Maternal inheritance of glucose intolerance via oocyte TET3 insufficiency.

Diabetes mellitus is prevalent among women of reproductive age, and many women are left undiagnosed or untreated1. Gestational diabetes has profound and enduring effects on the long-term health of the offspring2,3. However, the link between pregestational diabetes and disease risk into adulthood in the next generation has not been sufficiently investigated. Here we show that pregestational hyperglycaemia renders the offspring more vulnerable to glucose intolerance. The expression of TET3 dioxygenase, responsible for 5-methylcytosine oxidation and DNA demethylation in the zygote4, is reduced in oocytes from a mouse model of hyperglycaemia (HG mice) and humans with diabetes. Insufficient demethylation by oocyte TET3 contributes to hypermethylation at the paternal alleles of several insulin secretion genes, including the glucokinase gene (Gck), that persists from zygote to adult, promoting impaired glucose homeostasis largely owing to the defect in glucose-stimulated insulin secretion. Consistent with these findings, mouse progenies derived from the oocytes of maternal heterozygous and homozygous Tet3 deletion display glucose intolerance and epigenetic abnormalities similar to those from the oocytes of HG mice. Moreover, the expression of exogenous Tet3 mRNA in oocytes from HG mice ameliorates the maternal effect in offspring. Thus, our observations suggest an environment-sensitive window in oocyte development that confers predisposition to glucose intolerance in the next generation through TET3 insufficiency rather than through a direct perturbation of the oocyte epigenome. This finding suggests a potential benefit of pre-conception interventions in mothers to protect the health of offspring.

A bisulfite-assisted and ligation-based qPCR amplification technology for locus-specific pseudouridine detection at base resolution.

Over 150 types of chemical modifications have been identified in RNA to date, with pseudouridine (Ψ) being one of the most prevalent modifications in RNA. Ψ plays vital roles in various biological processes, and precise, base-resolution detection methods are fundamental for deep analysis of its distribution and function. In this study, we introduced a novel base-resolution Ψ detection method named pseU-TRACE. pseU-TRACE relied on the fact that RNA containing Ψ underwent a base deletion after treatment of bisulfite (BS) during reverse transcription, which enabled efficient ligation of two probes complementary to the cDNA sequence on either side of the Ψ site and successful amplification in subsequent real-time quantitative PCR (qPCR), thereby achieving selective and accurate Ψ detection. Our method accurately and sensitively detected several known Ψ sites in 28S, 18S, 5.8S, and even mRNA. Moreover, pseU-TRACE could be employed to measure the Ψ fraction in RNA and explore the Ψ metabolism of different pseudouridine synthases (PUSs), providing valuable insights into the function of Ψ. Overall, pseU-TRACE represents a reliable, time-efficient and sensitive Ψ detection method.

Boosting Electrocatalytic Ammonia Synthesis via Synergistic Effect of Iron-Based Single Atoms and Clusters.

Electrocatalytic reduction of nitrate to ammonia (NO3RR) is gaining attention for low carbon emissions and environmental protection. However, low ammonia production rate and poor selectivity have remained major challenges in this multi-proton coupling process. Herein, we report a facile strategy toward a novel Fe-based hybrid structure composed of Fe single atoms and Fe3C atomic clusters that demonstrates outstanding performance for synergistic electrocatalytic NO3RR. By operando synchrotron Fourier transform infrared spectroscopy and theoretical computation, we clarify that Fe single atoms serve as the active site for NO3RR, while Fe3C clusters facilitate H2O dissociation to provide protons (*H) for continued hydrogenation reactions. As a result, the Fe-based electrocatalyst exhibits ammonia Faradaic efficiency of nearly 100%, with a corresponding production rate of 24768 µg h-1 cm-2 at -0.4 V vs RHE, exceeding most reported metal-based catalysts. This research provides valuable guidance toward multi-step reactions.

Structural and molecular basis for urea recognition by Prochlorococcus.

