Bismuth-Based Electrocatalysts for Identical Value-Added Formic Acid Through Coupling CO2 Reduction and Methanol Oxidation.

It is an effective way to reduce atmospheric CO2 via electrochemical CO2 reduction reaction (CO2 RR), while the slow oxygen evolution reaction (OER) occurs at the anode with huge energy consumption. Herein, methanol oxidation reaction (MOR) is used to replace OER, coupling CO2 RR to achieve co-production of formate. Through enhancing OCHO* adsorption by oxygen vacancies engineering and synergistic effect by heteroatom doping, Bi/Bi2 O3 and Ni─Bi(OH)3 are synthesized for efficient production of formate via simultaneous CO2 RR and methanol oxidation reaction (MOR), achieving that the coupling of CO2 RR//MOR only required 7.26 kWh gformate -1 power input, much lower than that of CO2 RR//OER (13.67 kWh gformate -1 ). Bi/Bi2 O3 exhibits excellent electrocatalytic CO2 RR performance, achieving FEformate >80% in a wide potential range from -0.7 to -1.2 V (vs RHE). For MOR, Ni─Bi(OH)3 exhibits efficient MOR catalytic performance with the FEformate >98% in the potential range of 1.35-1.6 V (vs RHE). Not only demonstrates the two-electrode systems exceptional stability, working continuously for over 250 h under a cell voltage of 3.0 V, but the cathode and anode can maintain a FE of over 80%. DFT calculation results reveal that the oxygen vacancies of Bi/Bi2 O3 enhance the adsorption of OCHO* intermediate, and Ni─Bi(OH)3 reduce the energy barrier for the rate determining step, leading to high catalytic activity.

Acute and continuous exposure of airborne fine particulate matter (PM2.5): diverse outer blood-retinal barrier damages and disease susceptibilities.

BACKGROUND: The association between air pollution and retinal diseases such as age-related macular degeneration (AMD) has been demonstrated, but the pathogenic correlation is unknown. Damage to the outer blood-retinal barrier (oBRB), which consists of the retinal pigment epithelium (RPE) and choriocapillaris, is crucial in the development of fundus diseases. OBJECTIVES: To describe the effects of airborne fine particulate matter (PM2.5) on the oBRB and disease susceptibilities. METHODS: A PM2.5-exposed mice model was established through the administration of eye drops containing PM2.5. Optical coherence tomography angiography, transmission electron microscope, RPE immunofluorescence staining and Western blotting were applied to study the oBRB changes. A co-culture model of ARPE-19 cells with stretching vascular endothelial cells was established to identify the role of choroidal vasodilatation in PM2.5-associated RPE damage. RESULTS: Acute exposure to PM2.5 resulted in choroidal vasodilatation, RPE tight junctions impairment, and ultimately an increased risk of retinal edema in mice. These manifestations are very similar to the pachychoroid disease represented by central serous chorioretinopathy (CSC). After continuous PM2.5 exposure, the damage to the RPE was gradually repaired, but AMD-related early retinal degenerative changes appeared under continuous choroidal inflammation. CONCLUSION: This study reveals oBRB pathological changes under different exposure durations, providing a valuable reference for the prevention of PM2.5-related fundus diseases and public health policy formulation.

Long-term PM2.5 exposure disrupts corneal epithelial homeostasis by impairing limbal stem/progenitor cells in humans and rat models.

BACKGROUND: Limbal stem/progenitor cells (LSPCs) play a crucial role in maintaining corneal health by regulating epithelial homeostasis. Although PM2.5 is associated with the occurrence of several corneal diseases, its effects on LSPCs are not clearly understood. METHODS: In this study, we explored the correlation between PM2.5 exposure and human limbal epithelial thickness measured by Fourier-domain Optical Coherence Tomography in the ophthalmologic clinic. Long- and short-term PM2.5 exposed-rat models were established to investigate the changes in LSPCs and the associated mechanisms. RESULTS: We found that people living in regions with higher PM2.5 concentrations had thinner limbal epithelium, indicating the loss of LSPCs. In rat models, long-term PM2.5 exposure impairs LSPCs renewal and differentiation, manifesting as corneal epithelial defects and thinner epithelium in the cornea and limbus. However, LSPCs were activated in short-term PM2.5-exposed rat models. RNA sequencing implied that the circadian rhythm in LSPCs was perturbed during PM2.5 exposure. The mRNA level of circadian genes including Per1, Per2, Per3, and Rev-erbα was upregulated in both short- and long-term models, suggesting circadian rhythm was involved in the activation and dysregulation of LSPCs at different stages. PM2.5 also disturbed the limbal microenvironment as evidenced by changes in corneal subbasal nerve fiber density, vascular density and permeability, and immune cell infiltration, which further resulted in the circadian mismatches and dysfunction of LSPCs. CONCLUSION: This study systematically demonstrates that PM2.5 impairs LSPCs and their microenvironment. Moreover, we show that circadian misalignment of LSPCs may be a new mechanism by which PM2.5 induces corneal diseases. Therapeutic options that target circadian rhythm may be viable options for improving LSPC functions and alleviating various PM2.5-associated corneal diseases.

