Propargyl Alcohols as One-Carbon Synthons: Redox-Neutral Rhodium(III)-Catalyzed C–H Bond Activation for the Synthesis of Isoindolinones Bearing a Quaternary Carbon

Herein, rhodium­(III)-catalyzed C–H activation/subsequent [4 + 1] cyclization reactions between benzamides and propargyl alcohols are reported in which propargyl alcohols serve as unusual one-carbon units. This title transformation led to a series of isoindolinones bearing a quaternary carbon with moderate to good yields without the requirement for external metal oxidants. Due to the mild and simple reaction conditions, this reaction is compatible with various functional groups

Ruthenium-Catalyzed Redox-Neutral [4 + 1] Annulation of Benzamides and Propargyl Alcohols via C–H Bond Activation

Internal alkynes have been used widely in transition-metal-catalyzed cycloaddition reactions, in which they generally serve as two-carbon reaction partners. Herein, we report ruthenium­(II)-catalyzed redox-neutral [4 + 1] annulation of benzamides and propargyl alcohols, in which propargyl alcohols act as one-carbon units. This synthetic utility of propargyl alcohols led to a series of potentially bioactive N-substituted quaternary isoindolinones with moderate to high yields under mild conditions. Without the requirement for an external metal oxidant, this title transformation is compatible with various functional groups, which further underscores its synthetic utility and versatile applicability. In addition, preliminary mechanism experiments have been conducted and a plausible mechanism is proposed

All-Electrochem-Active Thick Electrode with Dual-Continuous TiO₂‑Carbon Integrated Skeletons for Low-Temperature Lithium Storage

Newly designed all-electrochem-active thick electrode (∼500 μm) with dual-continuous integrated skeletons of defective rutile-anatase TiO2 (D-R-A-TiO2) heterojunctions and carbon have been introduced to enhance efficient electron–ion transport for high-rate energy storage, which provides a new idea for low-temperature lithium storage. For the first time, we anneal anatase TiO2 integrated carbon under CO2 atmosphere for converting anatase to rutile and activating carbon simultaneously, to fabricate freestanding all-electrochem-active thick electrode. The D-R-A-TiO2 heterojunctions contain a type II staggered band alignment, which significantly induce highly localized electrons and lower the migration barrier of ions. The continuous D-R-A-TiO2 heterojunctions form synergistically advantageous electronic networks, and the thick electrode (up to 60.97 mg cm–2) delivers outstanding areal capacity (14.14 mAh cm–2 at 0.61 mA cm–2) under 30 °C. The areal capacity is 8.62 mAh cm–2 at 0.57 mA cm–2 under −10 °C. When the temperature drops to −20 °C, the areal capacity still delivers 4.92 mAh cm–2 at 0.57 mA cm–2. And the D-R-A-TiO2 electrode still delivers 3.2 mAh cm–2 capacity after 70 cycles at 0.57 mA cm–2 under −20 °C

Additional file 1 of LncRNA LBX2-AS1 promotes proliferation and migratory capacity of clear cell renal cell carcinoma through mitophagy

Additional file 1. Table S1. Sequences of primers used in qPCR

Table5_Prognostic and immunological significance of calcium-related gene signatures in renal clear cell carcinoma.XLSX

Background: Calcium signaling is implicated in multiple processes including immune response that important in tumor progression. Kidney renal clear cell carcinoma (KIRC) is the most frequent histological type of renal cell carcinoma with up to a third of cases develop metastases. As a result of a lack of in-depth understanding of the mechanisms underlying KIRC, treatment options have been limited. Here, we aim to comprehensively investigate the landscape of Ca2+ channels, pumps and exchangers in KIRC patients.Methods: The mRNA expression profiles and gene variations of 58 calcium-related genes (CRGs) in KIRC patients and normal control cases were downloaded from TCGA database. CRGs-related risk score was constructed to quantify calcium patterns by using least absolute shrinkage and selection operator (LASSO) regression. The prognostic value, biological functions, immune landscape and therapeutic sensitivities based on CRGs-related risk score were then evaluated using multiple methods. Finally, key gene of CRGs was identified by weighted gene co-expression network analysis (WGCNA). TCGA-CPTAC, GSE53757 datasets, as well as human tissues were used for validation.Results: KIRC patients had significant differences in CRG expression, prognosis, and biological functions between two CRG clusters. CRGs-related risk score was then determined. The prognosis, tumor mutation burden, immune cell infiltration, immune checkpoints, and the response of targeted inhibitors were remarkably different between high and low CRGs-related risk subtypes. CRGs-related high-risk subtype was characterized by immunosuppressive microenvironment with poor prognosis. Meanwhile, several targeted drugs showed distinct sensitivity between CRGs-related risk subtypes. Finally, TRPM3 was identified as a key CRG based on risk score in KIRC patients. TRPM3 mRNA and protein expression were significantly lower in KIRC tumors than in normal controls. Low TRPM3 expression was associated with poor prognosis in KIRC patients.Conclusion: Our study highlighted the promising prognostic value of CRGs in KIRC tumors. The evaluation of CRGs-related risk score will contribute to predicting prognosis and clinical therapy in KIRC patients.</p

