Efficient Capture and Electroreduction of Dilute CO2 into Highly Pure and Concentrated Formic Acid Aqueous Solution.

High-purity CO2 rather than dilute CO2 (15 vol %, CO2/N2/O2 = 15:80:5, v/v/v) similar to the flue gas is currently used as the feedstock for the electroreduction of CO2, and the liquid products are usually mixed up with the cathode electrolyte, resulting in high product separation costs. In this work, we showed that a microporous conductive Bi-based metal-organic framework (Bi-HHTP, HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) can not only efficiently capture CO2 from the dilute CO2 under high humidity but also catalyze the electroreduction of the adsorbed CO2 into formic acid with a high current density of 80 mA cm-2 and a Faradaic efficiency of 90% at a very low cell voltage of 2.6 V. Importantly, the performance in a dilute CO2 atmosphere was close to that under a high-purity CO2 atmosphere. This is the first catalyst that can maintain exceptional eCO2RR performance in the presence of both O2 and N2. Moreover, by using dilute CO2 as the feedstock, a 1 cm-2 working electrode coating with Bi-HHTP can continuously produce a 200 mM formic acid aqueous solution with a relative purity of 100% for at least 30 h in a membrane electrode assembly (MEA) electrolyzer. The product does not contain electrolytes, and such a highly concentrated and pure formic acid aqueous solution can be directly used as an electrolyte for formic acid fuel cells. Comprehensive studies revealed that such a high performance might be ascribed to the CO2 capture ability of the micropores on Bi-HHTP and the lower Gibbs free energy of formation of the key intermediate *OCHO on the open Bi sites.

Differential cytokine expression in gastric tissues highlights helicobacter pylori's role in gastritis.

Helicobacter pylori (H. pylori), known for causing gastric inflammation, gastritis and gastric cancer, prompted our study to investigate the differential expression of cytokines in gastric tissues, which is crucial for understanding H. pylori infection and its potential progression to gastric cancer. Focusing on Il-1ß, IL-6, IL-8, IL-12, IL-18, and TNF-α, we analysed gene and protein levels to differentiate between H. pylori-infected and non-infected gastritis. We utilised real-time quantitative polymerase chain reaction (RT-qPCR) for gene quantification, immunohistochemical staining, and ELISA for protein measurement. Gastric samples from patients with gastritis were divided into three groups: (1) non-gastritis (N-group) group, (2) gastritis without H. pylori infection (G-group), and (3) gastritis with H. pylori infection (GH-group), each consisting of 8 samples. Our findings revealed a statistically significant variation in cytokine expression. Generally, cytokine levels were higher in gastritis, but in H. pylori-infected gastritis, IL-1ß, IL-6, and IL-8 levels were lower compared to H. pylori-independent gastritis, while IL-12, IL-18, and TNF-α levels were higher. This distinct cytokine expression pattern in H. pylori-infected gastritis underscores a unique inflammatory response, providing deeper insights into its pathogenesis.

Utilisation of carbon dioxide and nitrate for urea electrosynthesis with a Cu-based metal-organic framework.

It is important and challenging to utilise CO2 and NO3- as a feedstock for electrosynthesis of urea. Herein, we reported a stable 2D metal-organic framework (MOF) Cu-HATNA, possessing planar CuO4 active sites, as an efficient electrocatalyst for coupling CO2 and NO3- into urea, achieving a high yield rate of 1.46 g h-1 gcat-1 with a current density of 44.2 mA cm-1 at -0.6 V vs. RHE. This performance surpasses most of the previously reported catalysts, revealing the great prospects of MOFs in sustainable urea synthesis.

Rifaximin treatment shapes a unique metagenome-metabolism network in patients with decompensated cirrhosis.

