Iron driven organic carbon capture, pretreatment, recovery and upgrade in wastewater: Process technologies, mechanisms, and implications.

Wastewater treatment plants face significant challenges in transitioning from energy-intensive systems to carbon-neutral, energy-saving systems, and a large amount of chemical energy in wastewater remains untapped. Iron is widely used in modern wastewater treatment. Research shows that leveraging the coupled redox relationship of iron and carbon can redirect this energy (in the form of carbon) towards resource utilization. Therefore, re-examining the application of iron in existing wastewater carbon processes is particularly important. In this review, we investigate the latest research progress on iron for wastewater carbon flow restructuring. During the iron-based chemically enhanced primary treatment (CEPT) process, organic carbon is captured into sludge and its bioavailability is enhanced through iron-based advanced oxidation processes (AOP) pretreatment, further being recovered or upgraded to value-added products in anaerobic biological processes. We discuss the roles and mechanisms of iron in CEPT, AOP, anaerobic biological processes, and biorefining in driving organic carbon conversion. The dosage of iron, as a critical parameter, significantly affects the recovery and utilization of sludge carbon resources, particularly by promoting effective electron transfer. We propose a pathway for beneficial conversion of wastewater organic carbon driven by iron and analyze the benefits of the main products in detail. Through this review, we hope to provide new insights into the application of iron chemicals and current wastewater treatment models.

Rescue path planning for urban flood: A deep reinforcement learning-based approach.

Urban flooding is among the costliest natural disasters worldwide. Timely and effective rescue path planning is crucial for minimizing loss of life and property. However, current research on path planning often fails to adequately consider the need to assess area risk uncertainties and bypass complex obstacles in flood rescue scenarios, presenting significant challenges for developing optimal rescue paths. This study proposes a deep reinforcement learning (RL) algorithm incorporating four main mechanisms to address these issues. Dual-priority experience replays and backtrack punishment mechanisms enhance the precise estimation of area risks. Concurrently, random noisy networks and dynamic exploration techniques encourage the agent to explore unknown areas in the environment, thereby improving sampling and optimizing strategies for bypassing complex obstacles. The study constructed multiple grid simulation scenarios based on real-world rescue operations in major urban flood disasters. These scenarios included uncertain risk values for all passable areas and an increased presence of complex elements, such as narrow passages, C-shaped barriers, and jagged paths, significantly raising the challenge of path planning. The comparative analysis demonstrated that only the proposed algorithm could bypass all obstacles and plan the optimal rescue path across nine scenarios. This research advances the theoretical progress for urban flood rescue path planning by extending the scale of scenarios to unprecedented levels. It also develops RL mechanisms adaptable to various extremely complex obstacles in path planning. Additionally, it provides methodological insights into artificial intelligence to enhance real-world risk management.

Plasmid-mediated azithromycin resistance in non-typhoidal Salmonella recovered from human infections.

OBJECTIVES: Mechanisms of non-typhoidal Salmonella (NTS) resistance to azithromycin have rarely been reported. Here we investigate the epidemiology and genetic features of 10 azithromycin-resistant NTS isolates. METHODS: A total of 457 NTS isolates were collected from a tertiary hospital in Guangzhou. We performed antimicrobial susceptibility tests, conjugation experiments, efflux pump expression tests, whole-genome sequencing and bioinformatics analysis to conduct the study. RESULTS: The results showed that 10 NTS isolates (2.8%) were resistant to azithromycin with minimum inhibitory concentration values ranging from 128 to 512 mg/L and exhibited multidrug resistance. The phylogenetic tree revealed that 5 S. London isolates (AR1-AR5) recognized at different times and departments were closely related [3-74 single-nucleotide polymorphisms (SNPs)] and 2 S. Typhimurium isolates (AR7 and AR8) were clones (<3 SNPs) at 3-month intervals. The azithromycin resistance was conferred by mph(A) gene found on different plasmids, including IncFIB, IncHI2, InFII, IncC and IncI plasmids. Among them, IncFIB, InFII and IncHI2 plasmids carried different IS26-class 1 integron (intI1) arrangement patterns that mediated multidrug resistance transmission. Conjugative IncC plasmid encoded resistance to ciprofloxacin, ceftriaxone and azithromycin. Furthermore, phylogenetic analysis demonstrated that mph(A)-positive plasmids closely related to 10 plasmids in this study were mainly discovered from NTS, Escherichia coli, Klebsiella pneumonia and Enterobacter hormaechei. The genetic environment of mph(A) in 10 NTS isolates was IS26-mph(A)-mrx(A)-mphR(A)-IS6100/IS26 that co-arranged with intI1 harbour multidrug-resistant (MDR) gene cassettes on diverse plasmids. CONCLUSIONS: These findings highlighted that the dissemination of these plasmids carrying mph(A) and various intI1 MDR gene cassettes would seriously restrict the availability of essential antimicrobial agents for treating NTS infections.

