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.

Facile Preparation of Raspberry-Like SiO2@Polyurea Microspheres with Tunable Wettability and Their Application for Oil-Water Separation.

Raspberry-like microspheres have been widely used as superhydrophobic materials, photonic crystals, drug carriers, etc. Nevertheless, their preparation methods, usually consisting of multiple steps, are generally time- and energy-consuming. Herein raspberry-like SiO2@polyurea microspheres (SiO2@PUM) are readily prepared via a one-step precipitation polymerization of isophorone diisocyanate in a H2O/acetone mixture with the presence of SiO2 particles. The sphere size, surface roughness, and SiO2 content of SiO2@PUM are easily adjustable by varying the experimental conditions. TEM and SEM observations reveal that the final SiO2@PUM exhibits a core-shell structure, with polyurea (PU) in the core and SiO2 particles as the shell. In the process, the SiO2 particles were initially located on the PUM surface as a monolayer. With the reaction proceeding, the monolayer of SiO2 particles became thicker, forming a thicker layer of SiO2 particles on PUM due to the accumulation of SiO2 particles, leading to a multilayer structure of SiO2 particles on the shell of SiO2@PUM. The formation mechanism of the raspberry-like SiO2@PUM was thoroughly discussed and ascribed to electrostatic attraction between the positively charged PU and negatively charged SiO2 particles. Once dried, SiO2@PUM was superhydrophobic and turned hydrophilic if water-wetted. Using a layer of SiO2@PUM, effective separation with good reusability for a variety of oil-water mixtures was achieved regardless of the oil density and types of oil-water emulsions. This work presents a novel protocol for the preparation of raspberry-like microspheres with tunable wettability via a rapid and green process, and the resulting microspheres are highly effective for the separation of diverse types of oil-water mixtures.

Evaluating heavy metals-related risk in staple crops and making financing strategy for corresponding soil remediation across China.

China's staple crops face heavy metal (HMs) contamination, a widespread issue lacking a national assessment. We used machine learning (ML) to assess risks of 8 HMs in rice, wheat, and maize, and estimated a financing strategy for soil remediation via linear optimization and computable general equilibrium (CGE). The accumulation of HMs in crops depends on Soil-HMs, climate, soil properties, and crop types. Cd and Hg pose major soil pollution risks, while Cr, Pb, and Cd are the most threatening in crops. High-risk zones are located at the warm temperature and subtropical zones, with wheat most vulnerable. Over a quarter (26.77 %) of the nation's croplands are classified as high-risk, with a significant 60.89 % falling into the medium-risk category, leaving merely 12.34 % of the agricultural land in a safe condition. The estimated remediation cost is 58596.73 billion RMB and the crop loss is 808.03 billion RMB in a ten-year remediation period at the context of secure crop supply. The reallocation of social investment rather than raising new taxation for the remediation is beneficial to the GDP increase and social welfare despite some loss in the household income and enterprise income. This study provides a comprehensive evaluation for Crop-HMs risk and remediation policy, crucial for national crop security.

K4Cd3Ge4O13: A Congruent-Melting Germanate Nonlinear Optical Crystal with a Moderate Second-Harmonic Generation Intensity and Broad Transparent Window.

Mid-infrared (IR) nonlinear optical (NLO) materials have generated extensive research interest because of their crucial role in laser technology applications. Here, we report the synthesis of a novel cadmium germanate NLO crystal, K4Cd3Ge4O13, using spontaneous crystallization. K4Cd3Ge4O13 demonstrates a distinct three-dimensional structural framework characterized by twisted [Ge4O13] and [Cd3O10] clusters, composed of [GeO4], [CdO4], [CdO5], and [CdO6] basic building units, respectively, which represents an unprecedented structural feature. The title compound undergoes a desirable congruent melting behavior at about 727 °C. Notably, K4Cd3Ge4O13 demonstrates a short UV cutoff edge at 261 nm, coupled with a wide energy gap of 4.4 eV, and maintains an extended IR transparency window at around 6.0 µm. More importantly, it demonstrates a strong second-harmonic generation activity comparable to that of KH2PO4 (KDP) at 1064 nm. Theoretical analyses further elucidate that the remarkable optical performances of K4Cd3Ge4O13 are predominantly attributed to the cooperative effects of Ge-O and Cd-O bond-based motifs. These desired characteristics underscore the potential of K4Cd3Ge4O13 as a good candidate material for mid-IR NLO applications.

Location Privacy Protection for the Internet of Things with Edge Computing Based on Clustering K-Anonymity.

With the development of the Internet of Things (IoT) and edge computing, more and more devices, such as sensor nodes and intelligent automated guided vehicles (AGVs), can serve as edge devices to provide Location-Based Services (LBS) through the IoT. As the number of applications increases, there is an abundance of sensitive information in the communication process, pushing the focus of privacy protection towards the communication process and edge devices. The challenge lies in the fact that most traditional location privacy protection algorithms are not suited for the IoT with edge computing, as they primarily focus on the security of remote servers. To enhance the capability of location privacy protection, this paper proposes a novel K-anonymity algorithm based on clustering. This novel algorithm incorporates a scheme that flexibly combines real and virtual locations based on the requirements of applications. Simulation results demonstrate that the proposed algorithm significantly improves location privacy protection for the IoT with edge computing. When compared to traditional K-anonymity algorithms, the proposed algorithm further enhances the security of location privacy by expanding the potential region in which the real node may be located, thereby limiting the effectiveness of "narrow-region" attacks.

Study on the removal of Cd from dewatered sludge by combined extraction agents: Peel extract and compound chemical extraction agent.