BACKGROUND: Patients with decompensated cirrhosis face poor prognosis and increased mortality risk. Rifaximin, a non-absorbable antibiotic, has been shown to have beneficial effects in preventing complications and improving survival in these patients. However, the underlying mechanisms of rifaximin's effects remain unclear. METHODS: We obtained fecal samples from decompensated cirrhotic patients undergoing rifaximin treatment and controls, both at baseline and after 6 months of treatment. Shotgun metagenome sequencing profiled the gut microbiome, and untargeted metabolomics analyzed fecal metabolites. Linear discriminant and partial least squares discrimination analyses were used to identify differing species and metabolites between rifaximin-treated patients and controls. RESULTS: Forty-two patients were enrolled and divided into two groups (26 patients in the rifaximin group and 16 patients in the control group). The gut microbiome's beta diversity changed in the rifaximin group but remained unaffected in the control group. We observed 44 species with reduced abundance in the rifaximin group, including Streptococcus_salivarius, Streptococcus_vestibularis, Haemophilus_parainfluenzae, etc. compared to only four in the control group. Additionally, six species were enriched in the rifaximin group, including Eubacterium_sp._CAG:248, Prevotella_sp._CAG:604, etc., and 14 in the control group. Furthermore, rifaximin modulated different microbial functions compared to the control. Seventeen microbiome-related metabolites were altered due to rifaximin, while six were altered in the control group. CONCLUSION: Our study revealed distinct microbiome-metabolite networks regulated by rifaximin intervention in patients with decompensated cirrhosis. These findings suggest that targeting these specific metabolites or related bacteria might be a potential therapeutic strategy for decompensated cirrhosis.

Continuously Producing Highly Concentrated and Pure Acetic Acid Aqueous Solution via Direct Electroreduction of CO2.

It is crucial to achieve continuous production of highly concentrated and pure C2 chemicals through the electrochemical CO2 reduction reaction (eCO2RR) for artificial carbon cycling, yet it has remained unattainable until now. Despite one-pot tandem catalysis (dividing the eCO2RR to C2 into two catalytical reactions of CO2 to CO and CO to C2) offering the potential for significantly enhancing reaction efficiency, its mechanism remains unclear and its performance is unsatisfactory. Herein, we selected different CO2-to-CO catalysts and CO-to-acetate catalysts to construct several tandem catalytic systems for the eCO2RR to acetic acid. Among them, a tandem catalytic system comprising a covalent organic framework (PcNi-DMTP) and a metal-organic framework (MAF-2) as CO2-to-CO and CO-to-acetate catalysts, respectively, exhibited a faradaic efficiency of 51.2% with a current density of 410 mA cm-2 and an ultrahigh acetate yield rate of 2.72 mmol m-2 s-1 under neutral conditions. After electrolysis for 200 h, 1 cm-2 working electrode can continuously produce 20 mM acetic acid aqueous solution with a relative purity of 95+%. Comprehensive studies revealed that the performance of tandem catalysts is influenced not only by the CO supply-demand relationship and electron competition between the two catalytic processes in the one-pot tandem system but also by the performance of the CO-to-C2 catalyst under diluted CO conditions.

Nationwide safety surveillance of COVID-19 mRNA vaccines following primary series and first booster vaccination in Singapore.

