Small-Molecule Uncoupling Protein Mimics: Synthetic Anion Receptors as Fatty Acid-Activated Proton Transporters

Uncoupling proteins (UCPs) regulate energy expenditure in living cells by inducing proton leakage across the mitochondrial inner membrane, thereby uncoupling adenosine diphosphate phosphorylation from nutrient oxidation. The proton transport activity of UCP1 and UCP2 requires activation by fatty acids. We report here the first examples of synthetic neutral anion receptors performing this biologically important fatty acid-activated function in phospholipid bilayers. We have shown that a tripodal thiourea possesses poor H⁺/OH^– transport activity without fatty acids, but in the presence of long-chain fatty acids is “switched on” as a proton transporter with an activity close to that of a commonly used protonophore. The fatty acid-enhanced proton transport was also observed for other hydrogen and halogen bond-based synthetic anion transporters. We propose that these compounds induce proton permeability by catalyzing trans­bilayer movement (“flip-flop”) of anionic forms of fatty acids, so allowing the fatty acids to complete a proton transport cycle. Several lines of evidence have been provided to support such a fatty acid cycling mechanism. Our findings open up new applications of anion receptor chemistry and provide important clues for understanding biological activities of synthetic anion transporters and potentially the uncoupling mechanism of naturally occurring membrane proteins

Semiempirical Quantum Chemical Calculations Accelerated on a Hybrid Multicore CPU–GPU Computing Platform

In this work, we demonstrate that semiempirical quantum chemical calculations can be accelerated significantly by leveraging the graphics processing unit (GPU) as a coprocessor on a hybrid multicore CPU–GPU computing platform. Semiempirical calculations using the MNDO, AM1, PM3, OM1, OM2, and OM3 model Hamiltonians were systematically profiled for three types of test systems (fullerenes, water clusters, and solvated crambin) to identify the most time-consuming sections of the code. The corresponding routines were ported to the GPU and optimized employing both existing library functions and a GPU kernel that carries out a sequence of noniterative Jacobi transformations during pseudodiagonalization. The overall computation times for single-point energy calculations and geometry optimizations of large molecules were reduced by one order of magnitude for all methods, as compared to runs on a single CPU core

Interface Designing over WS₂/W₂C for Enhanced Hydrogen Evolution Catalysis

Interface engineering is a promising strategy for boosting the catalytic performances via the optimized coordination. Herein, we developed a top-down strategy to <i>in situ</i> obtain the nanocomposite of N, S-decorated porous carbon matrix encapsulated WS₂/W₂C (WS₂/W₂C@NSPC). The as-synthesized hybrid is characterized by excellent interface coupling in atomic level, good electrical conductivity, and high active surface area. Electrochemical measurements show that the optimized catalyst exhibits remarkable electrocatalytic activity for hydrogen evolution in both acidic and alkaline media. These results should be attributed to the abundant active sites existing in the different phase boundaries, resulting from a synergistic effect of the activated WS₂/W₂C heterostructure and the highly conductive carbon matrix. This strategy opens new avenues toward understanding the relationship between chemical structure and catalytic performance in molecular level and thus providing a rational way to fabricate highly efficient and durable electrocatalysts

Table1_Potential value of the homologous recombination deficiency signature we developed in the prognosis and drug sensitivity of gastric cancer.DOCX

