poor overall survival in our study, were higher. The high-risk group had a high immunophenoscore, indicating a better response to ICIs. Taken together, we constructed a PRSM and identified four key prognostic IRGs for predicting survival and response to ICIs. Finally, the expression of these key genes in OC was evaluated using RT-qPCR. Thus, these genes provide a novel predictive biomarker for immunotherapy and immunomodulation.