Image_2_Comprehensive investigation into cuproptosis in the characterization of clinical features, molecular characteristics, and immune situations of clear cell renal cell carcinoma.tif

BackgroundCopper-induced cell death has been widely investigated in human diseases as a form of programmed cell death (PCD). The newly recognized mechanism underlying copper-induced cell death provided us creative insights into the copper-related toxicity in cells, and this form of PCD was termed cuproptosis.MethodsThrough consensus clustering analysis, ccRCC patients from TCGA database were classified into different subgroups with distinct cuproptosis-based molecular patterns. Analyses of clinical significance, long-term survival, and immune features were performed on subgroups accordingly. The cuproptosis-based risk signature and nomogram were constructed and validated relying on the ccRCC cohort as well. The cuproptosis scoring system was generated to better characterize ccRCC patients. Finally, in vitro validation was conducted using ccRCC clinical samples and cell lines.ResultPatients from different subgroups displayed diverse clinicopathological features, survival outcomes, tumor microenvironment (TME) characteristics, immune-related score, and therapeutic responses. The prognostic model and cuproptosis score were well validated and proved to efficiently distinguish the high risk/score and low risk/score patients, which revealed the great predictive value. The cuproptosis score also tended out to be intimately associated with the prognosis and immune features of ccRCC patients. Additionally, the hub cuproptosis-associated gene (CAG) FDX1 presented a dysregulated expression pattern in human ccRCC samples, and it was confirmed to effectively promote the killing effects of copper ionophore elesclomol as a direct target. In vitro functional assays revealed the prominent anti-cancer role of FDX1 in ccRCC.ConclusionCuproptosis played an indispensable role in the regulation of TME features, tumor progression, and long-term prognosis of ccRCC.</p

Table2_Prognostic and immunological significance of calcium-related gene signatures in renal clear cell carcinoma.XLSX

Background: Calcium signaling is implicated in multiple processes including immune response that important in tumor progression. Kidney renal clear cell carcinoma (KIRC) is the most frequent histological type of renal cell carcinoma with up to a third of cases develop metastases. As a result of a lack of in-depth understanding of the mechanisms underlying KIRC, treatment options have been limited. Here, we aim to comprehensively investigate the landscape of Ca2+ channels, pumps and exchangers in KIRC patients.Methods: The mRNA expression profiles and gene variations of 58 calcium-related genes (CRGs) in KIRC patients and normal control cases were downloaded from TCGA database. CRGs-related risk score was constructed to quantify calcium patterns by using least absolute shrinkage and selection operator (LASSO) regression. The prognostic value, biological functions, immune landscape and therapeutic sensitivities based on CRGs-related risk score were then evaluated using multiple methods. Finally, key gene of CRGs was identified by weighted gene co-expression network analysis (WGCNA). TCGA-CPTAC, GSE53757 datasets, as well as human tissues were used for validation.Results: KIRC patients had significant differences in CRG expression, prognosis, and biological functions between two CRG clusters. CRGs-related risk score was then determined. The prognosis, tumor mutation burden, immune cell infiltration, immune checkpoints, and the response of targeted inhibitors were remarkably different between high and low CRGs-related risk subtypes. CRGs-related high-risk subtype was characterized by immunosuppressive microenvironment with poor prognosis. Meanwhile, several targeted drugs showed distinct sensitivity between CRGs-related risk subtypes. Finally, TRPM3 was identified as a key CRG based on risk score in KIRC patients. TRPM3 mRNA and protein expression were significantly lower in KIRC tumors than in normal controls. Low TRPM3 expression was associated with poor prognosis in KIRC patients.Conclusion: Our study highlighted the promising prognostic value of CRGs in KIRC tumors. The evaluation of CRGs-related risk score will contribute to predicting prognosis and clinical therapy in KIRC patients.</p

Image_3_Comprehensive investigation into cuproptosis in the characterization of clinical features, molecular characteristics, and immune situations of clear cell renal cell carcinoma.tif