Background: Homologous recombination is an important DNA repair mechanism, which deficiency is a common feature of many cancers. Defining homologous recombination deficiency (HRD) status can provide information for treatment decisions of cancer patients. HRD score is a widely accepted method to evaluate HRD status. This study aimed to explored HRD in gastric cancer (GC) patients’ clinical outcomes with genes related to HRD score and HRD components score [HRD-loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (NtAI)].Methods: Based on LOH, NtAI scores, LST, and integrated HRD scores-related genes, a risk model for stratifying 346 TCGA GC cases were developed by Cox regression analysis and LASSO Cox regression. The risk scores of 33 cancers in TCGA were calculated to analyze the relationship between risk scores of each cancer and HRD scores and 3 HRD component scores. Relationship between the risk model and patient survival, BRCA1, BRCA2 mutation, response to Cisplatin and Talazoparib treatment was analyzed by generating Kaplan-Meier curve, mutations waterfall map and conducting Pearson correlation analysis.Results: An gene signature was constructed based on 11 HRD scores-related gene (BEX2, C1QL2, DKK1, DRC1, GLUD2, HCAR1, IGFBP1, NXPH1, PROC, SERPINA5, and SLCA1A2). Risk groups were stratified by risk score. Prognosis of the high-risk score group was worse than the low-risk ones. Risk score was associated with BRCA2 mutation, and patients grouped according to BRCA2 mutation status had distinguishable risk score, NtAI score, HRD-LOH, LST, and HRD scores. The low-score group showed higher sensitivity to Cisplatin and Talazoparib. The risk score of adrenocortical carcinoma (ACC), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), kidney renal clear cell carcinoma (KIRC), sarcoma (SARC), prostate adenocarcinoma (PRAD), breast invasive carcinoma (BRCA) was significantly positively correlated with HRD score.Conclusion: We developed an 11 HRD scores-related genes risk model and revealed the potential association between HRD status and GC prognosis, gene mutations, patients’ sensitivity to therapeutic drugs.</p

Table3_Potential value of the homologous recombination deficiency signature we developed in the prognosis and drug sensitivity of gastric cancer.DOCX

Background: Homologous recombination is an important DNA repair mechanism, which deficiency is a common feature of many cancers. Defining homologous recombination deficiency (HRD) status can provide information for treatment decisions of cancer patients. HRD score is a widely accepted method to evaluate HRD status. This study aimed to explored HRD in gastric cancer (GC) patients’ clinical outcomes with genes related to HRD score and HRD components score [HRD-loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (NtAI)].Methods: Based on LOH, NtAI scores, LST, and integrated HRD scores-related genes, a risk model for stratifying 346 TCGA GC cases were developed by Cox regression analysis and LASSO Cox regression. The risk scores of 33 cancers in TCGA were calculated to analyze the relationship between risk scores of each cancer and HRD scores and 3 HRD component scores. Relationship between the risk model and patient survival, BRCA1, BRCA2 mutation, response to Cisplatin and Talazoparib treatment was analyzed by generating Kaplan-Meier curve, mutations waterfall map and conducting Pearson correlation analysis.Results: An gene signature was constructed based on 11 HRD scores-related gene (BEX2, C1QL2, DKK1, DRC1, GLUD2, HCAR1, IGFBP1, NXPH1, PROC, SERPINA5, and SLCA1A2). Risk groups were stratified by risk score. Prognosis of the high-risk score group was worse than the low-risk ones. Risk score was associated with BRCA2 mutation, and patients grouped according to BRCA2 mutation status had distinguishable risk score, NtAI score, HRD-LOH, LST, and HRD scores. The low-score group showed higher sensitivity to Cisplatin and Talazoparib. The risk score of adrenocortical carcinoma (ACC), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), kidney renal clear cell carcinoma (KIRC), sarcoma (SARC), prostate adenocarcinoma (PRAD), breast invasive carcinoma (BRCA) was significantly positively correlated with HRD score.Conclusion: We developed an 11 HRD scores-related genes risk model and revealed the potential association between HRD status and GC prognosis, gene mutations, patients’ sensitivity to therapeutic drugs.</p

Catenation of Homochiral Metal–Organic Nanocages or Nanotubes

Catenation based on homochiral metal–organic nanocages or nanotubes is realized in this work for the first time. A flexible enantiopure ligand is employed to assemble metal ions, with the structure-directing effect of an auxiliary ligand, a triangular-prism-like nanocage, and a nanotube successfully built. Further 0D → 3D catenation is achieved by interlocking the nanocages, and 1D → 3D catenation based on nanotubes is also presented. This work reveals extraordinary catenating architectures from molecular cages and tubes

Image7_Potential value of the homologous recombination deficiency signature we developed in the prognosis and drug sensitivity of gastric cancer.JPEG

