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1.
J Med Virol ; 96(1): e29396, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38235848

ABSTRACT

The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8). The entry efficacy of SARS-CoV-2 considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. Furthermore, the polymerase activity and stability of SARS-CoV-2 RdRp were affected by the three splicing factors to varying degrees. In addition, NSP12 and its homologues from SARS-CoV and MERS-CoV suppressed the alternative splicing of cellular genes, which were influenced by the three splicing factors. Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Humans , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , COVID-19/genetics , RNA-Dependent RNA Polymerase/metabolism , Middle East Respiratory Syndrome Coronavirus/genetics , RNA Splicing Factors
2.
Ann Neurol ; 93(6): 1069-1081, 2023 06.
Article in English | MEDLINE | ID: mdl-36843248

ABSTRACT

OBJECTIVE: To investigate aquaporin-4 antibody (AQP4-IgG) dynamics and relapse risk in patients with seropositive neuromyelitis optica spectrum disorder treated with immunosuppressants. METHODS: This observational cohort study with prospectively collected data included 400 neuromyelitis optica spectrum disorder patients seropositive for AQP4-IgG and treated with immunosuppressants. Serum AQP4-IgG was detected by fixed cell-based assay every 6 months. RESULTS: After treatment with immunosuppressants, 128 patients became AQP4-IgG seronegative. The median time to become seronegative for 400 patients was 76.4 months (61.4 months, NA). Among those patients with negative change of AQP4-IgG, the mean annualized relapse rate significantly decreased after patients became seronegative (0.20 vs 0.77, p < 0.001), and a positive correlation was observed between time to become seronegative and relapse (OR 1.018, 95% CI 1.001-1.035, p < 0.05). Independent risk factors for AQP4-IgG becoming seronegative were older age at onset, initiation of immunosuppressants at onset, and shorter disease duration before maintenance therapy. Independent risk factors for relapse included younger age (≤46.4 years) at onset, poly-system involvement in the first attack, and unchanged or increased AQP4-IgG titer. The relapse risk was not associated with sex, combination with connective tissue disease, seropositivity for systemic autoimmune antibodies, or incomplete recovery from the first attack. INTERPRETATION: Patients with younger age at onset, poly-system involvement in the first attack, and unchanged or increased titer of AQP4-IgG are most likely to experience relapse under treatment with immunosuppressants. Time to AQP4-IgG becoming seronegative and change of AQP4-IgG titer may become the surrogate efficacy biomarkers in clinical trials. ANN NEUROL 2023;93:1069-1081.


Subject(s)
Neuromyelitis Optica , Humans , Middle Aged , Immunosuppressive Agents/therapeutic use , Aquaporin 4 , Autoantibodies , Chronic Disease , Biomarkers , Recurrence , Immunoglobulin G
3.
Glob Chang Biol ; 30(2): e17192, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38369693

ABSTRACT

Obtaining a holistic understanding of the impacts of atmospheric nitrogen deposition on multiple ecosystem services of forest is essential for developing comprehensive and sustainable strategies, particularly in heavy N deposition regions such as subtropical China. However, such impacts remain incompletely understood, with most previous studies focus on individual ecosystem function or service via understory N addition experiments. To address this knowledge gap, we quantified the effects of over-canopy and understory N additions on multiple ecosystem services based on a 7-year large-scale field experiment in a typical subtropical forest. Our results showed continued over-canopy N addition with 50 kg ha-1 year-1 over a period of 4-7 years significantly increased plant nutrient retention, but did not affect the services of soil nutrient accumulation, water yield, C sequestration (in plants and soil), or oxygen release. There were trade-offs between the soil and plant on providing the services of nutrient accumulation/retention and C sequestration under over-canopy N addition. However, without uptake and retention of tree canopy, the trade-off between soil and plant were more weaken under the understory N addition with 50 kg ha-1 year-1 , and their relationships were even synergetic under the understory N addition with 25 kg ha-1 year-1 . The results suggest that understory N addition cannot accurately simulate the effects of atmospheric N deposition on multiple services, along with mutual relationships. Interestingly, the services of plant N, P retention, and C sequestration exhibited a synergetic increase under the over-canopy N addition but a decrease under the understory N addition. Our results also found tree layer plays a primary role in providing plant nutrient retention service and is sensitive to atmospheric N deposition. Further studies are needed to investigate the generalized effects of forest canopy processes on alleviating the threaten of global change factors in different forest ecosystems.


