Regulation of FSP1 myristoylation by NADPH: A novel mechanism for ferroptosis inhibition.

Excitotoxicity is a prevalent pathological event in neurodegenerative diseases. The involvement of ferroptosis in the pathogenesis of excitotoxicity remains elusive. Transcriptome analysis has revealed that cytoplasmic reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels are associated with susceptibility to ferroptosis-inducing compounds. Here we show that exogenous NADPH, besides being reductant, interacts with N-myristoyltransferase 2 (NMT2) and upregulates the N-myristoylated ferroptosis suppressor protein 1 (FSP1). NADPH increases membrane-localized FSP1 and strengthens resistance to ferroptosis. Arg-291 of NMT2 is critical for the NADPH-NMT2-FSP1 axis-mediated suppression of ferroptosis. This study suggests that NMT2 plays a pivotal role by bridging NADPH levels and neuronal susceptibility to ferroptosis. We propose a mechanism by which the NADPH regulates N-myristoylation, which has important implications for ferroptosis and disease treatment.

Research on the coupling relationship and interaction between urbanization and eco-environment in urban agglomerations: A case study of the Chengdu-Chongqing urban agglomeration.

Urban agglomerations are emerging as new regional units for national participation in global competition and the international division of labor. However, they face increasingly severe resource and eco-environment pressures during urbanization. The coordination of the relationship between urbanization and the eco-environment has attracted global attention. In this study, we used Coupling Coordination Degree and Vector Autoregression models to examine the dynamic evolution, coupling relationships, coordinated development patterns, and interaction mechanisms between urbanization and the eco-environment. The results indicate that: (1) The level of urbanization in the Chengdu-Chongqing Urban agglomeration was relatively low, and the region showed a good eco-environment background. However, rapid urbanization is gradually straining the carrying capacity of the eco-environment. (2) A close and stable coupling relationship exists between urbanization and the eco-environment, which has reached an advanced coupling stage. The status of coordinated development among cities differs considerably, and multiple stable forms may exist simultaneously. (3) Urbanization has a substantial impact on environmental changes, whereas the restrictive effect of the eco-environment on urbanization development is not particularly notable. (4) Various interactive relationships exist between the urbanization and eco-environment subsystems, including positive promotion and negative constraint effects. The positive promotion effect mainly manifests between the economic, social, and ecological response subsystems, while the negative constraint effect is most evident in the mutual coercion and inhibition between the regional urbanization, economic urbanization, ecological status, and ecological pressure subsystems. These findings have important policy implications for decision makers exploring the path of coordinated and sustainable development in urbanization and the eco-environment in Urban agglomerations.

Diverse thermal desorption combined with self-aspirating corona discharge ionization for direct mass spectrometry analysis of complex samples.

The thermal desorption (TD) technique is widely employed in modern mass spectrometry to facilitate the detection of non-volatile analytes. In this study, we developed a compact TD device based on a small resistance wire and coupled it with a self-aspirating corona discharge ionization (CDI) source to conduct direct MS analysis of various liquid and solid samples. Due to its small size and low heat capacity, the temperature of the TD module can be flexibly and rapidly modulated by controlling the power sequence. Multiple heating modes, including pulse heating (PH), isothermal heating, and step heating (SH), are realized and characterized, and then applied for the detection of different real samples. In particular, the PH mode is suitable for the simultaneous detection of multiple components in samples with relatively simple matrices, while the SH mode is capable of component separation. In addition, the sensitivity and quantitative capability of the TD-CDI system for DEP solutions were tested, showing acceptable stability with a relative standard deviation of about 6.7% and a detection limit of 0.088 ng. Overall, the developed TD-CDI system provides a simple, convenient, and versatile tool for direct mass spectrometry analysis of real samples.

Mechanisms of biochar assisted di-2-ethylhexyl phthalate (DEHP) biodegradation in tomato rhizosphere by metabolic and metagenomic analysis.