Mauritone A, a new polyketide from a fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532.

A new polyketide, mauritone A (1) with six known polyketides curvulone B (2), curvularin (3), 12-oxocurvularin (4), (10E,15S)-10,11-dehydrocurvularin (5), (11R,15S)-11-hydroxycurvularin (6), and (11S,15S)-11-hydroxycurvularin (7) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica. Their structures were elucidated by extensive spectral analysis. All compounds (1-7) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4, 5, and 7 on nitric oxide (NO) production were found to be significant, with IC50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 µM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 µM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC50 values of 18.6 ± 0.53 and 12.7 ± 0.45 µM, respectively.

Mmp14-dependent remodeling of the pericellular-dermal collagen interface governs fibroblast survival.

Dermal fibroblasts deposit type I collagen, the dominant extracellular matrix molecule found in skin, during early postnatal development. Coincident with this biosynthetic program, fibroblasts proteolytically remodel pericellular collagen fibrils by mobilizing the membrane-anchored matrix metalloproteinase, Mmp14. Unexpectedly, dermal fibroblasts in Mmp14-/- mice commit to a large-scale apoptotic program that leaves skin tissues replete with dying cells. A requirement for Mmp14 in dermal fibroblast survival is recapitulated in vitro when cells are embedded within, but not cultured atop, three-dimensional hydrogels of crosslinked type I collagen. In the absence of Mmp14-dependent pericellular proteolysis, dermal fibroblasts fail to trigger ß1 integrin activation and instead actuate a TGF-ß1/phospho-JNK stress response that leads to apoptotic cell death in vitro as well as in vivo. Taken together, these studies identify Mmp14 as a requisite cell survival factor that maintains dermal fibroblast viability in postnatal dermal tissues.

Unveiling the Roles of Alloyed Boron in Hexavalent Chromium Removal Using Borohydride-Synthesized Nanoscale Zerovalent Iron: Electron Donor and Antipassivator.

Nanoscale zerovalent iron synthesized using borohydride (B-NZVI) has been widely applied in environmental remediation in recent decades. However, the contribution of boron in enhancing the inherent reactivity of B-NZVI and its effectiveness in removing hexavalent chromium [Cr(VI)] have not been well recognized and quantified. To the best of our knowledge, herein, a core-shell structure of B-NZVI featuring an Fe-B alloy shell beneath the iron oxide shell is demonstrated for the first time. Alloyed boron can reduce H+, contributing to more than 35.6% of H2 generation during acid digestion of B-NZVIs. In addition, alloyed B provides electrons for Fe3+ reduction during Cr(VI) removal, preventing in situ passivation of the reactive particle surface. Meanwhile, the amorphous oxide shell of B-NZVI exhibits an increased defect density, promoting the release of Fe2+ outside the shell to reduce Cr(VI), forming layer-structured precipitates and intense Fe-O bonds. Consequently, the surface-area-normalized capacity and surface reaction rate of B-NZVI are 6.5 and 6.9 times higher than those of crystalline NZVI, respectively. This study reveals the importance of alloyed B in Cr(VI) removal using B-NZVI and presents a comprehensive approach for investigating electron pathways and mechanisms involved in B-NZVIs for contaminant removal.