Nitrogen (N) is an essential element for microbial growth and metabolism. The growth and reproduction of microorganisms in more than 75% of areas of the ocean are limited by N. Prochlorococcus is numerically the most abundant photosynthetic organism on the planet. Urea is an important and efficient N source for Prochlorococcus. However, how Prochlorococcus recognizes and absorbs urea still remains unclear. Prochlorococcus marinus MIT 9313, a typical Cyanobacteria, contains an ABC-type transporter, UrtABCDE, which may account for the transport of urea. Here, we heterologously expressed and purified UrtA, the substrate-binding protein of UrtABCDE, detected its binding affinity toward urea, and further determined the crystal structure of the UrtA/urea complex. Molecular dynamics simulations indicated that UrtA can alternate between "open" and "closed" states for urea binding. Based on structural and biochemical analyses, the molecular mechanism for urea recognition and binding was proposed. When a urea molecule is bound, UrtA undergoes a state change from open to closed surrounding the urea molecule, and the urea molecule is further stabilized by the hydrogen bonds supported by the conserved residues around it. Moreover, bioinformatics analysis showed that ABC-type urea transporters are widespread in bacteria and probably share similar urea recognition and binding mechanisms as UrtA from P. marinus MIT 9313. Our study provides a better understanding of urea absorption and utilization in marine bacteria.

Alteration of gut microbiota in post-stroke depression patients with Helicobacter pylori infection.

BACKGROUND: Several studies have identified an association between the gut microbiome and post-stroke depression(PSD), and Helicobacter pylori(H. pylori) infection cause significant alterations in the composition of the gastrointestinal microbiome. However, evidence regarding the role of the H. pylori infection in promoting PSD is still lacking. Here, we conducted a retrospective study to explore risk factors associated with PSD. METHODS: Patients with cerebral infarction were consecutively enrolled from December 2021 to October 2022. The diagnosis of PSD is based on the DSM-V criteria, and the Hamilton Depression Rating Scale(HAMD) was used to identify patients with PSD. White matter lesions were evaluated using magnetic resonance imaging(MRI) and H. pylori infection was detected by 13C-urea breath test. Further, 16S rRNA gene sequencing was used to evaluate the changes in gut microbiota composition of fecal samples from PSD patients. The concentration of short-chain fatty acids(SCFAs) was determined by gas chromatography-mass spectrometry(GC-MS). RESULTS: Multivariate regression analysis showed that deep white matter lesions(DWMLs) [odds ratio(OR) 3.382, 95% confidence interval(CI) 1.756-6.512; P = 0.001] and H. pylori infection(OR 2.186, 95% CI 1.149-4.159; P = 0.017) were the independent risk factors for PSD. Patients with H. pylori infection had more severe depressive symptoms than patients without infection. Intestinal microbiota was significantly different between H. pylori-positive PSD[H. pylori(+)] patients and H. pylori-negative PSD[H. pylori (-)] patients. Fecal SCFAs concentrations were significantly reduced in the H. pylori(+) group compared to the negative ones. CONCLUSION: DWMLs and H. pylori infection may play important roles in the development of PSD. H. pylori infection is likely to be involved in the pathogenesis of PSD by altering the intestinal flora.

Downregulation of collagen XI during late postnatal corneal development is followed by upregulation after injury.

Collagen XI plays a role in nucleating collagen fibrils and in controlling fibril diameter. The aim of this research was to elucidate the role that collagen XI plays in corneal fibrillogenesis during development and following injury. The temporal and spatial expression of collagen XI was evaluated in C57BL/6 wild-type mice. For wound-healing studies in adult mice, stromal injuries were created using techniques that avoid caustic chemicals. The temporal expression and spatial localization of collagen XI was studied following injury in a Col11a1 inducible knockout mouse model. We found that collagen XI expression occurs during early maturation and is upregulated after stromal injury in areas of regeneration and remodeling. Abnormal fibrillogenesis with new fibrils of heterogeneous size and shape occurs after injury in a decreased collagen XI matrix. In conclusion, collagen XI is expressed in the stroma during development and following injury in adults, and is a regulator of collagen fibrillogenesis in regenerating corneal tissue.

Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.

BACKGROUND: Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS. METHODS: We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells. RESULTS: Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats. CONCLUSIONS: This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.

Divergent projections of the prelimbic cortex mediate autism- and anxiety-like behaviors.

The comorbidity of autism spectrum disorder and anxiety is common, but the underlying circuitry is poorly understood. Here, Tmem74-/- mice showed autism- and anxiety-like behaviors along with increased excitability of pyramidal neurons (PNs) in the prelimbic cortex (PL), which were reversed by Tmem74 re-expression and chemogenetic inhibition in PNs of the PL. To determine the underlying circuitry, we performed conditional deletion of Tmem74 in the PNs of PL of mice, and we found that alterations in the PL projections to fast-spiking interneurons (FSIs) in the dorsal striatum (dSTR) (PLPNs-dSTRFSIs) mediated the hyperexcitability of FSIs and autism-like behaviors and that alterations in the PL projections to the PNs of the basolateral amygdaloid nucleus (BLA) (PLPNs-BLAPNs) mediated the hyperexcitability of PNs and anxiety-like behaviors. However, the two populations of PNs in the PL had different spatial locations, optogenetic manipulations revealed that alterations in the activity in the PL-dSTR or PL-BLA circuits led to autism- or anxiety-like behaviors, respectively. Collectively, these findings highlight that the hyperactivity of the two populations of PNs in the PL mediates autism and anxiety comorbidity through the PL-dSTR and PL-BLA circuits, which may lead to the development of new therapeutics for the autism and anxiety comorbidity.

Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis.

BACKGROUND: The dynamic interaction between cancer cells and tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is an active barrier to the effector arm of the antitumour immune response. Cancer-secreted exosomes are emerging mediators of this cancer-stromal cross-talk in the TME; however, the mechanisms underlying this interaction remain unclear. METHODS: Exosomes were isolated with ExoQuick exosome precipitation solution. The polarizing effect of TAMs was evaluated by flow cytometry, western blot analysis, immunofluorescence staining and in vitro phagocytosis assays. Clinical cervical cancer specimens and an in vivo xenograft model were also employed. RESULTS: Our previous study showed that hypoxia increased the expression of ZEB1 in cervical squamous cell carcinoma (CSCC) cells, which resulted in increased infiltration of TAMs. Here, we found that hypoxia-induced ZEB1 expression is closely correlated with CD47-SIRPα axis activity in CSCC, which enables cancer cells to evade phagocytosis by macrophages and promotes tumour progression. ZEB1 was found to directly activate the transcription of the CD47 gene in hypoxic CSCC cells. We further showed that endogenous ZEB1 was characteristically enriched in hypoxic CSCC cell-derived exosomes and transferred into macrophages via these exosomes to promote SIRPα+ TAM polarization. Intriguingly, exosomal ZEB1 retained transcriptional activity and reprogrammed SIRPα+ TAMs via activation of the STAT3 signalling pathway in vitro and in vivo. STAT3 inhibition reduced the polarizing effect induced by exosomal ZEB1. Knockdown of ZEB1 increased the phagocytosis of CSCC cells by macrophages via decreasing CD47 and SIRPα expression. CONCLUSIONS: Our results suggest that hypoxia-induced ZEB1 promotes immune evasion in CSCC by strengthening the CD47-SIRPα axis. ZEB1-targeted therapy in combination with CD47-SIRPα checkpoint immunotherapy may improve the outcomes of CSCC patients in part by disinhibiting innate immunity.

Marinobacter qingdaonensis sp. nov., a moderately halotolerant bacterium isolated from intertidal sediment.

