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1.
Angew Chem Int Ed Engl ; : e202406110, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711195

ABSTRACT

The ability to finely tune/balance the structure and rigidity of enzymes to realize both high enzymatic activity and long-term stability is highly desired but highly challenging. In this work, we propose a new concept of silica-enzyme, referred to as "silicazyme", where solid inorganic silica was controlled hybridization with fragile enzyme under moderate condition at single-enzyme level, realizing simultaneous structure augmentation, long-term stability, and high enzymatic activity preservation. A multivariate silicification approach was utilized and occurred around individual enzymes to allow conformal coating. To realize a high activity-stability trade-off the structure flexibility/rigidity of silicazyme was optimized by a component-adjustment-ternary (CAT) plot method. Moreover, the multivariate organosilica frameworks bring great advantages including surface microenvironment adjustability, reversible modification capability, and functional extensibility through the rich chemistry of silica. Overall silicazymes represent a new class of enzymes that promise to broaden their utilization in catalysis, separations, and nanomedicine.

2.
Neuron ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38653248

ABSTRACT

White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.

3.
Med Princ Pract ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38565090

ABSTRACT

INTRODUCTION: Parkinson's disease (PD) is a most common neurodegenerative disease worldwide. Studies have shown that insulin-like growth factor-binding protein 5 (IGFBP5) may contribute to methamphetamine-induced neurotoxicity and neuronal apoptosis in PC-12 cells and rat striatum. Here, we studied the expression and role of IGFBP5 in the 6-OHDA-toxicant model of PD. METHODS: PC-12 and SH-SY5Y cells were exposed to 50 µM 6-OHDA for 24 h. qRT-PCR, western blotting, CCK-8 assay, EdU staining, annexin V staining, and immunofluorescence were performed to study the effects of IGFBP5 specific siRNAs. The effects of IGFBP5 on a rat 6-OHDA model of PD were confirmed by performing behavioral tests, tyrosine hydroxylase (TH) immunofluorescence staining, and western blotting. RESULTS: In the GSE7621 dataset, IGFBP5 was highly expressed in the substantia nigra tissues of PD patients compared to healthy controls. In PC-12 and SH-SY5Y cells, IGFBP5 was upregulated following 6-OHDA exposure in a dose-dependent manner. Silencing of IGFBP5 promoted PC-12 and SH-SY5Y proliferation while inhibited apoptosis under 6-OHDA stimulation. Silencing of IGFBP5 relieved 6-OHDA-induced TH-positive neuron loss. Hedgehog signalling pathway was predicted as a downstream signalling pathway of IGFBP5. Negative regulation between IGFBP5 and sonic hedgehog (SHH) signalling pathway was confirmed in vitro. The effects of IGFBP5 silencing on SH-SY5Y cells were partially reversed using cyclopamine, a direct inhibitor of the SHH signalling pathway. In addition, silencing of IGFBP5 attenuated motor deficits and neuronal damage in 6-OHDA-induced PD rats. CONCLUSION: Elevated IGFBP5 expression may be involved in 6-OHDA-induced neurotoxicity through regulation of the SHH signalling pathway.

4.
J Control Release ; 369: 53-62, 2024 May.
Article in English | MEDLINE | ID: mdl-38513728

ABSTRACT

Therapeutic approaches for triple-negative breast cancer (TNBC) have been continuously advancing, but inadequate control over release behavior, insufficient tumor selectivity, and limited drug availability continue to impede therapeutic outcomes in nanodrug systems. In this study, we propose a general hydrophobic antineoplastic delivery system, termed spatiotemporally-controlled hydrophobic antineoplastic delivery system (SCHADS) for enhanced TNBC treatment. The key feature of SCHADS is the formation of metastable photosensitive-antineoplastic complexes (PACs) through the self-assembly of hydrophobic drugs driven by photosensitive molecules. With the further decoration of tumor-targeting peptides coupled with the EPR effect, the PACs tend to accumulate in the tumor site tremendously, promoting drug delivery efficiency. Meanwhile, the disassembly behavior of the metastable PACs could be driven by light on demand to achieve in situ drug release, thus promoting chemotherapeutics availability. Furthermore, the abundant ROS generated by the photosensitizer could effectively kill tumor cells, ultimately realizing an effective combination of photodynamic and chemotherapeutic therapy. As an exemplary presentation, chlorin e6 has been chosen to drive the formation of PACs with the system xc- inhibitor sorafenib. Compared with pure drug treatment, the PACs with the above-described preponderances exhibit superior therapeutic effects both in vitro and in vivo and circumvent the side effects due to off-target. By manipulating the laser irradiation, the PACs-treated cell death mechanism could be dynamically regulated, thus providing the potential to remedy intrinsic/acquired resistance of tumor. Collectively, this SCHADS achieves spatio-temporal control of the drug that greatly enhances the availability of anticarcinogen and realizes synergistic antitumor effect in TNBC treatment, even ultimately being extended to the treatment of other types of tumors.