The intensive accumulation of di-2-ethylhexyl phthalate (DEHP) in agricultural soils has resulted in severe environmental pollution that endangers ecosystem and human health. Biochar is an eco-friendly material that can help in accelerating organic pollutant degradation; nevertheless, its roles in enhancing DEHP removal in rhizosphere remain unclear. This work investigated the impacts of biochar dosage (0%-2.0%) on DEHP degradation performance in tomato rhizosphere by comprehensively exploring the change in DEHP metabolites, bacterial communities and DEHP-degrading genes. Our results showed a significant increase of rhizosphere pH, organic matter and humus by biochar amendment, which achieved a satisfactorily higher DEHP removal efficiency, maximally 77.53% in treatments with 1.0% of biochar. Biochar addition also remarkably changed rhizosphere bacterial communities by enriching some potential DEHP degraders of Nocardioides, Sphingomonas, Bradyrhizobium and Rhodanobacter. The abundance of genes encoding key enzymes (hydrolase, esterase and cytochrome P450) and DEHP-degrading genes (pht3, pht4, pht5, benC-xylZ and benD-xylL) were increased after biochar amendment, leading to the change in DEHP degradation metabolism, primarily from benzoic acid pathway to protocatechuic acid pathway. Our findings evidenced that biochar amendment could accelerate DEHP degradation by altering rhizosphere soil physicochemical variables, bacterial community composition and metabolic genes, providing clues for the mechanisms of biochar-assisted DEHP degradation in organic contaminated farmland soils.

Research on the synergistic effects of urbanization and ecological environment in the Chengdu-Chongqing urban agglomeration based on the Haken model.

The development of urbanization and the protection of the ecological environment are important aspects of sustainable development in urban agglomerations; thus, their coordination and synergy are crucial. Scholars in both China and other countries have conducted extensive research on the relationship between urbanization and the ecological environment from the perspective of coordinated development. However, there is a lack of research on the synergistic effects of urbanization and the ecological environment. Taking the Chengdu-Chongqing urban agglomeration as an example, this study uses the Haken model to analyze the synergistic evolution mechanism, development patterns, and future trends of urbanization and the ecological environment. This study draws the following conclusions: (1) while a synergistic development mechanism has been established between urbanization and the ecological environment, the current system is still in a stage of low-level synergy, and the control system's parameter for the direction and path of evolution is urbanization. (2) From 2001 to 2020, the level of synergistic development between urbanization and the ecological environment was relatively low, mainly moving from low-level synergy to medium-low-level synergy to medium-level synergy. (3) There is a significant spatial disparity in the levels of synergistic development, for which the leading region centers on Chengdu and Chongqing in the northwest and southeast, respectively, and the lagging region comprises the eastern part of the urban agglomeration, mainly represented by Dazhou, Kaizhou, and Yunyang. (4) The future trend of synergistic development between urbanization and the ecological environment in the Chengdu-Chongqing urban agglomeration is promising but requires increased infrastructure construction in mountainous urban areas, enhanced cooperation and circulation in transportation, logistics, information and other aspects, and balanced improvements in the level of synergistic development between urbanization and the ecological environment. The study of the synergistic development effect of urbanization and the ecological environment in urban agglomerations is of great significance for reducing the negative impact of urbanization on the ecological environment, increasing the positive interaction between the two, and promoting sustainable development in urban agglomerations.

Thermal-Assisted Multiscale Patterning of Nonplanar Colloidal Nanostructures for Multi-Modal Anti-Counterfeiting.