Background: Homologous recombination is an important DNA repair mechanism, which deficiency is a common feature of many cancers. Defining homologous recombination deficiency (HRD) status can provide information for treatment decisions of cancer patients. HRD score is a widely accepted method to evaluate HRD status. This study aimed to explored HRD in gastric cancer (GC) patients’ clinical outcomes with genes related to HRD score and HRD components score [HRD-loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (NtAI)].Methods: Based on LOH, NtAI scores, LST, and integrated HRD scores-related genes, a risk model for stratifying 346 TCGA GC cases were developed by Cox regression analysis and LASSO Cox regression. The risk scores of 33 cancers in TCGA were calculated to analyze the relationship between risk scores of each cancer and HRD scores and 3 HRD component scores. Relationship between the risk model and patient survival, BRCA1, BRCA2 mutation, response to Cisplatin and Talazoparib treatment was analyzed by generating Kaplan-Meier curve, mutations waterfall map and conducting Pearson correlation analysis.Results: An gene signature was constructed based on 11 HRD scores-related gene (BEX2, C1QL2, DKK1, DRC1, GLUD2, HCAR1, IGFBP1, NXPH1, PROC, SERPINA5, and SLCA1A2). Risk groups were stratified by risk score. Prognosis of the high-risk score group was worse than the low-risk ones. Risk score was associated with BRCA2 mutation, and patients grouped according to BRCA2 mutation status had distinguishable risk score, NtAI score, HRD-LOH, LST, and HRD scores. The low-score group showed higher sensitivity to Cisplatin and Talazoparib. The risk score of adrenocortical carcinoma (ACC), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), kidney renal clear cell carcinoma (KIRC), sarcoma (SARC), prostate adenocarcinoma (PRAD), breast invasive carcinoma (BRCA) was significantly positively correlated with HRD score.Conclusion: We developed an 11 HRD scores-related genes risk model and revealed the potential association between HRD status and GC prognosis, gene mutations, patients’ sensitivity to therapeutic drugs.</p

Image1_Potential value of the homologous recombination deficiency signature we developed in the prognosis and drug sensitivity of gastric cancer.JPEG

Background: Homologous recombination is an important DNA repair mechanism, which deficiency is a common feature of many cancers. Defining homologous recombination deficiency (HRD) status can provide information for treatment decisions of cancer patients. HRD score is a widely accepted method to evaluate HRD status. This study aimed to explored HRD in gastric cancer (GC) patients’ clinical outcomes with genes related to HRD score and HRD components score [HRD-loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (NtAI)].Methods: Based on LOH, NtAI scores, LST, and integrated HRD scores-related genes, a risk model for stratifying 346 TCGA GC cases were developed by Cox regression analysis and LASSO Cox regression. The risk scores of 33 cancers in TCGA were calculated to analyze the relationship between risk scores of each cancer and HRD scores and 3 HRD component scores. Relationship between the risk model and patient survival, BRCA1, BRCA2 mutation, response to Cisplatin and Talazoparib treatment was analyzed by generating Kaplan-Meier curve, mutations waterfall map and conducting Pearson correlation analysis.Results: An gene signature was constructed based on 11 HRD scores-related gene (BEX2, C1QL2, DKK1, DRC1, GLUD2, HCAR1, IGFBP1, NXPH1, PROC, SERPINA5, and SLCA1A2). Risk groups were stratified by risk score. Prognosis of the high-risk score group was worse than the low-risk ones. Risk score was associated with BRCA2 mutation, and patients grouped according to BRCA2 mutation status had distinguishable risk score, NtAI score, HRD-LOH, LST, and HRD scores. The low-score group showed higher sensitivity to Cisplatin and Talazoparib. The risk score of adrenocortical carcinoma (ACC), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), kidney renal clear cell carcinoma (KIRC), sarcoma (SARC), prostate adenocarcinoma (PRAD), breast invasive carcinoma (BRCA) was significantly positively correlated with HRD score.Conclusion: We developed an 11 HRD scores-related genes risk model and revealed the potential association between HRD status and GC prognosis, gene mutations, patients’ sensitivity to therapeutic drugs.</p

Image5_Potential value of the homologous recombination deficiency signature we developed in the prognosis and drug sensitivity of gastric cancer.JPEG