A Gram-stain-negative, aerobic, rod-shaped and halotolerant bacterium, designated as strain ASW11-75T, was isolated from intertidal sediments in Qingdao, PR China, and identified using a polyphasic taxonomic approach. Growth of strain ASW11-75T occurred at 10-45 °C (optimum, 37 °C), pH 6.5-9.0 (optimum, pH 8.0) and 0.5-18.0 % NaCl concentrations (optimum, 2.5 %). Phylogenetic analyses based on 16S rRNA gene sequences and 1179 single-copy orthologous clusters indicated that strain ASW11-75T is affiliated with the genus Marinobacter. Strain ASW11-75T showed highest 16S rRNA gene sequence similarity to 'Marinobacter arenosus' CAU 1620T (98.5 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-75T and its closely related strains (Marinobacter salarius R9SW1T, Marinobacter similis A3d10T, 'Marinobacter arenosus' CAU 1620T, Marinobacter sediminum R65T, Marinobacter salinus Hb8T, Marinobacter alexandrii LZ-8T and Marinobacter nauticus ATCC 49840T) were 19.8-24.5 % and 76.6-80.7 %, respectively. The predominant cellular fatty acids were C16 : 0, C18 : 1 ω9c and C16 : 0 N alcohol. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminophospholipid and two unidentified lipids. The major isoprenoid quinone was ubiquinone-9. The genomic DNA G+C content was 62.2 mol%. Based on genomic and gene function analysis, strain ASW11-75T had lower protein isoelectric points with higher ratios of acidic residues to basic residues and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt. The results of polyphasic characterization indicated strain ASW11-75T represents a novel Marinobacter species, for which the name Marinobacter qingdaonensis sp. nov. with the type strain ASW11-75T is proposed. The type strain is ASW11-75T (=KCTC 82497T=MCCC 1K05587T).

Fluorescence Sensing Properties of a Bibranched Cyanostilbene Derivative Containing -NH2 for Trace Water and Picric Acid Determination.

In order to design organic small molecule fluorescent materials with multiple sensing, a bibranched -NH2 modified cyanostilbene derivative (AM) was synthesized. It exhibits solvent and aggregation-induced emission effects, with a solid-state quantum yield of 28%, which is seven times higher than that in THF. The synthesized sample AM demonstrated high sensitivity to trace water via a fluorescence "turn-off" response, achieving a low detection limit of 0.41 µM in THF and 0.80 µM in EtOH. AM also exhibits a "turn-off" response to picric acid, attributed to the photo-induced electron transfer effect it induces. The recognition of picric acid by AM demonstrates specificity and resistance to interference from nitro explosives, with a detection limit of 300 ppb and a linear relationship (R2 = 0.9981) at the range of 0-4 equivalents AM. Such acid recognition can facilitate the design of qualitative test papers and safety inks. Additionally, AM can function as a temperature sensor with a linear relationship (R2 = 0.9976) within the temperature range of 25-110 °C. Leveraging these unique characteristics, a series of methods were proposed for the direct quantitative determination of trace water in nonaqueous solvents, picric acid, and temperature.

Identification of a novel intronic variant of ATP6V0A2 in a Han-Chinese family with cutis laxa.