Multi-omics Analysis Reveals Key Gut Microbiota and Metabolites Closely Associated with Huntington's Disease.

Dysbiosis of the gut microbiota is closely associated with neurodegenerative diseases, including Huntington's disease (HD). Gut microbiome-derived metabolites are key factors in host-microbiome interactions. This study aimed to investigate the crucial gut microbiome and metabolites in HD and their correlations. Fecal and serum samples from 11 to 26 patients with HD, respectively, and 16 and 23 healthy controls, respectively, were collected. The fecal samples were used for shotgun metagenomics while the serum samples for metabolomics analysis. Integrated analysis of the metagenomics and metabolomics data was also conducted. Firmicutes, Bacteroidota, Proteobacteria, Uroviricota, Actinobacteria, and Verrucomicrobia were the dominant phyla. At the genus level, the presence of Bacteroides, Faecalibacterium, Parabacteroides, Alistipes, Dialister, and Christensenella was higher in HD patients, while the abundance of Lachnospira, Roseburia, Clostridium, Ruminococcus, Blautia, Butyricicoccus, Agathobaculum, Phocaeicola, Coprococcus, and Fusicatenibacter decreased. A total of 244 differential metabolites were identified and found to be enriched in the glycerophospholipid, nucleotide, biotin, galactose, and alpha-linolenic acid metabolic pathways. The AUC value from the integrated analysis (1) was higher than that from the analysis of the gut microbiota (0.8632). No significant differences were found in the ACE, Simpson, Shannon, Sobs, and Chao indexes between HD patients and controls. Our study determined crucial functional gut microbiota and potential biomarkers associated with HD pathogenesis, providing new insights into the role of the gut microbiota-brain axis in HD occurrence and development.

Perioperative Hypothermia in Elderly Patients During Pelvic Floor Reconstruction Surgery: An Observational Study.

INTRODUCTION AND HYPOTHESIS: The potential predictors of pelvic floor reconstruction surgery hypothermia remain unclear. This prospective cohort study was aimed at identifying these predictors and evaluating the outcomes associated with perioperative hypothermia. METHODS: Elderly patients undergoing pelvic floor reconstruction surgery were consecutively enrolled from April 2023 to September 2023. Perioperative temperature was measured at preoperative (T1), every 15 min after the start of anesthesia (T2), and 15 min postoperative (T3) using a temperature probe. Perioperative hypothermia was defined as a core temperature below 36°C at any point during the procedure. Multivariate logistic regression analysis was conducted to determine factors associated with perioperative hypothermia. RESULTS: A total of 229 patients were included in the study, with 50.7% experiencing hypothermia. Multivariate analysis revealed that the surgical method involving pelvic floor combined with laparoscopy, preoperative temperature < 36.5°C, anesthesia duration ≥ 120 min, and the high levels of anxiety were significantly associated with perioperative hypothermia. The predictive value of the multivariate model was 0.767 (95% CI, 0.706 to 0.828). CONCLUSIONS: This observational prospective study identified several predictive factors for perioperative hypothermia in elderly patients during pelvic floor reconstruction surgery. Strategies aimed at preventing perioperative hypothermia should target these factors. Further studies are required to assess the effectiveness of these strategies, specifically in elderly patients undergoing pelvic floor reconstruction surgery.

Dynamic Active Sites In Situ Formed in Metal Nanoparticle Reshaping under Reaction Conditions.

