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1.
BMC Cancer ; 24(1): 754, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38907215

ABSTRACT

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Brain Neoplasms , Glioma , Pyridines , Temozolomide , Humans , Temozolomide/administration & dosage , Temozolomide/therapeutic use , Temozolomide/adverse effects , Female , Male , Adult , Pyridines/administration & dosage , Pyridines/adverse effects , Pyridines/therapeutic use , Glioma/drug therapy , Glioma/pathology , Adolescent , Retrospective Studies , Child , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Young Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child, Preschool , Middle Aged , Treatment Outcome
2.
Exp Eye Res ; 244: 109936, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763351

ABSTRACT

Non-infectious uveitis is an intraocular autoimmune disease mainly characterized by immune dysregulation of the eye, which may cause blindness if not well treated. Interleukin 10 (IL-10) is a potent cytokine with multiple immunoregulatory functions. However, it's in vivo activity is unstable owing to its inherent protein instability and short plasma half-life. Therefore, our previous research tried to establish IL-10-overexpressing MSC-sEVs (sEVs-IL10) using lentiviral transfection. While this approach indeed improved drug delivery, it also suffered from tedious procedures and limited loading efficiency. Accordingly, we constructed a novel MSC-sEVs-based delivery system for IL-10 (IL-10@sEVs) by sonication. The obtained formulation (IL-10@sEVs) had relatively higher loading efficiency and exerted a more profound immunomodulatory effect than sEVs-IL10 in vitro. Furthermore, IL-10@sEVs had significant therapeutic effects in a mouse model of experimental autoimmune uveitis (EAU) by decreasing the percentage of Th17 cells, increasing regulatory T cells in the eye, and draining lymph nodes. In summary, sonication outperforms conventional transfection methods for loading IL-10 into MSC-sEVs.


Subject(s)
Autoimmune Diseases , Disease Models, Animal , Extracellular Vesicles , Interleukin-10 , Mice, Inbred C57BL , Uveitis , Animals , Interleukin-10/genetics , Uveitis/drug therapy , Mice , Autoimmune Diseases/drug therapy , Female , Th17 Cells/immunology , Transfection , T-Lymphocytes, Regulatory/immunology , Drug Delivery Systems
3.
Environ Sci Technol ; 58(26): 11342-11351, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38875720

ABSTRACT

Municipal solid waste (MSW) management systems play a crucial role in greenhouse gas (GHG) emissions in China. Although the government has implemented many policies to improve the MSW management system, the impact of these improvements on city-level GHG emission reduction remains largely unexplored. This study conducted a comprehensive analysis of both direct and downstream GHG emissions from the MSW sector, encompassing sanitary landfill, dump, incineration, and biological treatment, across 352 Chinese cities from 2001 to 2021 by adopting inventory methods recommended by the Intergovernmental Panel on Climate Change (IPCC). The results reveal that (1) GHG emissions from the MSW sector in China peaked at 70.6 Tg of CO2 equiv in 2018, followed by a significant decline to 47.6 Tg of CO2 equiv in 2021, (2) cities with the highest GHG emission reduction benefits in the MSW sector were historical emission hotspots over the past 2 decades, and (3) with the potential achievement of zero-landfilling policy by 2030, an additional reduction of 203.7 Tg of CO2 equiv is projected, with the emission reduction focus toward cities in South China (21.9%), Northeast China (17.8%), and Southwest China (17.3%). This study highlights that, even without explicit emission reduction targets for the MSW sector, the improvements of this sector have significantly reduced GHG emissions in China.


