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Conversion into high-value-added organic nitrogen compounds through electrochemical C-N coupling reactions under ambient conditions is regarded as a sustainable development strategy to achieve carbon neutrality and high-value utilization of harmful substances. Herein, we report an electrochemical process for selective synthesis of high-valued formamide from carbon monoxide and nitrite with a Ru 1 Cu single-atom alloy under ambient conditions, which achieves a high formamide selectivity with Faradaic efficiency of 45.65 ± 0.76% at −0.5 V vs. RHE. In situ X-ray absorption spectroscopy, coupled with in situ Raman spectroscopy and density functional theory calculations results reveal that the adjacent Ru-Cu dual active sites can spontaneously couple *CO and *NH 2 intermediates to realize a critical C-N coupling reaction, enabling high-performance electrosynthesis of formamide. This work offers insight into the high-value formamide electrocatalysis through coupling CO and NO 2 − under ambient conditions, paving the way for the synthesis of more-sustainable and high-value chemical products. Conversion into high-value-added organic nitrogen compounds through electrochemical C-N coupling reactions is considered a sustainable strategy to achieve carbon neutrality. Herein, we report the selective electrosynthesis of formamide from carbon monoxide and nitrite using Ru 1 Cu single-atoms catalyst.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by protein aggregation in the brain. Recent studies have revealed the critical role of microglia in AD pathogenesis. This review provides a comprehensive summary of the current understanding of microglial involvement in AD, focusing on genetic determinants, phenotypic state, phagocytic capacity, neuroinflammatory response, and impact on synaptic plasticity and neuronal regulation. Furthermore, recent developments in drug discovery targeting microglia in AD are reviewed, highlighting potential avenues for therapeutic intervention. This review emphasizes the essential role of microglia in AD and provides insights into potential treatments.

Electrocatalytic nitrite reduction to the valuable ammonia is a green and sustainable alternative to the conventional Haber-Bosch method for ammonia synthesis, while the activity and selectivity for ammonia production remains poor at low nitrite concentrations. Herein, we report a nanoporous intermetallic single-atom alloy CuZn (np/ISAA-CuZn) catalyst with completely isolated Cu-Zn active-sites, which achieves neutral nitrite reduction reaction with a remarkable NH 3 Faradaic efficiency over 95% and the highest energy efficiency of ≈ 59.1% in wide potential range from −0.2 to −0.8 V vs. RHE. The np/ISAA-CuZn electrocatalyst was able to operate stably at 500 mA cm −2 for 220 h under membrane electrode assembly conditions with a stabilized NH 3 Faraday efficiency of ~80% and high NO 2 ‒ removal rate of ~100%. A series of in situ experimental studies combined with density functional theory calculations reveal that strong electronic interactions of isolated Cu-Zn active-sites altered the protonation adsorption species, effectively alleviating the protonation barrier of *NO 2 and thus greatly facilitating the selective reduction of NO 2 − into NH 3 . Electrocatalytic nitrite reduction is a green alternative to the Haber-Bosch process, but its ammonia production remains inefficient at low nitrite levels. Here the authors report an intermetallic single atom alloy CuZn catalyst for nitrite reduction to ammonia with high efficiency and stability at low nitrite concentration of 1−10 mM.

CBP60b (CALMODULIN-BINDING PROTEIN 60b) is a member of the CBP60 transcription factor family. In Arabidopsis, AtCBP60b not only regulates growth and development but also activates the transcriptions in immune responses. So far, CBP60b has only been studied extensively in the model plant Arabidopsis and rarely in crops. In this study, Bean pod mottle virus (BPMV)-mediated gene silencing (BPMV-VIGS) was used to silence GmCBP60b.1/2 in soybean plants. The silencing of GmCBP60b.1/2 resulted in typical autoimmunity, such as dwarfism and enhanced resistance to both Soybean mosaic virus (SMV) and Pseudomonas syringae pv. glycinea (Psg). To further understand the roles of GmCBP60b in immunity and circumvent the recalcitrance of soybean transformation, we generated transgenic tobacco lines that overexpress GmCBP60b.1. The overexpression of GmCBP60b.1 also resulted in autoimmunity, including spontaneous cell death on the leaves, highly induced expression of PATHOGENESIS-RELATED (PR) genes, significantly elevated accumulation of defense hormone salicylic acid (SA), and significantly enhanced resistance to Pst DC3000 (Pseudomonas syrangae pv. tomato DC3000). The transient coexpression of a luciferase reporter gene driven by the promoter of soybean SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (GmSARD1) (ProGmSARD1::LUC), together with GmCBP60b.1 driven by the 35S promoter, led to the activation of the LUC reporter gene, suggesting that GmCBP60b.1 could bind to the core (A/T)AATT motifs within the promoter region of GmSARD1 and, thus, activate the expression of the LUC reporter. Taken together, our results indicate that GmCBP60b.1/2 play both positive and negative regulatory roles in immune responses. These results also suggest that the function of CBP60b is conserved across plant species.