Background: The real-world safety profile of COVID-19 mRNA vaccines remains incompletely elucidated. Methods: We performed a nationwide post-market safety surveillance analysis in Singapore, on vacinees aged 5 years and older, through mid-September 2022. Observed-over-expected (O/E) analyses were performed to identify potential safety signals among eight shortlisted adverse events of special interest (AESIs): strokes, cerebral venous thrombosis (CVT), acute myocardial infarction, myocarditis/pericarditis, pulmonary embolism, immune thrombocytopenia, convulsions and appendicitis. Self-controlled case series analyses (SCCS) were performed to validate signals of concern, occurring within 42 days of vaccination. Findings: Elevated risks were observed on O/E analyses for the following AESIs: myocarditis/pericarditis, [rate ratio (RR): 3.66, 95 % confidence interval (95 % CI): 2.71 to 4.94], appendicitis [RR: 1.14 (1.02 to 1.27)] and CVT [RR: 2.11 (1.18 to 3.77)]. SCCS analyses generated corroborative findings: myocarditis/pericarditis, [relative incidence (RI): 6.96 (3.95 to 12.27) at 1 to 7 days post-dose 2], CVT [RI: 4.30 (1.30 to 14.20) at 22 to 42 days post-dose 1] and appendicitis [RI: 1.31 (1.03 to 1.67) at 1 to 7 days post-dose 1]. Booster dose 1 continued to be associated with higher rates of myocarditis/pericarditis on O/E analysis [RR: 2.30, (1.39 to 3.80) and 1.69, (1.11 to 2.59)] at 21- and 42-days post-booster dose 1, respectively. Males aged 12 to 17 exhibited highest risks of both myocarditis/pericarditis [RI: 6.31 (1.36 to 29.3)] and appendicitis [RI: 2.01 (1.12 to 3.64)] after primary vaccination. Similarly, CVT was also predominantly observed in males aged above 50 (11 out of 16 cases), within 42-days of vaccination. Interpretation: Our data suggest that myocarditis/pericarditis, appendicitis and CVT are associated with primary vaccination using COVID-19 mRNA vaccines. Males at specific ages exhibit higher risks for all three AEs identified. The risk of myocarditis/pericarditis continues to be elevated after booster dose 1.

Covert hepatic encephalopathy is associated with aggressive disease progression and poor survival in patients with cirrhosis.

OBJECTIVES: Covert hepatic encephalopathy (CHE) negatively affects the health-related quality of life and increases the risk of overt HE (OHE) in patients with liver cirrhosis. However, the impact of CHE on long-term patient outcomes remains controversial. This study aimed to explore the association between CHE and disease progression and survival among cirrhotic patients. METHODS: This was a single-center prospective study that enrolled 132 hospitalized patients with cirrhosis, with an average follow-up period of 45.02 ± 23.06 months. CHE was diagnosed using the validated Chinese standardized psychometric hepatic encephalopathy score. RESULTS: CHE was detected in 35.61% cirrhotic patients. During the follow-up, patients with CHE had a higher risk of developing OHE (log-rank 5.840, P = 0.016), exacerbation of ascites (log-rank 4.789, P = 0.029), and portal vein thrombosis (PVT) (log-rank 8.738, P = 0.003). Cox multivariate regression analyses revealed that CHE was independently associated with the occurrence of OHE, exacerbation of ascites, and PVT. Furthermore, patients with progression of cirrhosis were more likely to be diagnosed as CHE (log-rank 4.462, P = 0.035). At the end of the follow-up, patients with CHE had a lower survival rate compared to those without CHE (log-rank 8.151, P = 0.004). CHE diagnosis (hazard ratio 2.530, P = 0.008), together with elder age and higher Child-Pugh score, were risk factors for impaired survival in cirrhotic patients. CONCLUSION: CHE is associated with disease progression and poor survival in patients with cirrhosis, indicating that CHE may serve as an independent predictor of poor prognosis among these patients.

Highly Efficient Electroreduction of CO2 to Ethanol via Asymmetric C-C Coupling by a Metal-Organic Framework with Heterodimetal Dual Sites.

The electroreduction of CO2 into value-added liquid fuels holds great promise for addressing global environmental and energy challenges. However, achieving highly selective yielding of multi-carbon oxygenates through the electrochemical CO2 reduction reaction (eCO2RR) is a formidable task, primarily due to the sluggish asymmetric C-C coupling reaction. In this study, a novel metal-organic framework (CuSn-HAB) with unprecedented heterometallic Sn···Cu dual sites (namely, a pair of SnN2O2 and CuN4 sites bridged by µ-N atoms) was designed to overcome this limitation. CuSn-HAB demonstrated an impressive Faradic efficiency (FE) of 56(2)% for eCO2RR to alcohols, achieving a current density of 68 mA cm-2 at a low potential of -0.57 V (vs RHE). Notably, no significant degradation was observed over a continuous 35 h operation at the specified current density. Mechanistic investigations revealed that, in comparison to the copper site, the SnN2O2 site exhibits a higher affinity for oxygen atoms. This enhanced affinity plays a pivotal role in facilitating the generation of the key intermediate *OCH2. Consequently, compared to homometallic Cu···Cu dual sites (generally yielding ethylene product), the heterometallic dual sites were proved to be more thermodynamically favorable for the asymmetric C-C coupling between *CO and *OCH2, leading to the formation of the key intermediate *CO-*OCH2, which is favorable for yielding ethanol product.

