Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.

Comprehensive sequencing of patient tumors reveals genomic mutations across tumor types that enable tumorigenesis and progression. A subset of oncogenic driver mutations results in neomorphic activity where the mutant protein mediates functions not engaged by the parental molecule. Here, we identify prevalent variant-enabled neomorph-protein-protein interactions (neoPPI) with a quantitative high-throughput differential screening (qHT-dS) platform. The coupling of highly sensitive BRET biosensors with miniaturized coexpression in an ultra-HTS format allows large-scale monitoring of the interactions of wild-type and mutant variant counterparts with a library of cancer-associated proteins in live cells. The screening of 17,792 interactions with 2,172,864 data points revealed a landscape of gain of interactions encompassing both oncogenic and tumor suppressor mutations. For example, the recurrent BRAF V600E lesion mediates KEAP1 neoPPI, rewiring a BRAFV600E/KEAP1 signaling axis and creating collateral vulnerability to NQO1 substrates, offering a combination therapeutic strategy. Thus, cancer genomic alterations can create neo-interactions, informing variant-directed therapeutic approaches for precision medicine.

Durable CO2 conversion in the proton-exchange membrane system.

Electrolysis that reduces carbon dioxide (CO2) to useful chemicals can, in principle, contribute to a more sustainable and carbon-neutral future1-6. However, it remains challenging to develop this into a robust process because efficient conversion typically requires alkaline conditions in which CO2 precipitates as carbonate, and this limits carbon utilization and the stability of the system7-12. Strategies such as physical washing, pulsed operation and the use of dipolar membranes can partially alleviate these problems but do not fully resolve them11,13-15. CO2 electrolysis in acid electrolyte, where carbonate does not form, has therefore been explored as an ultimately more workable solution16-18. Herein we develop a proton-exchange membrane system that reduces CO2 to formic acid at a catalyst that is derived from waste lead-acid batteries and in which a lattice carbon activation mechanism contributes. When coupling CO2 reduction with hydrogen oxidation, formic acid is produced with over 93% Faradaic efficiency. The system is compatible with start-up/shut-down processes, achieves nearly 91% single-pass conversion efficiency for CO2 at a current density of 600 mA cm-2 and cell voltage of 2.2 V and is shown to operate continuously for more than 5,200 h. We expect that this exceptional performance, enabled by the use of a robust and efficient catalyst, stable three-phase interface and durable membrane, will help advance the development of carbon-neutral technologies.

Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis.

During the repair of DNA double-strand breaks (DSBs), de novo synthesized DNA strands can displace the parental strand to generate single-strand DNAs (ssDNAs). Many programmed DSBs and thus many ssDNAs occur during meiosis. However, it is unclear how these ssDNAs are removed for the complete repair of meiotic DSBs. Here, we show that meiosis-specific depletion of Dna2 (dna2-md) results in an abundant accumulation of RPA and an expansion of RPA from DSBs to broader regions in Saccharomyces cerevisiae. As a result, DSB repair is defective and spores are inviable, although the levels of crossovers/non-crossovers seem to be unaffected. Furthermore, Dna2 induction at pachytene is highly effective in removing accumulated RPA and restoring spore viability. Moreover, the depletion of Pif1, an activator of polymerase δ required for meiotic recombination-associated DNA synthesis, and Pif1 inhibitor Mlh2 decreases and increases RPA accumulation in dna2-md, respectively. In addition, blocking DNA synthesis during meiotic recombination dramatically decreases RPA accumulation in dna2-md. Together, our findings show that meiotic DSB repair requires Dna2 to remove ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis. Additionally, we showed that Dna2 also regulates DSB-independent RPA distribution.

The ubiquitin-proteasome system regulates meiotic chromosome organization.

Meiotic crossover (CO) recombination is tightly regulated by chromosome architecture to ensure faithful chromosome segregation and to reshuffle alleles between parental chromosomes for genetic diversity of progeny. However, regulation of the meiotic chromosome loop/axis organization is poorly understood. Here, we identify a molecular pathway for axis length regulation. We show that the cohesin regulator Pds5 can interact with proteasomes. Meiosis-specific depletion of proteasomes and/or Pds5 results in a similarly shortened chromosome axis, suggesting proteasomes and Pds5 regulate axis length in the same pathway. Protein ubiquitination is accumulated in pds5 and proteasome mutants. Moreover, decreased chromosome axis length in these mutants can be largely rescued by decreasing ubiquitin availability and thus decreasing protein ubiquitination. Further investigation reveals that two ubiquitin E3 ligases, SCF (Skp­Cullin­F-box) and Ufd4, are involved in this Pds5­ubiquitin/proteasome pathway to cooperatively control chromosome axis length. These results support the hypothesis that ubiquitination of chromosome proteins results in a shortened chromosome axis, and cohesin­Pds5 recruits proteasomes onto chromosomes to regulate ubiquitination level and thus axis length. These findings reveal an unexpected role of the ubiquitin­proteasome system in meiosis and contribute to our knowledge of how Pds5 regulates meiotic chromosome organization. A conserved regulatory mechanism probably exists in higher eukaryotes.