Upregulation of EphA2 is associated with apoptosis in response to H2O2 and UV radiation-induced cataracts.

In this article, we examine the role of erythropoietin-producing hepatocellular receptor A2 (EphA2) in the apoptosis of lens epithelial cells (LECs) in H2O2 and UV radiation-induced cataracts. We treated SRA01/04 cells with H2O2 or ultraviolet (UV) radiation to create a cataract cell model. We constructed a cataract lens model by exposing mice to UV radiation. We used CCK8 assays, Annexin V-FITC analysis, and immunohistochemical staining to explore proliferation and apoptosis of the cataract model. Thereafter, we used quantitative real-time PCR (qPCR) analysis, Western blot assays, and immunofluorescence to determine gene and protein expression levels. We also employed Crispr/Cas9 gene editing to create an EphA2 knockout in SRA01/04 cells. Results: H2O2 or UV radiation induced SRA01/04 cells showed EphA2 gene upregulation. CCK8 and apoptosis assays showed that EphA2 over-expression (OE) reduced epithelial cell apoptosis, but knockout of EphA2 induced it in response to H2O2 and UV radiation, respectively. Mutation of the EphA2 protein kinase domain (c.2003G > A, p. G668D) had a limited effect on cell apoptosis. In vivo, the EphA2 protein level increased in the lenses of UV-treated mice. Our results showed that EphA2 was upregulated in SRA01/04 cells in response to H2O2 and UV radiation. Mutation of the EphA2 protein kinase domain (c.2003G > A, p. G668D) had a limited effect on H2O2 and UV radiation-induced cell apoptosis. We confirmed this change with an experiment on UV-treated mice. The present study established a novel association between EphA2 and LEC apoptosis.

CHAC1 as a Novel Contributor of Ferroptosis in Retinal Pigment Epithelial Cells with Oxidative Damage.

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. With aging and the accumulated effects of environmental stress, retinal pigment epithelial (RPE) cells are particularly susceptible to oxidative damage, which can lead to retinal degeneration. However, the underlying molecular mechanisms of how RPE responds and progresses under oxidative damage are still largely unknown. Here, we reveal that exogenous oxidative stress led to ferroptosis characterized by Fe2+ accumulation and lipid peroxidation in RPE cells. Glutathione specific gamma-glutamylcyclotransferase 1 (Chac1), as a component of the unfolded protein response (UPR) pathway, plays a pivotal role in oxidative-stress-induced cell ferroptosis via the regulation of glutathione depletion. These results indicate the biological significance of Chac1 as a novel contributor of oxidative-stress-induced ferroptosis in RPE, suggesting its potential role in AMD.

Airborne fine particulate matter (PM2.5) damages the inner blood-retinal barrier by inducing inflammation and ferroptosis in retinal vascular endothelial cells.

This study was the first to explore the effect of airborne fine particulate matter (PM2.5) exposure on the inner blood-retinal barrier (iBRB). In this study, retinal vascular permeability and diameter were enhanced in the PM2.5-exposed animal model (1 mg/mL PM2.5, 10 µL per eye, 4 times per day, 3 days), together with observable retinal edema and increased inflammation level in retina. PM2.5-induced cell damage in human retinal microvascular endothelial cells (HRMECs) occurred in a time- and dose-dependent manner. Decreased cell viability, proliferation, migration, and angiogenesis, as well as increased apoptosis and inflammation, were observed. Iron overload and excessive lipid oxidation were also discovered after PM2.5 exposure (25, 50, and 100 µg/mL PM2.5 for 24 h), along with significantly altered expression of ferroptosis-related genes, such as prostaglandin-endoperoxide synthase 2, glutathione peroxidase 4, and ferritin heavy chain 1. Moreover, Ferrostatin-1, an inhibitor of ferroptosis, evidently alleviated the PM2.5-induced cytotoxicity of HRMECs. The present study investigated the in vivo effects of PM2.5 on retinas, revealing that PM2.5 exposure induced retinal inflammation, vascular dilatation, and caused damage to the iBRB. The crucial role of ferroptosis was discovered during PM2.5-induced HRMEC cytotoxicity and dysfunction, indicating a potential precautionary target in air pollution-associated retinal vascular diseases.