Simultaneous Capture of CO2 Boosting Its Electroreduction in the Micropores of a Metal-organic Framework.

Integration of CO2 capture capability from simulated flue gas and electrochemical CO2 reduction reaction (eCO2 RR) active sites into a catalyst is a promising cost-effective strategy for carbon neutrality, but is of great difficulty. Herein, combining the mixed gas breakthrough experiments and eCO2 RR tests, we showed that an Ag12 cluster-based metal-organic framework (1-NH2 , aka Ag12 bpy-NH2 ), simultaneously possessing CO2 capture sites as "CO2 relays" and eCO2 RR active sites, can not only utilize its micropores to efficiently capture CO2 from simulated flue gas (CO2 : N2 =15 : 85, at 298 K), but also catalyze eCO2 RR of the adsorbed CO2 into CO with an ultra-high CO2 conversion of 60 %. More importantly, its eCO2 RR performance (a Faradaic efficiency (CO) of 96 % with a commercial current density of 120 mA cm-2 at a very low cell voltage of -2.3 V for 300 hours and the full-cell energy conversion efficiency of 56 %) under simulated flue gas atmosphere is close to that under 100 % CO2 atmosphere, and higher than those of all reported catalysts at higher potentials under 100 % CO2 atmosphere. This work bridges the gap between CO2 enrichment/capture and eCO2 RR.

[Effects of Chlorine-based and Sulfur-based Fertilizers on Rice Bioavailability of Cd in Soils].

To explore the effects of single or combined application of chlorine-and sulfur-based fertilizers on rice bioavailability of Cd in soils, pot experiments with reddish clayey soil (developed from quaternary red clay parent materials) under three exogenous Cd levels (0, 0.5, and 2.0 mg·kg-1) were conducted. Meanwhile, chlorine-based fertilizers (KCl, NH4Cl) and sulfur-based fertilizers[K2SO4, (NH4)2SO4] were added in different proportions. The soil pH, Cd morphology, and Cd accumulation in rice at different growth stages were analyzed. The results revealed that both chlorine-and sulfur-based fertilizers could acidify the soil; however, the effect of chlorine-based fertilizers was more significant. During the filling stage of rice, the soil pH value of the treatment of applying single chlorine-based fertilizer decreased by 0.28 on average compared with that of applying single sulfur-based fertilizer. At the maturity stage of rice, chlorine-based fertilizer could activate the residual Cd, whereas sulfur-based fertilizer passivated the acid-extracted Cd to its residual state. Compared with the single application of the same fertilizer, the combined application of chlorine-and sulfur-based fertilizers was more likely to promote the accumulation of Cd in rice plants. The highest Cd accumulation of brown rice was 0.21 mg·kg-1 (2.0 mg·kg-1 exogenous Cd level) in the 1:1 (mole ratios of Cl:S) treatment of chlorine-and sulfur-based fertilizers, which was 16.4% higher than that of single chlorine-based fertilizer and 113.3% higher than that of single sulfur-based fertilizer. Therefore, the combined application of chlorine-fertilizers and sulfur-based fertilizers will increase the concentration of Cd in brown rice. To ensure food quality and safety, it is more advisable to apply single sulfur-based fertilizer for rice planting.

Dicopper(I) Sites Confined in a Single Metal-Organic Layer Boosting the Electroreduction of CO2 to CH4 in a Neutral Electrolyte.