A temporal gradient of cytonuclear coordination of chaperonins and chaperones during RuBisCo biogenesis in allopolyploid plants.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) has long been studied from many perspectives. As a multisubunit (large subunits [LSUs] and small subunits[SSUs]) protein encoded by genes residing in the chloroplast (rbcL) and nuclear (rbcS) genomes, RuBisCo also is a model for cytonuclear coevolution following allopolyploid speciation in plants. Here, we studied the genomic and transcriptional cytonuclear coordination of auxiliary chaperonin and chaperones that facilitate RuBisCo biogenesis across multiple natural and artificially synthesized plant allopolyploids. We found similar genomic and transcriptional cytonuclear responses, including respective paternal-to-maternal conversions and maternal homeologous biased expression, in chaperonin/chaperon-assisted folding and assembly of RuBisCo in different allopolyploids. One observation is about the temporally attenuated genomic and transcriptional cytonuclear evolutionary responses during early folding and later assembly process of RuBisCo biogenesis, which were established by long-term evolution and immediate onset of allopolyploidy, respectively. Our study not only points to the potential widespread and hitherto unrecognized features of cytonuclear evolution but also bears implications for the structural interaction interface between LSU and Cpn60 chaperonin and the functioning stage of the Raf2 chaperone.

A Dual-Active Covalent Triazine Framework Film for Efficient Visible-Light-Driven Hydrogen Peroxide Production.

Photocatalytic hydrogen peroxide production from water and oxygen offers a clean and sustainable alternative to the conventional energy-intensive anthraquinone oxidation method. Compared to powdered covalent triazine frameworks (CTFs), the film morphology of CTFs provides better connectivity in 2D, yielding several advantages: more efficient connections between active sites, reduced electron-hole pair recombination, increased resistance to superoxide radical induced corrosion, and decreased light scattering. Leveraging these benefits, it has incorporated dual active sites for both the oxygen reduction reaction (ORR) and the water oxidation reaction (WOR) into a CTF film system. This dual-active CTF film demonstrated an exceptional hydrogen peroxide production rate of 19 460 µmol h⁻¹ m⁻2 after 1 h and 17 830 µmol h⁻¹ m⁻2 after 5 h under visible light irradiation (≥420 nm) without the need for sacrificial agents.

Re-Designing Cellulosic Core-Shell Composite Fibers for Advanced Photothermal and Thermal-Regulating Performance.

Flexible fibers and textiles featuring photothermal conversion and storage capacities are ideal platforms for solar-energy utilization and wearable thermal management. Other than using fossil-fuel-based synthetic fibers, re-designing natural fibers with nanotechnology is a sustainable but challenging option. Herein, advanced core-shell structure fibers based on plant-based nanocelluloses are obtained using a facile co-axial wet-spinning process, which has superior photothermal and thermal-regulating performances. Besides serving as the continuous matrix, nanocelluloses also have two other important roles: dispersing agent when exfoliating molybdenum disulfide (MoS2), and stabilizer for phase change materials (PCM) in the form of Pickering emulsion. Consequently, the shell layer contains well-oriented nanocelluloses and MoS2, and the core layer contains a high content of PCM in a leak-proof encapsulated manner. Such a hierarchical cellulosic supportive structure leads to high mechanical strength (139 MPa), favorable flexibility, and large latent heat (92.0 J g-1), surpassing most previous studies. Furthermore, the corresponding woven cloth demonstrates satisfactory thermal-regulating performance, high solar-thermal conversion and storage efficiency (78.4-84.3%), and excellent long-term performance. In all, this work paves a new way to build advanced structures by assembling nanoparticles and polymers for functional composite fibers in advanced solar-energy-related applications.

Growth inhibition of subcutaneous tumor with glioma cells in nude mice by silencing TLR4.