BACKGROUND: Cutis laxa is a connective tissue disease caused by abnormal synthesis or secretion of skin elastic fibers, leading to skin flabby and saggy in various body parts. It can be divided into congenital cutis laxa and acquired cutis laxa, and inherited cutis laxa syndromes is more common in clinic. METHODS: In this study, we reported a case of a Han-Chinese male newborn with ATP6V0A2 gene variant leading to cutis laxa. The proband was identified by whole-exome sequencing to determine the novel variant, and their parents were verified by Sanger sequencing. Bioinformatics analysis and minigene assay were used to verify the effect of this variant on splicing function. RESULTS: The main manifestations of the proband are skin laxity, abnormal facial features, and enlargement of the anterior fontanelle. Whole-exome sequencing showed that the newborn carried a non-canonical splicing-site variant c.117 + 5G > T, p. (?) in ATP6V0A2 gene. Sanger sequencing showed that both parents of the proband carried the heterozygous variant. The results of bioinformatics analysis and minigene assay displayed that the variant site affected the splicing function of pre-mRNA of the ATP6V0A2 gene. CONCLUSIONS: In this study, it was identified that ATP6V0A2 gene c. 117 + 5G > T may be the cause of the disease. The non-canonical splicing variants of ATP6V0A2 gene were rarely reported in the past, and this variant expanded the variants spectrum of the gene. The functional study of minigene assay plays a certain role in improving the level of evidence for the pathogenicity of splicing variants, which lays a foundation for prenatal counseling and follow-up gene therapy.

Alteromonas arenosi sp. nov., a novel bioflocculant-producing bacterium, isolated from intertidal sand.

A novel Gram-stain-negative, strictly aerobic and bioflocculant-producing bacterium, designated as ASW11-36T, was isolated from an intertidal sand collected from coastal areas of Qingdao, PR China. Growth occurred at 15-40 °C (optimum, 30 °C), pH 7.0-9.0 (optimum, pH 7.5) and with 1.5-7.0% (w/v) NaCl (optimum, 2.5-3.0%). In the whole-cell fatty acid pattern prevailed C16:0 and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The major isoprenoid quinone was determined to be Q-8 and the major polar lipids were phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), one unidentified aminolipid (AL), one unidentified glycolipid (GL), and two lipids (L1, L2). Based on the phylogenetic analyses of 16S rRNA gene sequences and 618 single-copy orthologous clusters, strain ASW11-36T could represent a novel member of the genus Alteromonas and was closely related to Alteromonas flava P0211T (98.4%) and Alteromonas facilis P0213T (98.3%). The pairwise average nucleotide identity and digital DNA-DNA hybridization values of the ASW11-36T genome assembly against the closely related species genomes were 71.8% and 21.7%, respectively, that clearly lower than the proposed thresholds for species. Based on phenotypic, phylogenetic, and chemotaxonomic analyses, strain ASW11-36T is considered to represent a novel species of the genus Alteromonas, for which the name Alteromonas arenosi sp. nov. is proposed. The type strain is ASW11-36T (= KCTC 82496T = MCCC 1K05585T). In addition, the strain yielded 65% of flocculating efficiency in kaolin suspension with CaCl2 addition. The draft genome of ASW11-36T shared abundant putative CAZy family related genes, especially involved in the biosynthesis of exopolysaccharides, implying its potential environmental and biological applications.

Zwitterionic Tröger's Base Microfiltration Membrane Prepared via Vapor-Induced Phase Separation with Improved Demulsification and Antifouling Performance.