It is challenging and important to achieve high performance for an electrochemical CO2 reduction reaction (eCO2RR) to yield CH4 under neutral conditions. So far, most of the reported active sites for eCO2RR to yield CH4 are single metal sites; the performances are far below the commercial requirements. Herein, we reported a nanosheet metal-organic layer in single-layer, namely, [Cu2(obpy)2] (Cuobpy-SL, Hobpy = 1H-[2,2']bipyridinyl-6-one), possessing dicopper(I) sites for eCO2RR to yield CH4 in a neutral aqueous solution. Detailed examination of Cuobpy-SL revealed high performance for CH4 production with a faradic efficiency of 82(1)% and a current density of ∼90 mA cm-2 at -1.4 V vs. reversible hydrogen electrode (RHE). No obvious degradation was observed over 100 h of continuous operation, representing a remarkable performance to date. Mechanism studies showed that compared with the conventional single-copper sites and completely exposed dicopper(I) sites, the dicopper(I) sites in the confined space formed by the molecular stacking have a strong affinity to key C1 intermediates such as *CO, *CHO, and *CH2O to facilitate the CH4 production, yet inhibiting C-C coupling.

Self-Accelerating Effect in a Covalent-Organic Framework with Imidazole Groups Boosts Electroreduction of CO2 to CO.

Solvent effect plays an important role in catalytic reaction, but there is little research and attention on it in electrochemical CO2 reduction reaction (eCO2 RR). Herein, we report a stable covalent-organic framework (denoted as PcNi-im) with imidazole groups as a new electrocatalyst for eCO2 RR to CO. Interestingly, compared with neutral conditions, PcNi-im not only showed high Faraday efficiency of CO product (≈100 %) under acidic conditions (pH ≈ 1), but also the partial current density was increased from 258 to 320 mA cm-2 . No obvious degradation was observed over 10 hours of continuous operation at the current density of 250 mA cm-2 . The mechanism study shows that the imidazole group on the framework can be protonated to form an imidazole cation in acidic media, hence reducing the surface work function and charge density of the active metal center. As a result, CO poisoning effect is weakened and the key intermediate *COOH is also stabilized, thus accelerating the catalytic reaction rate.

"Ship-in-a-Bottle" Integration of Ditin(IV) Sites into a Metal-Organic Framework for Boosting Electroreduction of CO2 in Acidic Electrolyte.

The electrochemical CO2 reduction reaction (eCO2RR) under acidic conditions has become a promising way to achieve high CO2 utilization because of the inhibition of undesirable carbonate formation that typically occurs under neutral and alkaline conditions. Herein, unprecedented and highly active ditin(IV) sites were integrated into the nanopores of a metal-organic framework, namely NU-1000-Sn, by a "ship-in-a-bottle" strategy. NU-1000-Sn delivers nearly 100% formic acid Faradaic efficiency at an industry current density of 260 mA cm-2 with a high single-pass CO2 utilization of 95% in an acidic solution (pH = 1.67). No obvious degradation was observed over 15 hours of continuous operation at the current density of 260 mA cm-2, representing the remarkable eCO2RR performance in acidic electrolyte to date. The mechanism study shows that both oxygen atoms of the key intermediate *HCOO can coordinate to the two adjacent Sn atoms in a ditin(IV) site simultaneously. Such bridging coordination is conducive to the hydrogenation of CO2, thus leading to high performance.

SPDEF enhances cancer stem cell-like properties and tumorigenesis through directly promoting GALNT7 transcription in luminal breast cancer.