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a potent anticancer drug with versatile biological activities, while the clinical translation of curcumin is severely limited due to its hydrophobicity, rapid elimination, and metabolism in the blood circulation. Herein, we aim to unravel the potential of curcumin as a synergistic agent with immunotherapy in the treatment of cancers. In an effort to minimize premature release and improve the systemic bioavailability, a superior blood stable and reduction sensitive curcumin micellar formulation, of which the release can be triggered by cancer cells, is rationally designed. We have synthesized a telodendrimer (mPEG-PLA-(LA) 4 ) capable of forming reversible disulfide crosslinked micelles (DCMs). The curcumin loaded DCMs (Cur/DCMs) are spherical with a uniform size of 24.6 nm. The in vitro release profile demonstrates that curcumin releases significantly slower from DCMs than that from non-crosslinked micelles (NCMs), while the release can be accelerated with the increasing concentration of reducing agent glutathione (GSH). Intravenous administration of Cur/DCMs stably retains curcumin in the bloodstream and efficiently improves the systemic bioavailability. Furthermore, Cur/DCMs exhibit synergistic anticancer efficacy when combined with the anti-PD-1 antibody in an MC-38 colon cancer xenograft model. Our results potentiate the integration of blood stable curcumin nanoformulation and immunotherapy for cancer treatment.

The pursuit of RuO 2 as an alternative acidic oxygen evolution reaction electrocatalyst to IrO 2 holds great promise, yet simultaneously achieving highly active and stable RuO 2 remains an urgent challenge, as conventional strategies often boost one property at the expense of the other. Here, we successfully construct Ta and B co-doped nanoporous RuO 2 with Ru-O-Ta frameworks and Ru-O-B active sites to overcome the activity-stability trade-off. The Ru-O-Ta frameworks stabilize the Ru sites by mediating bridging oxygen and preferentially replenishing oxygen vacancies, thereby facilitating the oxygen evolution reaction through the adsorbate evolution mechanism. Concurrently, the Ru-O-Ta/B sites not only switch the rate-determining step but also lower the energy barriers, thereby enhancing catalytic activity. The Ta/B-RuO 2 exhibits a low overpotential of 170 mV at 10 mA cm − 2 , a favorable Tafel slope of 44 mV dec −1 , and an outstanding durability. We demonstrate that proton-exchange membrane water electrolyzers equipped with Ta/B-RuO 2 achieves a current density of 1.0 A cm −2 at a low voltage of 1.6 V and maintains stable operation for 120 h at 200 mA cm −2 . An efficient and durable alternative catalyst to iridium oxide is essential for acidic oxygen evolution. Here, the authors report a catalyst based on RuO 2 co-doped with tantalum and boron, creating Ru-O-Ta frameworks and Ru-O-B active sites that stabilize the catalyst and enhance performance.

Background Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. Methods We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0–4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m 2 ) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. Discussion Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. Trial registration ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020–9-24, version 1.0).

Three new oxoaporphine Co(II), Ni(II) and Zn(II) complexes 1 – 3 have been synthesized and fully characterized. 1 – 3 have similar mononuclear structures with the metal and ligand ratio of 1:2. 1 – 3 exhibited higher cytotoxicity than the OD ligand and cisplatin against HepG2, T-24, BEL-7404, MGC80–3 and SK-OV-3/DDP cells, with IC 50 value of 0.23−4.31 μM. Interestingly, 0.5 μM 1 – 3 significantly caused HepG2 arrest at S-phase, which was associated with the up-regulation of p53, p21, p27, Chk1 and Chk2 proteins, and decrease in cyclin A, CDK2, Cdc25A, PCNA proteins. In addition, 1 – 3 induced HepG2 apoptosis via a caspase-dependent mitochondrion pathway as evidenced by p53 activation, ROS production, Bax up-regulation and Bcl-2 down-regulation, mitochondrial dysfunction, cytochrome c release, caspase activation and PARP cleavage. Furthermore, 3 inhibited tumor growth in HepG2 xenograft model, and displayed more safety profile in vivo than cisplatin.