The recycling of fruit peel resources is a current research hotspot. This study screened and configured a composite extractant consisting of peel and chemical extractant through extraction experiments and explored the heavy metals(HMs) release effect. The results showed that citrus reticulata(CR), citrullus lanatus (CL), 0.16 mol·L-1 nitrilotriacetic acid(NTA) with 0.04 mol·L-1 oxalic acid(NO5), and 0.12 mol·L-1NTA with 0.08 mol·L-1tartaric acid(NT4) had the strongest extraction ability. After the cross-combination was optimized, CR-NO5 (1:50, 6 h, 35 °C) and CL-NT4 (1:50, 36 h, 45 °C) had the highest extraction rates for Cd and Zn, which were 92.6 % and 98.4 %, respectively. The CL series increased the nutrient content of sludge (157.75-177.88 g·kg-1). The four combined extractants increased the proportion of soluble components of HMs in sludge (14-36 %). Therefore, the combined leaching agent will provide a valuable reference for the harmless treatment of HMs in sludge and the resource utilization of peel waste.

Influence of soil pH and organic carbon content on the bioaccessibility of lead and copper in four spiked soils.

Exploration of the association between heavy metal bioaccessibility (BAc) and soil properties is essential for rationalization of risk assessment and remediation of contaminated soil; however, the high complexity of soil systems often yield conflicting outcomes. To avoid erroneous conclusions, individual comparisons of soil properties is essential. Herein, we determined the changes in the BAc of Pb and Cu with the variation in soil pH and SOC content using Unified Bioaccessibility Research Group of Europe method, and validated these findings with in vivo mouse bioassays. Results indicated that the BAc of Pb and Cu in gastric and intestinal phases decreased by 1.76%-3.92% and 0.90%-3.27%, and by 0.41%-6.01% and 0.67%-1.59%, respectively, with every unit increase in soil pH. Furthermore, with every 1% increase in the absolute content of SOC, the BAc of Pb and Cu decreased by 4.04%-13.94% and 4.01%-34.7%, and by 8.98%-30.15% and 9.58%-20.03%, respectively. The in vivo bioassays results confirmed decrease in Pb concentrations in the liver, kidney, and blood of mice with the increase in Ferralosol pH and SOC content. These findings revealed that the health risks associated with accidental exposures to Pb- and Cu-contaminated soils with high pH and SOC level were relatively low, and the consistent in vivo and in vitro results for the BAc of Pb and Cu suggest the requirement for a swift and simple approach for assessing the risks of heavy metal contaminated soils. Thus, this study enhanced our understanding of the variations in risk assessments with soil properties of Pb- and Cu-contaminated soils, highlighting the role of soil characteristics in health risk assessment and remediation of contaminated soils.

Heterogeneous and interactive effects of payments for ecosystem services on household income across giant panda nature reserves.

Numerous Payments for Ecosystem Services (PES) programs have been implemented simultaneously around the world but their outcomes in the literature are not consistent and their interactive effects remain understudied. The Natural Forest Conservation Program (NFCP) and Grain to Green Program (GTGP) are two largest PES programs in the world, and many studies have evaluated their effects on household income. However, the identified effects often varied across different studies and the factors explaining this variation are poorly understood. This study used linear regression and geographic detector analysis, based on questionnaire survey data from 14 giant panda natural reserves (NRs) in southwestern China, to evaluate the effects of the NFCP and GTGP on household income and the factors which moderate these effects. The results revealed that the effects of two PES programs on household income were spatially heterogeneous and enhanced by each other and livelihood activities, suggesting a synergistic interaction between policies and livelihood activities, particularly tourism. This study also found that livelihoods activities (e.g., labor migration and tourism), household capital (i.e., house area and farmland area) and demographic factors (i.e., number of labor and non-labor members), exhibit spatial heterogeneity in their effects on household income across NRs. These findings underscore the importance of considering local socioeconomic conditions and the interaction between policy and socio-economic conditions in PES program design to achieve desired outcomes, providing insights for policymakers and practitioners worldwide.

Effect of environmental factors on adsorption of ciprofloxacin from wastewater by microwave alkali modified fly ash.

Antibiotics, as emerging persistent pollutants, pose significant threats to human health. The effective and low-cost removal of ciprofloxacin (CIP) from wastewater has become an important research focus. In this study, fly ash (FA) was used as the raw material, and modified fly ash (MFA) was prepared by varying microwave power, alkali concentration, and immersion time to investigate its adsorption characteristics for CIP. Results showed that the optimal preparation conditions for MFA with the most effective adsorption of CIP, using the Box-Behnken response surface methodology, were a microwave power of 480 W, an alkali concentration of 1.5 mol/L, and a modification time of 3 h. Scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analyses revealed that after modification, the glassy structure of FA is destroyed, the specific surface area is increased, and obvious hydroxyl O-H absorption peaks appear. Both FA and MFA exhibited adsorption processes for CIP that conformed to pseudo-second-order kinetics and the Langmuir equation. Maximum adsorption of CIP (9.61 and 12.67 mg/g) was achieved at pH = 6. With increasing temperature, the adsorption capacity of both FA and MFA for CIP decreased, indicating an exothermic process. The adsorption capacity of CIP decreased with increasing ion concentration, with the impact order of ions being Al3+ > Ca2+ > Na+. The results show that pore filling, electrostatic interaction, ion exchange and complexation are the main ways of CIP adsorption by FA. Microwave alkali modified fly ash is an economical and efficient adsorbent for CIP removal in water, realizing the purpose of "treating waste with waste". This study provides a scientific basis for controlling CIP treatment in wastewater.

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.

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.

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.

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.

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.

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.

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.