Subject(s)
Ecosystem , Nitrogen , Nitrogen/analysis , Forests , Trees , Plants , Soil
4.
Chemistry ; : e202401293, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828487

ABSTRACT

Herein, we report a general copper-catalyzed method for the tunable oxygenative rearrangement of tetrahydrocarbazoles to cyclopentyl-bearing spiroindolin-2-ones and spiroindolin-3-ones. The method demonstrates excellent chemoselectivity, regioselectivity, and product control simply by using the H2O and O2 as oxygen source, respectively. This open-flask method is safe and simple to operate, and no other chemical oxidants are required. Besides, inspired from the unique pathway of 1, 2-migration rearrangement, a highly controllable hydroxylation of indoles for the construction of C3a-hydroxyl iminium indolines was also developed. Mechanistic experiments suggest that a single-electron transfer-induced oxidation process is responsible for the tunable selectivity control.

5.
J Magn Reson Imaging ; 59(3): 1034-1042, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37272790

ABSTRACT

BACKGROUND: The assessment of resectability after neoadjuvant chemotherapy of hepatoblastoma is dependent on Post-Treatment EXTENT of Disease (POSTTEXT) staging and its annotation factors P (portal venous involvement) and V (hepatic venous/inferior vena cava [IVC] involvement), but MR performance in assessing them remains unclear. PURPOSE: To assess the diagnostic performance of contrast-enhanced MR imaging for preoperative POSTTEXT staging and diagnosing vascular involvement in terms of annotation factors P and V in pediatric hepatoblastoma following neoadjuvant chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Thirty-five consecutive patients (17 males, median age, 24 months; age range, 6-98 months) with proven hepatoblastoma underwent preoperative MR imaging following neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 3.0 T; T2-weighted imaging (T2WI), T2WI with fat suppression, diffusion weighted imaging, radial stack-of-the-star/Cartesian 3D Dixon T1-weighted gradient echo imaging. ASSESSMENT: Three radiologists independently assessed the POSTTEXT stages and annotation factors P and V based on the 2017 PRE/POSTTEXT system. The sensitivities and specificities were calculated for 1) diagnosing each POSTTEXT stage; 2) discrimination of stages III and IV (advanced) from those stages I and II (non-advanced) hepatoblastomas; and 3) annotation factors P and V. The combination of pathologic findings and surgical records served as the reference standard. STATISTICAL TESTS: Sensitivity, specificity, Fleiss kappa test. RESULTS: The sensitivity and specificity ranges for discriminating advanced from non-advanced hepatoblastomas were 73.3%-80.0% and 80.0%-90.0%, respectively. For annotation factor P, they were 66.7%-100.0% and 90.6%, respectively. For factor V, they were 75.0% and 67.7%-83.9%, respectively. There was excellent, substantial, and moderate agreement on POSTTEXT staging (Fleiss kappa = 0.82), factors P (Fleiss kappa = 0.64), and factors V (Fleiss kappa = 0.60), respectively. DATA CONCLUSION: MR POSTTEXT provides reliable discrimination between advanced and non-advanced tumors, and MR has moderate to excellent specificity at identifying portal venous and hepatic venous/IVC involvement. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.