Understanding the nonequilibrium transformation of nanocatalysts under reaction conditions is important because metastable atomic structures may be created during the process, which offers unique activities in reactions. Although reshaping of metal nanoparticles (NPs) under reaction conditions has been widely recognized, the dynamic reshaping process has been less studied at the atomic scale. Here, we develop an atomistic kinetic Monte Carlo model to simulate the complete reshaping process of Pt nanoparticles in a CO environment and reveal the in situ formation of atomic clusters on the NP surface, a new type of active site beyond conventional understanding, boosting the reactivities in the CO oxidation reaction. Interestingly, highly active peninsula and inactive island clusters both form on the (111) facets and interchange in varying states of dynamic equilibrium, which influences the catalytic activities significantly. This study provides new fundamental knowledge of nanocatalysis and new guidance for the rational design of nanocatalysts.

Bimetallic Metal Sites in Metal-Organic Frameworks Facilitate the Production of 1-Butene from Electrosynthesized Ethylene.

Converting CO2 to synthetic hydrocarbon fuels is of increasing interest. In light of progress in electrified CO2 to ethylene, we explored routes to dimerize to 1-butene, an olefin that can serve as a building block to ethylene longer-chain alkanes. With goal of selective and active dimerization, we investigate a series of metal-organic frameworks having bimetallic catalytic sites. We find that the tunable pore structure enables optimization of selectivity and that periodic pore channels enhance activity. In a tandem system for the conversion of CO2 to 1-C4H8, wherein the outlet cathodic gas from a CO2-to-C2H4 electrolyzer is fed directly (via a dehumidification stage) into the C2H4 dimerizer, we study the highest-performing MOF found herein: M' = Ru and M″ = Ni in the bimetallic two-dimensional M'2(OAc)4M″(CN)4 MOF. We report a 1-C4H8 production rate of 1.3 mol gcat-1 h-1 and a C2H4 conversion of 97%. From these experimental data, we project an estimated cradle-to-gate carbon intensity of -2.1 kg-CO2e/kg-1-C4H8 when CO2 is supplied from direct air capture and when the required energy is supplied by electricity having the carbon intensity of wind.

Developmental toxicity and mechanism of dibutyl phthalate and alternative diisobutyl phthalate in the early life stages of zebrafish (Danio rerio).

Diisobutyl phthalate (DiBP), is widely chemical replacement for Dibutyl phthalate (DBP). Although DBP and DiBP have been detected in surface water worldwide, few studies to date have systematically assessed the risks of DBP and its alternatives to aquatic organisms. The present study compared DBP and DiBP for their individual and joint toxicity as well as thyroid hormone levels in zebrafish embryo. Transcripts of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were investigated in developing zebrafish larvae by application of real time polymerase chain reaction. The median half-lethal concentrations of DBP and DiBP to zebrafish at 96 h were 0.545 mg L-1 and 1.149 mg L-1, respectively. The joint toxic effect of DBP-DiBP (0.25-0.53 mg L-1) with the same ratio showed a synergistic effect. Thyroid hormones levels increased with exposure to 10 µg L-1 of DBP or 50 µg L-1 of DiBP, and exposure to both compounds significantly increased thyroid gland-specific transcription of thyroglobulin gene (tg), hyronine deiodinase (dio2), and transthyretin (ttr), indicating an adverse effect associated with the HPT axis. Molecular docking results indicated that DBP (-7.10 kcal/M and -7.53 kcal/M) and DiBP (-6.63 kcal/M and -7.42 kcal/M) had the same docking energy with thyroid hormone receptors. Our data facilities an understand of potential harmful effects of DBP and its alternative (DiBP).

Phthalic acid esters: Are they a big concern for rivers flowing into reservoir with ecological facilities?