Subject(s)
Greenhouse Gases , Solid Waste , China , Cities , Refuse Disposal , Carbon Dioxide/analysis
4.
Proc Natl Acad Sci U S A ; 118(48)2021 11 30.
Article in English | MEDLINE | ID: mdl-34810252

ABSTRACT

Vascular endothelial cells are exposed to shear stresses with disturbed vs. laminar flow patterns, which lead to proinflammatory vs. antiinflammatory phenotypes, respectively. Effective treatment against endothelial inflammation and the consequent atherogenesis requires the identification of new therapeutic molecules and the development of drugs targeting these molecules. Using Connectivity Map, we have identified vitexin, a natural flavonoid, as a compound that evokes the gene-expression changes caused by pulsatile shear, which mimics laminar flow with a clear direction, vs. oscillatory shear (OS), which mimics disturbed flow without a clear direction. Treatment with vitexin suppressed the endothelial inflammation induced by OS or tumor necrosis factor-α. Administration of vitexin to mice subjected to carotid partial ligation blocked the disturbed flow-induced endothelial inflammation and neointimal formation. In hyperlipidemic mice, treatment with vitexin ameliorated atherosclerosis. Using SuperPred, we predicted that apurinic/apyrimidinic endonuclease1 (APEX1) may directly interact with vitexin, and we experimentally verified their physical interactions. OS induced APEX1 nuclear translocation, which was inhibited by vitexin. OS promoted the binding of acetyltransferase p300 to APEX1, leading to its acetylation and nuclear translocation. Functionally, knocking down APEX1 with siRNA reversed the OS-induced proinflammatory phenotype, suggesting that APEX1 promotes inflammation by orchestrating the NF-κB pathway. Animal experiments with the partial ligation model indicated that overexpression of APEX1 negated the action of vitexin against endothelial inflammation, and that endothelial-specific deletion of APEX1 ameliorated atherogenesis. We thus propose targeting APEX1 with vitexin as a potential therapeutic strategy to alleviate atherosclerosis.


Subject(s)
Apigenin/genetics , Apigenin/physiology , DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics , Endothelial Cells/metabolism , Active Transport, Cell Nucleus , Animals , Atherosclerosis , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Inflammation , Mice , Phenotype , Phosphorylation , Protein Binding , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , p300-CBP Transcription Factors/metabolism
5.
Int J Mol Sci ; 25(10)2024 May 11.
Article in English | MEDLINE | ID: mdl-38791272

ABSTRACT

Renal fibrosis (RF) stands as a pivotal pathological process in the advanced stages of chronic kidney disease (CKD), and impeding its progression is paramount for delaying the advancement of CKD. The miR-10 family, inclusive of miR-10a and miR-10b, has been implicated in the development of various fibrotic diseases. Nevertheless, the precise role of miR-10 in the development of RF remains enigmatic. In this study, we utilized both an in vivo model involving unilateral ureteral obstruction (UUO) in mice and an in vitro model employing TGF-ß1 stimulation in HK-2 cells to unravel the mechanism underlying the involvement of miR-10a/b in RF. The findings revealed heightened expression of miR-10a and miR-10b in the kidneys of UUO mice, accompanied by a substantial increase in p-Smad3 and renal fibrosis-related proteins. Conversely, the deletion of these two genes led to a notable reduction in p-Smad3 levels and the alleviation of RF in mouse kidneys. In the in vitro model of TGF-ß1-stimulated HK-2 cells, the co-overexpression of miR-10a and miR-10b fostered the phosphorylation of Smad3 and RF, while the inhibition of miR-10a and miR-10b resulted in a decrease in p-Smad3 levels and RF. Further research revealed that miR-10a and miR-10b, through binding to the 3'UTR region of Vasohibin-1 (VASH-1), suppressed the expression of VASH-1, thereby promoting the elevation of p-Smad3 and exacerbating the progression of RF. The miR-10 family may play a pivotal role in RF.


Subject(s)
Fibrosis , MicroRNAs , Signal Transduction , Smad3 Protein , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Smad3 Protein/metabolism , Smad3 Protein/genetics , Mice , Humans , Ureteral Obstruction/metabolism , Ureteral Obstruction/pathology , Ureteral Obstruction/genetics , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Male , Cell Line , Kidney/metabolism , Kidney/pathology , Disease Models, Animal , Kidney Diseases/metabolism , Kidney Diseases/genetics , Kidney Diseases/pathology , Mice, Inbred C57BL , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/genetics , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/pathology
6.
Angew Chem Int Ed Engl ; 63(19): e202400177, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38488857

