Investigating the molecular mechanisms between type 1 diabetes and mild cognitive impairment using bioinformatics analysis, with a focus on immune response.

The immune system is involved in the development and progression of several diseases. Type 1 diabetes mellitus (T1DM), an autoimmune disorder, influences the progression of several other conditions; however, the link between T1DM and mild cognitive impairment (MCI) remains unclear. This study investigated the underlying immune response mechanisms that contribute to the development and progression of T1DM and MCI. Microarray datasets for MCI (GSE63060) and T1DM (GSE30208) were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the limma package. To explore the functional implications of these DEGs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted using ClusterProfiler. Protein-protein interaction networks for the DEGs were constructed using the STRING database and visualized using Cytoscape. The Molecular Complex Detection algorithm was used to analyze DEGs. Immune cell infiltration in patients with T1DM and MCI was analyzed using the xCell method. Gene set enrichment analysis was used to gain in-depth insights into the functional characteristics of T1DM and MCI. Immune-related genes were obtained from the GeneCards and ImmPort databases. Machine learning algorithms were used to identify potential hub genes associated with immunity for T1DM and MCI diagnosis, and the diagnostic value was assessed using the receiver operating characteristic curve. The identified genes were validated using quantitative polymerase chain reaction. In the T1DM and MCI datasets, 610 DEGs showed consistent trends, of which 232 and 378 were upregulated and downregulated, respectively. Immune response analysis revealed significant changes in the immune cells associated with MCI and T1DM. Using immune-related genes, DEGs, and machine learning techniques, we identified CD3D in the MCI and T1DM groups. We observed a gradual decline in the cognitive function of mice with T1DM as the disease progressed. CD3D expression increased with increasing disease severity; CD3D primarily affected CD4+ T cells. This study revealed a complex interaction between T1DM and MCI, providing novel insights into the intricate relationship between immune dysregulation and cognitive impairment and expanding our understanding of these two interconnected disorders. These findings will facilitate the development of therapeutic interventions and identification of potential therapeutic targets.

TNFSF15 inhibits progression of diabetic retinopathy by blocking pyroptosis via interacting with GSDME.

Diabetic retinopathy is a common microvascular complication of diabetes and a leading cause of blindness. Pyroptosis has emerged as a mechanism of cell death involved in diabetic retinopathy pathology. This study explored the role of GSDME-mediated pyroptosis and its regulation by TNFSF15 in diabetic retinopathy. We found GSDME was upregulated in the progression of diabetic retinopathy. High glucose promoted GSDME-induced pyroptosis in retinal endothelial cells and retinal pigment epithelial cells, attributed to the activation of caspase-3 which cleaves GSDME to generate the pyroptosis-executing N-terminal fragment. TNFSF15 was identified as a binding partner and inhibitor of GSDME-mediated pyroptosis. TNFSF15 expression was increased by high glucose but suppressed by the caspase-3 activator Raptinal. Moreover, TNFSF15 protein inhibited high glucose- and Raptinal-induced pyroptosis by interacting with GSDME in retinal cells. Collectively, our results demonstrate TNFSF15 inhibits diabetic retinopathy progression by blocking GSDME-dependent pyroptosis of retinal cells, suggesting the TNFSF15-GSDME interaction as a promising therapeutic target for diabetic retinopathy.

Catalytic Asymmetric Intermolecular [3 + 2] Photocycloaddition of Cyclopropylamines with Electron-Deficient Olefins.

An enantioselective intermolecular [3 + 2] cycloaddition of N-arylcyclopropylamines with 2-aryl acrylates/ketones and cyclic ketone-derived terminal olefins via asymmetric photoredox catalysis is reported. A dual catalyst system involving DPZ and a chiral phosphoric acid is effective for the transformations, leading to a wide array of valuable cyclopentylamines with high yields, ee's, and drs. Among them, elaborate modulation of the ester group of 2-aryl acrylates was shown to be effective in improving reactivity, thereby enabling the success of the transformations.

"Dark under the lamp": ecological equity of urban agglomeration from the perspective of natural capital in China.