The city-river-reservoir system is an important system for safeguarding drinking water. Phthalic acid esters (PAEs) are emerging contaminants in drinking water sources that are gaining attention, and they could pose risks to human health and aquatic organisms. In this study, field studies that lasted four years were conducted to analyze the concentrations, spatial-temporal distribution, and removal effects of six PAEs. The total concentrations of the Σ6PAEs in the water and sediment samples were 0.2-7.4 µg L-1 (mean: 1.3 µg L-1) and 9.2-9594.1 ng g-1 (mean: 847.5 ng g-1), respectively. Di-n-butyl phthalate (DBP) and, bis(2-ethylhexyl) phthalate (DEHP) were the predominant congeners, accounting for 57.2 % in the water samples and 94.1 % in the sediment samples. The urban area contributed 72 % of the PAEs in the system. A significant removal effect of PAEs was observed in the wetland, with a removal rate of 40.2 %. The partitioning of PAEs between the water and sediment was attributed to the removal of dimethyl phthalate and diethyl phthalate that occurred during the water phase, while the removal of DBP and DEHP primarily occurred during the sediment phase. The ecological risk calculation based on the sensitivity distribution model indicated that DBP (HQwater = 0.19, HQsediment = 0.46) and DEHP (HQwater = 0.20, HQsediment = 0.13) possessed moderate risks according to some water and sediment samples. The ecological projects were verified to be effective engineering strategies to reduce ecological risk in the drinking water source.

Discrimination and quantification of volatile compounds in beer by FTIR combined with machine learning approaches.

The composition of volatile compounds in beer is crucial to the quality of beer. Herein, we identified 23 volatile compounds, namely, 12 esters, 4 alcohols, 5 acids, and 2 phenols, in nine different beer types using GC-MS. By performing PCA of the data of the flavor compounds, the different beer types were well discriminated. Ethyl caproate, ethyl caprylate, and phenylethyl alcohol were identified as the crucial volatile compounds to discriminate different beers. PLS regression analysis was performed to model and predict the contents of six crucial volatile compounds in the beer samples based on the characteristic wavelength of the FTIR spectrum. The R2 value of each sample in the prediction model was 0.9398-0.9994, and RMSEP was 0.0122-0.7011. The method proposed in this paper has been applied to determine flavor compounds in beer samples with good consistency compared with GC-MS.

Mechanism of peroxymonosulfate activation by nanoparticle Co@N-C: Experimental investigation and theoretical calculation.

The release of organic dyes, such as Rhodamine B (RhB), into industrial wastewater has led to significant issues with color pollution in aquatic environments. Herein, we prepared a cobalt nanoparticles (NPs)-based catalyst with the nitrogen-doped carbon-support (Co@N-C) for effective PMS activation. The Co@N-C/PMS system demonstrated the excellent catalytic activity of Co@N-C for activating PMS, achieving nearly 100% degradation of RhB. Singlet oxygen (1O2) and sulfate radicals (SO4•-) were dominant reactive oxygen species for RhB degradation. Density functional theory (DFT) calculations substantiated that the production of 1O2 commenced with the initial generation of *OH through hydrogen abstraction from PMS, culminating in the direct release of oxygen to form 1O2 (PMS→*OH→O*→1O2). The generation of SO4•- was attributed to electron transfer to PMS from the surface of Co NPs (Co0→Co2+→Co3+) and the C-N shell (Co2+→Co3+). The research findings provided new insights into the development of Co-based heterogeneous catalysis for advanced oxidation of refractory organic pollutants in wastewater treatment.

sh- Ambra1 inhibits IRS-1/PI3K/Akt signalling pathway to reduce autophagy in gestational diabetes.

