Subretinal fibrosis secondary to neovascular age-related macular degeneration: mechanisms and potential therapeutic targets.

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration. It causes local damage to photoreceptors, retinal pigment epithelium, and choroidal vessels, which leads to permanent central vision loss of patients with neovascular age-related macular degeneration. The pathogenesis of subretinal fibrosis is complex, and the underlying mechanisms are largely unknown. Therefore, there are no effective treatment options. A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments. The current article reviews several aspects of subretinal fibrosis, including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis; multimodal imaging techniques for subretinal fibrosis; animal models for studying subretinal fibrosis; cellular and non-cellular constituents of subretinal fibrosis; pathophysiological mechanisms involved in subretinal fibrosis, such as aging, infiltration of macrophages, different sources of mesenchymal transition to myofibroblast, and activation of complement system and immune cells; and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis, such as vascular endothelial growth factor, connective tissue growth factor, fibroblast growth factor 2, platelet-derived growth factor and platelet-derived growth factor receptor-ß, transforming growth factor-ß signaling pathway, Wnt signaling pathway, and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10. This review will improve the understanding of the pathogenesis of subretinal fibrosis, allow the discovery of molecular targets, and explore potential treatments for the management of subretinal fibrosis.

Next-Generation Green Hydrogen: Progress and Perspective from Electricity, Catalyst to Electrolyte in Electrocatalytic Water Splitting.

Green hydrogen from electrolysis of water has attracted widespread attention as a renewable power source. Among several hydrogen production methods, it has become the most promising technology. However, there is no large-scale renewable hydrogen production system currently that can compete with conventional fossil fuel hydrogen production. Renewable energy electrocatalytic water splitting is an ideal production technology with environmental cleanliness protection and good hydrogen purity, which meet the requirements of future development. This review summarizes and introduces the current status of hydrogen production by water splitting from three aspects: electricity, catalyst and electrolyte. In particular, the present situation and the latest progress of the key sources of power, catalytic materials and electrolyzers for electrocatalytic water splitting are introduced. Finally, the problems of hydrogen generation from electrolytic water splitting and directions of next-generation green hydrogen in the future are discussed and outlooked. It is expected that this review will have an important impact on the field of hydrogen production from water.

Long-term Application of Agricultural Amendments Regulate Hydroxyl Radicals Production during Oxygenation of Paddy Soils.

Hydroxyl radicals (•OH) play a significant role in contaminant transformation and element cycling during redox fluctuations in paddy soil. However, these important processes might be affected by widely used agricultural amendments, such as urea, pig manure, and biochar, which have rarely been explored, especially regarding their impact on soil aggregates and associated biogeochemical processes. Herein, based on five years of fertilization experiments in the field, we found that agricultural amendments, especially coapplication of fertilizers and biochar, significantly increased soil organic carbon contents and the abundances of iron (Fe)-reducing bacteria. They also substantially altered the fraction of soil aggregates, which consequently enhanced the electron-donating capacity and the formation of active Fe(II) species (i.e., 0.5 M HCl-Fe(II)) in soil aggregates (0-2 mm), especially in small aggregates (0-3 µm). The highest contents of active Fe(II) species in small aggregates were mainly responsible for the highest •OH production (increased by 1.7-2.4-fold) and naphthalene attenuation in paddy soil with coapplication of fertilizers and biochar. Overall, this study offers new insights into the effects of agricultural amendments on regulating •OH formation in paddy soil and proposes feasible strategies for soil remediation in agricultural fields, especially in soils with frequent occurrences of redox fluctuations.

Clinical and genetic analysis of a case of O'Donnell-Luria-Rodan syndrome manifesting as growth retardation. / 以生长发育迟缓为表现的1例O'Donnell-Luria-Rodanç»¼åˆå¾ä¸´åºŠä¸Žé—ä¼ å­¦ç‰¹å¾åˆ†æž.