Although equity is an important aspect of sustainable development, equity research has mainly focused on income and economics while paying insufficient attention to ecological equity. Therefore, aiming to improve our understanding of equity and promote environmental protection, this study introduced natural capital to measure regional ecological equity and analyze its driving factors. Based on ecological footprint (EF) and ecosystem service value (ESV), we constructed evaluation indexes and drew an "ecological Lorentz curve bundle" to analyze ecological equity in the Jing-Jin-Ji urban agglomeration (JUA) from 2009 to 2020. The results showed that economic development in JUA resulted in the severe depletion of natural capital, especially biological and energy resources, and the supply and demand of natural capital was in a low-level equilibrium state. Based on JUA's population base, natural capital utilization in the region had exceeded ecological equity, and the Gini coefficient of EF based on population was close to the international warning value of 0.4. Although economic development in JUA has promoted economic equity, it has also led to environmental inequity. Large cities such as Beijing and Tianjin, as well as industrial cities such as Tangshan and Handan, have had the greatest effects on ecological equity. Moreover, the excessive consumption of natural capital stock and energy-dependent industrial structures threaten ecological equity.

Asymmetric [3 + 2] photocycloadditions of cyclopropylamines with electron-rich and electron-neutral olefins.

Radical addition to olefins is a common and useful chemical transformation. In the context of offering enantioenriched three-dimensional molecules via such a highly reactive process, chiral hydrogen-bonding (H-bonding) catalysis has been widely used to provide enantiocontrol. The current strategies for operating H-bonding induction are confined to following that are prevalent in ionic-type manifolds. Here, we report a novel protocol towards electron-rich olefins based on converting these species from acting as H-bonding donors to acceptors. It facilitates the first development of asymmetric [3 + 2] photocycloadditions with cyclopropylamines. The method is also effective for electron-neutral olefins, in which the successful construction of all-carbon quaternary stereocentres from 1,1-diaryl ethylenes that feature two structurally similar aryl substituents demonstrates the versatility of this new chiral H-bonding catalytic strategy. Furthermore, the importance of the obtained six kinds of products in pharmaceuticals and asymmetric catalysis underscores the practicability of this work.

Mitigating cadmium contamination of rice soils supporting tobacco-rice rotation in southern China: Win-win or lose-lose?

The present study evaluates the sustainability of tobacco-rice rotation by reducing the phytoavailability of cadmium (Cd) to rice by combining large-scale field sampling and regional investigations in southern China. The rotation involves frequent tillage and liberal application of nitrogen and phosphorus fertilizers, which increases yields but lowers soil pH. As a result, manganese is lost from soil and, at the same time, more soil Cd is taken up by rice and tobacco. The tendency to overcompensate for the Mn loss is influenced by soil properties, crop type, and economics of cultivation. Based on the scenario analysis, this tendency and the Cd uptake risks were estimated. Dietary intake of 83.3% of rice grain produced on the rotation fields would have adverse health effects on local male nonsmokers. Besides the rice, Cd in local tobacco leaf may lead to an increase in the kidney Cd levels of local male smokers (21.5 cigarettes per day) by 16.2-fold at age 50. Field trials and model estimations indicated that for a Cd concentration below 0.2 mg dry weight kg-1 in rice grain, the critical pH value in rice soils was ~ 6.0, and that for amorphous Mn oxide at pH 4.5-6.0 was 120 mg kg-1.

Derivation of human health risk-based thresholds for lead in soils promote the production of safer wheat and rice.

A reliable and accurate soil threshold helps prevent excessive dietary Pb intake risks to consumers of locally grown wheat and rice crops. Based on a three-year investigation of 206 wheat fields and 358 rice fields throughout China, this study aimed to improve the soil protection guidelines by investigating Pb accumulation in soil-wheat and soil-rice systems and by assessing Pb exposure risks through the soil-grain-human pathway. A site-specific bioconcentration factor (BCF, ratio of Pb concentration in plant to that in soil) was calculated and used to assess grain Pb intake risks instead of a generic BCF value to reduce data uncertainty. In addition to soil pH, cation-exchange capacity exerted a major influence on the Pb BCF variations in wheat, whereas the organic carbon dynamics affected the BCF variations in rice. Once normalized BCF against those soil variables, the distributions of BCF were log-normal in nature. Optimizing the pH and cation-exchange capacity of wheat soils would help protect 49.8% of local adults from excessive Pb dietary intake. The scenario soil thresholds linked to soil variables and grain Pb intake risks were then derived and validated by independent data from field surveys and published articles. Poor production practices in the wheat fields under study included using soils with low fertility.

Exposure to potentially toxic elements through the soil-tobacco-human pathway: causative factors and probabilistic model.