INTRODUCTION: Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnancy. However, studies of activating molecule of Beclin1-regulated autophagy (Ambra1) affecting the insulin substrate receptor 1/phosphatidylinositol 3 kinase/protein kinase B (IRS-1/PI3K/Akt) signalling pathway in GDM have not been reported. The aim of the study was to detect the difference of Ambra1 expression in the placenta of normal pregnant women and GDM patients. MATERIAL AND METHODS: An in vitro model of gestational diabetes mellitus was established by inducing HTR8/Svneo cells from human chorionic trophoblast layer with high glucose. The changes of cell morphology were observed by inverted microscope, and the expression levels of Ambra1 gene and protein in model cells were detected. After this, Ambra1 gene was silenced by shRNA transfection, and PI3K inhibitor was added to detect changes in Ambra1, autophagy, and insulin (INS) signalling pathways. RESULTS: The protein expression levels of Ambra1, Bcl-2 interacting protein (Beclin-1), and microtubule-associated proteins 1A/1B light chain 3B (LC3-II) in the placentas of GDM pregnant women were higher than those of normal pregnant women. High glucose induces morphological changes in HTR8/Svneo cells and increases Ambra1 transcription and translation levels. sh-Ambra1 increased survival of HTR8/SvNEO-HG cells and inhibited Ambra1, Beclin1, and LC3-II transcription and translation levels. Also, sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels and inhibited the IRS-1/PI3K/Akt signalling pathway and its resulting autophagy. CONCLUSIONS: sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels to reduce autophagy in gestational diabetes.

Selective Electrified Propylene-to-Propylene Glycol Oxidation on Activated Rh-Doped Pd.

Renewable-energy-powered electrosynthesis has the potential to contribute to decarbonizing the production of propylene glycol, a chemical that is used currently in the manufacture of polyesters and antifreeze and has a high carbon intensity. Unfortunately, to date, the electrooxidation of propylene under ambient conditions has suffered from a wide product distribution, leading to a low faradic efficiency toward the desired propylene glycol. We undertook mechanistic investigations and found that the reconstruction of Pd to PdO occurs, followed by hydroxide formation under anodic bias. The formation of this metastable hydroxide layer arrests the progressive dissolution of Pd in a locally acidic environment, increases the activity, and steers the reaction pathway toward propylene glycol. Rh-doped Pd further improves propylene glycol selectivity. Density functional theory (DFT) suggests that the Rh dopant lowers the energy associated with the production of the final intermediate in propylene glycol formation and renders the desorption step spontaneous, a concept consistent with experimental studies. We report a 75% faradic efficiency toward propylene glycol maintained over 100 h of operation.

Alzheimer's disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling.

Amyloid-ß, tau pathology, and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease (AD). However, these proteins represent only a fraction of the complex biological processes underlying AD, and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers. More AD-specific early diagnostic and disease staging biomarkers are needed. In this study, we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid (CSF) and serum samples in a discovery cohort comprising 98 participants. Candidate biomarkers were validated by parallel reaction monitoring-based targeted proteomic assays in an independent multicenter cohort comprising 288 participants. We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort, identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers, respectively. In the validation cohort, 58 and 21 CSF proteins, as well as 12 and 18 serum proteins, were verified as early diagnostic and staging biomarkers, respectively. Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment (MCI) due to AD from normal cognition with areas under the curve of 0.984 and 0.881, respectively. The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases. Moreover, we identified 21 CSF and 18 serum stage-associated proteins reflecting AD stages. Our findings provide a foundation for developing blood-based tests for AD screening and staging in clinical practice.

Double-Masked, Vehicle-Controlled, Randomized, Phase II Study of the Ocular Hypotensive Activity and Safety of VVN539 Ophthalmic Solution.