O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant genetic disorder caused by mutations in the KMT2E (lysine methyltransferase 2E) gene. The Third Xiangya Hospital of Central South University admitted a 12-year and 9-month-old male patient who presented with growth retardation, intellectual disability, and distinctive facial features. Peripheral blood was collected from the patient, and DNA was extracted for genetic testing. Chromosome karyotyping showed 46XY. Whole-exome sequencing and low-coverage massively parallel copy number variation sequencing (CNV-seq) revealed a 506 kb heterozygous deletion in the 7q22.3 region, which includes 6 genes, including KMT2E. The patient was diagnosed with ODLURO syndrome. Both the patient's parents and younger brother had normal clinical phenotypes and genetic test results, indicating that this deletion was a de novo mutation. The clinical and genetic characteristics of this case can help increase clinicians' awareness of ODLURO syndrome.

Photocatalytic CO2 Reduction by Near-Infrared-Light (1200 nm) Irradiation and a Ruthenium-Intercalated NiAl-Layered Double Hydroxide.

Near-infrared light-driven photocatalytic CO2 reduction (NIR-CO2PR) holds tremendous promise for the production of valuable commodity chemicals and fuels. However, designing photocatalysts capable of reducing CO2 with low energy NIR photons remains challenging. Herein, a novel NIR-driven photocatalyst comprising an anionic Ru complex intercalated between NiAl-layered double hydroxide nanosheets (NiAl-Ru-LDH) is shown to deliver efficient CO2 photoreduction (0.887 µmol h-1) with CO selectivity of 84.81% under 1200 nm illumination and excellent stability over 50 testing cycles. This remarkable performance results from the intercalated Ru complex lowering the LDH band gap (0.98 eV) via a compression-related charge redistribution phenomenon. Furthermore, transient absorption spectroscopy data verified light-induced electron transfer from the Ru complex towards the LDH sheets, increasing the availability of electrons to drive CO2PR. The presence of hydroxyl defects in the LDH sheets promotes the adsorption of CO2 molecules and lowers the energy barriers for NIR-CO2PR to CO. To our knowledge, this is one of the first reports of NIR-CO2PR at wavelengths up to 1200 nm in LDH-based photocatalyst systems.

Hsa_circ_0010023 promotes the development of papillary thyroid carcinoma by sponging miR-1250-5p.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common thyroid tumor (TC). However, there is still a lack of effective indicators for PTC detection and prognosis. We intended to find a novel tumor marker for the progression of PTC. METHODS: The expression of circRNAs was measured by quantitative real-time polymerase chain reaction (qRT-PCR). SiRNA transfection was used to knockdown the expression of hsa_circ_0010023 in K1 cells. Cell proliferation was evaluated using cell counting and CCK8. Cell apoptosis was analyzed using flow cytometry. Hsa_circ_0010023 downstream pathways were predicted with bio-informatics analysis. The miR-1250-5p and MAPK1 were measured by qRT-PCR. The interaction between miR-1250-5p and hsa_circ_0010023 was vertified by dual-luciferase reporter assay. RESULTS: Among the four circRNAs screened, only hsa_circ_0010023 and hsa_circ_0128482 were highly expressed in PTC (P < 0.05). The expression of hsa_circ_0010023 was significantly correlated with lymph node metastasis and extrathyroid infiltration (P < 0.05). Compared with the control group, the cell proliferation of the si-circ-0010023 group was significantly inhibited (P < 0.05). Knockdown of hsa_circ_0010023 promotes apoptosis of K1 cells (P < 0.001). The expression of hsa_circ_0010023 was negatively correlated with miR-1250-5p and positively correlated with MAPK1. MiR-1250-5p overexpression significantly reduced the luciferase activity of wild type plasmid (hsa_circ_0010023 WT), but not that of mutant type plasmid (hsa_circ_0010023 MUT). CONCLUSION: The expression level of hsa_circ_0010023 was positive related to the progression of PTC, and hsa_circ_0010023 may promote PTC through sponging miR-1250-5p. Hsa_circ_0010023 may be a potential bio-marker for the diagnosis of PTC.