Subject(s)
Hepatoblastoma , Liver Neoplasms , Male , Child , Humans , Child, Preschool , Infant , Hepatoblastoma/drug therapy , Hepatoblastoma/pathology , Hepatoblastoma/surgery , Neoadjuvant Therapy , Retrospective Studies , Magnetic Resonance Imaging/methods , Hepatic Veins , Sensitivity and Specificity , Liver Neoplasms/pathology , Neoplasm Staging
6.
Langmuir ; 40(14): 7384-7394, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38530344

ABSTRACT

Photocatalytic technology is a popular research area for converting solar energy into environmentally friendly chemicals and is considered the greenest approach for producing H2O2. However, the corresponding reactive oxygen species (ROS) and pathway involved in the photocatalytic generation of H2O2 by the Bi2.15WO6-glucose system are still not clear. Quenching experiments have established that neither •OH nor h+ contribute to the formation of H2O2, and show that the formed surface superoxo (≡Bi-OO•) and peroxo (≡Bi-OOH) species are the predominant ROS in H2O2 generation. In addition, various characterizations indicate the enhanced electron-transfer on the surface of Bi2.15WO6 with increasing contents of glucose via the ligand-to-metal charge transfer pathway, confirming H-transfer from glucose to ≡Bi-OO• or ≡Bi-OOH. The increased production of H2O2 with decreasing bond dissociation energy (BDEO-H) values of various phenolic compounds again supports the H-transfer mechanism from phenolic compounds to ≡Bi-OO• and then to ≡Bi-OOH. DFT calculations further reveal that on the Bi2.15WO6 surface, oxygen is sequentially reduced to ≡Bi-OO• and ≡Bi-OOH, while H-transfer from H2O or glucose to ≡Bi-OO• and ≡Bi-OOH, resulting in the production of H2O2. The lower energy barrier of H-transfer from adsorbed glucose (0.636 eV) than that from H2O (1.157 eV) indicates that H-transfer is more favorable from adsorbed glucose. This work gives new insight into the photocatalytic generation of H2O2 by Bi2.15WO6 in the presence of glucose/phenolic compounds via the H-abstraction pathway.

7.
Langmuir ; 40(23): 12250-12263, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38818891

ABSTRACT

Bismaleimide (BMI) is often used as the cross-linking reagent in Diels-Alder (D-A)-type intrinsic self-healing materials (DISMs) to promote the connectivity of damaged surfaces based on reversible D-A bond formation on the molecular scale. Until now, although DISMs have exhibited great potential in the applications of various sensors, electronic skin, and artificial muscles, it is still difficult to prepare DISMs with satisfactory self-healing abilities and high tensile strengths and strains at the same time, thus largely limiting their applications in self-healing anticorrosive coatings. Herein, symmetrical trimaleimide (TMI) was successfully synthesized, and trimaleimide-structured D-A self-healing polyurethane (TMI-DA-PU) was prepared via the reversible D-A reaction (cycloaddition of furan and maleimide). As a DISM, TMI-DA-PU exhibits apparently higher self-healing efficiency (98.7%), tensile strength (25.4 MPa), and strain (1378%) compared to bismaleimide-structured D-A self-healing polyurethane (BMI-DA-PU) (self-healing efficiency, 90.2%; tensile strength, 19.3 MPa; strain, 1174%). In addition, TMI-DA-PU shows a high recycling efficiency (>95%) after 4 cycles of recycling. A series of characterizations indicate that TMI provides more monoene rings as the self-healing sites, forms denser cross-linked structures compared to BMI, and is, thus, more appropriate to be used for DISM applications. Moreover, the barrier abilities of coatings can be semi-quantitatively expressed by the impedance value at 0.01 Hz (|Z|0.01 Hz). The |Z|0.01 Hz value of the TMI-DA-PU coating is 3.93 × 109 Ω cm2 on day 0, which is significantly higher than that of the BMI-DA-PU coating (6.76 × 108 Ω cm2 on day 0), indicating that the denser rigid cross-linked structure of TMI results in the small porosity in the TMI-DA-PU coating, thus effectively improving the anticorrosion performance. The construction of DISMs with the structure of TMI demonstrates immense potential in self-healing anticorrosive coatings.

8.
Org Biomol Chem ; 22(4): 741-744, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38170630

ABSTRACT

An unexpected isomerization of azomethine ylides generated in situ from isatin with indoline-2-carboxylic acid has been disclosed, providing direct access to N-functionalized indole scaffolds. This protocol has good functional group tolerance and provides various 3-(1H-indol-1-yl)indolin-2-one derivatives in moderate to high yields simply by using alcohol as the solvent, with no additional additive being required.