BackgroundCopper-induced cell death has been widely investigated in human diseases as a form of programmed cell death (PCD). The newly recognized mechanism underlying copper-induced cell death provided us creative insights into the copper-related toxicity in cells, and this form of PCD was termed cuproptosis.MethodsThrough consensus clustering analysis, ccRCC patients from TCGA database were classified into different subgroups with distinct cuproptosis-based molecular patterns. Analyses of clinical significance, long-term survival, and immune features were performed on subgroups accordingly. The cuproptosis-based risk signature and nomogram were constructed and validated relying on the ccRCC cohort as well. The cuproptosis scoring system was generated to better characterize ccRCC patients. Finally, in vitro validation was conducted using ccRCC clinical samples and cell lines.ResultPatients from different subgroups displayed diverse clinicopathological features, survival outcomes, tumor microenvironment (TME) characteristics, immune-related score, and therapeutic responses. The prognostic model and cuproptosis score were well validated and proved to efficiently distinguish the high risk/score and low risk/score patients, which revealed the great predictive value. The cuproptosis score also tended out to be intimately associated with the prognosis and immune features of ccRCC patients. Additionally, the hub cuproptosis-associated gene (CAG) FDX1 presented a dysregulated expression pattern in human ccRCC samples, and it was confirmed to effectively promote the killing effects of copper ionophore elesclomol as a direct target. In vitro functional assays revealed the prominent anti-cancer role of FDX1 in ccRCC.ConclusionCuproptosis played an indispensable role in the regulation of TME features, tumor progression, and long-term prognosis of ccRCC.</p

Table4_Prognostic and immunological significance of calcium-related gene signatures in renal clear cell carcinoma.XLSX

Background: Calcium signaling is implicated in multiple processes including immune response that important in tumor progression. Kidney renal clear cell carcinoma (KIRC) is the most frequent histological type of renal cell carcinoma with up to a third of cases develop metastases. As a result of a lack of in-depth understanding of the mechanisms underlying KIRC, treatment options have been limited. Here, we aim to comprehensively investigate the landscape of Ca2+ channels, pumps and exchangers in KIRC patients.Methods: The mRNA expression profiles and gene variations of 58 calcium-related genes (CRGs) in KIRC patients and normal control cases were downloaded from TCGA database. CRGs-related risk score was constructed to quantify calcium patterns by using least absolute shrinkage and selection operator (LASSO) regression. The prognostic value, biological functions, immune landscape and therapeutic sensitivities based on CRGs-related risk score were then evaluated using multiple methods. Finally, key gene of CRGs was identified by weighted gene co-expression network analysis (WGCNA). TCGA-CPTAC, GSE53757 datasets, as well as human tissues were used for validation.Results: KIRC patients had significant differences in CRG expression, prognosis, and biological functions between two CRG clusters. CRGs-related risk score was then determined. The prognosis, tumor mutation burden, immune cell infiltration, immune checkpoints, and the response of targeted inhibitors were remarkably different between high and low CRGs-related risk subtypes. CRGs-related high-risk subtype was characterized by immunosuppressive microenvironment with poor prognosis. Meanwhile, several targeted drugs showed distinct sensitivity between CRGs-related risk subtypes. Finally, TRPM3 was identified as a key CRG based on risk score in KIRC patients. TRPM3 mRNA and protein expression were significantly lower in KIRC tumors than in normal controls. Low TRPM3 expression was associated with poor prognosis in KIRC patients.Conclusion: Our study highlighted the promising prognostic value of CRGs in KIRC tumors. The evaluation of CRGs-related risk score will contribute to predicting prognosis and clinical therapy in KIRC patients.</p

Image1_Prognostic and immunological significance of calcium-related gene signatures in renal clear cell carcinoma.tif

Background: Calcium signaling is implicated in multiple processes including immune response that important in tumor progression. Kidney renal clear cell carcinoma (KIRC) is the most frequent histological type of renal cell carcinoma with up to a third of cases develop metastases. As a result of a lack of in-depth understanding of the mechanisms underlying KIRC, treatment options have been limited. Here, we aim to comprehensively investigate the landscape of Ca2+ channels, pumps and exchangers in KIRC patients.Methods: The mRNA expression profiles and gene variations of 58 calcium-related genes (CRGs) in KIRC patients and normal control cases were downloaded from TCGA database. CRGs-related risk score was constructed to quantify calcium patterns by using least absolute shrinkage and selection operator (LASSO) regression. The prognostic value, biological functions, immune landscape and therapeutic sensitivities based on CRGs-related risk score were then evaluated using multiple methods. Finally, key gene of CRGs was identified by weighted gene co-expression network analysis (WGCNA). TCGA-CPTAC, GSE53757 datasets, as well as human tissues were used for validation.Results: KIRC patients had significant differences in CRG expression, prognosis, and biological functions between two CRG clusters. CRGs-related risk score was then determined. The prognosis, tumor mutation burden, immune cell infiltration, immune checkpoints, and the response of targeted inhibitors were remarkably different between high and low CRGs-related risk subtypes. CRGs-related high-risk subtype was characterized by immunosuppressive microenvironment with poor prognosis. Meanwhile, several targeted drugs showed distinct sensitivity between CRGs-related risk subtypes. Finally, TRPM3 was identified as a key CRG based on risk score in KIRC patients. TRPM3 mRNA and protein expression were significantly lower in KIRC tumors than in normal controls. Low TRPM3 expression was associated with poor prognosis in KIRC patients.Conclusion: Our study highlighted the promising prognostic value of CRGs in KIRC tumors. The evaluation of CRGs-related risk score will contribute to predicting prognosis and clinical therapy in KIRC patients.</p