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.

Structure evolution at the gate-tunable suspended graphene-water interface.

Graphitic electrode is commonly used in electrochemical reactions owing to its excellent in-plane conductivity, structural robustness and cost efficiency1,2. It serves as prime electrocatalyst support as well as a layered intercalation matrix2,3, with wide applications in energy conversion and storage1,4. Being the two-dimensional building block of graphite, graphene shares similar chemical properties with graphite1,2, and its unique physical and chemical properties offer more varieties and tunability for developing state-of-the-art graphitic devices5-7. Hence it serves as an ideal platform to investigate the microscopic structure and reaction kinetics at the graphitic-electrode interfaces. Unfortunately, graphene is susceptible to various extrinsic factors, such as substrate effect8-10, causing much confusion and controversy7,8,10,11. Hereby we have obtained centimetre-sized substrate-free monolayer graphene suspended on aqueous electrolyte surface with gate tunability. Using sum-frequency spectroscopy, here we show the structural evolution versus the gate voltage at the graphene-water interface. The hydrogen-bond network of water in the Stern layer is barely changed within the water-electrolysis window but undergoes notable change when switching on the electrochemical reactions. The dangling O-H bond protruding at the graphene-water interface disappears at the onset of the hydrogen evolution reaction, signifying a marked structural change on the topmost layer owing to excess intermediate species next to the electrode. The large-size suspended pristine graphene offers a new platform to unravel the microscopic processes at the graphitic-electrode interfaces.

Bifunctional Electrocatalysts for Overall and Hybrid Water Splitting.

Electrocatalytic water splitting driven by renewable electricity has been recognized as a promising approach for green hydrogen production. Different from conventional strategies in developing electrocatalysts for the two half-reactions of water splitting (e.g., the hydrogen and oxygen evolution reactions, HER and OER) separately, there has been a growing interest in designing and developing bifunctional electrocatalysts, which are able to catalyze both the HER and OER. In addition, considering the high overpotentials required for OER while limited value of the produced oxygen, there is another rapidly growing interest in exploring alternative oxidation reactions to replace OER for hybrid water splitting toward energy-efficient hydrogen generation. This Review begins with an introduction on the fundamental aspects of water splitting, followed by a thorough discussion on various physicochemical characterization techniques that are frequently employed in probing the active sites, with an emphasis on the reconstruction of bifunctional electrocatalysts during redox electrolysis. The design, synthesis, and performance of diverse bifunctional electrocatalysts based on noble metals, nonprecious metals, and metal-free nanocarbons, for overall water splitting in acidic and alkaline electrolytes, are thoroughly summarized and compared. Next, their application toward hybrid water splitting is also presented, wherein the alternative anodic reactions include sacrificing agents oxidation, pollutants oxidative degradation, and organics oxidative upgrading. Finally, a concise statement on the current challenges and future opportunities of bifunctional electrocatalysts for both overall and hybrid water splitting is presented in the hope of guiding future endeavors in the quest for energy-efficient and sustainable green hydrogen production.

Constructing nickel-iron oxyhydroxides integrated with iron oxides by microorganism corrosion for oxygen evolution.

Developing facile approaches for preparing efficient electrocatalysts is of significance to promote sustainable energy technologies. Here, we report a facile iron-oxidizing bacteria corrosion approach to construct a composite electrocatalyst of nickel­iron oxyhydroxides combined with iron oxides. The obtained electrocatalyst shows improved electrocatalytic activity and stability for oxygen evolution, with an overpotential of ∼230 mV to afford the current density of 10 mA cm−2. The incorporation of iron oxides produced by iron-oxidizing bacteria corrosion optimizes the electronic structure of nickel­iron oxyhydroxide electrodes, which accounts for the decreased free energy of oxygenate generation and the improvement of OER activity. This work demonstrates a natural bacterial corrosion approach for the facile preparation of efficient electrodes for water oxidation, which may provide interesting insights in the multidisciplinary integration of innovative nanomaterials and emerging energy technologies.