Nanotransfer printing of colloidal nanoparticles is a promising technique for the fabrication of functional materials and devices. However, patterning nonplanar nanostructures pose a challenge due to weak adhesion from the extremely small nanostructure-substrate contact area. Here, the study proposes a thermal-assisted nonplanar nanostructure transfer printing (NP-NTP) strategy for multiscale patterning of polystyrene (PS) nanospheres. The printing efficiency is significantly improved from ≈3.1% at low temperatures to ≈97.2% under the glass transition temperature of PS. Additionally, the arrangement of PS nanospheres transitioned from disorder to long-range order. The mechanism of printing efficiency enhancement is the drastic drop of Young's modulus of nanospheres, giving rise to an increased contact area, self-adhesive effect, and inter-particle necking. To demonstrate the versatility of the NP-NTP strategy, it is combined with the intaglio transfer printing technique, and multiple patterns are created at both micro and macro scales at a 4-inch scale with a resolution of ≈2757 pixels per inch (PPI). Furthermore, a multi-modal anti-counterfeiting concept based on structural patterns at hierarchical length scales is proposed, providing a new paradigm of imparting multiscale nanostructure patterning into macroscale functional devices.

Iridium Catalysts with f-Amphbinol Ligands: Highly Stereoselective Hydrogenation of a Variety of Ketones.

A series of novel and modular ferrorence-based amino-phosphine-binol (f-amphbinol) ligands have been successfully synthesized. The f-amphbinol ligands exhibited extremely high air stability and catalytic efficiency in the Ir-catalyzed stereoselective hydrogenation of various ketones to afford corresponding stereodefined alcohols with excellent results (full conversions, cis/trans >99:1, and 83% → 99% ee, TON up to 500 000). Control experiments have shown that -OH and -NH groups played a key role in this stereoselective hydrogenation.

New mechanisms of biochar-assisted vermicomposting by recognizing different active di-(2-ethylhexyl) phthalate (DEHP) degraders across pedosphere, charosphere and intestinal sphere.

Biochar-assisted vermicomposting can significantly accelerate soil DEHP degradation, but little information is known about the underlying mechanisms as different microspheres exist in soil ecosystem. In this study, we identified the active DEHP degraders in biochar-assisted vermicomposting by DNA stable isotope probing (DNA-SIP) and surprisingly found their different compositions in pedosphere, charosphere and intestinal sphere. Thirteen bacterial lineages (Laceyella, Microvirga, Sphingomonas, Ensifer, Skermanella, Lysobacter, Archangium, Intrasporangiaceae, Pseudarthrobacter, Blastococcus, Streptomyces, Nocardioides and Gemmatimonadetes) were responsible for in situ DEHP degradation in pedosphere, whereas their abundance significantly changed in biochar or earthworm treatments. Instead, some other active DEHP degraders were identified in charosphere (Serratia marcescens and Micromonospora) and intestinal sphere (Clostridiaceae, Oceanobacillus, Acidobacteria, Serratia marcescens and Acinetobacter) with high abundance. In biochar-assisted vermicomposting, the majority of active DEHP degraders were found in charosphere, followed by intestinal sphere and pedosphere. Our findings for the first time unraveled the spatial distribution of active DEHP degraders in different microspheres in soil matrices, explained by DEHP dynamic adsorption on biochar and desorption in earthworm gut. Our work highlighted that charosphere and intestinal sphere exhibited more contribution to the accelerated DEHP biodegradation than pedosphere, providing novel insight into the mechanisms of biochar and earthworm in improving contaminant degradation.

How does home and host-country policy uncertainty affect outward FDI? Firm-level evidence from China.

How the foreign direct investment behavior of enterprises changes in response to the risks and instability of government economic policy changes is a relevant issue which, however, has not been extensively studied yet. Accordingly, this paper establishes a linear probability regression model to study the foreign direct investment behavior of Chinese A-share listed companies in 13 countries between 2003 and 2020 and explores whether multinational companies change their OFDI decisions when the economic policy environment of China and trade-related countries are unstable. A firm heterogeneity analysis and phased discussions were conducted, and a robust conclusion was finally drawn. The results show that (1) China's economic policy uncertainty promotes China's foreign direct investment, while the host country's monetary policy uncertainty inhibits China's foreign direct investment. (2) The foreign direct investment decisions of enterprises are affected not only by the macroeconomic and policy environment of the two trading countries but also by their development characteristics. (3) Sino-US trade frictions and the financial crisis have different effects on China's foreign direct investment.

