A global dataset of terrestrial evapotranspiration and soil moisture dynamics from 1982 to 2020.

Quantifying terrestrial evapotranspiration (ET) and soil moisture dynamics accurately is crucial for understanding the global water cycle and surface energy balance. We present a novel, long-term dataset of global ET and soil moisture derived from the newly developed Simple Terrestrial Hydrosphere model, version 2 (SiTHv2). This ecohydrological model, driven by multi-source satellite observations and hydrometeorological variables from reanalysis data, provides daily global ET-related estimates (e.g., total ET, plant transpiration, soil evaporation, intercepted evaporation) and three-layer soil moisture dynamics at a 0.1° spatial resolution. Validation with in-situ measurements and comparisons with mainstream global ET and soil moisture products demonstrate robust performance of SiTHv2 in both magnitude and temporal dynamics of ET and soil moisture at multiple scales. The comprehensive water path characterization in the SiTHv2 model makes this seamless dataset particularly valuable for studies requiring synchronized water budget and vegetation response to water constraints. With its long-term coverage and high spatiotemporal resolution, the SiTHv2-derived ET and soil moisture product will be suitable to support analyses related to the hydrologic cycle, drought assessment, and ecosystem health.

The self-designed reactor to achieve efficient degradation of polyvinyl alcohol under high-pressure and high-temperature conditions.

A huge amount of polyvinyl alcohol (PVA) fabric is abandoned from nuclear power plants every year, the traditional treatment process will occupy land resources and pollute the environment; therefore, a lot of research has been carried out on the chemical treatment of PVA fabric. Herein, the performance of degradation of polyvinyl alcohol under high-pressure and high-temperature conditions is investigated. The effects of the initial pH value, reaction temperature, molar ratio of H2O2/Fe2+, and H2O2 dosage on PVA degradation were evaluated. In the tested ranges in this work, the degradation of PVA fabric via high-pressure and high-temperature method was optimum at the initial pH value of 4, reaction temperature of 300℃, molar ratio of H2O2/Fe2+ as 10, and H2O2 dosage of 13 g/L. The PVA removal rate and TOC removal rate were 99.99% and 97.36%, respectively. Meanwhile, the high-pressure and high-temperature methods also had a great effect on the removal of Rhodamine-B and Reactive Red X-3B, the removal rates of Rhodamine-B and Reactive Red X-3B were 99.83% and 99.76%, respectively. The reaction mechanism of high-pressure and high-temperature methods was also discussed in this study.

Exploring the ecological meanings of temperature sensitivity of ecosystem respiration from different methods.

Temperature sensitivity (Q10) of ecosystem respiration (Re) is a critical parameter for predicting global terrestrial carbon dynamics and its response to climate warming. However, the determination of Q10 has been controversial. In this study, we scrutinized the underpinnings of three mainstream methods to reveal their relationships in estimating Q10 for Re in the Heihe River Basin, northwest China. Specifically, these methods are Q10 estimated from the long-term method (Q10_long), short-term method (Q10_short), and the low-frequency (Q10_lf) and high-frequency (Q10_hf) signals decomposed by the singular spectrum analysis (SSA) method. We found that: 1) Q10_lf and Q10_long are affected by the confounding effects caused by non-temperature factors, and are 1.8 ± 0.3 and 1.7 ± 0.3, respectively. 2) The high-frequency signals of the SSA method and short-term method have consistent roles in removing the confounding effects. Both Q10_short and Q10_hf reflect the actual response of respiration to temperature. 3) Overall, Q10_long has a larger variability (1.7 ± 0.3) across different biomes, whereas Q10_short and Q10_hf show convergence (1.4 ± 0.2 and 1.3 ± 0.1, respectively). These results highlight the fact that Q10 can be overestimated by the long-term method, whereas the short-term method and high-frequency signals decomposed by the SSA method can obtain closer and convergent values after removing the confounding effects driven by non-temperature factors. Therefore, it is recommended to use the Q10 value estimated by the short-term method or high-frequency signals decomposed by the SSA method to predict carbon dynamics and its response to global warming in Earth system models.

Design and Synthesis of Novel Phthalide Derivatives containing 1,3,4-Oxadiazole/1,2,4-Triazole Units as Potential Antifungal Agents.