ABSTRACT

Mn(I)-catalyzed enantioselective C-C bond-forming reactions represent a great challenge in homogeneous catalysis primarily due to a limited understanding of its mechanistic principles. Herein, we have developed an interesting catalytic strategy that leverages a synergistic combination of a dimeric manganese(I) catalyst and a chiral aminocatalyst to address this issue. A range of conjugated dienals and trienals can exclusively proceed 1,4-hydroalkenylation by using readily available aromatic and aliphatic alkenyl boronic acids as coupling partners, producing a rich library of skipped diene aldehydes in synthetically useful yields and high levels of enantioselectivities. Notably, downstream transformations of these products can not only afford a concise approach to construct enantioenriched skipped trienes but also realize enantioselective total synthesis of analogues to (-)-Blepharocalyxin D in four steps. DFT calculations suggest the 1,4-hydroalkenylation is kinetically more favorable than 1,6-hydroalkenylation.

7.
Angew Chem Int Ed Engl ; 63(7): e202317987, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38152839

ABSTRACT

Platinum metal (PtM, M=Ni, Fe, Co) alloys catalysts show high oxygen reduction reaction (ORR) activity due to their well-known strain and ligand effects. However, these PtM alloys usually suffer from a deficient ORR durability in acidic environment as the alloyed metal is prone to be dissolved due to its high electronegativity. Herein, we report a new class of PtMn alloy nanodendrite catalyst with low-electronegativity Mn-contraction for boosting the oxygen reduction durability of fuel cells. The moderate strain in PtMn, induced by Mn contraction, yields optimal oxygen reduction activity at 0.53 A mg-1 at 0.9 V versus reversible hydrogen electrode (RHE). Most importantly, we show that relative to well-known high-electronegativity Ni-based Pt alloy counterpart, the PtMn nanodendrite catalyst experiences less transition metals' dissolution in acidic solution and achieves an outstanding mass activity retention of 96 % after 10,000 degradation cycles. Density functional theory calculation reveals that PtMn alloys are thermodynamically more stable than PtNi alloys in terms of formation enthalpy and cohesive energy. The PtMn nanodendrite-based membrane electrode assembly delivers an outstanding peak power density of 1.36 W cm-2 at a low Pt loading and high-performance retention over 50 h operations at 0.6 V in H2 -O2 hydrogen fuel cells.

8.
Anal Chem ; 95(2): 1498-1504, 2023 01 17.
Article in English | MEDLINE | ID: mdl-36598384

ABSTRACT

Simultaneous imaging and especially visualizing the association of survivin mRNA and telomerase in living cells are of great value for the diagnosis and prognosis of cancer because their co-expression facilitates the development of cancer and identifies patients at high risk of tumor-related death. The challenge is to develop methods that enable visualizing the association of multiplex targets and avoid the distorted signals due to the different delivery efficiency of probes. Herein, we engineered a DNA triangular prism nanomachine (DTPN) for simultaneous multicolor imaging of survivin mRNA and telomerase and visualizing their association in living cells. Two recognizing probes targeted survivin mRNA and telomerase, and the reporter probe was assembled on the DTP in equal amounts, ensuring the same delivery efficiency of the probes to the living cells. The results showed that this DTPN could quantify intracellular survivin mRNA expression and telomerase activity. Moreover, it also enabled us to visualize the effect of the down-regulation of one target on the expression of another target under different drug stimulations. The results implied that our DTPN provided a promising platform for cancer diagnosis, prognosis, drug screening, and related biological research.


Subject(s)
Telomerase , Humans , Survivin/genetics , Survivin/metabolism , RNA, Messenger/genetics , Telomerase/genetics , Telomerase/metabolism , DNA/genetics , Down-Regulation
9.
Small ; 19(52): e2305616, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37635122

ABSTRACT

The electrochemical nitrogen reduction reaction holds great potential for ammonia production using electricity generated from renewable energy sources and is sustainable. The low solubility of nitrogen in aqueous media, poor kinetics, and intrinsic competition by the hydrogen evolution reaction result in meager ammonia production rates. Attributing measured ammonia as a valid product, not an impurity, is challenging despite rigorous analytical experimentation. In this regard, Li-mediated electrochemical nitrogen reduction is a proven method providing significant ammonia yields. Herein, fundamental advances and insights into the Li-mediated strategy are summarized, emphasizing the role of lithium, reaction parameters, cell designs, and mechanistic evaluation. Challenges and perspectives are presented to highlight the prospects of this strategy as a continuous, stable, and modular approach toward sustainable ammonia production.