Soil environmental carrying capacity and its spatial high-precision accounting framework.

Human activity intensity should be controlled within the carrying capacity of soil units, which is crucial for environmental sustainability. However, the existing assessment methods for soil environmental carrying capacity (SECC) rarely consider the relationship between human activity intensity and pollutant emissions, making it difficult to provide effective early warning of human activity intensity. Moreover, there is a lack of spatial high-precision accounting methods for SECC. This study first established a spatial soil environmental capacity (SEC) model based on the pollutant thresholds corresponding to the specific protection target. Next, a spatial net-input flux model was proposed based on soil pollutants' input/output fluxes. Then, the quantitative relationship between human activity intensity and pollutant emissions was established and further incorporated into the SECC model. Finally, the spatial high-precision accounting framework of SECC was proposed. The methodology was used to assess the SECC for the copper production capacity in a typical copper smelting area in China. The results showed that (i) the average SECs for Cu, Cd, Pb, Zn, As and Cr are 427.89, 16.84, 306.41, 376.8, 71.63, and 392.7 kg hm-2, respectively; (ii) heavy metal (HM) concentrations and land-use types jointly influence the spatial distribution pattern of SEC; (iii) atmospheric deposition is the dominant HM input pathway and the high net-input fluxes are mainly located in the southeast of the study area; (iv) with the current human activity intensity for 50 years, the average SECs for Cu, Cd, Pb, Zn, As and Cr are 202.31, 1.71, 20.9, 66.15, 36.73, and 3 kg hm-2, respectively; and (v) to maintain the protection target at the acceptable risk level within 50 years, the SECC for the increased copper production capacity is 1.53 × 106 t. This study provided an effective tool for early warning of human activity intensity.

Microbiota-derived 3-phenylpropionic acid promotes myotube hypertrophy by Foxo3/NAD+ signaling pathway.

BACKGROUND: Gut microbiota and their metabolites play a regulatory role in skeletal muscle growth and development, which be known as gut-muscle axis. 3-phenylpropionic acid (3-PPA), a metabolite produced by colonic microorganisms from phenylalanine in the gut, presents in large quantities in the blood circulation. But few study revealed its function in skeletal muscle development. RESULTS: Here, we demonstrated the beneficial effects of 3-PPA on muscle mass increase and myotubes hypertrophy both in vivo and vitro. Further, we discovered the 3-PPA effectively inhibited protein degradation and promoted protein acetylation in C2C12 and chick embryo primary skeletal muscle myotubes. Mechanistically, we supported that 3-PPA reduced NAD+ synthesis and subsequently suppressed tricarboxylic acid cycle and the mRNA expression of SIRT1/3, thus promoting the acetylation of total protein and Foxo3. Moreover, 3-PPA may inhibit Foxo3 activity by directly binding. CONCLUSIONS: This study firstly revealed the effect of 3-PPA on skeletal muscle growth and development, and newly discovered the interaction between 3-PPA and Foxo3/NAD+ which mechanically promote myotubes hypertrophy. These results expand new understanding for the regulation of gut microbiota metabolites on skeletal muscle growth and development.

Determining soil conservation strategies: Ecological risk thresholds of arsenic and the influence of soil properties.