Subject(s)
Antineoplastic Agents , Drug Delivery Systems , Hydrophobic and Hydrophilic Interactions , Photosensitizing Agents , Porphyrins , Triple Negative Breast Neoplasms , Triple Negative Breast Neoplasms/drug therapy , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Female , Animals , Humans , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Porphyrins/administration & dosage , Porphyrins/chemistry , Chlorophyllides , Mice, Nude , Mice, Inbred BALB C , Photochemotherapy/methods , Sorafenib/administration & dosage , Sorafenib/pharmacology , Sorafenib/chemistry , Drug Liberation
5.
Chem Biol Drug Des ; 103(2): e14480, 2024 02.
Article in English | MEDLINE | ID: mdl-38369620

ABSTRACT

Cerebral ischaemia-reperfusion (CIR) injury occurs in stroke patients after the restoration of cerebral perfusion. Sinigrin, a phytochemical found in cruciferous vegetables, exhibits strong antioxidant activity. This study investigated the role of sinigrin in oxidative stress using a CIR injury model. The effects of sinigrin were studied in middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-injured SH-SY5Y cells. Sinigrin treatment improved brain injury and neurological deficits induced by MCAO surgery in rats. Sinigrin inhibited apoptosis in brain tissues and SH-SY5Y cells following OGD/R induction. Additionally, sinigrin elevated the levels of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) while reducing malondialdehyde (MDA) levels. Furthermore, sinigrin inhibited the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signalling pathway. The anti-apoptotic and antioxidant activities of sinigrin in OGD/R-injured SH-SY5Y cells were reversed by TLR4 overexpression. In conclusion, sinigrin inhibits oxidative stress in CIR injury by suppressing the TLR4/MyD88 signalling pathway.


Subject(s)
Brain Ischemia , Glucosinolates , Neuroblastoma , Reperfusion Injury , Humans , Rats , Animals , Toll-Like Receptor 4/metabolism , Myeloid Differentiation Factor 88/metabolism , Oxidative Stress , Antioxidants/pharmacology , Antioxidants/metabolism , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/metabolism , Glutathione/metabolism , Oxygen/metabolism , Reperfusion Injury/drug therapy , Brain Ischemia/drug therapy , Apoptosis
6.
Insects ; 15(1)2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38249056

ABSTRACT

Monolepta is one of the diverse genera in the subfamily Galerucinae, including 708 species and 6 sub-species worldwide. To explore the information on the mitogenome characteristics and phylogeny of the section "Monoleptites", especially the genus Monolepta, we obtained the newly completed mitochondrial genomes (mitogenomes) of four Monolepta species using high-throughput sequencing technology. The lengths of these four new mitochondrial genomes are 16,672 bp, 16,965 bp, 16,012 bp, and 15,866 bp in size, respectively. All four mitochondrial genomes include 22 transfer RNA genes (tRNAs), 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), and one control region, which is consistent with other Coleoptera. The results of the nonsynonymous with synonymous substitution rates showed that ND6 had the highest evolution rate, while COI displayed the lowest evolution rate. The substitution saturation of three datasets (13 PCGs_codon1, 13 PCGs_codon2, 13 PCGs_codon3) showed that there was no saturation across all datasets. Phylogenetic analyses based on three datasets (ND1, 15 genes of mitogenomes, and 13 PCGs_AA) were carried out using maximum likelihood (ML) and Bayesian inference (BI) methods. The results showed that mitogenomes had a greater capacity to resolve the main clades than the ND1 gene at the suprageneric and species levels. The section "Monoleptites" was proven to be a monophyletic group, while Monolepta was a non-monophyletic group. Based on ND1 data, the newly sequenced species whose antennal segment 2 was shorter than 3 were split into several clades, while, based on the mitogenomic dataset, the four newly sequenced species had close relationships with Paleosepharia. The species whose antennal segment 2 was as long as 3 were split into two clades, which indicated that the characteristic of "antennal segment 2 as long as 3" of the true "Monolepta" evolved multiple times in several subgroups. Therefore, to explore the relationships among the true Monolepta, the most important thing is to perform a thorough revision of Monolepta and related genera in the future.