Four series of novel 1,3,4-oxadiazole/1,2,4-triazole hybrids of phthalide derivatives were designed and synthesized to search for novel potential antifungal agents. Preliminary antifungal activity assay results showed that compounds 4 a, 4 b, 4 m, 5 b, 5 f, 5 h, and 7 h exhibited moderate to excellent inhibitory activity against some phytopathogenic fungi. Among them, compound 5 b displayed the most outstanding antifungal effects against V. mali and S. sclerotiorum, with the EC50 mean of 3.96 µg/mL and 5.60 µg/mL, respectively, which was superior to those of commercial fungicides hymexazol and chlorothalonil. Furthermore, compound 5 b could completely suppress the spore germination of V. mali at a concentration of 10 µg/mL. Finally, molecular docking revealed that the potential target for the antifungal activity of compound 5 b was succinate dehydrogenase (SDH). This research provides novel candidate compounds for the prevention of phytopathogenic fungi.

Cemiplimab combined with chemotherapy versus chemotherapy in advanced non-small cell lung cancer: an updated EMPOWER-Lung 3 trial-based cost-effectiveness analysis.

Objective: Cemiplimab combined with chemotherapy has emerged as a promising treatment option for advanced non-small cell lung cancer (NSCLC). Accordingly, this study has been conducted to evaluate the cost-effectiveness of this combination therapy in comparison to chemotherapy alone from the perspective of the United States healthcare system. Methods: The present study is based on a partitioned survival model developed from clinical data obtained during the 2-year follow-up of the phase III EMPOWER-Lung 3 part 2 trial. The purpose of this investigation is to estimate the 10-year life expectancy and total healthcare costs of patients with advanced NSCLC by leveraging primary outcomes that evaluated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER).To establish the willingness-to-pay (WTP) threshold for the analysis, a value of $150,000/QALY was adopted. Sensitivity analysis was performed to determine the impact of varying levels of uncertainty on the results of this study. Results: When compared to chemotherapy alone, the addition of cemiplimab to chemotherapy has been demonstrated to result in an incremental gain of 1.593 QALY at an additional cost of $109351.298. This equates to an incremental cost-effectiveness ratio (ICER) of $68644.883/QALY. One-way sensitivity analyses were conducted on the model, which acknowledged the influence of several parameters, such as subsequent costs, the utility of progressive disease, the cost of best supportive care, the cost of cemiplimab per mg, and the utility of progression-free survival on the outcomes. Nonetheless, none of these parameters yielded an ICER lower than the WTP threshold. Conclusions: From the perspective of the United States healthcare system, the utilization of cemiplimab in combination with chemotherapy as a first-line treatment option for NSCLC appears to be a cost-effective approach as compared to using chemotherapy as a standalone therapy.

p-Cresol-Enabled Nickel-Catalyzed Intermolecular Redox-Economical Coupling of Allyl Alcohols with Alkynes through oxa-Nickelacycle.

An intermolecular redox-economical coupling reaction of allyl alcohols with alkynes, catalyzed by Ni-Brønsted acid cocatalysis, has been developed. This method allows for the synthesis of a diverse range of γ,δ-unsaturated ketones with yields ranging from 40% to 94%, while maintaining excellent compatibility with various functional groups. The transformation of the resulting product demonstrates the significant practical value of this method. Further mechanistic investigations have revealed that the reaction proceeds through the formation of an oxa-nickelacycle intermediate.

The autophagy machinery interacts with EBV capsids during viral envelope release.

Autophagy serves as a defense mechanism against intracellular pathogens, but several microorganisms exploit it for their own benefit. Accordingly, certain herpesviruses include autophagic membranes into their infectious virus particles. In this study, we analyzed the composition of purified virions of the Epstein-Barr virus (EBV), a common oncogenic γ-herpesvirus. In these, we found several components of the autophagy machinery, including membrane-associated LC3B-II, and numerous viral proteins, such as the capsid assembly proteins BVRF2 and BdRF1. Additionally, we showed that BVRF2 and BdRF1 interact with LC3B-II via their common protein domain. Using an EBV mutant, we identified BVRF2 as essential to assemble mature capsids and produce infectious EBV. However, BdRF1 was sufficient for the release of noninfectious viral envelopes as long as autophagy was not compromised. These data suggest that BVRF2 and BdRF1 are not only important for capsid assembly but together with the LC3B conjugation complex of ATG5-ATG12-ATG15L1 are also critical for EBV envelope release.