Expression profiles of long noncoding RNAs in human corneal epithelial cells exposed to fine particulate matter.

PURPOSE: The aim of this study was to investigate the expression profiles of long noncoding RNAs (lncRNAs) in human corneal epithelial cells (HCECs) exposed to fine particulate matter (PM2.5) and to identify potential biological pathways involved in PM2.5-induced toxicity in HCECs. METHODS: Using RNA sequencing (RNA-seq) and hierarchy clustering analysis, lncRNA expression profiles in PM2.5-treated and untreated HCECs were examined. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to predict the role of altered lncRNAs in biological processes and pathways. A quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assay was conducted to verify the RNA-seq results in HCECs and human corneal epithelial cell sheets. RESULTS: In total, 65 lncRNAs were altered in the PM2.5-treated HCECs, including 41 upregulated and 24 downregulated lncRNAs. The results of the qRT-PCR assay were consistent with those of the RNA-seq analysis. The expression of two significantly upregulated lncRNAs was confirmed in human corneal epithelial cell sheets. The GO analysis demonstrated that altered lncRNAs in the PM2.5-treated HCECs were significantly enriched in three domains: cellular component, molecular function, and biological process. The KEGG pathway analysis revealed enriched pathways of lncRNA co-expressed mRNAs, including cancer, RNA transport, and Rap1 signaling. CONCLUSIONS: Our results suggest that lncRNAs are involved in the pathogenesis of PM2.5-induced ocular diseases, exerting their effects through biological processes and pathogenic pathways. Among the altered lncRNAs, RP3-406P24.3 and RP11-285E9.5 may play significant roles in PM2.5-induced ocular surface injury.

Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells.

Congenital cataracts are the leading cause of childhood blindness. To date, surgical removal of cataracts is the only established treatment, but surgery is associated with multiple complications, which often lead to visual impairment. Therefore, mechanistic studies and drug-candidate screening have been intrigued by the aims of developing novel therapeutic strategies. However, these studies have been hampered by a lack of an appropriate human-disease model of congenital cataracts. Herein, we report the establishment of a human congenital cataract in vitro model through differentiation of patient-specific induced pluripotent stem cells (iPSCs) into regenerated lenses. The regenerated lenses derived from patient-specific iPSCs with known causative mutations of congenital cataracts (CRYBB2 [p. P24T] and CRYGD [p. Q155X]) showed obvious opacification that closely resembled that seen in patients' cataracts in terms of opacification severity and disease course accordingly, as compared with lentoid bodies (LBs) derived from healthy individuals. Increased protein aggregation and decreased protein solubility corresponding to the patients' cataract severity were observed in the patient-specific LBs and were attenuated by lanosterol treatment. Taken together, the in vitro model described herein, which recapitulates patient-specific clinical manifestations of congenital cataracts and protein aggregation in patient-specific LBs, provides a robust system for research on the pathological mechanisms of cataracts and screening of drug candidates for cataract treatment.

Association between outpatient visits for pterygium and air pollution in Hangzhou, China.

Air pollution could be a risk factor for the development of pterygium. This study aimed to investigate the potential associations between outpatient visits for pterygium and air pollutants. Using a time-stratified case-crossover design, the data of 3017 outpatients with pterygium visiting an eye center in Hangzhou, China, and the air pollution data of the Environmental Protection Department of Zhejiang Province between July 1, 2014, and November 30, 2019, were examined. The relationships between the air pollutants nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone, and fine particulate matter (PM) with median aerometric diameter <2.5 µm (PM2.5) and <10 µm (PM10) and outpatient visits for primary pterygium were assessed using single- and multiple-pollutant models. Significant associations between outpatient visits for pterygium and air pollutants (PM2.5, PM10, SO2, and NO2) were observed. Younger patients were found to be more sensitive to air pollution. Interestingly, the younger female patients with pterygium were more vulnerable to PM2.5 exposure during the warm season, while the younger male patients with pterygium were more sensitive to NO2 during the cold season. Significant effects were also observed between the pterygium outpatients and PM2.5 (odds ratio [OR] = 1.06, P = 0.02), PM10 (OR = 1.04, P = 0.01), and SO2 (OR = 1.26, P = 0.01) during the warm season, as well as NO2 (OR = 1.06, P = 0.01) during the cold season. Our study provides evidence that outpatient visits for pterygium are positively associated with increases in the air pollutants PM2.5, PM10, SO2, and NO2, revealing the important role of air pollution in the occurrence and development of pterygium.

Research advances in pathogenic mechanisms underlying air pollution-induced ocular surface diseases.