The impact of rapid urbanization on residential energy consumption in China.

Due to the rapid progress of urbanization in China, the percentage of residential energy consumption out of total energy consumption has increased. This paper uses statistical data from 30 Chinese provinces (autonomous regions and municipalities) from 2000 to 2020 to analyze the impact of urbanization on residential energy consumption and construct an econometric model to test the mechanism. The empirical tests show that the consumption of direct energy (energy that exists in nature in its original form and has not been transformed) is positively U-shaped about the urbanization rate. Furthermore, the impact of economic development on direct and indirect energy consumption is significantly positive. In contrast, the effects of population agglomeration on immediate energy consumption are adverse, and the indirect energy consumption is positive.

Hydroxyapatite tailored hierarchical porous biochar composite immobilized Cd(II) and Pb(II) and mitigated their hazardous effects in contaminated water and soil.

A novel composite of hydroxyapatite tailored hierarchical porous biochar (HA-HPB) was synthesized and used for the adsorptive immobilization of Cd(II) and Pb(II) in water and soil. The hierarchical porous biochar (HPB) was prepared from rice husk through a molten-salt-assisted pyrolysis approach; then, a series of HA-HPB (with 0.5, 1, 2, 3, and 4 g of HPB) was prepared with co-precipitation procedure. All HA-HPBs, particularly HA-3HPB, revealed significantly higher removal efficiency of Cd(II) and Pb(II) (≥99.5%) in water than pristine biochar (5.79 - 24.12%). The immobilization efficiency of HA-3HPB for Cd(II) and Pb(II) was slightly inhibited by the ionic strength and co-existing cations. The Langmuir adsorption capacities of Cd(II) and Pb(II) were 88.1 and 110.2 mg/g, respectively. Ion exchange, complexation, cation-π interaction, and precipitation were the key mechanisms involved in the immobilization of Cd(II) and Pb(II) using HA-3HPB. The HA-3HPB reduced the availability of soil Cd (63.5 - 87.8%) and Pb (64.6 - 92.9%) compared to the unamended soil, and thus reduced their content in the Chinese cabbage shoots by 69.3 -95.4% for Cd and 66.5 -97.2% for Pb. These findings demonstrate the effectiveness of HA-HPB for remediation of Cd(II) and Pb(II) contaminated water and soil and mitigating the potential risks.

Coordination effect enabled palladium-catalyzed regioselective O-alkylation of 2-pyridones.

A novel tactic for the regioselective O-alkylation of 2-pyridones has been realized through palladium catalysis in moderate to high yields. The coordination effect between palladium and nitrogen on the pyridine ring plays a versatile role.

Electrochemical Synthesis of Cyclic Diaryl Phosphinamides via Intramolecular sp2 C-H Phosphinamidation.

We developed an oxidant- and transition-metal-free approach to construct six-membered cyclic phosphinamides via an intramolecular electrochemical C-H phosphinamidation process. With nBu4NBr as the catalyst and electrolyte, cyclic phosphinamides bearing a variety of functional groups (22 examples) were readily accessed under mild conditions. Meanwhile, this protocol provided an alternative route to organic electroluminescent materials and P-N ligands.

Can the income level of rural residents be improved by the Chinese "Broadband Village?": Evidence from a regression discontinuity design of the six pilot provinces.