This study investigated the regulatory impact of Toll-like receptor 4 (TLR4) gene on glioma cell proliferation and apoptosis, elucidating the molecular mechanisms underlying TLR4-induced growth inhibition in vivo. U-87MG-Sh and U-87MG-NC cells, with silenced TLR4 and negative control plasmid respectively, were established. Eighteen nude mice, divided into transfection, negative control, and blank control groups, were inoculated with corresponding cells. Over four weeks, the transfection group exhibited significantly reduced tumor growth rates, smaller mass and volume, and lower growth activity compared to controls. Histological analysis revealed sparse tumor cells, increased fibrous connective tissue, and slower angiogenesis in the transfection group. Flow cytometry demonstrated a lower proliferation index and increased G0/1 cell count in the transfection group. mRNA levels of TLR4, NF-κB, and CyclinD1 were significantly lower in the transfection group. TLR4 silencing correlated with U-87MG cell proliferation regulation, growth inhibition, NF-κB and CyclinD1 modulation, and induction of cell cycle arrest and apoptosis. These findings suggest TLR4 as a potential gene therapy target for glioma.

Audiovisual integration in the human brain: a coordinate-based meta-analysis.

People can seamlessly integrate a vast array of information from what they see and hear in the noisy and uncertain world. However, the neural underpinnings of audiovisual integration continue to be a topic of debate. Using strict inclusion criteria, we performed an activation likelihood estimation meta-analysis on 121 neuroimaging experiments with a total of 2,092 participants. We found that audiovisual integration is linked with the coexistence of multiple integration sites, including early cortical, subcortical, and higher association areas. Although activity was consistently found within the superior temporal cortex, different portions of this cortical region were identified depending on the analytical contrast used, complexity of the stimuli, and modality within which attention was directed. The context-dependent neural activity related to audiovisual integration suggests a flexible rather than fixed neural pathway for audiovisual integration. Together, our findings highlight a flexible multiple pathways model for audiovisual integration, with superior temporal cortex as the central node in these neural assemblies.

Associations between sarcopenia and circulating branched-chain amino acids: a cross-sectional study over 100,000 participants.

BACKGROUND: Emerging evidence suggests that alterations in BCAA metabolism may contribute to the pathogenesis of sarcopenia. However, the relationship between branched-chain amino acids (BCAAs) and sarcopenia is incompletely understood, and existing literature presents conflicting results. In this study, we conducted a community-based study involving > 100,000 United Kingdom adults to comprehensively explore the association between BCAAs and sarcopenia, and assess the potential role of muscle mass in mediating the relationship between BCAAs and muscle strength. METHODS: Multivariable linear regression analysis examined the relationship between circulating BCAAs and muscle mass/strength. Logistic regression analysis assessed the impact of circulating BCAAs and quartiles of BCAAs on sarcopenia risk. Subgroup analyses explored the variations in associations across age, and gender. Mediation analysis investigated the potential mediating effect of muscle mass on the BCAA-muscle strength relationship. RESULTS: Among 108,017 participants (mean age: 56.40 ± 8.09 years; 46.23% men), positive associations were observed between total BCAA, isoleucine, leucine, valine, and muscle mass (beta, 0.56-2.53; p < 0.05) and between total BCAA, leucine, valine, and muscle strength (beta, 0.91-3.44; p < 0.05). Logistic regression analysis revealed that increased circulating valine was associated with a 47% reduced sarcopenia risk (odds ratio = 0.53; 95% confidence interval = 0.3-0.94; p = 0.029). Subgroup analyses demonstrated strong associations between circulating BCAAs and muscle mass/strength in men and individuals aged ≥ 60 years. Mediation analysis suggested that muscle mass completely mediated the relationship between total BCAA, and valine levels and muscle strength, partially mediated the relationship between leucine levels and muscle strength, obscuring the true effect of isoleucine on muscle strength. CONCLUSION: This study suggested the potential benefits of BCAAs in preserving muscle mass/strength and highlighted muscle mass might be mediator of BCAA-muscle strength association. Our findings contribute new evidence for the clinical prevention and treatment of sarcopenia and related conditions involving muscle mass/strength loss.

Negative supercoils regulate meiotic crossover patterns in budding yeast.