BACKGROUND: Luminal breast cancer (BC) is the predominant subtype of breast cancer with a sustained risk of late recurrence and death. Understanding the molecular mechanisms for the oncogenesis of luminal BC would improve the prognosis for this large subset of patients. SPDEF was reported to be dysregulated in breast cancers. However, the biological functions and underlying molecular mechanism of SPDEF in luminal BC remains largely unknown. The aim of the present study was to elucidate the potential roles of SPDEF underlying subtype-specific functions in BC, especially in luminal subtypes. METHODS: The expressions and clinicopathological characteristics of SPDEF in luminal BC patients were evaluated bioinformatically. In vitro and in vivo assays were performed to investigate the oncogenic function and stemness maintenance of SPDEF in luminal BC. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were conducted to determine the transcription regulation of GALNT7 by SPDEF. GALNT7 levels in serum from luminal BC patients were further detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: SPDEF is markedly upregulated in luminal BC and positively associated with tumor progression and poor prognosis. Furthermore, we confirmed that SPDEF enhanced the proliferation, migration, invasion and stemness of luminal BC cells in vitro as well the tumorigenicity in vivo. Mechanistically, we demonstrated the stimulative effect of SPDEF on the progression and stemness of luminal BC, which is mediated by its directly transcriptional target GALNT7. Clinically, we verified that the GALNT7 can be used as a noninvasive diagnostic marker. Noteworthy, the combined detection of serum GALNT7 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of luminal BC. CONCLUSIONS: Our study reveals a novel mechanism by which SPDEF transcriptionally activates GALNT7 via directly binding to its promoter to promote cell proliferation, motility and stemness, and led to luminal BC tumorigenesis and poor prognosis.

Artificial neural network-based diagnostic models for lung cancer combining conventional indicators with tumor markers.

This study set out to establish a lung cancer diagnosis and prediction model uses conventional laboratory indicators combined with tumor markers, so as to help early screening and auxiliary diagnosis of lung cancer through a convenient, fast, and cheap way, and improve the early diagnosis rate of lung cancer. A total of 221 patients with lung cancer, 100 patients with benign pulmonary diseases, and 184 healthy subjects were retrospectively studied. General clinical data, the results of conventional laboratory indicators, and tumor markers were collected. Statistical Product and Service Solutions 26.0 was used for data analysis. The diagnosis and prediction model of lung cancer was established by artificial neural network - multilayer perceptron. After correlation and difference analysis, five comparison groups (lung cancer-benign lung disease group, lung cancer-health group, benign lung disease-health group, early-stage lung cancer-benign lung disease group, and early-stage lung cancer-health group) obtained 5, 28, 25, 16, and 25 valuable indicators for predicting lung cancer or benign lung disease, and then established five diagnostic prediction models, respectively. The area under the curve (AUC) of each combined diagnostic prediction model (0.848, 0.989, 0.949, 0.841, and 0.976) was higher than that of the diagnostic prediction model established only using tumor markers (0.799, 0.941, 0.830, 0.661, and 0.850), and the difference in the lung cancer-health group, the benign lung disease-health group, the early-stage lung cancer-benign lung disease group, and early-stage lung cancer-health group was statistically significant (P < 0.05). The artificial neural network-based diagnostic models for lung cancer combining conventional indicators with tumor markers have high performance and clinical significance in assisting the diagnosis of early lung cancer.

Efficient electroreduction of CO to acetate using a metal-azolate framework with dicopper active sites.

Electrochemical reduction of CO to value-added products, especially C2 products, provides a potential approach to achieve carbon neutrality and overcome the energy crisis. Herein, we report a metal-azolate framework (CuBpz) with dicopper active sites as an electrocatalyst for the electrochemical CO reduction reaction (eCORR). As a result, CuBpz achieved an impressive faradaic efficiency (FE) of 47.8% for yielding acetate with a current density of -200 mA cm-2, while no obvious degradation was observed over 60 hours of continuous operation at a current density of -200 mA cm-2. Mechanism studies revealed that the dicopper site can promote C-C coupling between two C1 intermediates, thereby being conducive to the generation of the key *CH2COOH intermediate.

Cyclic Trinickel(II) Clusters in a Metal-Azolate Framework for Efficient Overall Water Splitting.