Background Calcium ions (Ca 2+ ), secondary messengers, are crucial for the signal transduction process of the interaction between plants and pathogens. Ca 2+ signaling also regulates autophagy. As plant calcium signal-decoding proteins, calcium-dependent protein kinases (CDPKs) have been found to be involved in biotic and abiotic stress responses. However, information on their functions in response to powdery mildew attack in wheat crops is limited. Result In the present study, the expression levels of TaCDPK27 , four essential autophagy-related genes (ATGs) ( TaATG5 , TaATG7 , TaATG8 , and TaATG10 ), and two major metacaspase genes, namely, TaMCA1 and TaMCA9 , were increased by powdery mildew ( Blumeria graminis f. sp. tritici , Bgt ) infection in wheat seedling leaves. Silencing TaCDPK27 improves wheat seedling resistance to powdery mildew, with fewer Bgt hyphae occurring on TaCDPK27 -silenced wheat seedling leaves than on normal seedlings. In wheat seedling leaves under powdery mildew infection, silencing TaCDPK27 induced excess contents of reactive oxygen species (ROS); decreased the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT); and led to an increase in programmed cell death (PCD). Silencing TaCDPK27 also inhibited autophagy in wheat seedling leaves, and silencing TaATG7 also enhanced wheat seedling resistance to powdery mildew infection. TaCDPK27-mCherry and GFP-TaATG8h colocalized in wheat protoplasts. Overexpressed TaCDPK27-mCherry fusions required enhanced autophagy activity in wheat protoplast under carbon starvation. Conclusion These results suggested that TaCDPK27 negatively regulates wheat resistance to PW infection, and functionally links with autophagy in wheat.

Background Gut microbiota and microbiota-derived metabolites have been implicated in the regulation of stress-related diseases, yet their associations with chronic stress in adolescents remain unclear. Multi-omics studies on this topic in adolescents are still limited. This study aimed to characterize gut microbiota and metabolites in adolescents under chronic stress. Methods In this cross-sectional study, we assessed chronic stress in 124 adolescents aged 12–16 years using the Adolescent Life Events Scale and the Study Stress Scale. Participants were stratified by stress level into low ( n  = 42), medium ( n  = 41), and high stress ( n  = 41) groups. Fecal samples were collected from all participants for 16S rRNA gene sequencing. Subsequently, a subset of 30 adolescents with high stress and 29 low stress adolescents underwent metagenomic sequencing and untargeted metabolomics. Results Adolescents experiencing high-chronic stress showed lower alpha diversity, differential beta diversity, and a more complicated microbial network compared to those experiencing lower stress. Spearman’s rank correlation and Kruskal-Wallis test identified five genera with decreased abundances in high stress adolescents, including Faecalibacterium , Bacteroides , Akkermansia , Lachnospiraceae unclassified , and Ruminococcus ( P fdr <0.05). Additionally, 12 species showed decreased abundances and 5 increased abundances, and logistic regression analysis further revealed that the relative abundances of Bifidobacterium catenulatum , Streptococcus suis , Ruminococcus sp. CAG 108 , and Phascolarctobacterium faecium were associated with chronic stress ( P fdr <0.05), after adjusting for sex, age, fruit consumption, and body mass index. We identified 21 differential metabolites, predominantly enriched in metabolic pathways based on KEGG analysis. Moreover, 19 out of these metabolites were significantly correlated with at least one of the four species significantly associated with chronic stress. These metabolites may explain health effects of species associated with chronic stress. Conclusions Chronic stress in adolescents is associated with altered gut microbiota composition and metabolite profiles, providing insights into possible mechanisms underlying stress-related diseases and highlighting the importance of longitudinal studies to clarify temporal and causal relationships.