10.
Small ; 19(27): e2208076, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36971280

ABSTRACT

Developing low-cost and high-performance transition metal-based electrocatalysts is crucial for realizing sustainable hydrogen evolution reaction (HER) in alkaline media. Here, a cooperative boron and vanadium co-doped nickel phosphide electrode (B, V-Ni2 P) is developed to regulate the intrinsic electronic configuration of Ni2 P and promote HER processes. Experimental and theoretical results reveal that V dopants in B, V-Ni2 P greatly facilitate the dissociation of water, and the synergistic effect of B and V dopants promotes the subsequent desorption of the adsorbed hydrogen intermediates. Benefiting from the cooperativity of both dopants, the B, V-Ni2 P electrocatalyst requires a low overpotential of 148 mV to attain a current density of -100 mA cm-2  with excellent durability. The B, V-Ni2 P is applied as the cathode in both alkaline water electrolyzers (AWEs) and anion exchange membrane water electrolyzers (AEMWEs). Remarkably, the AEMWE delivers a stable performance to achieve 500 and 1000 mA cm-2  current densities at a cell voltage of 1.78 and 1.92 V, respectively. Furthermore, the developed AWEs and AEMWEs also demonstrate excellent performance for overall seawater electrolysis.

11.
Small ; 19(2): e2204694, 2023 01.
Article in English | MEDLINE | ID: mdl-36403215

ABSTRACT

Disturbed blood flow induces endothelial pro-inflammatory responses that promote atherogenesis. Nanoparticle-based therapeutics aimed at treating endothelial inflammation in vasculature where disturbed flow occurs may provide a promising avenue to prevent atherosclerosis. By using a vertical-step flow apparatus and a microfluidic chip of vascular stenosis, herein, it is found that the disk-shaped versus the spherical nanoparticles exhibit preferential margination (localization and adhesion) to the regions with the pro-atherogenic disturbed flow. By employing a mouse model of carotid partial ligation, superior targeting and higher accumulation of the disk-shaped particles are also demonstrated within disturbed flow areas than that of the spherical particles. In hyperlipidemia mice, administration of disk-shaped particles loaded with hypomethylating agent decitabine (DAC) displays greater anti-inflammatory and anti-atherosclerotic effects compared with that of the spherical counterparts and exhibits reduced toxicity than "naked" DAC. The findings suggest that shaping nanoparticles to disk is an effective strategy for promoting their delivery to atheroprone endothelia.


Subject(s)
Atherosclerosis , Nanoparticles , Animals , Mice , Atherosclerosis/drug therapy , Atherosclerosis/prevention & control , Carotid Arteries
12.
Exp Eye Res ; 234: 109572, 2023 09.
Article in English | MEDLINE | ID: mdl-37451566