Stiffness promotes cell migration, invasion, and invadopodia in nasopharyngeal carcinoma by regulating the WT-CTTN level.

Matrix stiffness potently promotes the malignant phenotype in various biological contexts. Therefore, identification of gene expression to participate in mechanical force signals transduced into downstream biochemical signaling will contribute substantially to the advances in nasopharyngeal carcinoma (NPC) treatment. In the present study, we detected that cortactin (CTTN) played an indispensable role in matrix stiffness-induced cell migration, invasion, and invadopodia formation. Advances in cancer research have highlighted that dysregulated alternative splicing contributes to cancer progression as an oncogenic driver. However, whether WT-CTTN or splice variants (SV1-CTTN or SV2-CTTN) regulate matrix stiffness-induced malignant phenotype is largely unknown. We proved that alteration of WT-CTTN expression modulated matrix stiffness-induced cell migration, invasion, and invadopodia formation. Considering that splicing factors might drive cancer progression through positive feedback loops, we analyzed and showed how the splicing factor PTBP2 and TIA1 modulated the production of WT-CTTN. Moreover, we determined that high stiffness activated PTBP2 expression. Taken together, our findings showed that the PTBP2-WT-CTTN level increases upon stiffening and then promotes cell migration, invasion, and invadopodia formation in NPC.

Dynamic Electrodeposition on Bubbles: An Effective Strategy toward Porous Electrocatalysts for Green Hydrogen Cycling.

ConspectusClosed-loop cycling of green hydrogen is a promising alternative to the current hydrocarbon economy for mitigating the energy crisis and environmental pollution. It stores energy from renewable energy sources like solar, wind, and hydropower into the chemical bond of dihydrogen (H2) via (photo)electrochemical water splitting, and then the stored energy can be released on demand through the reverse reactions in H2-O2 fuel cells. The sluggish kinetics of the involved half-reactions like hydrogen evolution reaction (HER), oxygen evolution reaction (OER), hydrogen oxidation reaction (HOR), and oxygen reduction reaction (ORR) limit its realization. Moreover, considering the local gas-liquid-solid triphase microenvironments during H2 generation and utilization, rapid mass transport and gas diffusion are critical as well. Accordingly, developing cost-effective and active electrocatalysts featuring three-dimensional hierarchically porous structures are highly desirable to promote the energy conversion efficiency. Traditionally, the synthetic approaches of porous materials include soft/hard templating, sol-gel, 3D printing, dealloying, and freeze-drying, which often need tedious procedures, high temperature, expensive equipment, and/or harsh physiochemical conditions. In contrast, dynamic electrodeposition on bubbles using the in situ formed bubbles as templates can be conducted at ambient conditions with an electrochemical workstation. Moreover, the whole preparation process can be finished within minutes/hours, and the resulting porous materials can be employed as catalytic electrodes directly, avoiding the use of polymeric binders like Nafion and the consequent issues like limited catalyst loading, reduced conductivity, and inhibited mass transport.In this Account, we summarize our contributions to the dynamic electrodeposition on bubbles toward advanced porous electrocatalysts for green hydrogen cycling. These dynamic electrosynthesis strategies include potentiodynamic electrodeposition that linearly scans the applied potentials, galvanostatic electrodeposition that fixes the applied currents, and electroshock which quickly switches the applied potentials. The resulting porous electrocatalysts range from transition metals to alloys, nitrides, sulfides, phosphides, and their hybrids. We mainly focus on the 3D porosity design of the electrocatalysts by tuning the electrosynthesis parameters to tailor the behaviors of bubble co-generation and thus the reaction interface. Then, their electrocatalytic applications for HER, OER, overall water splitting (OWS), biomass oxidation (to replace OER), and HOR are introduced, with a special emphasis on the porosity-promoted activity. Finally, the remaining challenges and future perspective are also discussed. We hope this Account will encourage more efforts into this attractive research field of dynamic electrodeposition on bubbles for various energy catalytic reactions like carbon dioxide/monoxide reduction, nitrate reduction, methane oxidation, chlorine evolution, and others.