7.
CNS Neurol Disord Drug Targets ; 23(3): 315-330, 2024.
Article in English | MEDLINE | ID: mdl-36999187

ABSTRACT

The blood-brain barrier (BBB) plays a crucial role in the central nervous system by tightly regulating the influx and efflux of biological substances between the brain parenchyma and peripheral circulation. Its restrictive nature acts as an obstacle to protect the brain from potentially noxious substances such as blood-borne toxins, immune cells, and pathogens. Thus, the maintenance of its structural and functional integrity is vital in the preservation of neuronal function and cellular homeostasis in the brain microenvironment. However, the barrier's foundation can become compromised during neurological or pathological conditions, which can result in dysregulated ionic homeostasis, impaired transport of nutrients, and accumulation of neurotoxins that eventually lead to irreversible neuronal loss. Initially, the BBB is thought to remain intact during neurodegenerative diseases, but accumulating evidence as of late has suggested the possible association of BBB dysfunction with Parkinson's disease (PD) pathology. The neurodegeneration occurring in PD is believed to stem from a myriad of pathogenic mechanisms, including tight junction alterations, abnormal angiogenesis, and dysfunctional BBB transporter mechanism, which ultimately causes altered BBB permeability. In this review, the major elements of the neurovascular unit (NVU) comprising the BBB are discussed, along with their role in the maintenance of barrier integrity and PD pathogenesis. We also elaborated on how the neuroendocrine system can influence the regulation of BBB function and PD pathogenesis. Several novel therapeutic approaches targeting the NVU components are explored to provide a fresh outlook on treatment options for PD.


Subject(s)
Blood-Brain Barrier , Parkinson Disease , Humans , Blood-Brain Barrier/physiology , Parkinson Disease/pathology , Brain/pathology , Central Nervous System , Biological Transport/physiology
8.
Adv Sci (Weinh) ; 11(5): e2305126, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38054350

ABSTRACT

Hyperuricemia, caused by an imbalance between the rates of production and excretion of uric acid (UA), may greatly increase the mortality rates in patients with cardiovascular and cerebrovascular diseases. Herein, for fast-acting and long-lasting hyperuricemia treatment, armored red blood cell (RBC) biohybrids, integrated RBCs with proximal, cascaded-enzymes of urate oxidase (UOX) and catalase (CAT) encapsulated within ZIF-8 framework-based nanoparticles, have been fabricated based on a super-assembly approach. Each component is crucial for hyperuricemia treatment: 1) RBCs significantly increase the circulation time of nanoparticles; 2) ZIF-8 nanoparticles-based superstructure greatly enhances RBCs resistance against external stressors while preserving native RBC properties (such as oxygen carrying capability); 3) the ZIF-8 scaffold protects the encapsulated enzymes from enzymatic degradation; 4) no physical barrier exists for urate diffusion, and thus allow fast degradation of UA in blood and neutralizes the toxic by-product H2 O2 . In vivo results demonstrate that the biohybrids can effectively normalize the UA level of an acute hyperuricemia mouse model within 2 h and possess a longer elimination half-life (49.7 ± 4.9 h). They anticipate that their simple and general method that combines functional nanomaterials with living cell carriers will be a starting point for the development of innovative drug delivery systems.


Subject(s)
Hyperuricemia , Metal-Organic Frameworks , Humans , Animals , Mice , Hyperuricemia/drug therapy , Hyperuricemia/metabolism , Disease Models, Animal , Uric Acid , Erythrocytes/metabolism
9.
Adv Sci (Weinh) ; 11(2): e2304146, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38010981