ABSTRACT

Our previous research shown that tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) is elevated in the plasma extracellular vesicles and vitreous humor in diabetic retinopathy (DR). TNFAIP8 also significantly increases the viability of human retinal microvascular endothelial cells (HRMECs) and promotes cell migration and tube formation in vitro. To comprehensively explore its role in DR, we investigated the effect of TNFAIP8 on DR development using an animal model in this study. A TNFAIP8-overexpressing adeno-associated virus (AAV) vector and streptozotocin-induced mouse model was used. The AAV-TNFAIP8 vector was injected into the mice intravitreally, and the effect was evaluated. The evaluation included analysis of retinal structure and function using electroretinography, optical coherence tomography, and histological assessment. The influence of TNFAIP8 on the avascular area, retinal leukostasis, and the expression levels of inflammatory factors was also determined. TNFAIP8 significantly decreased a/b-wave amplitude and retinal thickness in diabetic mice. Histological assessment showed that TNFAIP8 aggravated pathological abnormalities with distorted organization of the retina. TNFAIP8 also significantly increased the avascular area, leukostasis, and the expression of inflammatory factors, such as TNFα, IL1ß, ICAM1, and GFAP, in the retina. The results of this study support the role of TNFAIP8 in DR pathogenesis. A mechanistic understanding of TNFAIP8 may offer novel therapeutic strategies.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Retinopathy , Leukostasis , Mice , Humans , Animals , Diabetic Retinopathy/metabolism , Tumor Necrosis Factor-alpha/metabolism , Diabetes Mellitus, Experimental/metabolism , Factor VIII/metabolism , Factor VIII/pharmacology , Factor VIII/therapeutic use , Endothelial Cells/metabolism , Leukostasis/metabolism , Retina/metabolism , Apoptosis Regulatory Proteins/metabolism
13.
Exp Eye Res ; 235: 109640, 2023 10.
Article in English | MEDLINE | ID: mdl-37673368

ABSTRACT

Cataract is the leading cause of blindness in the world, and there is a lack of effective treatment drugs. CircRNA plays an important part in a variety of diseases, however, the role of circRNA in cataracts remains largely unknown. In this study, we constructed a cataract model of rats and obtained the circRNAs related to cataracts by whole transcriptome sequencing and circRNA-mRNA co-expression network. To investigate the effect and mechanism of circRNA 06209 on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, dual luciferase reporter assay, RIP assay, actinomycin D assay, and Western blot analysis. We identify that a necroptosis-related circRNA, circRNA 06209, is down-regulated in cataracts. Vitro experiments showed that up-regulation of circRNA 06209 could promote cell proliferation and inhibit cell apoptosis. Vivo experiments revealed that circRNA 06209 overexpression could inhibit the development of cataracts. Mechanistically, circRNA 06209 acts as a miRNA sponge and competitively binds to miR-6848-5p to curb the inhibitory effect of miR-6848-5p on ALOX15, thereby affecting cell viability and apoptosis. This study found that circRNA 06209 plays a critical part in inhibiting cataracts through the miR-6848-5p/ALOX15 pathway, suggesting that circRNA 06209 may be a promising therapeutic target for cataracts.


Subject(s)
Cataract , MicroRNAs , RNA, Circular , Animals , Rats , Apoptosis , Cataract/genetics , MicroRNAs/genetics , RNA, Circular/genetics , Humans , Enzyme Assays
14.
Br J Clin Pharmacol ; 89(4): 1329-1337, 2023 04.
Article in English | MEDLINE | ID: mdl-36278948

ABSTRACT

AIM: Drug-induced liver injury (DILI) poses significant challenges to clinical practice. Currently, there is no recommended therapy to treat DILI; therefore, it is vital to explore new therapeutic agents. This study aimed to investigate the efficacy and safety of silybin meglumine tablets in treating DILI. METHODS: This study analysed 34 296 DILI cases assessed by the updated RUCAM from a nationwide database. A total of 301 patients with RUCAM scores ≥6 were directly enrolled in this study, while an additional 340 patients with RUCAM scores <6 who were adjudged as probable DILI by a panel of three hepatologists were also included in the analysis. The enrolled patients were divided into the silybin meglumine group and the control group. The propensity score matching (PSM) method was used to obtain comparable characteristics between the two groups. RESULTS: There were 129 cases in the silybin meglumine group and 512 cases in the control group. After applying PSM, 129 matched pairs were obtained. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) resumption rates in the silybin meglumine group were significantly higher than the control group (58.91% vs. 20.93%, P ≤ .0001 and 63.49% vs. 37.50%, P ≤ .0001). The univariate and multivariate logistic regression analysis revealed that grouping factor (odds raio [OR], 5.42; 95% confidenxe interval [CI], 3.12-9.39; P < .0001 and OR, 6.10; 95% CI, 2.98-12.48; P < .0001) and ALT levels (OR, 0.95; 95% CI, 0.93-0.98; P = .0015 and OR, 0.95; 95% CI, 0.92-0.99; P = .0157) were essential influencing factors for ALT normalization. CONCLUSIONS: Silybin meglumine tablets are safe and effective in DILI treatment. Large-scale and randomized controlled trials are required to further confirm their efficacy.