A cost-effectiveness analysis of first-line toripalimab plus chemotherapy in advanced nonsquamous non-small cell lung cancer in China.

BACKGROUND: This study compares first-line toripalimab with chemotherapy for advanced nonsquamous non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. RESEARCH DESIGN AND METHODS: A three-state Markov model was established to compare the quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) of first-line toripalimab plus chemotherapy versus chemotherapy. Clinical outcomes data were acquired from the CHOICE-01 clinical trials. Costs and utilities were gathered from regional databases or published publications. One-way sensitivity and probability sensitivity analyses were used to investigate the stability of the model parameters. RESULTS: First-line toripalimab treatment for advanced nonsquamous NSCLC resulted in an incremental cost of $16,214.03 and added 0.77 QALYs compared to chemotherapy, which had an ICER of $21,057.18 per QALY gained. The ICER was substantially lower than the willingness to pay (WTP) threshold in China, which was $37,663.26 per QALY. The toripalimab cycle used was shown to have the greatest impact on the ICERs, according to sensitivity analysis, although none of the factors significantly affected the model's outcomes. CONCLUSIONS: Toripalimab plus chemotherapy is likely to be a cost-effective option compared with chemotherapy alone for patients with advanced nonsquamous NSCLC from the perspective of the Chinese healthcare system.

Development of the "hidden" multi-target-directed ligands by AChE/BuChE for the treatment of Alzheimer's disease.

Accumulation of evidences suggested that excessive amounts of AChE and BuChE in the brain of AD patients at the different stage of AD, which could hydrolyze ACh and accelerated Aß aggregation. To develop new "hidden" multifunctional agents through AChE/BuChE would be a promising strategy to treat AD. To this end, firstly, a series of chalcone derivatives with chelating property was designed and synthesized. The in vitro results showed that compound 3f indicated significant selective MAO-B inhibitory activity (IC50 = 0.67 µM) and remarkable anti-inflammatory property. It also significantly inhibited self-induced Aß1-42 aggregation and showed remarkable neuroprotective effects on Aß25-35-induced PC12 cell injury. Furthermore, compound 3f was a selective metal chelator and could inhibit Cu2+-induced Aß1-42 aggregation. Based on this, the carbamate fragment was introduced to compound 3f to obtain carbamate derivatives. The biological activity results exhibited that compound 4b showed good BBB permeability, good AChE inhibitory potency (IC50 = 5.3 µM), moderate BuChE inhibitory potency (IC50 = 12.4 µM), significant MAO-B inhibitory potency, anti-inflammation potency on LPS-induced BV-2 cells and neuroprotective effects on Aß25-35-induced PC12 cell injury. Compared with 3f, compound 4b did not show obvious chelation property. Significantly, compound 4b could be activated by AChE/BuChE following inhibition of AChE/BuChE to liberate an active multifunctional chelator 3f, which was consistent with our original intention. More importantly, compounds 3f and 4b presented favorable ADME properties and good stability in artificial gastrointestinal fluid, blood plasma and rat liver microsomes. The in vivo results suggested that compound 4b (0.0195 µg/mL) could significantly improve dyskinesia and reaction capacity of the AlCl3-induced zebrafish AD model by increasing the level of ACh. Together our data suggest that compound 4b was a promising "hidden" multifunctional agent by AChE/BuChE, and this strategy deserved further development for the treatment of AD.

Type I Interferonopathy due to a Homozygous Loss-of-Inhibitory Function Mutation in STAT2.