9.
Nature ; 559(7713): 193-204, 2018 07.
Article in English | MEDLINE | ID: mdl-29995865

ABSTRACT

China has responded to a national land-system sustainability emergency via an integrated portfolio of large-scale programmes. Here we review 16 sustainability programmes, which invested US$378.5 billion (in 2015 US$), covered 623.9 million hectares of land and involved over 500 million people, mostly since 1998. We find overwhelmingly that the interventions improved the sustainability of China's rural land systems, but the impacts are nuanced and adverse outcomes have occurred. We identify some key characteristics of programme success, potential risks to their durability, and future research needs. We suggest directions for China and other nations as they progress towards the Sustainable Development Goals of the United Nations' Agenda 2030.


Subject(s)
Soil , Sustainable Development/trends , Agriculture , Biodiversity , China , Conservation of Natural Resources , Food Supply , Forests , Goals , Grassland , Sustainable Development/economics , Sustainable Development/legislation & jurisprudence , Time Factors , United Nations , Water
10.
Pestic Biochem Physiol ; 202: 105936, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38879328

ABSTRACT

The fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), is one of the most destructive agricultural pests. The entomopathogenic fungus Beauveria bassiana (Hypocreales: Clavicipitaceae) is a biopesticide widely used for biocontrol of various pests. Secreted fungal proteases are critical for insect cuticle destruction and successful infection. We have previously shown that the serine protease BbAorsin in B. bassiana has entomopathogenic and antiphytopathogenic activities. However, the contribution of BbAorsin to fungal growth, conidiation, germination, virulence and antiphytopathogenic activities remains unclear. In this study, the deletion (ΔBbAorsin), complementation (Comp), and overexpression (BbAorsinOE) strains of B. bassiana were generated for comparative studies. The results showed that ΔBbAorsin exhibited slower growth, reduced conidiation, lower germination rate, and longer germination time compared to WT and Comp. In contrast, BbAorsinOE showed higher growth rate, increased conidiation, higher germination rate and shorter germination time. Injection of BbAorsinOE showed the highest virulence against S. frugiperda larvae, while injection of ΔBbAorsin showed the lowest virulence. Feeding BbAorsinOE resulted in lower pupation and adult eclosion rates and malformed adults. 16S rRNA sequencing revealed no changes in the gut microbiota after feeding either WT or BbAorsinOE. However, BbAorsinOE caused a disrupted midgut, leakage of gut microbiota into the hemolymph, and upregulation of apoptosis and immunity-related genes. BbAorsin can disrupt the cell wall of the phytopathogen Fusarium graminearum and alleviate symptoms in wheat seedlings and cherry tomatoes infected with F. graminearum. These results highlight the importance of BbAorsin for B. bassiana and its potential as a multifunctional biopesticide.


Subject(s)
Beauveria , Beauveria/pathogenicity , Beauveria/genetics , Beauveria/physiology , Animals , Virulence , Fungal Proteins/genetics , Fungal Proteins/metabolism , Spodoptera/microbiology , Spores, Fungal , Larva/microbiology , Serine Proteases/metabolism , Serine Proteases/genetics , Pest Control, Biological , Fusarium/pathogenicity , Fusarium/genetics
11.
Glob Chang Biol ; 29(2): 533-546, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36251710