Background: Homologous recombination is an important DNA repair mechanism, which deficiency is a common feature of many cancers. Defining homologous recombination deficiency (HRD) status can provide information for treatment decisions of cancer patients. HRD score is a widely accepted method to evaluate HRD status. This study aimed to explored HRD in gastric cancer (GC) patients’ clinical outcomes with genes related to HRD score and HRD components score [HRD-loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (NtAI)].Methods: Based on LOH, NtAI scores, LST, and integrated HRD scores-related genes, a risk model for stratifying 346 TCGA GC cases were developed by Cox regression analysis and LASSO Cox regression. The risk scores of 33 cancers in TCGA were calculated to analyze the relationship between risk scores of each cancer and HRD scores and 3 HRD component scores. Relationship between the risk model and patient survival, BRCA1, BRCA2 mutation, response to Cisplatin and Talazoparib treatment was analyzed by generating Kaplan-Meier curve, mutations waterfall map and conducting Pearson correlation analysis.Results: An gene signature was constructed based on 11 HRD scores-related gene (BEX2, C1QL2, DKK1, DRC1, GLUD2, HCAR1, IGFBP1, NXPH1, PROC, SERPINA5, and SLCA1A2). Risk groups were stratified by risk score. Prognosis of the high-risk score group was worse than the low-risk ones. Risk score was associated with BRCA2 mutation, and patients grouped according to BRCA2 mutation status had distinguishable risk score, NtAI score, HRD-LOH, LST, and HRD scores. The low-score group showed higher sensitivity to Cisplatin and Talazoparib. The risk score of adrenocortical carcinoma (ACC), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), kidney renal clear cell carcinoma (KIRC), sarcoma (SARC), prostate adenocarcinoma (PRAD), breast invasive carcinoma (BRCA) was significantly positively correlated with HRD score.Conclusion: We developed an 11 HRD scores-related genes risk model and revealed the potential association between HRD status and GC prognosis, gene mutations, patients’ sensitivity to therapeutic drugs.</p

Image4_Potential value of the homologous recombination deficiency signature we developed in the prognosis and drug sensitivity of gastric cancer.JPEG

Background: Homologous recombination is an important DNA repair mechanism, which deficiency is a common feature of many cancers. Defining homologous recombination deficiency (HRD) status can provide information for treatment decisions of cancer patients. HRD score is a widely accepted method to evaluate HRD status. This study aimed to explored HRD in gastric cancer (GC) patients’ clinical outcomes with genes related to HRD score and HRD components score [HRD-loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (NtAI)].Methods: Based on LOH, NtAI scores, LST, and integrated HRD scores-related genes, a risk model for stratifying 346 TCGA GC cases were developed by Cox regression analysis and LASSO Cox regression. The risk scores of 33 cancers in TCGA were calculated to analyze the relationship between risk scores of each cancer and HRD scores and 3 HRD component scores. Relationship between the risk model and patient survival, BRCA1, BRCA2 mutation, response to Cisplatin and Talazoparib treatment was analyzed by generating Kaplan-Meier curve, mutations waterfall map and conducting Pearson correlation analysis.Results: An gene signature was constructed based on 11 HRD scores-related gene (BEX2, C1QL2, DKK1, DRC1, GLUD2, HCAR1, IGFBP1, NXPH1, PROC, SERPINA5, and SLCA1A2). Risk groups were stratified by risk score. Prognosis of the high-risk score group was worse than the low-risk ones. Risk score was associated with BRCA2 mutation, and patients grouped according to BRCA2 mutation status had distinguishable risk score, NtAI score, HRD-LOH, LST, and HRD scores. The low-score group showed higher sensitivity to Cisplatin and Talazoparib. The risk score of adrenocortical carcinoma (ACC), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), kidney renal clear cell carcinoma (KIRC), sarcoma (SARC), prostate adenocarcinoma (PRAD), breast invasive carcinoma (BRCA) was significantly positively correlated with HRD score.Conclusion: We developed an 11 HRD scores-related genes risk model and revealed the potential association between HRD status and GC prognosis, gene mutations, patients’ sensitivity to therapeutic drugs.</p