The establishment of ecological risk thresholds for arsenic (As) plays a pivotal role in developing soil conservation strategies. However, despite many studies regarding the toxicological profile of As, such thresholds varying by diverse soil properties have rarely been established. This study aims to address this gap by compiling and critically examining an extensive dataset of As toxicity data sourced from existing literature. Furthermore, to augment the existing information, experimental studies on As toxicity focusing on barley-root elongation were carried out across various soil types. The As concentrations varied from 12.01 to 437.25 mg/kg for the effective concentrations that inhibited 10% of barley-root growth (EC10). The present study applied a machine-learning approach to investigate the complex associations between the toxicity thresholds of As and diverse soil properties. The results revealed that Mn-/Fe-ox and clay content emerged as the most influential factors in predicting the EC10 contribution. Additionally, by using a species sensitivity distribution model and toxicity data from 21 different species, the hazardous concentration for x% of species (HCx) was calculated for four representative soil scenarios. The HC5 values for acidic, neutral, alkaline, and alkaline calcareous soils were 80, 47, 40, and 28 mg/kg, respectively. This study establishes an evidence-based methodology for deriving soil-specific guidance concerning As toxicity thresholds.

Factors driving antimony accumulation in soil-pakchoi and wheat agroecosystems: Insights and predictive models.

The accumulation of antimony (Sb) in plants and its potential effects on human health are of increasing concern. Nevertheless, only a few countries or regions have established soil Sb thresholds for agricultural purposes, and soil properties have not been taken into account. This study investigated the accumulation of Sb in the edible parts of pakchoi and wheat grain by adding exogenous Sb to 21 soils with varying properties. The results revealed a positive correlation between bioavailable Sb (Sbava, extracted by 0.1 M K2HPO4) in soil and Sb in the edible parts of pakchoi (R2 = 0.77, p < 0.05) and wheat grain (R2 = 0.54, p < 0.05). Both machine learning and traditional multiple regression analysis indicated Sbava was the most critical feature and the main soil properties that contributed to Sb uptake by pakchoi and wheat were CaCO3 and clay, respectively. The advisory food limits for Sb in pakchoi and wheat were estimated based on health risk assessment, and used to derive soil thresholds for safe pakchoi and wheat production based on Sbtot and Sbava, respectively. These findings hold potential for predicting Sb uptake by crops with different soil properties and informing safe production management strategies.

Generating 2D Barcode for DNA Barcode Sequences.

DNA barcode sequence is a short DNA sequence representing a sample from a particular species. The commonly used DNA barcodes are at least 200 bps long. This large number of characters cannot be encoded in two-dimensional codes for sample recognition and tracking. In the present study, we described a method that can be used to compress the DNA sequences and then generate the corresponding QR code. With the large numbers of software and hardware, the QR code can be used efficiently for printing, labeling, and scanning.

Activated Carbon Application Simultaneously Alleviates Paddy Soil Arsenic Mobilization and Carbon Emission by Decreasing Porewater Dissolved Organic Matter.

Flooding of paddy fields during the rice growing season enhances arsenic (As) mobilization and greenhouse gas (e.g., methane) emissions. In this study, an adsorbent for dissolved organic matter (DOM), namely, activated carbon (AC), was applied to an arsenic-contaminated paddy soil. The capacity for simultaneously alleviating soil carbon emissions and As accumulation in rice grains was explored. Soil microcosm incubations and 2-year pot experimental results indicated that AC amendment significantly decreased porewater DOM, Fe(III) reduction/Fe2+ release, and As release. More importantly, soil carbon dioxide and methane emissions were mitigated in anoxic microcosm incubations. Porewater DOM of pot experiments mainly consisted of humic-like fluorophores with a molecular structure of lignins and tannins, which could mediate microbial reduction of Fe(III) (oxyhydr)oxides. Soil microcosm incubation experiments cospiking with a carbon source and AC further consolidated that DOM electron shuttling and microbial carbon source functions were crucial for soil Fe(III) reduction, thus driving paddy soil As release and carbon emission. Additionally, the application of AC alleviated rice grain dimethylarsenate accumulation over 2 years. Our results highlight the importance of microbial extracellular electron transfer in driving paddy soil anaerobic respiration and decreasing porewater DOM in simultaneously remediating As contamination and mitigating methane emission in paddy fields.