The fouling of separation membranes has consistently been a primary factor contributing to the decline in membrane performance. Enhancing the surface hydrophilicity of the membrane proves to be an effective strategy in mitigating membrane fouling in water treatment processes. Zwitterionic polymers (containing an equimolar number of homogeneously distributed anionic and cationic groups on the polymer chains) have been used extensively as one of the best antifouling materials for surface modification. The conventional application of zwitterionic compounds as surface modifiers is intricate and inefficient, adding complexity and length to the membrane preparation process, particularly on an industrial scale. To overcome these limitations, zwitterionic polymer, directly used as a main material, is an effective method. In this work, a novel zwitterionic polymer (TB)-zwitterionic Tröger's base (ZTB)-was synthesized by quaternizing Tröger's base (TB) with 1,3-propane sultone. The obtained ZTB is blended with TB to fabricate microfiltration (MF) membranes via the vapor-induced phase separation (VIPS) process, offering a strategic solution for separating emulsified oily wastewater. Atomic force microscopy (AFM), scanning electron microscopy (SEM), water contact angle, and zeta potential measurements were employed to characterize the surface of ZTB/TB blended membranes, assessing surface morphology, charge, and hydrophilic/hydrophobic properties. The impact of varying ZTB levels on membrane surface morphology, hydrophilicity, water flux, and rejection were investigated. The results showed that an increase in ZTB content improved hydrophilicity and surface roughness, consequently enhancing water permeability. Due to the attraction of water vapor, the enrichment of zwitterionic segments was enriched, and a stable hydration layer was formed on the membrane surface. The hydration layer formed by zwitterions endowed the membrane with good antifouling properties. The proposed mechanism elucidates the membrane's proficiency in demulsification and the reduction in irreversible fouling through the synergistic regulation of surface charge and hydrophilicity, facilitated by electrostatic repulsion and the formation of a hydration layer. The ZTB/TB blended membranes demonstrated superior efficiency in oil-water separation, achieving a maximum flux of 1897.63 LMH bar-1 and an oil rejection rate as high as 99% in the oil-water emulsion separation process. This study reveals the migration behavior of the zwitterionic polymer in the membrane during the VIPS process. It enhances our comprehension of the antifouling mechanism of zwitterionic membranes and provides guidance for designing novel materials for antifouling membranes.

Atroposelective Formal [2 + 5] Macrocyclization Synthesis for a Novel All-Hydrocarbon Cyclo[7] Meta-Benzene Macrocycle.

A novel axially chiral all-hydrocarbon cyclo[7] (1,3-(4,6-dimethyl)benzene (CDMB-7) was designed and synthesized using atroposelective[2 + 5] cyclization through Suzuki-Miyaura coupling. CDMB-7 adopts an irregular bowl-like shape with C2 symmetry and exhibits two diastereoisomers in its crystallographic structure. The conformational isomers of CDMB-7 racemates remain stable at high temperatures (393 K). High-performance liquid chromatography (HPLC) confirmed that a single chiral isomer will spontaneously undergo racemization within 30 min at room temperature. This finding opens up possibilities for achieving adaptive chirality in all-hydrocarbon cyclo[7] m-benzene macrocycles.

Fabrication of Loose Nanofiltration Membrane by Crosslinking TEMPO-Oxidized Cellulose Nanofibers for Effective Dye/Salt Separation.

Dye/salt separation has gained increasing attention in recent years, prompting the quest to find cost-effective and environmentally friendly raw materials for synthesizing high performance nanofiltration (NF) membrane for effective dye/salt separation. Herein, a high-performance loose-structured NF membrane was fabricated via a simple vacuum filtration method using a green nanomaterial, 2,2,6,6-tetramethylpiperidine-1-oxide radical (TEMPO)-oxidized cellulose nanofiber (TOCNF), by sequentially filtrating larger-sized and finer-sized TOCNFs on a microporous substrate, followed by crosslinking with trimesoyl chloride. The resulting TCM membrane possessed a separating layer composed entirely of pure TOCNF, eliminating the need for other polymer or nanomaterial additives. TCM membranes exhibit high performance and effective dye/salt selectivity. Scanning Electron Microscope (SEM) analysis shows that the TCM membrane with the Fine-TOCNF layer has a tight layered structure. Further characterizations via Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirmed the presence of functional groups and chemical bonds of the crosslinked membrane. Notably, the optimized TCM-5 membrane exhibits a rejection rate of over 99% for various dyes (Congo red and orange yellow) and 14.2% for NaCl, showcasing a potential candidate for efficient dye wastewater treatment.

Novel Metal-Free Synthesis of 3-Substituted Isocoumarins and Evaluation of Their Fluorescence Properties for Potential Applications.

A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1H-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%.

One-Step Construction of 1,3,4-Oxadiazoles with Anticancer Activity from Tertiary Amines via a Sequential Copper(I)-Catalyzed Oxidative Ugi/aza-Wittig Reaction.