ABSTRACT

Microbial metabolic products play a vital role in maintaining ecosystem multifunctionality, such as soil physical structure and soil organic carbon (SOC) preservation. Afforestation is an effective strategy to restore degraded land. Glomalin-related soil proteins (GRSP) and amino sugars are regarded as stable microbial-derived C, and their distribution within soil aggregates affects soil structure stability and SOC sequestration. However, the information about how afforestation affects the microbial contribution to SOC pools within aggregates is poorly understood. We assessed the accumulation and contribution of GRSP and amino sugars within soil aggregates along a restoration chronosequence (Bare land, Eucalyptus exserta plantation, native species mixed forest, and native forest) in tropical coastal terraces. Amino sugars and GRSP concentrations increased, whereas their contributions to the SOC pool decreased along the restoration chronosequence. Although microaggregates harbored greater microbial abundances, amino sugars and GRSP concentrations were not significantly affected by aggregate sizes. Interestingly, the contributions of amino sugars and GRSP to SOC pools decreased with decreasing aggregate size which might be associated with increased accumulation of plant-derived C. However, the relative change rate of GRSP was consistently greater in all restoration chronosequences than that of amino sugars. The accumulation of GRSP and amino sugars in SOC pools was closely associated with the dynamics of soil fertility and the microbial community. Our findings suggest that GRSP accumulates faster and contributes more to SOC pools during restoration than amino sugars did which was greatly affected by aggregate sizes. Afforestation substantially enhanced soil quality with native forest comprising species sequestering more SOC than the monoculture plantation did. Such information is invaluable for improving our mechanistic understanding of microbial control over SOC preservation during degraded ecosystem restoration. Our findings also show that plantations using arbuscular mycorrhizal plants can be an effective practice to sequester more soil carbon during restoration.


Subject(s)
Carbon , Soil , Soil/chemistry , Carbon/analysis , Ecosystem , Amino Sugars , Fungal Proteins/metabolism , Carbon Sequestration , China
12.
Langmuir ; 39(30): 10601-10610, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37467429

ABSTRACT

Although the photocatalytic reduction of Cr(VI) to Cr(III) by traditional powder photocatalysts is a promising method, the difficulty and poor recovery of photocatalysts from water hinder their wide practical applications. Herein, we present that FeC2O4/Bi2.15WO6 (FeC2O4/BWO) composites were tightly bonded to modified polyvinylidene fluoride (PVDF) membranes by chemical grafting with the aid of polyvinyl alcohol (PVA) to form photocatalytic composite membranes (PVDF@PVA-FeC2O4/BWO). The contact angle of PVDF@PVA-FeC2O4/BWO (0.06 wt % of FeC2O4/BWO) is 48.0°, which is much lower than that of the pure PVDF membrane (80.5°). Meanwhile, the permeate flux of 61.43 g m-2 h-1 and water flux of 250.60 L m-2 h-1 were observed for PVDF@PVA-FeC2O4/BWO composite membranes. The tensile strength of composite membranes reached 48.84 MPa, which was 9.8 times higher than that of PVDF membrane. It was found that the PVDF@PVA-FeC2O4/BWO membrane exhibited excellent photocatalytic Cr(VI) reduction performance under both simulated and real sunlight irradiation. The adsorption for Cr(VI) by PVDF@PVA-FeC2O4/BWO can reach 47.6% in the dark process within 30 min, and the removal percentage of Cr(VI) could reach 100% with a rate constant k value of 0.2651 min-1 after 10 min of light exposure, indicating a synergistic effect of adsorption and photoreduction for Cr(VI) removal by the composite membrane. The PVDF@PVA-FeC2O4/BWO membrane had good stability and reusability after seven consecutive cycles. Most importantly, the influences of foreign ions on Cr(VI) reduction were investigated to mimic real sewage, which revealed that no obvious adverse effects can be found with the presence of common foreign ions in sewage. The photocatalytic membrane material developed in this study provides a new idea for treating Cr(VI)-containing wastewater and has a more significant application prospect.