CHOP regulated by METTL14-m6A affects cell cycle arrest and regorafenib sensitivity in HCC cells.

BACKGROUND: Regorafenib, a multi-targeted kinase inhibitor, has been used in the treatment of Hepatocellular carcinoma (HCC). The purpose of this study is to investigate the mechanism of Regorafenib in HCC. METHODS: Regorafenib's impact on the sensitivity of HCC cells was assessed using CCK8. Differential gene expression analysis was performed by conducting mRNA sequencing after treatment with Regorafenib. The m6A methylation status of CHOP and differential expression of m6A methylation-related proteins were assessed by RIP and Western Blot. To explore the molecular mechanisms involved in the therapeutic effects of Regorafenib in HCC and the impact of METTL14 and CHOP on Regorafenib treatment, we employed shRNA/overexpression approaches to transfect METTL14 and CHOP genes, as well as conducted in vivo experiments. RESULTS: Treatment with Regorafenib led to a notable decrease in viability and proliferation of SK-Hep-1 and HCC-LM3 cells. The expression level of CHOP was upregulated after Regorafenib intervention, and CHOP underwent m6A methylation. Among the m6A methylation-related proteins, METTL14 exhibited the most significant downregulation. Mechanistic studies revealed that Regorafenib regulated the cell cycle arrest in HCC through METTL14-mediated modulation of CHOP, and the METTL14/CHOP axis affected the sensitivity of HCC to Regorafenib. In vivo, CHOP enhanced the anticancer effect of Regorafenib. CONCLUSION: The inhibition of HCC development by Regorafenib is attributed to its modulation of m6A expression of CHOP, mediated by METTL14, and the METTL14/CHOP axis enhances the sensitivity of HCC to Regorafenib. These findings provide insights into the treatment of HCC and the issue of drug resistance to Regorafenib.

A Cas6-based RNA tracking platform functioning in a fluorescence-activation mode.

Given the fact that the localization of RNAs is closely associated with their functions, techniques developed for tracking the distribution of RNAs in live cells have greatly advanced the study of RNA biology. Recently, innovative application of fluorescent protein-labelled Cas9 and Cas13 into live-cell RNA tracking further enriches the toolbox. However, the Cas9/Cas13 platform, as well as the widely-used MS2-MCP technique, failed to solve the problem of high background noise. It was recently reported that CRISPR/Cas6 would exhibit allosteric alteration after interacting with the Cas6 binding site (CBS) on RNAs. Here, we exploited this feature and designed a Cas6-based switch platform for detecting target RNAs in vivo. Conjugating split-Venus fragments to both ends of the endoribonuclease-mutated Escherichia coli Cas6(dEcCas6) allowed ligand (CBS)-activated split-Venus complementation. We name this platform as Cas6 based Fluorescence Complementation (Cas6FC). In living cells, Cas6FC could detect target RNAs with nearly free background noise. Moreover, as minimal as one copy of CBS (29nt) tagged in an RNA of interest was able to turn on Cas6FC fluorescence, which greatly reduced the odds of potential alteration of conformation and localization of target RNAs. Thus, we developed a new RNA tracking platform inherently with high sensitivity and specificity.

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.

Low-coordination Nanocrystalline Copper-based Catalysts through Theory-guided Electrochemical Restructuring for Selective CO2 Reduction to Ethylene.

Revealing the dynamic reconstruction process and tailoring advanced copper (Cu) catalysts is of paramount significance for promoting the conversion of CO2 into ethylene (C2H4), paving the way for carbon neutralization and facilitating renewable energy storage. In this study, we initially employed density functional theory (DFT) and molecular dynamics (MD) simulations to elucidate the restructuring behavior of a catalyst under electrochemical conditions and delineated its restructuring patterns. Leveraging insights into this restructuring behavior, we devised an efficient, low-coordination copper-based catalyst. The resulting synthesized catalyst demonstrated an impressive Faradaic efficiency (FE) exceeding 70 % for ethylene generation at a current density of 800 mA cm-2. Furthermore, it showed robust stability, maintaining consistent performance for 230 hours at a cell voltage of 3.5 V in a full-cell system. Our research not only deepens the understanding of the active sites involved in designing efficient carbon dioxide reduction reaction (CO2RR) catalysts but also advances CO2 electrolysis technologies for industrial application.