An unparalleled copper(I)-catalyzed synthesis of 1,3,4-oxadiazoles from tertiary amines in one step has been described. The one-pot reactions involving (N-isocyanimine)triphenylphosphorane, tertiary amines, and carboxylic acids resulted in the formation of 1,3,4-oxadiazoles in moderate to good yields through a consecutive oxidative Ugi/aza-Wittig reaction, enabling the direct functionalization of sp3 C-H bonds adjacent to the nitrogen atom. This method offered several notable advantages, including ligands-free, exceptional productivity and a high functional group tolerance. The preliminary biological evaluation demonstrated that compound 4f inhibited hepatoma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

Study of the multitarget mechanism of Astragalus (HUANGQI) in the treatment of Alzheimer's disease based on network pharmacology and molecular docking technology.

CONTEXT: In China, HUANGQI is widely used for the treatment of Alzheimer's disease (AD). However, a comprehensive understanding of its mechanism of anti-AD effects is lacking. OBJECTIVE: To explore the active ingredients of HUANGQI and its potential targets and mechanisms of action in AD. MATERIALS AND METHODS: The active ingredients and targets of HUANGQI were screened from databases (TCSMP, ETCM, and BATMan), and AD-related genes were obtained from DrugBank and GeneCards. The same target genes were screened, and a drug-target disease network was constructed. The PPI network was constructed and GO and KEGG pathway enrichment analyses of the targets. The Cell Counting Kit-8 (CCK-8) assay was used to determine suitable HUANGQI treatment concentrations for HT-22 cells between 0-480 µg/mL. CCK-8, FITC-phalloidin and propidium iodide (PI) assays were used to examine the protective effect of (0, 60, 120, 240 µg/mL) of HUANGQI on 20 µM Aß1-42-induced HT-22 cell cytotoxicity. RESULTS: Twelve active ingredients of HUANGQI were selected, with 679 common targets associated with AD. GO and KEGG analysis revealed that the therapeutic mechanisms of HUANGQI involve TNF, AGE, the NF-κB pathway, and nuclear receptor activity-related processes. The CCK-8 assay indicated that HUANGQI was not cytotoxic to HT-22 cells at concentrations less than 240 µg/mL and was able to attenuate Aß1-42-induced cellular damage (EC50 = 83.46 µg/mL). FITC-phalloidin and PI assays suggested that HUANGQI could alleviate 20 µM Aß1-42-induced neuronal cell cytotoxicity in a dose-dependent manner. CONCLUSION: HUANGQI has a protective effect on Aß1-42-induced nerve cell injury; further mechanism research was needed.

Edge-Rich Pt-O-Ce Sites in CeO2 Supported Patchy Atomic-Layer Pt Enable a Non-CO Pathway for Efficient Methanol Oxidation.

Rational design of efficient methanol oxidation reaction (MOR) catalyst that undergo non-CO pathway is essential to resolve the long-standing poisoning issue. However, it remains a huge challenge due to the rather difficulty in maximizing the non-CO pathway by the selective coupling between the key *CHO and *OH intermediates. Here, we report a high-performance electrocatalyst of patchy atomic-layer Pt epitaxial growth on CeO2 nanocube (Pt ALs/CeO2) with maximum electronic metal-support interaction for enhancing the coupling selectively. The small-size monolayer material achieves an optimal geometrical distance between edge Pt-O-Ce sites and *OH absorbed on CeO2, which well restrains the dehydrogenation of *CHO, resulting in the non-CO pathway. Meanwhile, the *CHO/*CO intermediate generated at inner Pt-O-Ce sites can migrate to edge, inducing the subsequent coupling reaction, thus avoiding poisoning while promoting reaction efficiency. Consequently, Pt ALs/CeO2 exhibits exceptionally catalytic stability with negligible degradation even under 1000 s pure CO poisoning operation and high mass activity (14.87 A/mgPt), enabling it one of the best-performing alkali-stable MOR catalysts.