13.
Langmuir ; 39(41): 14638-14651, 2023 Oct 17.
Article in English | MEDLINE | ID: mdl-37782834

ABSTRACT

In harsh environments, it is crucial to design personal protective materials that possess both puncture/cut resistance and chemical resistance. In order to fulfill these requirements, this study introduces an innovative approach that combines hydrophobically modified rigid nanoparticles with thermoplastic polyurethane elastomers. These materials are then laminated with high-performance aramid fabrics through a scraping process, resulting in a multifunctional composite with puncture/cut resistance, superhydrophobicity, self-cleaning properties, and acid/alkali resistance. The quasi-static puncture tests conducted reveal the remarkable performance of the composite. The maximum spike puncture resistance reaches 267.62 N, which is 17.14 times higher than that of the pure fabric (15.61 N). Similarly, the maximum knife puncture resistance reaches 115.02 N, exhibiting a 5.01 times increase compared to that of the pure aramid fabric (22.97 N). Furthermore, the results obtained from the yarn pull-out, fabric burst strength, and tearing experiments demonstrate that the incorporation of rigid nanoparticles significantly enhances the friction between the yarns, enabling a greater number of yarns to participate in the dissipation of impact energy. As a result, the puncture resistance of the fabric is greatly improved. Significantly, the composite exhibits sustained superhydrophobicity even after exposure to harsh chemicals such as concentrated sulfuric acid and sodium hydroxide as well as undergoing cyclic mechanical wear. These findings highlight the composite's exceptional durability and resistance to corrosion. Overall, this study offers insights and methods for the development of multifunctional flexible puncture-resistant equipment for individuals.

14.
Org Biomol Chem ; 21(36): 7290-7294, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37650516

ABSTRACT

Electrophilic bromocyclization reactions are widely used as key steps in the synthesis of diverse functionalized tetrahydrofuroindolines and hexahydropyrroloindolines. However, the direct dibromination variants of these reactions for the synthesis of 3,5-dibromoindolines remain undeveloped. Here, we report a protonic-acid-promoted electrooxidative protocol for the dearomative C3,C5-dibromocyclizations of tryptophol and tryptamine derivatives. This electrosynthetic approach, which enables direct selective construction of heterocyclic 3a,5a-dibromoindolines with inexpensive, non-hazardous NaBr as both the electrolyte and Br source, provides a convenient, practical method for the late-stage 3,5-diversification of heterocyclic indolines.

15.
Acta Pharmacol Sin ; 44(6): 1135-1148, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36536076

ABSTRACT

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons and the accumulation of Lewy bodies (LB) in the substantia nigra (SN). Evidence shows that microglia-mediated neuroinflammation plays a key role in PD pathogenesis. Using TNF-α as an indicator for microglial activation, we established a cellular model to screen compounds that could inhibit neuroinflammation. From 2471 compounds in a small molecular compound library composed of FDA-approved drugs, we found 77 candidates with a significant anti-inflammatory effect. In this study, we further characterized pazopanib, a pan-VEGF receptor tyrosine kinase inhibitor (that was approved by the FDA for the treatment of advanced renal cell carcinoma and advanced soft tissue sarcoma). We showed that pretreatment with pazopanib (1, 5, 10 µM) dose-dependently suppressed LPS-induced BV2 cell activation evidenced by inhibiting the transcription of proinflammatory factors iNOS, COX2, Il-1ß, and Il-6 through the MEK4-JNK-AP-1 pathway. The conditioned medium from LPS-treated microglia caused mouse DA neuronal MES23.5 cell damage, which was greatly attenuated by pretreatment of the microglia with pazopanib. We established an LPS-stimulated mouse model by stereotactic injection of LPS into mouse substantia nigra. Administration of pazopanib (10 mg·kg-1·d-1, i.p., for 10 days) exerted significant anti-inflammatory and neuronal protective effects, and improved motor abilities impaired by LPS in the mice. Together, we discover a promising candidate compound for anti-neuroinflammation and provide a potential repositioning of pazopanib in the treatment of PD.


Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Mice , Animals , Dopaminergic Neurons/metabolism , Lipopolysaccharides/pharmacology , Transcription Factor AP-1/metabolism , Neurodegenerative Diseases/drug therapy , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Microglia/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/metabolism
16.
Acta Pharmacol Sin ; 44(10): 1948-1961, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37225849

ABSTRACT

Parkinson's disease (PD) is a common neurodegenerative motor disorder characterized by a dramatic reduction in pars compacta of substantia nigra dopaminergic neurons and striatal dopamine (DA) levels. Mutations or deletions in the PARK7/DJ-1 gene are associated with an early-onset familial form of PD. DJ-1 protein prevents neurodegeneration via its regulation of oxidative stress and mitochondrial function as well as its roles in transcription and signal transduction. In this study, we investigated how loss of DJ-1 function affected DA degradation, ROS generation and mitochondrial dysfunction in neuronal cells. We showed that loss of DJ-1 significantly increased the expression of monoamine oxidase (MAO)-B but not MAO-A in both neuronal cells and primary astrocytes. In DJ-1-knockout (KO) mice, MAO-B protein levels in the substantia nigra (SN) and striatal regions were significantly increased. We demonstrated that the induction of MAO-B expression by DJ-1 deficiency depended on early growth response 1 (EGR1) in N2a cells. By coimmunoprecipitation omics analysis, we found that DJ-1 interacted with receptor of activated protein C kinase 1 (RACK1), a scaffolding protein, and thus inhibited the activity of the PKC/JNK/AP-1/EGR1 cascade. The PKC inhibitor sotrastaurin or the JNK inhibitor SP600125 completely inhibited DJ-1 deficiency-induced EGR1 and MAO-B expression in N2a cells. Moreover, the MAO-B inhibitor rasagiline inhibited mitochondrial ROS generation and rescued neuronal cell death caused by DJ-1 deficiency, especially in response to MPTP stimulation in vitro and in vivo. These results suggest that DJ-1 exerts neuroprotective effects by inhibiting the expression of MAO-B distributed at the mitochondrial outer membrane, which mediates DA degradation, ROS generation and mitochondrial dysfunction. This study reveals a mechanistic link between DJ-1 and MAO-B expression and contributes to understanding the crosslinks among pathogenic factors, mitochondrial dysfunction and oxidative stress in PD pathogenesis.


Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Mice , Animals , Parkinson Disease/metabolism , Monoamine Oxidase/genetics , Monoamine Oxidase/metabolism , Monoamine Oxidase/pharmacology , Up-Regulation , Reactive Oxygen Species/metabolism , Dopaminergic Neurons/metabolism , Signal Transduction , Neurodegenerative Diseases/metabolism , Receptors for Activated C Kinase/genetics , Receptors for Activated C Kinase/metabolism , Receptors for Activated C Kinase/pharmacology , Protein Deglycase DJ-1/genetics , Protein Deglycase DJ-1/metabolism
17.
J Environ Manage ; 344: 118512, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37384992

ABSTRACT

Poor regeneration of natural vegetation is a major factor contributing to the degradation of tropical coral islands. Soil seed banks (SSB) are important for maintaining the resilience of plant communities. However, the community characteristics and spatial distribution of SSBs and the controlling factors along human disturbance on coral islands are unclear. To fill this gap, we measured the community structure and spatial distributions of forest SSBs on three coral islands in the South China Sea, with varying degrees of human disturbance. The results showed that strong human disturbance increased the diversity, richness, and density of SSBs, as well as increased the richness of invasive species. With increased human disturbance, the heterogeneity pattern of SSBs spatial distribution changed from difference between forest east and west to forest center and edge. The similarity between the SSBs and above-ground vegetation also increased, and the distribution of invasive species extended from the edge to the central area of the forests, demonstrating that human disturbance limited the outward dispersal of seeds of resident species but increased the inward dispersal of seeds of invasive species. Interaction between soil properties, plant characteristics, and human disturbance explained 23-45% of the spatial variation of forest SSBs on the coral islands. However, human disturbance reduced the correlations of plant communities and spatial distribution of SSBs with soil factors (i.e., available phosphorus and total nitrogen) and increased the correlations of the community characteristics of SSB with landscape heterogeneity index, road distance, and shrub and litter cover. Resident seed dispersal on tropical coral islands might be enhanced by reducing building height, constructing buildings in down-wind locations, and preserving corridors that support animal movement among forest fragments.