Atomically Dispersed Co-N/C Catalyst for Divergent Synthesis of Nitrogen-Containing Compounds from Alkenes.

Alkene functionalization with a single-atom catalyst (SAC) which merges homogeneous and heterogeneous catalysis is a fascinating route to obtain high-value-added molecules. However, C-N bond formation of alkene with SAC is still unexplored. Herein, a bimetal-organic framework-derived Co-N/C catalyst with an atomically dispersed cobalt center is reported to show good activity of chemoselective aziridination/oxyamination reactions from alkene and hydroxylamine, and late-stage functionalization of complex alkenes and diversified synthetic transformations of the aziridine product further expand the utility of this method. Moreover, this system proceeds without external oxidants and exhibits mild, atom-economic, and recyclable characters. Detailed spectroscopic characterizations and mechanistic studies revealed the structure of the catalytic center and possible intermediates involved in the mechanism cycle.

Hypoxic nasopharyngeal carcinoma-derived exosomal miR-455 increases vascular permeability by targeting ZO-1 to promote metastasis.

Nasopharyngeal carcinoma (NPC), the most frequent reason for treatment failure in head and neck tumors, has the greatest incidence of distant metastases. Increased vascular permeability facilitates metastasis. Exosomal microRNAs (miRNAs) have been implicated in the development of the premetastatic niche and are emerging as prospective biomarkers in cancer patients. We discovered that a higher level of miR-455 was connected to a larger propensity for NPC metastasis based on deep sequencing and RT-qPCR. We found that hypoxia promoted NPC exosomes release and increased miR-455 expression in a way that was hypoxia-inducible factor 1-alpha (HIF-1α) dependent. Exosomes from NPC cells with high levels of miR-455 were found to specifically target zonula occludens 1 (ZO-1), increasing the permeability of endothelial monolayers in vitro vascular permeability and transendothelial invasion experiments. Additional in vivo studies showed that zebrafish with sustained miR-455-overexpressing NPC cell xenografts displayed increased tumor cell mass throughout the body. In vivo, zebrafish vascular tight junction integrity was disrupted by exosomes produced by NPC cells with elevated miR-455 expression. Mice-bearing xenografts further supported the finding that exosomes containing miR-455 might reduce ZO-1 expression in addition to promote NPC cell growth. These findings suggest that in a hypoxic microenvironment, exosomal miR-455 released by NPC cells enhances vascular permeability and promotes metastasis by targeting ZO-1. The HIF-1α-miR-455-ZO-1 signaling pathway may be a promising predictor and potential therapeutic target for NPC with metastasis.

EBV promotes vascular mimicry of dormant cancer cells by potentiating stemness and EMT.

Vascular mimicry (VM) is defined as a vascular channel-like structure composed of tumor cells that correlates with the growth of cancer cells by providing blood circulation. However, whether VM can be formed in dormant cancer cells remains unclear. Our previous research revealed that polyploid giant cancer cells (PGCCs) are specific dormant cells related to the poor prognosis of head and neck cancer. Here, we demonstrated that EBV could promote VM formation by PGCCs in vivo and in vitro. Furthermore, we revealed that the activation of the ERK pathway partly mediated by LMP2A is responsible for stemness, and the acquisition of the stemness phenotype is crucial to the malignant biological behavior of PGCCs. The epithelial-to-mesenchymal transition (EMT) process plays a considerable role in PGCCs, and EMT progression is vital for EBV-positive PGCCs to form VM. This is the first study to reveal that EBV creates plasticity in PGCC-VM and provide a new strategy for targeted anti-tumor therapy.

A Simultaneous Localization and Mapping System Using the Iterative Error State Kalman Filter Judgment Algorithm for Global Navigation Satellite System.