Herein, a stable metal-azolate framework with cyclic trinickel(II) clusters, namely [Ni3 (µ3 -O)(BTPP)(OH)(H2 O)2 ] (Ni-BTPP, H3 BTPP=1,3,5-tris((1H-pyrazol-4-yl)phenylene)benzene), achieved a current density of 50 mA cm-2 at a cell voltage of 1.8 V in 1.0 M KOH solution, while the current density of 20%Pt/C@NF||IrO2 @NF is just 35.8 mA cm-2 at 2.0 V under the same condition. Moreover, no obvious degradation was observed over 12 hours of continuous operation at a large current density of 50 mA cm-2 . Theoretical calculations revealed that the µ3 -O atom in the cyclic trinickel(II) cluster serves as hydrogen-bonding acceptor to facilitate the dissociation of a H2 O molecule adsorbed on the adjacent Ni(II) ion, giving a lower energy barrier of H2 O dissociation compared with Pt/C; meanwhile, the µ3 -O atom can also participate in the water oxidation reaction to couple with the adjacent *OH adsorbed on Ni(II) ion, providing a low-energy coupling pathway, thus Ni-BTPP achieves a high performance for overall water splitting.

Divergent Metabolomic Signatures of TGFß2 and TNFα in the Induction of Retinal Epithelial-Mesenchymal Transition.

Epithelial-mesenchymal transition (EMT) is a dedifferentiation program in which polarized, differentiated epithelial cells lose their cell-cell adhesions and transform into matrix-producing mesenchymal cells. EMT of retinal pigment epithelial (RPE) cells plays a crucial role in many retinal diseases, including age-related macular degeneration, proliferative vitreoretinopathy, and diabetic retinopathy. This dynamic process requires complex metabolic reprogramming to accommodate the demands of this dramatic cellular transformation. Both transforming growth factor-beta 2 (TGFß2) and tumor necrosis factor-alpha (TNFα) have the capacity to induce EMT in RPE cells; however, little is known about their impact on the RPE metabolome. Untargeted metabolomics using high-resolution mass spectrometry was performed to reveal the metabolomic signatures of cellular and secreted metabolites of primary human fetal RPE cells treated with either TGFß2 or TNFα for 5 days. A total of 638 metabolites were detected in both samples; 188 were annotated as primary metabolites. Metabolomics profiling showed distinct metabolomic signatures associated with TGFß2 and TNFα treatment. Enrichment pathway network analysis revealed alterations in the pentose phosphate pathway, galactose metabolism, nucleotide and pyrimidine metabolism, purine metabolism, and arginine and proline metabolism in TNFα-treated cells compared to untreated control cells, whereas TGFß2 treatment induced perturbations in fatty acid biosynthesis metabolism, the linoleic acid pathway, and the Notch signaling pathway. These results provide a broad metabolic understanding of the bioenergetic rewiring processes governing TGFß2- and TNFα-dependent induction of EMT. Elucidating the contributions of TGFß2 and TNFα and their mechanistic differences in promoting EMT of RPE will enable the identification of novel biomarkers for diagnosis, management, and tailored drug development for retinal fibrotic diseases.

Isolated Tin(IV) Active Sites for Highly Efficient Electroreduction of CO2 to CH4 in Neutral Aqueous Solution.

The development of efficient electrocatalysts with non-copper metal sites for electrochemical CO2 reduction reactions (eCO2 RR) to hydrocarbons and oxygenates is highly desirable, but still a great challenge. Herein, a stable metal-organic framework (DMA)4 [Sn2 (THO)2 ] (Sn-THO, THO6- = triphenylene-2,3,6,7,10,11-hexakis(olate), DMA = dimethylammonium) with isolated and distorted octahedral SnO6 2- active sites is reported as an electrocatalyst for eCO2 RR, showing an exceptional performance for eCO2 RR to the CH4 product rather than the common products formate and CO for reported Sn-based catalysts. The partial current density of CH4 reaches a high value of 34.5 mA cm-2 , surpassing most reported copper-based and all non-Cu metal-based catalysts. Our experimental and theoretical results revealed that the isolated SnO6 2- active site favors the formation of key *OCOH species to produce CH4 and can greatly inhibit the formation of *OCHO and *COOH species to produce *HCOOH and *CO, respectively.