The "Broadband Village" (B&V) initiative is a substantial investment in internet construction in rural areas in six western provinces implemented by the Chinese government since 2014. This study evaluates the effect this policy has had. Panel data of 1,049 counties in China from 2015 to 2019 are used for the regression discontinuity design (RD) to estimate the impact of B&V on the improvement of the income level of rural residents. The results show that, compared to the counties without the B&V policy, the income of rural residents in counties with B&V has increased by 1.468-1.518 times, which is nearly 1.3 times the sample mean of survey data, indicating that the income level of rural residents has been improved significantly by B&V. However, the quantile regression results show that the higher the income level of rural residents, the smaller the effect of this policy. From the dynamic effect of years, the influence curve of B&V on rural residents' income is an inverted U-shaped, first increasing and then decreasing, and the impact of this policy on the income level of highly-educated farmers is greater. Finally, three different methods are used to verify the robustness of the model.

An automatic calibration framework based on the InfoWorks ICM model: the effect of multiple objectives during multiple water pollutant modeling.

An automatic calibration framework of water quality parameters for surface runoff during modeling with InfoWorks ICM was constructed. The framework is based on a genetic algorithm (GA) and fully considers the calibration sequence for multiple water pollutants, namely, total suspended solids (TSS), chemical oxygen demand (COD), total nitrogen (TN), and total phosphorous (TP). Meanwhile, four different objective functions including the Nash-Sutcliff efficiency coefficient (NSE), coefficient of determination (R2), percentage error in the peak (PEP), and percentage bias (PBIAS) were selected as fitness evaluators for the GA. The framework was applied successfully to a specific area of Fuzhou in China, and the multi-objective results were compared with the single-objective results. The comprehensive indexes of TSS, COD, TN, and TP by multi-objective calibration were lower than that of the single-objective calibration in both scenarios. Compared with single-objective calibration, the iterations to reach the optimal value were shortened 9, 5, 13, and 15 iterations by multi-objective calibration. Therefore, the findings showed that the multi-objective function GA was more balanced and more efficient than the single-objective function GA. Then, the uncertainty of the model was evaluated by using the samples generated by automatic calibration, which provided a reliable basis for the subsequent application of the model. This framework can be applied to other programs through adjustments of the number and weight of objective functions according to the specific situation, which will make the modeling more efficient and accurate.

Alterations in peripheral T cell and B cell subsets in patients with osteoarthritis.

OBJECTIVES: Our study objective was to explore whether abnormalities in the subtypes of T cells and B cells were present in peripheral blood of patients with osteoarthritis (OA) and healthy controls (HCs). METHOD: Demographic and clinical variables and blood were collected. OA severity was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. Flow cytometry was used to establish the frequencies of lineage subsets. Monoclonal antibodies against 21 surface markers were used to distinguish and evaluate T cells' and B cells' subpopulation. The proportion of each subset was compared and correlations between age, immune cells, and clinical data were analyzed. RESULTS: A total of 30 OA patients (male/female = 9/21) and 45 HCs (male/female = 14/31) were included. Median WOMAC pain was 3.0 (2.0). There was no difference in the proportion of T cells, CD8+ T cells, and B cells (p > 0.05). The proportion of CD4+ T cells was higher in OA groups, together with an increased CD4 to CD8 ratio (p = 0.016). CD8+CD45RA+ T cells were reduced after adjustment for age, while CD8+CD45RA- T cells were elevated in OA (p < 0.05). CD4+CD45RA-CCR7+ T cells and CD4+CD45RA-CCR7- T cells were increased (p < 0.004). The proportion of T helper (Th) 17 and T follicular helper (Tfh) 2 cells was higher, but cytotoxic T (Tc) 17 cells were fewer in OA (p < 0.05). CD3-CD19+IgD-IgM-CD27+CD38+ B cells were decreased in OA (p ≤ 0.001). The WOMAC pain score correlated with CD3+CD4+CXCR5-PD-1+ T cells positively (B = 0.404, p = 0.027). CD3-CD19+CD27-IgD+ cells correlated negatively with erythrocyte sedimentation rate (ESR) (B = -0.550, p = 0.005). CONCLUSIONS: The T cell and B cell profiles were proved to have alteration suggesting that acquired immune system may play a substantial role in the pathogenesis of OA.Key Points• The T cell and B cell profiles were proved to have alteration suggesting that acquired immune system may play a substantial role in the pathogenesis of OA.• The WOMAC pain score correlated with CD3+CD4+CXCR5-PD-1+ T cells and T helper 17 cells positively.• Memory T cells were increased in OA patients, suggesting they could play an important role in OA.