Interference exists ubiquitously in many biological processes. Crossover interference patterns meiotic crossovers, which are required for faithful chromosome segregation and evolutionary adaption. However, what the interference signal is and how it is generated and regulated is unknown. We show that yeast top2 alleles which cannot bind or cleave DNA accumulate a higher level of negative supercoils and show weaker interference. However, top2 alleles which cannot religate the cleaved DNA or release the religated DNA accumulate less negative supercoils and show stronger interference. Moreover, the level of negative supercoils is negatively correlated with crossover interference strength. Furthermore, negative supercoils preferentially enrich at crossover-associated Zip3 regions before the formation of meiotic DNA double-strand breaks, and regions with more negative supercoils tend to have more Zip3. Additionally, the strength of crossover interference and homeostasis change coordinately in mutants. These findings suggest that the accumulation and relief of negative supercoils pattern meiotic crossovers.

Risk stratification and predictive modeling of postoperative delirium in chronic subdural hematoma.

Background- Postoperative delirium is a common complication associated with the elderly, causing increased morbidity and prolonged hospital stay. However, its risk factors in chronic subdural hematoma patients have not been well studied. Methods- A total of 202 consecutive patients with chronic subdural hematoma at Peking University Third Hospital between January 2018 and January 2023 were enrolled. Various clinical indicators were analyzed to identify independent risk factors for postoperative delirium using univariate and multivariate regression analyses. Delirium risk prediction models were developed as a nomogram and a Markov chain. Results- Out of the 202 patients (age, 71 (IQR, 18); female-to-male ratio, 1:2.7) studied, 63 (31.2%) experienced postoperative delirium. Univariate analysis identified age (p < 0.001), gender (p = 0.014), restraint belt use (p < 0.001), electrolyte imbalance (p < 0.001), visual analog scale score (p < 0.001), hematoma thickness (p < 0.001), midline shift (p < 0.001), hematoma side (p = 0.013), hematoma location (p = 0.018), and urinal catheterization (p = 0.028) as significant factors. Multivariate regression analysis confirmed the significance of restraint belt use (B = 7.657, p < 0.001), electrolyte imbalance (B = -3.993, p = 0.001), visual analog scale score (B = 2.331, p = 0.016), and midline shift (B = 0.335, p = 0.007). Hematoma thickness and age had no significant impact. Conclusion- Increased midline shift and visual analog scale scores, alongside restraint belt use and electrolyte imbalance elevate delirium risk in chronic subdural hematoma surgery. Our prediction models may offer reference value in this context.

Potency boost of a Mycobacterium tuberculosis dihydrofolate reductase inhibitor by multienzyme F420H2-dependent reduction.

Triaza-coumarin (TA-C) is a Mycobacterium tuberculosis (Mtb) dihydrofolate reductase (DHFR) inhibitor with an IC50 (half maximal inhibitory concentration) of ∼1 µM against the enzyme. Despite this moderate target inhibition, TA-C shows exquisite antimycobacterial activity (MIC50, concentration inhibiting growth by 50% = 10 to 20 nM). Here, we investigated the mechanism underlying this potency disconnect. To confirm that TA-C targets DHFR and investigate its unusual potency pattern, we focused on resistance mechanisms. In Mtb, resistance to DHFR inhibitors is frequently associated with mutations in thymidylate synthase thyA, which sensitizes Mtb to DHFR inhibition, rather than in DHFR itself. We observed thyA mutations, consistent with TA-C interfering with the folate pathway. A second resistance mechanism involved biosynthesis of the redox coenzyme F420 Thus, we hypothesized that TA-C may be metabolized by Mtb F420-dependent oxidoreductases (FDORs). By chemically blocking the putative site of FDOR-mediated reduction in TA-C, we reproduced the F420-dependent resistance phenotype, suggesting that F420H2-dependent reduction is required for TA-C to exert its potent antibacterial activity. Indeed, chemically synthesized TA-C-Acid, the putative product of TA-C reduction, displayed a 100-fold lower IC50 against DHFR. Screening seven recombinant Mtb FDORs revealed that at least two of these enzymes reduce TA-C. This redundancy in activation explains why no mutations in the activating enzymes were identified in the resistance screen. Analysis of the reaction products confirmed that FDORs reduce TA-C at the predicted site, yielding TA-C-Acid. This work demonstrates that intrabacterial metabolism converts TA-C, a moderately active "prodrug," into a 100-fold-more-potent DHFR inhibitor, thus explaining the disconnect between enzymatic and whole-cell activity.

Phase Engineering of Intermetallic PtBi2 Nanoplates for Formic Acid Electrochemical Oxidation.