PURPOSE: STAT2 is both an effector and negative regulator of type I interferon (IFN-I) signalling. We describe the characterization of a novel homozygous missense STAT2 substitution in a patient with a type I interferonopathy. METHODS: Whole-genome sequencing (WGS) was used to identify the genetic basis of disease in a patient with features of enhanced IFN-I signalling. After stable lentiviral reconstitution of STAT2-null human fibrosarcoma U6A cells with STAT2 wild type or p.(A219V), we performed quantitative polymerase chain reaction, western blotting, immunofluorescence, and co-immunoprecipitation to functionally characterize the p.(A219V) variant. RESULTS: WGS identified a rare homozygous single nucleotide transition in STAT2 (c.656C > T), resulting in a p.(A219V) substitution, in a patient displaying developmental delay, intracranial calcification, and up-regulation of interferon-stimulated gene (ISG) expression in blood. In vitro studies revealed that the STAT2 p.(A219V) variant retained the ability to transduce an IFN-I stimulus. Notably, STAT2 p.(A219V) failed to support receptor desensitization, resulting in sustained STAT2 phosphorylation and ISG up-regulation. Mechanistically, STAT2 p.(A219V) showed defective binding to ubiquitin specific protease 18 (USP18), providing a possible explanation for the chronic IFN-I pathway activation seen in the patient. CONCLUSION: Our data indicate an impaired negative regulatory role of STAT2 p.(A219V) in IFN-I signalling and that mutations in STAT2 resulting in a type I interferonopathy state are not limited to the previously reported R148 residue. Indeed, structural modelling highlights at least 3 further residues critical to mediating a STAT2-USP18 interaction, in which mutations might be expected to result in defective negative feedback regulation of IFN-I signalling.

Design, synthesis and biological evaluation of cajanonic acid A analogues as potent PPAR γ antagonists.

Peroxisome proliferator-activated receptor γ (PPAR γ) antagonists are a key instrument of insulin sensitizers since they have the ability to sensitize insulin and can avoid adverse reactions caused by receptor agonist. In this paper, two series of 28 novel Cajanonic acid A (CAA) derivatives were designed and synthesized. The biological activity showed that a novel CAA derivative 9f was identified as a potential PPAR γ antagonist by medicinal chemistry efforts. The results in vitro displayed that compound 9f could improve the PPAR γ antagonist activity (96.2 % / 50.2 % decrease in PPAR γ transactivation at 10 µM / 1 µM, respectively). It also could improve the glucose consumption activity of insulin-resistant HepG2/3T3-L1 cell line (33.27 % / 72.61 % increase in glucose consumption). And in 3 T3-L1 adipocytes, it showed anti-adipogenesis activity (7.04 % increase in oil red staining). Further, in vivo study suggested that compound 9f could improve the oral glucose tolerance in db/db mice. Taken together, derivative 9f served as a promising candidate for anti-diabetic drug discovery and deserve further study.

Downregulation of TNFAIP1 alleviates OGD/R­induced neuronal damage by suppressing Nrf2/GPX4­mediated ferroptosis.

TNFα-induced protein 1 (TNFAIP1) serve a role in neurovascular disease. However, the potential role and molecular mechanism of TNFAIP1 in cerebral ischemia-reperfusion (I/R) remains elusive. In the present study, reverse transcription-quantitative PCR and western blotting were used to assess TNFAIP1 mRNA and protein expression levels in PC12 cells. Furthermore, using Cell Counting Kit-8, flow cytometry and western blotting, cell viability and apoptosis were evaluated. Oxidative stress was evaluated using DCFH-DA staining and ELISA was used for assessment of inflammatory factors. Expression of components in the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and ferroptosis were assessed using western blotting analysis and an iron assay kit. TNFAIP1 expression was significantly upregulated in oxygen glucose deprivation and reperfusion (OGD/R)-injured PC12 cells. However, knocking down TNFAIP1 expression restored PC12 cell viability and decreased apoptosis following OGD/R-challenge. Furthermore, TNFAIP1 silencing significantly suppressed OGD/R-induced oxidative stress and inflammatory damage in PC12 cells. TNFAIP1 knockdown inhibited ferroptosis via activation of the Nrf2 signaling pathway in OGD/R-injured PC12 cells. Erastin treatment reversed the beneficial effects of TNFAIP1 knockdown on PC12 cell viability, apoptosis alleviation, oxidative stress and inflammation following OGD/R treatment. These results suggested that TNFAIP1 knockdown could alleviate OGD/R-induced neuronal cell damage by suppressing Nrf2-mediated ferroptosis, which might lay the foundation for the investigation of targeted-therapy for cerebral I/R injury in clinic.