Background: The harmful effect of aerial fine particulate matter（PM2.5）has been a serious public health issue and has attracted worldwide attention, especially in developing countries. Main Text: Numerous previous clinical and experimental studies have demonstrated that PM2.5 has a clear pathogenic effect on diseases related to the respiratory and cardiovascular systems. Recent researches have pointed out that PM2.5 plays a pivotal role in the occurrence and progression of ocular surface diseases. The current studies have shown that PM2.5 may promote the appearance of conjunctivitis, keratitis, blepharitis, dry eye, meibomian gland dysfunction（MGD） and other ocular surface diseases through regulating a series of mechanisms such as inflammation, immune reaction, oxidative stress, autophagy, cell migration, and epigenetics. Conclusions: This review aims to summarize the current research progress on the pathogenic mechanism of PM2.5-related ocular surface diseases.

Boosting electrocatalytic reduction of nitrogen to ammonia under ambient conditions by alloy engineering.

Electrochemical reduction of nitrogen to ammonia under ambient conditions is regarded as a potential approach to tackle the energy-intensive Haber-Bosch process. However, it usually suffers from extremely low ammonia yield and faradaic efficiency due to the lack of highly active and selective electrocatalysts. Herein, fusiform-like ruthenium-copper alloy nanosheets (RuCu-FNs) were prepared by alloy engineering and utilized for the electrocatalytic NRR under ambient conditions. A high FE of 7.2% and an NH3 yield rate of 53.6 µg h-1 mgcat-1 were achieved at -0.1 V vs. RHE, which were better than those of the corresponding non-metallic catalyst and most alloy catalysts. The superior performance was ascribed to the differentiated second catalytic site for achieving both effectively adsorptive activation of chemically inert N2 and intermediate desorption from the catalyst surface. The source of NH3 was also identified with isotopic labeling via a self-developed simple and economic pathway. We provided a feasible pathway for the rational design of electrocatalysts for artificial N2 fixation.

A highly efficient FeP/CeO2-NF hybrid electrode for the oxygen evolution reaction.

Transition metal phosphides have been proven as highly efficient electrocatalysts. In this study, a FeP/CeO2-NF hybrid electrode was prepared by a simple electrodeposition and high-temperature phosphorization method. The electrode exhibits outstanding performance for the OER with an overpotential of only 245 mV at a current density of 100 mA cm-2, a Tafel slope as low as 39.1 mV dec-1 and an excellent durability for 50 h at a current density of 10 mA cm-2 in an alkaline solution. Such significant high performances are attributed to a combined effect of the excellent electron conductivity of CeO2 and unique uneven columnar structure of the electrode.

Long noncoding RNA THAP9-AS1 is induced by Helicobacter pylori and promotes cell growth and migration of gastric cancer.

BACKGROUND: Long noncoding RNAs (LncRNAs) have been confirmed to play crucial roles in cancer biology. Gastric cancer (GC) is the third leading cause of cancer related death, and Helicobacter pylori (H. pylori) is the major risk factor for GC. In this study, we focused on the roles of H. pylori-related lncRNAs in the progression of GC. METHOD: Differentially expressed lncRNAs were identified through RNA-seq analysis of H. pylori-infected GC cells. RESULTS: We found that the expression of the lncRNA THAP9-AS1 was up-regulated after infection of GC cells with H. pylori and was higher in GC tissues than in gastritis tissues. Colony formation, CCK8 and transwell assays were executed to show that THAP9-AS1 can promote GC cell proliferation and migration in vitro. Our study identified the pro-oncogenic lncRNA THAP9-AS1, which has a higher expression level in GC tissues than in gastritis tissues and which promoted the proliferation and migration of GC cells in vitro. CONCLUSION: These findings may provide a potential therapeutic target for H. pylori-associated GC.

MiRNA-491-5p inhibits cell proliferation, invasion and migration via targeting JMJD2B and serves as a potential biomarker in gastric cancer.

Our previous work discovered that the histone demethylase JMJD2B (KDM4B) plays oncogenic roles in gastric carcinogenesis, but the regulatory mechanism of JMJD2B in gastric cancer has not been well defined. It has been revealed that microRNAs function as gene regulators by binding to the 3'UTR of mRNAs to inhibit gene expression. In this study, we found that miR-491-5p suppressed cell proliferation, invasion and migration by directly targeting the JMJD2B 3'UTR in gastric cancer. Moreover, miR-491-5p was decreased in GC tissues compared with adjacent normal tissues, and JMJD2B had the inverse expression pattern. In contrast to healthy individuals, GC patients had lower miR-491-5p expression in serum (P<0.0001). Our data indicate that miR-491-5p serves as a tumor suppressor in GC and might be a novel potential biomarker for the detection of gastric cancer.