Enhancement of surface bioactivity on carbon fiber-reinforced polyether ether ketone via graphene modification.

BACKGROUND AND OBJECTIVE: The modulus of carbon fiber-reinforced polyether ether ketone (CFR-PEEK), a composite containing layers of carbon fiber sheets, can be precisely controlled to match bone. However, CFR-PEEK is biologically inert and cannot promote bone apposition. The objective of this study was to investigate whether graphene modification could enhance the bioactivity of CFR-PEEK. METHODS AND RESULTS: In vitro, the proliferation and differentiation of rat bone marrow stromal cells on scaffolds were quantified via cell-counting kit-8 assay and Western blotting analysis of osteoblast-specific proteins. Graphene modification significantly promoted bone marrow stromal cell proliferation and accelerated induced differentiation into osteogenic lineages compared to cells seeded onto nongraphene-coated CFR-PEEK. An in vivo rabbit extraarticular graft-to-bone healing model was established. At 4, 8, and 12 weeks after surgery, microcomputed tomography analyses and histological observations revealed significantly better microstructural parameters and higher average mineral apposition rates for graphene-modified CFR-PEEK implants than CFR-PEEK implants (P<0.05). van Gieson staining indicated more new bone was formed around graphene-modified CFR-PEEK implants than CFR-PEEK implants. CONCLUSION: Graphene may have considerable potential to enhance the bioactivity and osseointegration of CFR-PEEK implants for clinical applications.

Enantioselective and Diastereoselective Construction of Chiral Amino Alcohols by Iridium-f-Amphox-Catalyzed Asymmetric Hydrogenation via Dynamic Kinetic Resolution.

The iridium-f-amphox-catalyzed asymmetric hydrogenation of racemic α-amino ß-unfunctionalized ketones proceeds via a DKR (dynamic kinetic resolution) process for the construction of various chiral N,N-disubstituted α-amino ß-unfunctionalized alcohols in quantitative yields with excellent enantioselectivities and diastereoselectivities (all products >99% ee and >99:1 dr, TON up to 100 000). Importantly, this catalytic asymmetric hydrogenation with a DKR process provided a highly efficient and powerful synthetic strategy for the preparation of key chiral intermediates of the preclinical antitumor agent (S,S)-R116010.

Iridium-Catalyzed Asymmetric Hydrogenation of Ketones with Accessible and Modular Ferrocene-Based Amino-phosphine Acid (f-Ampha) Ligands.

A series of tridentate ferrocene-based amino-phosphine acid (f-Ampha) ligands have been successfully developed. The f-Ampha ligands are extremely air stable and exhibited excellent performance in the Ir-catalyzed asymmetric hydrogenation of ketones (full conversions, up to >99% ee, and 500 000 TON). DFT calculations were performed to elucidate the reaction mechanism and the importance of the -COOH group. Control experiments also revealed that the -COOH group played a key role in this reaction.

Readily Accessible and Highly Efficient Ferrocene-Based Amino-Phosphine-Alcohol (f-Amphol) Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Simple Ketones.

We have successfully developed a series of novel and modular ferrorence-based amino-phosphine-alcohol (f-Amphol) ligands, and applied them to iridium-catalyzed asymmetric hydrogenation of various simple ketones to afford the corresponding chiral alcohols with excellent enantioselectivities and conversions (98-99.9 % ee, >99 % conversion, turnover number up to 200 000). Control experiments and density functional theory (DFT) calculations have shown that the hydroxyl group of our f-Amphol ligands played a key role in this asymmetric hydrogenation.