Synthesis of Novel 3-Butylphthalide Derivatives Containing Isopentenylphenol Moiety as Potential Antiplatelet Agents for the Treatment of Ischemic Stroke.

In order to find novel antiplatelet drugs for the treatment of ischemic stroke, a series of 3-butylphthalide derivatives containing isopentenylphenol moiety were designed, synthesized and characterized with spectroscopic analyses. The in vitro antiplatelet activity results indicated that compound 3 better inhibited the arachidonic acid (AA) induced platelet aggregation than aspirin (ASP) and 3-butylphthalide (NBP). Additionally, compared with precursor NBP, compound 3 possessed outstanding antithrombotic activity in the animal experiment model, which could effectively alleviate the formation of tail thrombus and carotid artery thrombus in mice. More importantly, intraperitoneal administration of compound 3 can well protected the rats against ischemia/reperfusion-induced brain injury. Further pharmacokinetic (PK) assay indicated that compound 3 had good absorption characteristics and metabolic stability in vivo. Overall, the present research provides a new candidate compound for the treatment of ischemic stroke caused by platelet aggregation.

Icariin and Competing Endogenous RNA Network: A Potential Protective Strategy Against Contrast-Induced Acute Kidney Injury.

Background: Icariin presents protective effect in several kidney diseases. However, the role of icariin in contrast-induced acute kidney injury (CIAKI) is still unclear. This study aimed to investigate the effect of icariin in CIAKI, as well as exploring the underlying mechanism from the aspect of interaction between protein-coding genes and non-coding RNAs. Methods: The effect of icariin was evaluated in both in vivo and in vitro CIAKI models. Rat kidneys were collected for genome-wide sequencing. The differentially expressed genes (DEGs) were screened and visualized by R software. The function annotation of DEGs was analyzed by Metascape. By Cytoscape software, the competing endogenous RNA (ceRNA) network was constructed, and hub genes were selected. Expressions of hub genes were validated by PCR. Association of hub genes in the ceRNA network and renal function was also examined. Results: Icariin protected against CIAKI in both in vivo and in vitro models. Based on DEGs in icariin pretreated CIAKI rats, lncRNA- and circRNA-associated ceRNA networks were constructed, respectively. Function annotation showed the ceRNA networks were enriched in ERK1 and ERK2 cascade, MAPK signaling and NF-κB signaling. Further, two circRNAs, six lncRNAs, four miRNAs and nine mRNAs were selected as hub genes of the ceRNA network. Among them, eight mRNAs (Acot1, Cbwd1, Ly6i, Map3k14, Mettl2b, Nyap1, Set and Utp20) were negatively correlated with renal function, while one mRNA (Tmem44) was positively correlated with renal function. Conclusion: Icariin presented a protective effect against CIAKI. The ceRNA network, involving Acot1, Cbwd1, Ly6i, Map3k14, Mettl2, Nyap1, Set, Tmem44 and Utp20, might partially contribute to the underlying mechanism of icariin protection by regulation of ERK1 and ERK2 cascade, MAPK signaling and NF-κB signaling.