A polylactic acid degrading lipase from Bacillus safensis: Characterization and structural analysis.

A polylactic acid degrading triacylglycerol lipase (TGL) was identified from Bacillus safensis based on genome annotation and validated by real-time quantitative PCR. TGL displayed optimal activity at pH 9.0 and 55 °C. It maintained stability at pH 9.0 and temperatures 45 °C. The activity of TGL was found to benefit from the presence of potassium sodium ions, and low concentrations of Triton X-100. The TGL could erode the surface of polylactic acid films and increase its hydrophilicity. The hydrolysis products of polylactic acid by TGL were lactate monomer and dimer. TGL contains a classical catalytic triad structure of lipase (Ser77, Asp133, and His156) and an Ala-X-Ser-X-Gly sequence. Compared with some lipases produced by the same genus Bacillus, TGL is highly conserved in its amino acid sequence, mainly reflected in the amino acid residues that exercise the enzyme activity, including the catalytic activity center and the substrate binding sites.

Discovery of an Ortho-Substituted N-Cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaine Derivative as a Selective and Potent Kappa Opioid Receptor Agonist with Subsided Sedative Effect.

Research into kappa opioid receptor (KOR) agonists with attenuated central-nervous-system side effects is a critical focus for developing productive and safe analgesics. Herein, a series of ortho-substituted N-cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaines were designed, synthesized, and subjected to bioassays. Compound 7a exhibited high subtype selectivity and potent agonistic activity toward KOR (KOR, Ki = 3.9 nM, MOR/KOR = 270, DOR/KOR = 1075; [35S]GTPγS binding, EC50 = 3.4 nM). Additionally, this compound exhibited robust and persistent antinociceptive effects in rodent models with different animal strains (hot plate test, ED50 = 0.20-0.30 mg/kg, i.p.; abdominal constriction test, ED50 = 0.20-0.60 mg/kg, i.p.), with its KOR-mediated mechanism for antinociception firmly established. Notably, compound 7a, unlike conventional KOR agonists, displayed minimal sedation and aversion at the antinociceptive ED50 dose. This feature addresses a crucial limitation in existing KOR agonists, positioning compound 7a as a promising novel therapeutic agent.

Determining the net input fluxes of pollutants based on the spatial source apportionment receptor model for early warning of regional soil pollution.

Understanding the soil pollutants' net input fluxes is essential for accurate early warning of regional soil pollution. However, the traditional input-output investigation method for soil pollutants' net input fluxes is often costly, especially at the regional scale. This study first assessed the land-use effects on soil heavy metals around a typical copper smelting area in China. Next, an improved spatial source apportionment receptor model, namely robust absolute principal component scores/robust geographically weighted regression with category land-use information (RAPCS/RGWR-CLU), was proposed to apportion the net source contributions, and its performance was compared with those of RAPCS/RGWR and the traditional absolute principal component scores/multiple linear regression (APCS/MLR). Finally, the net input fluxes of soil heavy metals were determined based on RAPCS/RGWR-CLU, and its performance was compared with that of the traditional input-output investigation method. Results showed that (i) land-use effects are significant for soil As, Cu, Pb, and Zn; (ii) RAPCS/RGWR-CLU achieves higher source apportionment accuracy than RAPCS/RGWR and APCS/MLR; and (iii) the net input fluxes determined by RAPCS/RGWR-CLU have similar accuracy to those determined by the traditional input-output investigation method but with significantly lower costs. Therefore, this study provided a cost-effective solution to determine the net input fluxes of soil pollutants.

Studying of anti-inflammatory and antioxidant effects of tectorigenin in ovalbumin-induced asthma mice models.