Phase engineering of Pt-based intermetallic catalysts has been demonstrated as a promising strategy to optimize catalytic properties for a direct formic acid fuel cell. Pt-Bi intermetallic catalysts are attracting increasing interest due to their high catalytic activity, especially for inhibiting CO poisoning. However, the phase transformation and synthesis of intermetallic compounds usually occurring at high temperatures leads to a lack of control of the size and composition. Here, we report the synthesis of intermetallic ß-PtBi2 and γ-PtBi2 two-dimensional nanoplates with controlled sizes and compositions under mild conditions. The different phases of intermetallic PtBi2 can significantly affect the catalytic performance of the formic acid oxidation reaction (FAOR). The obtained ß-PtBi2 nanoplates exhibit an excellent mass activity of 1.1 ± 0.01 A mgPt-1 for the FAOR, which is 30-fold higher than that of commercial Pt/C catalysts. Moreover, intermetallic PtBi2 demonstrates high tolerance to CO poisoning, as confirmed by in situ infrared absorption spectroscopy.

Mechanism-Driven Technology Development for Solving the Intracellular Delivery Problem of Hard-To-Transfect Cells.

The so-called "hard-to-transfect cells" are well-known to present great challenges to intracellular delivery, but detailed understandings of the delivery behaviors are lacking. Recently, we discovered that vesicle trapping is a likely bottleneck of delivery into a type of hard-to-transfect cells, namely, bone-marrow-derived mesenchymal stem cells (BMSCs). Driven by this insight, herein, we screened various vesicle trapping-reducing methods on BMSCs. Most of these methods failed in BMSCs, although they worked well in HeLa cells. In stark contrast, coating nanoparticles with a specific form of poly(disulfide) (called PDS1) nearly completely circumvented vesicle trapping in BMSCs, by direct cell membrane penetration mediated by thiol-disulfide exchange. Further, in BMSCs, PDS1-coated nanoparticles dramatically enhanced the transfection efficiency of plasmids of fluorescent proteins and substantially improved osteoblastic differentiation. In addition, mechanistic studies suggested that higher cholesterol content in plasma membranes of BMSCs might be a molecular-level reason for the greater difficulty of vesicle escape in BMSCs.

The risk of Alzheimer's disease and cognitive impairment characteristics in eight mental disorders: A UK Biobank observational study and Mendelian randomization analysis.

INTRODUCTION: The cognitive impairment patterns and the association with Alzheimer's disease (AD) in mental disorders remain poorly understood. METHODS: We analyzed data from 486,297 UK Biobank participants, categorizing them by mental disorder history to identify the risk of AD and the cognitive impairment characteristics. Causation was further assessed using Mendelian randomization (MR). RESULTS: AD risk was higher in individuals with bipolar disorder (BD; hazard ratio [HR] = 2.37, P < 0.01) and major depressive disorder (MDD; HR = 1.63, P < 0.001). MR confirmed a causal link between BD and AD (ORIVW = 1.098), as well as obsessive-compulsive disorder (OCD) and AD (ORIVW = 1.050). Cognitive impairments varied, with BD and schizophrenia showing widespread deficits, and OCD affecting complex task performance. DISCUSSION: Observational study and MR provide consistent evidence that mental disorders are independent risk factors for AD. Mental disorders exhibit distinct cognitive impairment prior to dementia, indicating the potential different mechanisms in AD pathogenesis. Early detection of these impairments in mental disorders is crucial for AD prevention. HIGHLIGHTS: This is the most comprehensive study that investigates the risk and causal relationships between a history of mental disorders and the development of Alzheimer's disease (AD), alongside exploring the cognitive impairment characteristics associated with different mental disorders. Individuals with bipolar disorder (BD) exhibited the highest risk of developing AD (hazard ratio [HR] = 2.37, P < 0.01), followed by those with major depressive disorder (MDD; HR = 1.63, P < 0.001). Individuals with schizophrenia (SCZ) showed a borderline higher risk of AD (HR = 2.36, P = 0.056). Two-sample Mendelian randomization (MR) confirmed a causal association between BD and AD (ORIVW = 1.098, P < 0.05), as well as AD family history (proxy-AD, ORIVW = 1.098, P < 0.001), and kept significant after false discovery rate correction. MR also identified a nominal significant causal relationship between the obsessive-compulsive disorder (OCD) spectrum and AD (ORIVW = 1.050, P < 0.05). Individuals with SCZ, BD, and MDD exhibited impairments in multiple cognitive domains with distinct patterns, whereas those with OCD showed only slight declines in complex tasks.