ABSTRACT

Conversion-type electrodes offer a promising multielectron transfer alternative to intercalation hosts with potentially high-capacity release in batteries. However, the poor cycle stability severely hinders their application, especially in aqueous multivalence-ion systems, which can fundamentally impute to anisotropic ion diffusion channel collapse in pristine crystals and irreversible bond fracture during repeated conversion. Here, an amorphous bismuth sulfide (a-BS) formed in situ with unprecedentedly self-controlled moderate conversion Cu2+ storage is proposed to comprehensively regulate the isotropic ion diffusion channels and highly reversible bond evolution. Operando synchrotron X-ray diffraction and substantive verification tests reveal that the total destruction of the Bi─S bond and unsustainable deep alloying are fully restrained. The amorphous structure with robust ion diffusion channels, unique self-controlled moderate conversion, and high electrical conductivity discharge products synergistically boosts the capacity (326.7 mAh g-1 at 1 A g-1 ), rate performance (194.5 mAh g-1 at 10 A g-1 ), and long-lifespan stability (over 8000 cycles with a decay rate of only 0.02 ‰ per cycle). Moreover, the a-BS Cu2+ ‖Zn2+ hybrid ion battery can well supply a stable energy density of 238.6 Wh kg-1 at 9760 W kg-1 . The intrinsically high-stability conversion mechanism explored on amorphous electrodes provides a new opportunity for advanced aqueous storage.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1006519

ABSTRACT

Objective@#To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.@*Methods@#The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells.@*Results@#A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner.@*Conclusion@#RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.

11.
Environ Sci Technol ; 57(45): 17189-17200, 2023 11 14.
Article in English | MEDLINE | ID: mdl-37917731

ABSTRACT

As the world grapples with the challenges of energy transition and industrial decarbonization, the development of carbon capture technologies presents a promising solution. The Scalable Modeling, Artificial Intelligence (AI), and Rapid Theoretical calculations, referred as SMART here, is an interdisciplinary approach that combines high-throughput calculation and data-driven modeling with expertise from chemical, materials, environmental, computer and data science and engineering, leading to the development of advanced capabilities in simulating and optimizing carbon capture processes. This perspective discusses the state-of-the-art material discovery research enabled by high-throughput calculation and data-driven modeling. Further, we propose a framework for material discovery, and illustrate the synergies among deep learning models, pretrained models, and comprehensive data sets, emerging as a robust framework for data-driven design and development in carbon capture. In essence, the adoption of the SMART approach promises a revolutionary impact on efforts in energy transition and industrial decarbonization.


Subject(s)
Artificial Intelligence , Machine Learning , Technology , Carbon , Industry
12.
Se Pu ; 41(11): 976-985, 2023 Nov.
Article in Chinese | MEDLINE | ID: mdl-37968816

ABSTRACT

The discovery and identification of mushroom toxins has long been an important area in the fields of toxicology and food safety. Mushrooms are widely favored for their culinary and medicinal value; however, the presence of potentially lethal toxins in some species poses a substantial challenge in ensuring their safe consumption. Therefore, the development of a robust and sensitive analytical method is necessary for accurately identifying the risks associated with mushroom consumption. The study of mushroom toxins, which are characterized by their diversity and substantial variations in chemical structures, present a considerable challenge for achieving precise and high-throughput analysis. To address this issue, the present study employed a robust approach combining a solid-phase extraction (SPE) purification technique with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to establish an analytical method for the detection and quantification of five amatoxins and two tryptamines (psilocybin and bufotenine) present in some mushrooms. Several optimization procedures were undertaken, including optimizing the chromatographic conditions, mass spectrometric parameters, and sample extraction and purification. The procedure involved the extraction of dry mushroom powder with methanol containing 0.3% formic acid, followed by purification using a strong cation exchange cartridge (SCX). The analytes were separated on a T3 chromatographic column (100 mm×2.1 mm, 1.8 µm) using mobile phases of acetonitrile and 5 mmol/L ammonium acetate solution containing 0.1% formic acid. The multiple reaction monitoring (MRM) mode was employed for data acquisition. Amatoxins were quantified using matrix-matched standard calibration curves, whereas isotopic internal standards were used to quantify tryptamine. The results showed that all seven toxins exhibited good linearities (r2>0.99) within the optimized concentration range. The limits of detection (LODs) for bufotenine, psilocybin, and amatoxins were determined as 2.0, 5.0, and 10 µg/kg, respectively, while the limits of quantification (LOQs) were determined as 5.0, 10, and 20 µg/kg, respectively. The LOD and LOQ values further underscore the ability of the method to detect minute quantities of toxins, making it particularly well suited for screening food samples for potential contamination. Using dried shiitake mushroom powder as the matrix, the recoveries of the two tryptamines ranged from 80.6% to 117%, with relative standard deviations (RSDs) ranging from 1.73% to 5.98%, while the recoveries of amatoxins ranged from 71.8% to 115%, with RSDs varying from 2.14% to 9.92% at the three concentration levels. The consistent and satisfactory recoveries of amatoxins and tryptamines demonstrated the ability of this method to accurately quantify the target analytes even in a complex matrix. Comparison with the results of supplementary test method recognized by State Administration for Market Regulation for food (BJS 202008) demonstrated comparable results, indicating no significant differences (p>0.05) in amatoxin contents. The newly developed method is rapid, accurate, precise, meets the required standards, and is suitable for the detection of seven toxins in wild mushrooms. As part of the application of this method, a comprehensive investigation of the distribution of toxins in wild mushrooms from Fujian Province was undertaken. In this study, 59 wild mushroom samples from nine cities were collected in the Fujian province. Species identification was conducted using rDNA-internal transcribed space (rDNA-ITS) molecular barcode technology, which revealed the presence of toxins in the two samples. Notably, one specimen named Amanita fuligineoides contained α-amanitin, ß-amanitin, and phalloidin in quantities of 607, 377, and 69.0 mg/kg, respectively. Additionally, another sample, identified as Tricholomataceae, had a psilocybin concentration of 12.6 mg/kg.