BACKGROUND: Allergic asthma is an important respiratory system problem characterized by airway inflammation, breathlessness, and bronchoconstriction. Allergic asthma and its outcomes are triggered by type 2 allergic immune responses. Tectorigenin is a methoxy-isoflavone with anti-inflammatory effects. In this study, we investigated the effects of tectorigenin on the pathophysiology of allergic asthma in an animal model. METHODS: Asthmatic mice were treated with tectorigenin. Then airway hyperresponsiveness (AHR), eosinophil percentage, levels of interleukin (IL)-33, IL-25, IL-13, IL-5, IL-4, total and ovalbumin (OVA)-specific immunoglobulin (Ig)E, and lung histopathology were evaluated. RESULT: Tectorigenin significantly (P 〈 0.05) reduced eosinophil infiltration (41 ± 7%) in the broncho-alveolar lavage fluid (BALF), serum IL-5 level (41 ± 5, pg/mL), and bronchial and vascular inflammation (scores of 1.3 ± 0.2 and 1.1 ± 0.3, respectively) but had no significant effects on AHR, serum levels of IL-33, -25, -13, and -4 (403 ± 24, 56 ± 7, 154 ± 11, and 89 ± 6 pg/mL, respectively), total and OVA-specific IgE (2684 ± 265 and 264 ± 19 ng/mL, respectively), goblet cell hyperplasia, and mucus production. CONCLUSION: Tectorigenin could control inflammation and the secretion of inflammatory mediators of asthma, so it can be regarded as a potential antiasthma treatment with the ability to control eosinophilia-related problems.

Continuous and low-carbon production of biomass flash graphene.

Flash Joule heating (FJH) is an emerging and profitable technology for converting inexhaustible biomass into flash graphene (FG). However, it is challenging to produce biomass FG continuously due to the lack of an integrated device. Furthermore, the high-carbon footprint induced by both excessive energy allocation for massive pyrolytic volatiles release and carbon black utilization in alternating current-FJH (AC-FJH) reaction exacerbates this challenge. Here, we create an integrated automatic system with energy requirement-oriented allocation to achieve continuous biomass FG production with a much lower carbon footprint. The programmable logic controller flexibly coordinated the FJH modular components to realize the turnover of biomass FG production. Furthermore, we propose pyrolysis-FJH nexus to achieve biomass FG production. Initially, we utilize pyrolysis to release biomass pyrolytic volatiles, and subsequently carry out the FJH reaction to focus on optimizing the FG structure. Importantly, biochar with appropriate resistance is self-sufficient to initiate the FJH reaction. Accordingly, the medium-temperature biochar-based FG production without carbon black utilization exhibited low carbon emission (1.9 g CO2-eq g-1 graphene), equivalent to a reduction of up to ~86.1% compared to biomass-based FG production. Undoubtedly, this integrated automatic system assisted by pyrolysis-FJH nexus can facilitate biomass FG into a broad spectrum of applications.

Formation of reactive intermediates in paddy water from different temperature zones for the promotion of abiotic ammonification.

The paddy field is a hot area of biogeochemical process. The paddy water has a large capacity in photo-generation of reactive intermediates (RIs) due to abundant photosensitive dissolved organic matter (DOM), which is influenced by the spatial heterogeneity of paddy soils but rarely been explored. Our work presents the first investigation of the role of soil properties on photochemistry in paddy water. Soil organic matter (SOM), determined by the temperature, was the dominant factor for the photo-generation of RIs in paddy water of main rice producing areas. The RI concentrations generated with abundant SOM from cool regions are 0.05-8.71 times higher than those for the warm regions in China. The humic-like substance and aromatic-like compounds of DOM plays an essential role in RIs generation, which is abundant in paddy soils rich in SOM from Chinese cool regions. In addition, RIs can efficiently accelerate the photo-ammonification of urea and free amino acids by 15.2 %-164 %, leading to 0.13-0.17 mmol/L/d photo-produced ammonium after fertilization, which is preferentially absorbed by rice. The findings of this study will extend our knowledge of the geochemistry of global paddy field ecosystem. The potential role of RIs in nitrogen cycle should be highlighted in the agroecosystem.