Subject(s)
Chemical and Drug Induced Liver Injury , Silybin , Humans , Alanine Transaminase , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/drug therapy , Databases, Factual , Risk Factors , Silybin/therapeutic use
15.
Chem Rev ; 121(17): 10271-10366, 2021 09 08.
Article in English | MEDLINE | ID: mdl-34228446

ABSTRACT

Global energy and environmental crises are among the most pressing challenges facing humankind. To overcome these challenges, recent years have seen an upsurge of interest in the development and production of renewable chemical fuels as alternatives to the nonrenewable and high-polluting fossil fuels. Photocatalysis, photoelectrocatalysis, and electrocatalysis provide promising avenues for sustainable energy conversion. Single- and dual-component catalytic systems based on nanomaterials have been intensively studied for decades, but their intrinsic weaknesses hamper their practical applications. Multicomponent nanomaterial-based systems, consisting of three or more components with at least one component in the nanoscale, have recently emerged. The multiple components are integrated together to create synergistic effects and hence overcome the limitation for outperformance. Such higher-efficiency systems based on nanomaterials will potentially bring an additional benefit in balance-of-system costs if they exclude the use of noble metals, considering the expense and sustainability. It is therefore timely to review the research in this field, providing guidance in the development of noble-metal-free multicomponent nanointegration for sustainable energy conversion. In this work, we first recall the fundamentals of catalysis by nanomaterials, multicomponent nanointegration, and reactor configuration for water splitting, CO2 reduction, and N2 reduction. We then systematically review and discuss recent advances in multicomponent-based photocatalytic, photoelectrochemical, and electrochemical systems based on nanomaterials. On the basis of these systems, we further laterally evaluate different multicomponent integration strategies and highlight their impacts on catalytic activity, performance stability, and product selectivity. Finally, we provide conclusions and future prospects for multicomponent nanointegration. This work offers comprehensive insights into the development of cost-competitive multicomponent nanomaterial-based systems for sustainable energy-conversion technologies and assists researchers working toward addressing the global challenges in energy and the environment.


Subject(s)
Catalysis , Metals , Nanostructures/chemistry , Renewable Energy , Metals/chemistry , Water/chemistry
16.
Acta Pharmacol Sin ; 44(1): 189-200, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35778489

ABSTRACT

The high incidence of lymphatic metastasis is closely related to poor prognosis and mortality in cancers. Potent inhibitors to prevent pathological lymphangiogenesis and lymphatic spread are urgently needed. The VEGF-C-VEGFR3 pathway plays a vital role in driving lymphangiogenesis and lymph node metastasis. In addition, COX2 in tumor cells and tumor-associated macrophages (TAMs) facilitates lymphangiogenesis. We recently reported that aiphanol, a natural stilbenolignan, attenuates tumor angiogenesis by repressing VEGFR2 and COX2. In this study, we evaluated the antilymphangiogenic and antimetastatic potency of aiphanol using in vitro, ex vivo and in vivo systems. We first demonstrated that aiphanol directly bound to VEGFR3 and blocked its kinase activity with an half-maximal inhibitory concentration (IC50) value of 0.29 µM in an in vitro ADP-GloTM kinase assay. Furthermore, we showed that aiphanol (7.5-30 µM) dose-dependently counteracted VEGF-C-induced proliferation, migration and tubular formation of lymphatic endothelial cells (LECs), which was further verified in vivo. VEGFR3 knockdown markedly mitigated the inhibitory potency of aiphanol on lymphangiogenesis. In 4T1-luc breast tumor-bearing mice, oral administration of aiphanol (5 and 30 mg· kg-1 ·d-1) dose-dependently decreased lymphatic metastasis and prolonged survival time, which was associated with impaired lymphangiogenesis, angiogenesis and, interestingly, macrophage infiltration. In addition, we found that aiphanol decreased the COX2-dependent secretion of PGE2 and VEGF-C from tumor cells and macrophages. These results demonstrate that aiphanol is an appealing agent for preventing lymphangiogenesis and lymphatic dissemination by synergistically targeting VEGFR3 and inhibiting the COX2-PGE2-VEGF-C signaling axis.