High concentrations of potentially toxic elements (PTEs) in tobacco leaves are possible from the soil contamination and would have adverse health risks on residents. A large-scale survey of 306 tobacco fields in southern China was conducted to investigate the accumulation of PTEs in tobacco leaves through the soil-tobacco-human pathway and the associated health risks for local smokers and passive smokers. Significant enrichment of As, Cd, Hg, and Pb was observed in the investigated tobacco fields, with industrial emissions and applied fertilizers as the major potential sources. Dynamic interactions between factors in the soil acidic labile pool showed site-specific effects on the uptake of PTEs by tobacco plants. It was 99.6% and 91.8% probable that exposure of local adult men smokers to Cd and As exceeded the permitted safety limits, respectively. The population of men smokers had a 20-fold higher Cd exposure risk than did passive smokers. A probability-based transfer model was developed to demonstrate that interactions between soil factors could affect the Cd exposure risk of men smokers of locally harvested tobacco. Optimizing the pH (>6.0) and organic matter content (>40 g kg-1) of tobacco-growing soils, and setting a safe tobacco consumption rate of 2.80 g dry weight per day would help protect 90.4% of men smokers from excessive risks of exposure to Cd.

Quantifying source-specific intake risks of wheat cadmium by associating source contributions of soil cadmium with human health risk.

Sources of cadmium (Cd) contamination of farmlands and the potential risk to human health via dietary intake of wheat Cd are of great concern to consumers. A source-specific risk assessment (SSRA) model, which combined a positive matrix factorization receptor model and spatial analysis with a health risk assessment model, was developed based on a wheat field investigation in northern China. It was used to estimate the daily intake risk from different sources of ingesting Cd from wheat. The mixed source of wastewater and residues from industrial activities and atmospheric deposition were identified as the dominant sources of Cd contamination. Wheat Cd uptake could be predicted reliably from the pH and total Cd concentration of field soil. Based on the predictive model of Cd transfer from soil to wheat, the SSRA model then linked sources to the Cd intake risk from wheat grain. Results showed that the mixed source and the atmospheric deposition source accounted for 52.8% and 29.3%, respectively, of the wheat Cd intake risk. In combination with the spatial analysis, the potential risk of Cd contamination in western and central eastern areas was mainly attributed to the mixed source of wastewater and industrial residues, whereas the risk in the northwestern area was associated mainly with atmospheric deposition. Regionalized risk management strategies, focusing on different sources, were proposed to minimize the Cd input to field cropping system and to mitigate health risk for local residents.

Historical and future trends of cadmium in rice soils deduced from long-term regional investigation and probabilistic modeling.

When rice soils are contaminated by cadmium (Cd), the sources and timing of such contaminations need to be identified. In this study, we aimed to quantify the sources, history, and fate of Cd in the rice soils of southern China, by combining a near 10-year regional investigation, by developing a normalized positive matrix factorization algorithm, a Cd mass balance model, and probabilistic simulation. We simulated the historical contamination process of Cd in rice soils from 1991 to 2019 and the future changes from 2019 to 2069 under varying input parameters, as affected by different environmental management measures. Over the period of 1991-2019, the input flux of Cd through atmospheric deposition was estimated at 421 g ha-1, which contributed 52.1% of the total increments in soil Cd concentration. Over the next decade, a 25.6% probability is predicted that the Cd concentration of local rice soils would increase from the baseline to the upper level of soil threshold, despite the efforts of environmental regulators. Removing the rice straw from production fields, cleaning up the irrigation channels, and strengthening environmental regulations would take approximately 50 years (2019-2069) to ensure that 90% of soils were safe for rice cultivation.

Limestone dosage response of cadmium phytoavailability minimization in rice: A trade-off relationship between soil pH and amorphous manganese content.

Limestone shows great potential to reduce the production of cadmium (Cd)-contaminated rice in acidic paddy soils, but has generated uncertainty effects. We conducted batch sorption and greenhouse experiments to investigate optimal conditions of pH and amorphous manganese content (Mnox) in limestone treated-soil for suppressing the Cd uptake by rice plants. The adsorption/desorption behavior of Cd in a soil/limestone mixture was dominated by the composition and density of sorption sites, followed by sorption conditions, which were mainly influenced by soil pH and exchangeable Ca2+. Interactions among soil factors were influenced both by the limestone effects and plant responses. The Cd uptake of rice plants did not matched to the doses of limestone applied. The increase in pH and decrease in Mnox following higher dosages of limestone treatment might produce contradictory effects on rice Cd uptake. We proposed a trade-off model to demonstrate how did the interactions of soil pH and Mnox affect the rice Cd uptake. To minimize the accumulation of Cd in rice grain harvested from acidic paddy soils, limestone was applied at 0.25 % to achieve an optimal pH of 6.5 and a Mnox of 95 mg kg-1.

[Simulation Cadmium (Cd) Accumulation in Typical Paddy Soils in South China].