A detection model of cognitive impairment via the integrated gait and eye movement analysis from a large Chinese community cohort.

INTRODUCTION: Whether the integration of eye-tracking, gait, and corresponding dual-task analysis can distinguish cognitive impairment (CI) patients from controls remains unclear. METHODS: One thousand four hundred eighty-one participants, including 724 CI and 757 controls, were enrolled in this study. Eye movement and gait, combined with dual-task patterns, were measured. The LightGBM machine learning models were constructed. RESULTS: A total of 105 gait and eye-tracking features were extracted. Forty-six parameters, including 32 gait and 14 eye-tracking features, showed significant differences between two groups (P < 0.05). Of these, the Gait_3Back-TurnTime and Dual-task cost-TurnTime patterns were significantly correlated with plasma phosphorylated tau 181 (p-tau181) level. A model based on dual-task gait, dual-task smooth pursuit, prosaccade, and anti-saccade achieved the best area under the receiver operating characteristics curve (AUC) of 0.987 for CI detection, while combined with p-tau181, the model discriminated mild cognitive impairment from controls with an AUC of 0.824. DISCUSSION: Combining dual-task gait and dual-task eye-tracking analysis is feasible for the detection of CI. HIGHLIGHTS: This is the first study to report the efficiency of integrated parameters of dual-task gait and eye-tracking for cognitive impairment (CI) detection in a large cohort. We identified 46 gait and eye-tracking features associated with CI, and two were correlated to plasma phosphorylated tau 181. We constructed the model based on dual-task gait, smooth pursuit, prosaccade, and anti-saccade, achieving the best area under the curve of 0.987 for CI detection.

Abscisic acid reduced methoxypyrazines concentration and its derived unpleasant odors in Cabernet Sauvignon grapes and wines.

BACKGROUND: The influences of abscisic acid (ABA) applications on precursors and gene expression in 3-alkyl-2-methoxypyrazines (MPs) biosynthetic pathway, MPs concentration and sensory evaluation of its derived peculiar odors in Cabernet Sauvignon grapes and wines were investigated. At the vineyard, ABA solution with 25, 100 and 400 mg L-1 (AT1, AT2 and AT3, respectively) and an aqueous solution (control) were sprayed three times from veraison to pre-harvest. RESULTS: Higher concentration ABA applications (AT2 and AT3) in grapes could significantly reduce MPs concentration and its derived peculiar odors in grapes and wines compared to a lower concentration ABA application (AT1) and control, with AT2 application having the strongest effect. The changes in MPs were mainly a result of the downregulated expression of VvOMTs genes at higher concentration ABA applications, independent of the levels of their potential precursors. CONCLUSION: The present study reveals that ABA application had the potential to decrease production of MPs in Cabernet Sauvignon grapes and wines, and this result provides reference values for the removal of unpleasant vegetable odors from Cabernet Sauvignon wines in production. © 2024 Society of Chemical Industry.

Tandem Electro-Thermo-Catalysis for the Oxidative Aminocarbonylation of Arylboronic Acids to Amides from CO2 and Water.

Direct CO2 electroreduction to valuable chemicals is critical for carbon neutrality, while its main products are limited to simple C1 /C2 compounds, and traditionally, the anodic O2 byproduct is not utilized. We herein report a tandem electrothermo-catalytic system that fully utilizes both cathodic (i.e., CO) and anodic (i.e., O2 ) products during overall CO2 electrolysis to produce valuable organic amides from arylboronic acids and amines in a separate chemical reactor, following the Pd(II)-catalyzed oxidative aminocarbonylation mechanism. Hexamethylenetetramine (HMT)-incorporated silver and nickel hydroxide carbonate electrocatalysts were prepared for efficient coproduction of CO and O2 with Faradaic efficiencies of 99.3 % and 100 %, respectively. Systematic experiments, operando attenuated total reflection surface-enhanced Fourier transform infrared spectroscopy characterizations and theoretical studies reveal that HMT promotes *CO2 hydrogenation/*CO desorption for accelerated CO2 -to-CO conversion, and O2 inhibits reductive deactivation of the Pd(II) catalyst for enhanced oxidative aminocarbonylation, collectively leading to efficient synthesis of 10 organic amides with high yields of above 81 %. This work demonstrates the effectiveness of a tandem electrothermo-catalytic strategy for economically attractive CO2 conversion and amide synthesis, representing a new avenue to explore the full potential of CO2 utilization.