Outdoor autonomous mobile robots heavily rely on GPS data for localization. However, GPS data can be erroneous and signals can be interrupted in highly urbanized areas or areas with incomplete satellite coverage, leading to localization deviations. In this paper, we propose a SLAM (Simultaneous Localization and Mapping) system that combines the IESKF (Iterated Extended Kalman Filter) and a factor graph to address these issues. We perform IESKF filtering on LiDAR and inertial measurement unit (IMU) data at the front-end to achieve a more accurate estimation of local pose and incorporate the resulting laser inertial odometry into the back-end factor graph. Furthermore, we introduce a GPS signal filtering method based on GPS state and confidence to ensure that abnormal GPS data is not used in the back-end processing. In the back-end factor graph, we incorporate loop closure factors, IMU preintegration factors, and processed GPS factors. We conducted comparative experiments using the publicly available KITTI dataset and our own experimental platform to compare the proposed SLAM system with two commonly used SLAM systems: the filter-based SLAM system (FAST-LIO) and the graph optimization-based SLAM system (LIO-SAM). The experimental results demonstrate that the proposed SLAM system outperforms the other systems in terms of localization accuracy, especially in cases of GPS signal interruption.

Simultaneous Generation of H2 O2 and Formate by Co-Electrolysis of Water and CO2 over Bifunctional Zn/SnO2 Nanodots.

Hydrogen peroxide (H2 O2 ) and formate are important chemicals used in various chemical manufacturing industries. One promising approach for the simultaneous production of these chemicals is coupling anodic two-electron water oxidation with cathodic CO2 reduction in an electrolyzer using nonprecious bifunctional electrocatalysts. Herein, we report an innovative hybrid electrosynthesis strategy using Zn-doped SnO2 (Zn/SnO2 ) nanodots as bifunctional redox electrocatalysts to achieve Faradaic efficiencies of 80.6 % and 92.2 % for H2 O2 and formate coproduction, respectively, along with excellent stability for at least 60 h at a current density of ≈150 mA cm-2 . Through a combination of physicochemical characterizations, including operando attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), isotope labeling mass spectrometry (MS)/1 H NMR and quasi-in situ electron paramagnetic resonance (EPR), with density functional theory (DFT) calculations, we discovered that the Zn dopant facilitates the coupling of *OH intermediates to promote H2 O2 production and optimizes the adsorption of *OCHO intermediates to accelerate formate formation. Our findings offer new insights into designing more efficient bifunctional electrocatalyst-based pair-electrosynthesis system for the coproduction of H2 O2 and formate feedstocks.

Direct C-C Double Bond Cleavage of Alkenes Enabled by Highly Dispersed Cobalt Catalyst and Hydroxylamine.

The utilization of a single-atom catalyst to break C-C bonds merges the merits of homogeneous and heterogeneous catalysis and presents an intriguing pathway for obtaining high-value-added products. Herein, a mild, selective, and sustainable oxidative cleavage of alkene to form oxime ether or nitrile was achieved by using atomically dispersed cobalt catalyst and hydroxylamine. Diversified substrate patterns, including symmetrical and unsymmetrical alkenes, di- and tri-substituted alkenes, and late-stage functionalization of complex alkenes were demonstrated. The reaction was successfully scaled up and demonstrated good performance in recycling experiments. The hot filtration test, catalyst poisoning and radical scavenger experiment, time kinetics, and studies on the reaction intermediate collectively pointed to a radical mechanism with cobalt/acid/O2 promoted C-C bond cleavage as the key step.

Bromine-Enhanced Generation and Epoxidation of Ethylene in Tandem CO2 Electrolysis Towards Ethylene Oxide.