The simulation analysis of the migration path and soil accumulation trend of Cd in paddy soil systems could contribute to improved scientific and reasonable risk decision-making. In this study, based on a regional survey of environmental media in Youxian County, Hunan Province, a pollutant accumulation model (PAM) was built to predict the cumulative trend of Cd in paddy soils. Combined with Monte Carlo simulation, the PAM model was used to evaluate the effectiveness and sustainability of various remediation measures. Results showed that the probability of Cd accumulation in paddy soils in Youxian County exceeded that of the national soil environmental quality standard by 2-fold and was up to 82.1%, and the average accumulation rate reached 4.28 µg·(kg·a)-1 after 50 years of cultivation under current input pattern. Sensitivity analysis results showed that atmospheric deposition and rice uptake were the key processes affecting Cd accumulation in paddy soils. Results of a multi-scenario simulation showed that the comprehensive measures, such as reducing the straw returning, optimizing the layout of industrial and mining enterprises that reduce the atmospheric deposition of Cd, and cleaning irrigation water, could reduce the Cd accumulation in paddy soils by 43.7% and reduce the probability of light Cd pollution by 80.6% after 50 years, which would be an effective long-term measure to prevent and control Cd pollution risk in paddy soils.

Dynamic interactions between soil cadmium and zinc affect cadmium phytoavailability to rice and wheat: Regional investigation and risk modeling.

Characterizing the interactions between Cd and Zn with respect to the soil soluble Cd and crop Cd uptake allows the development of risk-based approaches to the performance of grain crops. By means of a three-year survey of 358 rice fields and 206 wheat fields across China, this study investigated the effect of Cd-Zn interactions on the phytoavailability of Cd to rice and wheat. The interactive nature between the Cd:Zn ratio and pH of soil affected crop Cd uptake, and the resulting grain Cd intake risk, were examined by the Free-Ion Activity-based model and probability analysis. In highly acidic rice soils (pH < 5.9), soil Zn had no effect on rice Cd uptake, whereas, under near-neutral conditions (pH > 5.9), a site-specific influence of soil Zn on grain Cd concentration was found. Soil Zn could inhibit Cd uptake and translocation by the plant in soil-wheat system when the soil Cd:Zn ratio decreased to 0.0083 and lower. Rice grain poses a significant health risk to local consumers due to its high Cd accumulation and its low Zn accumulation. In order to reduce the health risks from dietary Cd to local consumers, approximately 63.9% of the rice fields and 30.5% of the wheat fields require strategies ameliorating soil acidity in rice soils and increasing Zn concentrations in wheat soils.

Conjugate Addition-Enantioselective Protonation of N-Aryl Glycines to α-Branched 2-Vinylazaarenes via Cooperative Photoredox and Asymmetric Catalysis.

An enantioselective protonation strategy has been successfully applied to the synthesis of chiral α-tertiary azaarenes. With a dual catalytic system involving a chiral phosphoric acid and a dicyanopyrazine-derived chromophore (DPZ) photosensitizer that is mediated by visible light, a variety of α-branched 2-vinylpyridines and 2-vinylquinolines with N-aryl glycines underwent a redox-neutral, radical conjugate addition-protonation process and provided valuable chiral 3-(2-pyridine/quinoline)-3-substituted amines in high yields with good to excellent enantioselectivities (up to >99% ee). An application of this methodology to a two-step synthesis of the enantiomerically pure medicinal compound pheniramine (Avil) is also presented.

[Ecosystem carbon exchange in Artemisia ordosica shrubland of Ordos Plateau in two different precipitation years].

Characteristics of ecosystem carbon exchange and its impact factors in Artemisia ordosica shrubland in 2011 (low precipitation) and 2012 (high precipitation), Ordos Plateau, were studied using eddy covariance methods. The results showed that the diurnal dynamics of ecosystem carbon exchange could be expressed as single-peak and double-peak curves in the two different precipitation years. In 2011, three carbon absorption peaks and three carbon release peaks of ecosystem carbon exchange presented in the growing season. In 2012, four carbon absorption peaks and one carbon release peak appeared in the growing season. The A. ordosica shrubland was a net carbon sink from June to September and a carbon source in October in 2011. In 2012, A. ordosica shrubland was a net carbon sink in the whole growing season. The amount of carbon fixed by A. ordosica shrubland in the growing season in 2012 was 268.90 mg CO2 x m(-2) x s(-1) higher than that in 2011. The ecosystem carbon exchange of A. ordosica shrubland was controlled by PAR (photosynthetically active radiation) on the day scale, and affected by both abiotic (precipitation and soil water content) and biotic (aboveground net primary, productivity) factors on the growing season scale.