Subject(s)
Lymphangiogenesis , Vascular Endothelial Growth Factor C , Animals , Mice , Cell Line, Tumor , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Endothelial Cells/metabolism , Lymphatic Metastasis , Vascular Endothelial Growth Factor C/metabolism
17.
BMC Ophthalmol ; 23(1): 461, 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37974089

ABSTRACT

BACKGROUND: A sight-threatening, cataract is a common degenerative disease of the ocular lens. This study aimed to explore the regulatory mechanism of age-related cataract (ARC) formation and progression. METHODS: Cataracts in Sprague Dawley rats were induced by adopting the method that injected selenite subcutaneously in the nape. We performed high-throughput RNA sequencing technology to identify the mRNA and microRNA(miRNA) expression profiles of the capsular membrane of the lens from Na2SeO3-induced and saline-injected Sprague Dawley rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to forecast the regulatory and functional role of mRNAs in cataracts by DAVID and Metascape. The protein-protein interaction(PPI) network of differentially expressed mRNA(DEmRNAs) was built via the STRING. Target miRNAs of hub genes were predicted by miRBD and TargetScan. Furthermore, differentially expressed miRNA(DEmiRNAs) were selected as hub genes' targets, validated by quantitative real-time polymerase chain reaction(qRT-PCR), and a DEmiRNA-DEmRNA regulatory network was constructed via Cytoscape. RESULT: In total, 329 DEmRNAs including 40 upregulated and 289 downregulated genes were identified. Forty seven DEmiRNAs including 29 upregulated and 18 downregulated miRNAs were detected. The DEmRNAs are involved in lens development, visual perception, and aging-related biological processes. A protein-protein interaction network including 274 node genes was constructed to explore the interactions of DEmRNAs. Furthermore, a DEmiRNA-DEmRNA regulatory network related to cataracts was constructed, including 8 hub DEmRNAs, and 8 key DEmiRNAs which were confirmed by qRT-PCR analysis. CONCLUSION: We identified several differentially expressed genes and established a miRNA-mRNA-regulated network in a Na2SeO3-induced Sprague Dawley rat cataract model. These results may provide novel insights into the clinical treatment of cataracts, and the hub DEmRNAs and key DEmiRNAs could be potential therapeutic targets for ARC.


Subject(s)
Cataract , MicroRNAs , Rats , Animals , MicroRNAs/genetics , Rats, Sprague-Dawley , RNA, Messenger/genetics , Transcriptome , Cataract/genetics , Gene Regulatory Networks
18.
J Obstet Gynaecol Res ; 49(8): 2056-2062, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37265015

ABSTRACT

AIMS: To investigate the associations of serum trace elements (iron, zinc, and copper) between women with different pregnancy outcomes. METHODS: About 774 pregnant women who came to The Fourth Hospital of Shijiazhuang for prenatal examination were investigated. The concentrations of trace elements in the serum of pregnant women in the third trimester were collected. Multivariate logistic regression was used to analyze the relationship between serum trace element levels and the different pregnancy outcomes. Multiple linear regression was used to analyze the relationship between serum trace elements levels and hypersensitive-C-reactive-protein. RESULTS: Results of the multiple logistic regression showed that zinc, copper and copper/zinc ratio were found to be associated with the risk of gestational diabetes mellitus, and zinc was a protective factor (p = 0.002) while copper and copper/zinc ratio as risk factors (p = 0.030 and p = 0.001, respectively) after adjusting for major confounders. It was found that iron and zinc were negatively associated with the risk of moderate or severe anemia (p = 0.022 and p = 0.001, respectively). In contrast, the copper/zinc ratio was positively related to the risk of moderate or severe anemia (p = 0.021). The adjusted relationships between copper and copper/zinc ratio with premature rupture of membranes were statistically significant (p = 0.007 and p = 0.037). Iron and zinc were negatively associated with the risk of chorioamnionitis, while copper and copper/zinc ratio were positively associated with the risk of chorioamnionitis (all p < 0.05). CONCLUSIONS: Serum iron, zinc and copper levels are closely related to pregnancy outcomes.