Evaluation of the antimicrobial function of Ginkgo biloba exocarp extract against clinical bacteria and its effect on Staphylococcus haemolyticus by disrupting biofilms.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Ginkgo biloba L. (Ginkgo nuts) has been used for a long time as a critical Chinese medicine material to treat cough and asthma, as well as a disinfectant. Similar records were written in the Compendium of Materia Medica (Ben Cao Gang Mu, pinyin in Chinese) and Sheng Nong's herbal classic (Shen Nong Ben Cao Jing, pinyin in Chinese). Recent research has shown that Ginkgo biloba exocarp extract (GBEE) has the functions of unblocking blood vessels and improving brain function, as well as antitumour activity and antibacterial activity. GBEE was shown to inhibit methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation as a traditional Chinese herb in our previous report in this journal. AIM OF THE STUD: yThe antibiotic resistance of clinical bacteria has recently become increasingly serious. Thus, this study aimed to investigate the Ginkgo biloba exocarp extract (GBEE) antibacterial lineage, as well as its effect and mechanism on S. haemolyticus biofilms. This study will provide a new perspective on clinical multidrug resistant (MDR) treatment with ethnopharmacology herbs. METHODS: The microbroth dilution assay was carried out to measure the antibacterial effect of GBEE on 13 types of clinical bacteria. Bacterial growth curves with or without GBEE treatment were drawn at different time points. The potential targets of GBEE against S. haemolyticus were screened by transcriptome sequencing. The effects of GBEE on bacterial biofilm formation and mature biofilm disruption were determined by crystal violet staining and scanning electron microscopy. The metabolic activity of bacteria inside the biofilm was assessed by colony-forming unit (CFU) counting and (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2HY-tetrazolium bromide (MTT) assay. Quantitative polymerase chain reaction (qPCR) was used to measure the gene expression profile of GBEE on S. haemolyticus biofilm-related factors. RESULTS: The results showed that GBEE has bacteriostatic effects on 3 g-positive (G+) and 2 g-negative (G-) bacteria among 13 species of clinical bacteria. The antibacterial effect of GBEE supernatant liquid was stronger than the antibacterial effect of GBEE supernviaould-like liquid. GBEE supernatant liquid inhibited the growth of S. epidermidis, S. haemolyticus, and E. faecium at shallow concentrations with minimum inhibitory concentrations (MICs) of 2 µg/ml, 4 µg/ml and 8 µg/ml, respectively. Genes involved in quorum sensing, two-component systems, folate biosynthesis, and ATP-binding cassette (ABC) transporters were differentially expressed in GBEE-treated groups compared with controls. Crystal violet, scanning electron microscopy (SEM) and MTT assays showed that GBEE suppressed S. haemolyticus biofilm formation in a dose-dependent manner. Moreover, GBEE supernatant liquid downregulated cidA, cidB and atl, which are involved in cell lysis and extracellular DNA (eDNA) release, as well as downregulated the cbp, ebp and fbp participation in encoding cell-surface binding proteins. CONCLUSIONS: GBEE has an excellent antibacterial effect on gram-positive bacteria and also inhibits the growth of gram-negative bacteria, such as A. baumannii (carbapenem-resistant Acinetobacter baumannii) CRABA and S. maltophilia. GBEE inhibits the biofilm formation of S. haemolyticus by altering the regulation and biofilm material-related genes, including the release of eDNA and cell-surface binding proteins.

Novel donepezil-chalcone-rivastigmine hybrids as potential multifunctional anti-Alzheimer's agents: Design, synthesis, in vitro biological evaluation, in vivo and in silico studies.

Alzheimer's disease (AD) is a chronic, progressive brain neurodegenerative disorder. Up to now, there is no effective drug to halt or reverse the progress of AD. Given the complex pathogenesis of AD, the multi-target-directed ligands (MTDLs) strategy is considered as the promising therapy. Herein, a series of novel donepezil-chalone-rivastigmine hybrids was rationally designed and synthesized by fusing donepezil, chalone and rivastigmine. The in vitro bioactivity results displayed that compound 10c was a reversible huAChE (IC50 = 0.87 µM) and huBuChE (IC50 = 3.3 µM) inhibitor. It also presented significant anti-inflammation effects by suppressing the level of IL-6 and TNF-α production, and significantly inhibited self-mediated Aß1-42 aggregation (60.6%) and huAChE-mediated induced Aß1-40 aggregation (46.2%). In addition, 10c showed significant neuroprotective effect on Aß1-42-induced PC12 cell injury and activated UPS pathway in HT22 cells to degrade tau and amyloid precursor protein (APP). Furthermore, compound 10c presented good stabilty in artificial gastrointestinal fluids and liver microsomes in vitro. The pharmacokinetic study showed that compound 10c was rapidly absorbed in rats and distributed in rat brain after intragastric administration. The PET-CT imaging demonstrated that [11C]10c could quickly enter the brain and washed out gradually in vivo. Further, compound 10c at a dose of 5 mg/kg improved scopolamine-induced memory impairment, deserving further investigations.

Cobalt-promoted synthesis of sulfurated oxindoles via radical annulation of N-arylacrylamides with disulfides.