Subject(s)
Amanita , Mycotoxins , Chromatography, High Pressure Liquid , Amanita/chemistry , Tandem Mass Spectrometry , Psilocybin , Bufotenin , Powders , Tryptamines , DNA, Ribosomal
13.
BMC Complement Med Ther ; 23(1): 415, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37978381

ABSTRACT

BACKGROUND: Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology. METHODS: The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease-target-component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients. RESULTS: We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin. CONCLUSIONS: This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/therapeutic use , Atorvastatin/pharmacology , Atorvastatin/therapeutic use , Matrix Metalloproteinase 12/therapeutic use
14.
ACS Nano ; 17(19): 19144-19154, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37772918

ABSTRACT

Electronic structure defines the conductivity and ion absorption characteristics of a functional electrode, significantly affecting the charge transfer capability in batteries, while it is rarely thought to be involved in mesoscopic volume and diffusion kinetics of the host lattice for promoting ion storage. Here, we first correlate the evolution in electronic structure of the Mo6S8 cathode with the ability to bound volume expansion and accelerate diffusion kinetics for high-performance aqueous Cu2+ storage. Operando synchrotron energy-dispersive X-ray absorption spectroscopy reveals that accumulative delocalized Mo 4d electrons enhance the Mo-Mo interaction with distinctly contracting and uniformizing Mo6 clusters during the reduction of Mo6S8, which potently restrain lattice expansion and release space to promote Cu2+ diffusion kinetics. Operando synchrotron X-ray diffraction and comprehensive characterizations further validate the structural and electrochemical properties induced by the Cu2+ intercalation electronic structure, endowing the Mo6S8 cathode a high specific capacity with small volume expansion, fast ions diffusion, and long-term cycling stability.

15.
Adv Mater ; 35(52): e2306810, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37722006

ABSTRACT

Titanium selenide (TiSe2 ), a model transition metal chalcogenide material, typically relies on topotactic ion intercalation/deintercalation to achieve stable ion storage with minimal disruption of the transport pathways but has restricted capacity (<130 mAh g-1 ). Developing novel energy storage mechanisms beyond conventional intercalation to break capacity limits in TiSe2 cathodes is essential yet challenging. Herein, the ion storage properties of TiSe2 are revisited and an unusual thermodynamically stable twin topotactic/nontopotactic Cu2+ accommodation mechanism for aqueous batteries is unraveled. In situ synchrotron X-ray diffraction and ex situ microscopy jointly demonstrated that topotactic intercalation sustained the ion transport framework, nontopotactic conversion involved localized multielectron reactions, and these two parallel reactions are miraculously intertwined in nanoscale space. Comprehensive experimental and theoretical results suggested that the twin-reaction mechanism significantly improved the electron transfer ability, and the reserved intercalated TiSe2 structure anchored the reduced titanium monomers with high affinity and promoted efficient charge transfer to synergistically enhance the capacity and reversibility. Consequently, TiSe2 nanoflake cathodes delivered a never-before-achieved capacity of 275.9 mAh g-1 at 0.1 A g-1 , 93.5% capacity retention over 1000 cycles, and endow hybrid batteries (TiSe2 -Cu||Zn) with a stable energy supply of 181.34 Wh kg-1 at 2339.81 W kg-1 , offering a promising model for aqueous ion storage.