Subject(s)
Chorioamnionitis , Trace Elements , Female , Pregnancy , Humans , Zinc , Iron , Copper , Pregnancy Outcome
19.
J Craniofac Surg ; 34(2): 674-679, 2023.
Article in English | MEDLINE | ID: mdl-36730451

ABSTRACT

OBJECTIVE: To analyze the changes in the white matter structure of the whole brain in hemifacial spasm (HFS) patients by using the tract-based spatial statistics (TBSS) method. MATERIALS AND METHODS: 29 HFS patients without anxiety and depression and 29 healthy controls with matching age, sex, and education were selected. All subjects received a 3.0T magnetic resonance (MR) brain diffusion tensor imaging scan. Tract-based spatial statistics method was used to analyze the changes in white matter structure in the whole brain and obtained the cerebral white matter fibrous areas exhibiting significant intergroup differences. The fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity of these areas were abstracted. Analyzed the correlation between these diffusion metrics and clinical variables (disease duration, spasm severity). RESULTS: Compared with the healthy controls group, the HFS group exhibited significantly lower FA in the forceps minor, bilateral anterior thalamic radiation, and right superior longitudinal fasciculus ( P <0.05, threshold-free cluster enhancement corrected). Cohen grading scale of HFS patients was negatively correlated with FA of forceps minor. CONCLUSION: Based on TBSS analysis, the injury of white matter fiber tracts in HFS patients was found, including forceps minor, bilateral anterior thalamic radiation, and right superior longitudinal fasciculus. The changes of FA values in forceps minor were negatively correlated with the Cohen grading scale, suggesting that the alteration of white matter fiber in the genu-of-corpus-callosum-cortex circuit plays an important role in the neuro-pathological mechanism of HFS. Combined with previous research, it is also necessary to further explore the change of the superior longitudinal fasciculus in the future.


Subject(s)
Hemifacial Spasm , White Matter , Humans , Diffusion Tensor Imaging/methods , White Matter/pathology , Brain/pathology , Magnetic Resonance Imaging
20.
Hum Factors ; 65(3): 382-402, 2023 05.
Article in English | MEDLINE | ID: mdl-34006135

ABSTRACT

OBJECTIVE: The purpose of this study was to develop an approach to predict hand posture (pinch versus grip) and grasp force using forearm surface electromyography (sEMG) and artificial neural networks (ANNs) during tasks that varied repetition rate and duty cycle. BACKGROUND: Prior studies have used electromyography with machine learning models to predict grip force but relatively few studies have assessed whether both hand posture and force can be predicted, particularly at varying levels of duty cycle and repetition rate. METHOD: Fourteen individuals participated in this experiment. sEMG data for five forearm muscles and force output data were collected. Calibration data (25, 50, 75, 100% of maximum voluntary contraction (MVC)) were used to train ANN models to predict hand posture (pinch versus grip) and force magnitude while performing tasks that varied load, repetition rate, and duty cycle. RESULTS: Across all participants, overall hand posture prediction accuracy was 79% (0.79 ± .08), whereas overall hand force prediction accuracy was 73% (0.73 ± .09). Accuracy ranged between 0.65 and 0.93 based on varying repetition rate and duty cycle. CONCLUSION: Hand posture and force prediction were possible using sEMG and ANNs, though there were important differences in the accuracy of predictions based on task characteristics including duty cycle and repetition rate. APPLICATION: The results of this study could be applied to the development of a dosimeter used for distal upper extremity biomechanical exposure measurement, risk assessment, job (re)design, and return to work programs.


Subject(s)
Hand , Muscle, Skeletal , Humans , Electromyography , Muscle, Skeletal/physiology , Hand/physiology , Forearm/physiology , Posture/physiology , Hand Strength/physiology
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