The indirect electro-epoxidation of ethylene (C2 H4 ), produced from CO2 electroreduction (CO2 R), holds immense promise for CO2 upcycling to valuable ethylene oxide (EO). However, this process currently has a mediocre Faradaic efficiency (FE) due to sluggish formation and rapid dissociation of active species, as well as reductive deactivation of Cu-based electrocatalysts during the conversion of C2 H4 to EO and CO2 to C2 H4 , respectively. Herein, we report a bromine-induced dual-enhancement strategy designed to concurrently promote both C2 H4 -to-EO and CO2 -to-C2 H4 conversions, thereby improving EO generation, using single-atom Pt on N-doped CNTs (Pt1 /NCNT) and Br- -bearing porous Cu2 O as anode and cathode electrocatalysts, respectively. Physicochemical characterizations including synchrotron X-ray absorption, operando infrared spectroscopy, and quasi in situ Raman spectroscopy/electron paramagnetic resonance with theoretical calculations reveal that the favorable Br2 /HBrO generation over Pt1 /NCNT with optimal intermediate binding facilitates C2 H4 -to-EO conversion with a high FE of 92.2 %, and concomitantly, the Br- with strong nucleophilicity protects active Cu+ species in Cu2 O effectively for improved CO2 -to-C2 H4 conversion with a FE of 66.9 % at 800 mA cm-2 , superior to those in the traditional chloride-mediated case. Consequently, a single-pass FE as high as 41.1 % for CO2 -to-EO conversion can be achieved in a tandem system.

The human mediodorsal thalamus: Organization, connectivity, and function.

The human mediodorsal thalamic nucleus (MD) is crucial for higher cognitive functions, while the fine anatomical organization of the MD and the function of each subregion remain elusive. In this study, using high-resolution data provided by the Human Connectome Project, an anatomical connectivity-based method was adopted to unveil the topographic organization of the MD. Four fine-grained subregions were identified in each hemisphere, including the medial (MDm), central (MDc), dorsal (MDd), and lateral (MDl), which recapitulated previous cytoarchitectonic boundaries from histological studies. The subsequent connectivity analysis of the subregions also demonstrated distinct anatomical and functional connectivity patterns, especially with the prefrontal cortex. To further evaluate the function of MD subregions, partial least squares analysis was performed to examine the relationship between different prefrontal-subregion connectivity and behavioral measures in 1012 subjects. The results showed subregion-specific involvement in a range of cognitive functions. Specifically, the MDm predominantly subserved emotional-cognition domains, while the MDl was involved in multiple cognitive functions especially cognitive flexibility and inhibition. The MDc and MDd were correlated with fluid intelligence, processing speed, and emotional cognition. In conclusion, our work provides new insights into the anatomical and functional organization of the MD and highlights the various roles of the prefrontal-thalamic circuitry in human cognition.

Theoretical Study on the Electro-Reduction of Carbon Dioxide to Methanol Catalyzed by Cobalt Phthalocyanine.

Density functional theory (DFT) calculations have been conducted to investigate the mechanism of cobalt(II) tetraamino phthalocyanine (CoPc-NH2) catalyzed electro-reduction of CO2. Computational results show that the catalytically active species 1 (4[CoII(H4L)]0) is formed by a four-electron-four-proton reduction of the initial catalyst CoPc-NH2. Complex 1 can attack CO2 after a one-electron reduction to give a [CoIII-CO22-]- intermediate, followed by a protonation and a one-electron reduction to give intermediate [CoII-COOH]- (4). Complex 4 is then protonated on its hydroxyl group by a carbonic acid to generate the critical species 6 (CoIII-L•--CO), which can release the carbon monoxide as an intermediate (and also as a product). In parallel, complex 6 can go through a successive four-electron-four-proton reduction to produce the targeted product methanol without forming formaldehyde as an intermediate product. The high-lying π orbital and the low-lying π* orbital of the phthalocyanine endow the redox noninnocent nature of the ligand, which could be a dianion, a radical monoanion, or a radical trianion during the catalysis. The calculated results for the hydrogen evolution reaction indicate a higher energy barrier than the carbon dioxide reduction. This is consistent with the product distribution in the experiments. Additionally, the amino group on the phthalocyanine ligand was found to have a minor effect on the barriers of critical steps, and this accounts for the experimentally observed similar activity for these two catalysts, namely, CoPc-NH2 and CoPc.