Purpose: To assess safety and ocular hypotensive efficacy of VVN539 ophthalmic solution in a first-in-human study. Design: Multicenter, double-masked, randomized, vehicle-controlled, dose-response, parallel-comparison study. Participants: Sixty-eight subjects with ocular hypertension (OHT) or open-angle glaucoma enrolled at 5 private practices. Methods: After washout of ocular hypotensive medications as required, the subjects were randomized to receive either VVN539 ophthalmic solution 0.02%, 0.04%, or vehicle once-daily (QD) in the morning (5 days), once-daily in the evening (6 days) and then twice-daily (6 days). Main Outcome Measures: Comparison of VVNM539 to its vehicle in mean intraocular pressure (IOP) at each diurnal time point (8:00am, 10:00am, and 4:00pm) at visit 4 (day 7), visit 5 (day 14), and visit 6 (day 21). Results: Mean IOP decreased throughout dosing in the active groups to between 18 and 20 mmHg in both active groups, to between 22 to 23 mmHg in the vehicle group. VVN539 0.04% was statistically superior to vehicle at all 9 diurnal time points (QD AM, QD PM, and twice daily, P ≤ 0.0109). VVN539 0.02% was statistically superior to vehicle at only 6 of 9 diurnal time points (selected QD times and twice daily). The most common ocular treatment-emergent adverse event was conjunctival hyperemia (11 [47.8%], 10 [4.5%], and 1 [4.3%]), followed by ocular hyperemia (3 [13.0%], 5 [22.7%] and 0), respectively. There were no clinically significant changes of note in visual acuity, biomicroscopy, dilated ophthalmoscopy, blood chemistry, hematology, or cardiovascular measures. Conclusions: In conclusion, the results of this initial phase II study indicate that VVN539 ophthalmic solution showed clinically and statistically significant ocular hypertensive activity and was relatively well tolerated for the treatment of subjects with primary open-angle glaucoma or OHT. Additional studies will be required for a more complete evaluation of the utility of VVN539 ophthalmic solution. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Site-selective protonation enables efficient carbon monoxide electroreduction to acetate.

Electrosynthesis of acetate from CO offers the prospect of a low-carbon-intensity route to this valuable chemical--but only once sufficient selectivity, reaction rate and stability are realized. It is a high priority to achieve the protonation of the relevant intermediates in a controlled fashion, and to achieve this while suppressing the competing hydrogen evolution reaction (HER) and while steering multicarbon (C2+) products to a single valuable product--an example of which is acetate. Here we report interface engineering to achieve solid/liquid/gas triple-phase interface regulation, and we find that it leads to site-selective protonation of intermediates and the preferential stabilization of the ketene intermediates: this, we find, leads to improved selectivity and energy efficiency toward acetate. Once we further tune the catalyst composition and also optimize for interfacial water management, we achieve a cadmium-copper catalyst that shows an acetate Faradaic efficiency (FE) of 75% with ultralow HER (<0.2% H2 FE) at 150 mA cm-2. We develop a high-pressure membrane electrode assembly system to increase CO coverage by controlling gas reactant distribution and achieve 86% acetate FE simultaneous with an acetate full-cell energy efficiency (EE) of 32%, the highest energy efficiency reported in direct acetate electrosynthesis.

Association of FAT1 with focal epilepsy and correlation between seizure relapse and gene expression stage.

PURPOSE: The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy. METHODS: Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy. Additional cases with FAT1 variants were collected from the China Epilepsy Gene V.1.0 Matching Platform. RESULTS: Four pairs of compound heterozygous missense FAT1 variants were identified in four unrelated patients with partial (focal) epilepsy and/or febrile seizures, but without intellectual disability/developmental abnormalities. These variants presented no/very low frequencies in the gnomAD database, and the aggregate frequencies in this cohort were significantly higher than those in controls. Two additional compound heterozygous missense variants were identified in two unrelated cases using the gene-matching platform. All patients experienced infrequent (yearly/monthly) complex partial seizures or secondary generalised tonic-clonic seizures. They responded well toantiseizure medication, but seizures relapsed in three cases when antiseizure medication were decreased or withdrawn after being seizure-free for three to six years, which correlated with the expression stage of FAT1. Genotype-phenotype analysis showed that epilepsy-associated FAT1 variants were missense, whereas non-epilepsy-associated variants were mainly truncated. The relationship between FAT1 and epilepsy was evaluated to be "Strong" by the Clinical Validity Framework of ClinGen. CONCLUSIONS: FAT1 is a potential causative gene of partial epilepsy and febrile seizures. Gene expression stage was suggested to be one of the considerations in determining the duration ofantiseizure medication. Genotype-phenotype correlation helps to explain the mechanisms underlying phenotypic variation.