An efficient radical annulation of N-arylacrylamides with disulfides is developed for the synthesis of sulfurated oxindoles. The reaction occurs in a facile manner using CoBr2 as both an initiator and a promoter for the first time and (NH4)2S2O8 as the oxidant. By controlling the CoBr2/(NH4)2S2O8 ratio, a wide range of sulfurated and brominated/sulfurated oxindoles are selectively prepared in good to excellent yields. The present protocol is simple and highly atom economical, and can tolerate a broad range of substrates.

Design, synthesis, and evaluation of novel O-alkyl ferulamide derivatives as multifunctional ligands for treating Alzheimer's disease.

Herein, a series of novel O-alkyl ferulamide derivatives were designed and synthesised through the multi-target-directed ligands (MTDLs) strategy. The biological activities in vitro showed that compounds 5a, 5d, 5e, 5f, and 5h indicated significantly selective MAO-B inhibitory potency (IC50 = 0.32, 0.56, 0.54, 0.73, and 0.86 µM, respectively) and moderate antioxidant activity. Moreover, compounds 5a, 5d, 5e, 5f, and 5h showed potent anti-inflammatory properties, remarkable effects on self-induced Aß1-42 aggregation, and potent neuroprotective effect on Aß1-42-induced PC12 cell injury. Furthermore, compounds 5a, 5d, 5e, 5f, and 5h presented good blood-brain barrier permeation in vitro and drug-like properties. More interesting, the PET/CT images with [11C]5f demonstrated that [11C]5f could penetrate the BBB with a high brain uptake and exhibited good brain clearance kinetic property. Therefore, compound 5f would be a promising multi-functional agent for the treatment of AD.

Simple preparation of a CuO@γ-Al2O3 Fenton-like catalyst and its photocatalytic degradation function.

We designed a photocatalyst and developed sustainable wastewater purification technology, which have significant advantages in effectively solving the global problem of drinking water shortage. In this study, a new nanocomposite was reported and shown to be a catalyst with excellent performance; CuO was coated successively onto functionalized nano γ-Al2O3, and this novel structure could provide abundant active sites. We evaluated the performance of the CuO@γ-Al2O3 nanocomposite catalyst for polyvinyl alcohol (PVA) degradation under visible light irradiation. Under optimized conditions (calcination temperature, 450 °C; mass ratio of γ-Al2O3:Cu(NO3)2·3H2O, 1:15; pH value, 7; catalyst dosage, 2.6 g/L; reaction temperature, 20 °C; and H2O2 dosage, 0.2 g/mL), the CuO@γ-Al2O3 nanocomposite catalyst presented an excellent PVA removal rate of 99.21%. After ten consecutive degradation experiments, the catalyst could still maintain a PVA removal rate of 97.58%, thus demonstrating excellent reusability. This study provides an efficient and easy-to-prepare photocatalyst and proposes a mechanism for the synergistic effect of the photocatalytic reaction and the Fenton-like reaction.

Development of naringenin-O-alkylamine derivatives as multifunctional agents for the treatment of Alzheimer's disease.

In this study, a series of naringenin-O-alkylamine derivatives were designed and obtained by introducing an alkylamine fragment into the naringenin skeleton. The in vitro biological activity results revealed that compounds 5f and 7k showed good antioxidant activity with ORAC values of 2.3eq and 1.2eq, respectively. Compounds 5f and 7k were reversible and excellent huAChE inhibitors with IC50 values of 0.91 µM and 0.57 µM, respectively. Moreover, compounds 5f and 7k could inhibit self-induced Aß1-42 aggregation with 62.1% and 43.8% inhibition rate, respectively, and significantly inhibited huAChE-Aß1-40 aggregation with 51.7% and 43.4% inhibition rate, respectively. In addition, compounds 5f and 7k were selective metal chelators and remarkably inhibited Cu2+-induced Aß1-42 aggregation with 73.5% and 68.7% inhibition rates, respectively. Furthermore, compounds 5f and 7k could cross the blood-brain barrier in vitro and displayed good neuroprotective effects and anti-inflammatory properties. Further investigation showed that compound 5f did not show obvious hepatotoxicity and displayed a good hepatoprotective effect by its antioxidant activity. The in vivo study displayed that compound 5f significantly improved scopolamine-induced mice memory impairment. Therefore, compound 5f was a potential multifunctional candidate for the treatment of AD.