Subject(s)
Anthozoa , Ecosystem , Animals , Humans , Soil/chemistry , Seed Bank , Anthropogenic Effects , Islands , Forests , Plants , Seeds , Introduced Species
18.
J Environ Manage ; 340: 118009, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37105101

ABSTRACT

Canopies play an important role in nitrogen (N) redistribution in forest ecosystems, and ignoring the canopy's role might bias estimates of the ecological consequences of anthropogenic atmospheric N deposition. We investigated the effects of the approach of N addition (Canopy addition vs. Understory addition) and level of N addition (25 kg N ha-1yr-1 vs. 50 kg N ha-1yr-1) on microbial residual carbon (MRC) accumulation in topsoil and subsoil. We found that the response of MRC to both approach and level of N addition varied greatly with soil depth in a tropical forest over eight years of continuous N addition. Specifically, N addition enhanced the accumulation of fungal and total MRC and their contribution to soil organic C (SOC) pools in the topsoil, whereas it decreased the contribution of fungal and total MRC to SOC in the subsoil. The contrasting effects of N addition on MRC contribution at varying soil depths were associated with the distinct response of microbial residues production. Understory N addition showed overall greater effects on MRC accumulation than canopy N addition did. Our results suggest that the canopy plays an important role in buffering the impacts of anthropogenic atmospheric N deposition on soil C cycling in tropical forests. The depth-dependent response of microbial residues to N addition also highlights the urgent need for further studies of different response mechanisms at different soil depths.


Subject(s)
Ecosystem , Nitrogen , Nitrogen/analysis , Carbon , Forests , Soil/chemistry , Trees
19.
Angew Chem Int Ed Engl ; 62(51): e202313687, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-37950324

ABSTRACT

Herein, we report an unprecedented skeletal rearrangement reaction of tetrahydro-ß-carbolines enabled by copper-catalyzed single-electron oxidative oxygenation, in which H2 O and O2 act as oxygen sources to generate a unique 2-hydroxyl-3-peroxide indoline intermediate. The synthetic reactivity of 2-hydroxyl-3-peroxide indoline species was demonstrated by a unique multi-step bond cleavage and formation cascade. Using a readily available copper catalyst under open-air conditions, highly important yet synthetically difficult spiro[pyrrolidone-(3,1-benzoxazine)] products were obtained in a single operation. The synthetic utility of this methodology is demonstrated by the efficient synthesis of the natural products donaxanine and chimonamidine, as well as the 3-hydroxyl-pyrroloindoline scaffold, in just one or two steps.

20.
Phys Chem Chem Phys ; 24(22): 13661-13670, 2022 Jun 08.
Article in English | MEDLINE | ID: mdl-35611917

ABSTRACT

Photooxidation of As(III) by TiO2 is a complicated process in which the oxidation mechanisms are always controversial. In this study, the enhanced photooxidation rates of As(III) with increasing pH values from 8.0 to 11.0 indicate the high photocatalytic reactivity of TiO2 under alkaline conditions. Moreover, As(III) improves the production of H2O2, indicating H-abstraction from As(III) (soluble or adsorbed) for H2O2 production. Although O2˙-, h+, ˙OH and -OOH are always regarded as the reactive oxygen species in the UV-TiO2 system, the superoxo and peroxo species formed on the surface of TiO2 also contribute to As(III) oxidation. The As(III)-O-Ti(IV) surface complexes formed on TiO2, as well as the decreased bandgaps of TiO2 with increasing concentrations of As(III) indicate that the ligand-to-metal charge transfer (LMCT) pathway also contributes to the oxidation of As(III) under alkaline conditions. Electrochemical analyses further reveal that As(III) enhances the electron density on the surface of TiO2, thereby improving the catalytic reactivity of TiO2. We therefore suggest that H-abstraction from As(III) or H2O to the formed superoxo and peroxo species results in the formation of H2O2, accompanied by the oxidation of As(III). This enriches our knowledge on the oxidation of As(III), as well as other contaminants rich in -OH groups during the photocatalytic oxidation processes.


Subject(s)
Arsenites , Arsenites/chemistry , Hydrogen Peroxide/chemistry , Ligands , Metals , Titanium/chemistry
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