16.
Adv Mater ; 35(48): e2305087, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37572369

ABSTRACT

High-energy metal anodes for large-scale reversible batteries with inexpensive and nonflammable aqueous electrolytes promise the capability of supporting higher current density, satisfactory lifetime, nontoxicity, and low-cost commercial manufacturing, yet remain out of reach due to the lack of reliable electrode-electrolyte interphase engineering. Herein, in situ formed robust interphase on copper metal electrodes (CMEs) induced by a trace amount of potassium dihydrogen phosphate (0.05 m in 1 m CuSO4 -H2 O electrolyte) to fulfill all aforementioned requirements is demonstrated. Impressively, an unprecedented ultrahigh-speed copper plating/stripping capability is achieved at 100 mA cm-2  for over 12 000 cycles, corresponding to an accumulative areal capacity up to tens of times higher than previously reported CMEs. The use of solid-electrolyte interface-protection strategy brings at least an order of magnitude improvement in cycling stability for symmetric cells (Cu||Cu, 2800 h) and full batteries with CMEs using either sulfur cathodes (S||Cu, 1000 cycles without capacity decay) or zinc anodes (Cu||Zn with all-metal electrodes, discharge voltage ≈1.02 V). The comprehensive analysis reveals that the hydrophilic phosphate-rich interphase nanostructures homogenize copper-ion deposition and suppress nucleation overpotential, enabling dendrite-free CMEs with sustainability and ability to tolerate unusual-high power densities. The findings represent an elegant forerunner toward the promising goal of metal electrode applications.

17.
Environ Toxicol ; 38(11): 2645-2655, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37647369

ABSTRACT

BACKGROUND: BRCA1 associated protein (BRAP) participates in the regulation of myocardial infarction and atherosclerosis. But the function of BRAP in cerebral ischemia-reperfusion (CIR) injury has not been elucidated yet. METHODS: BRAP expression in PC12 cells in response to oxygen-glucose deprivation/reoxygenation (OGD/R) treatment was examined with Western blot assay. PC12 cells underwent OGD/R-treatment and were subsequently transfected with pcDNA-BRAP or sh-BRAP, followed by determination of viability, lactate dehydrogenase (LDH) production, apoptosis, inflammatory cytokine secretion, and oxidative stress marker protein levels. Paraoxonase 1 (PON1) promoter methylation was evaluated with methylation-specific PCR assay. the effect of BRAP/PON1 axis on CIR injury was investigated by rescue experiments. Additionally, sh-BRAP was injected into a middle cerebral artery occlusion (MCAO) rat model, and the changes of neurological damage were evaluated. RESULTS: BRAP overexpression exacerbated OGD/R-induced viability reduction, LDH production, apoptosis, inflammatory cytokine secretion and oxidative stress in PC12 neuronal cells. In contrast, BRAP silencing showed the opposite results. Mechanistically, BRAP reduced PON1 expression by promoting DNA methyl transferase1 (DNMT1)-mediated PON1 promoter methylation. PON1 silencing reversed BRAP-mediated neuroprotection. Additionally, BRAP silencing alleviated CIR-induced neurological damage in MCAO rats. CONCLUSION: BRAP silencing suppressed OGD/R-induced neuronal apoptosis, inflammation, and oxidative stress, and alleviated CIR-induced neurological damage in MCAO rats through facilitating PON1 expression.


Subject(s)
Aryldialkylphosphatase , Reperfusion Injury , Ubiquitin-Protein Ligases , Animals , Rats , Apoptosis/genetics , Aryldialkylphosphatase/genetics , Aryldialkylphosphatase/metabolism , Cytokines/metabolism , Glucose/pharmacology , Infarction, Middle Cerebral Artery/metabolism , Inflammation/genetics , Oxidative Stress , Oxygen/metabolism , Reperfusion Injury/genetics , Reperfusion Injury/prevention & control , Reperfusion Injury/metabolism , Ubiquitin-Protein Ligases/genetics
18.
Huan Jing Ke Xue ; 44(6): 3426-3438, 2023 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-37309960

ABSTRACT

To explore the effects of mulching and the application of organic and chemical fertilizer on N2O, CO2, and CH4 emission; maize yield; water use efficiency (WUE); and nitrogen fertilizer use efficiency under the conditions of the same nitrogen fertilizer input in summer maize farmland, an experiment was conducted in the Guanzhong Plain of China. In this experiment, the two main experimental factors were mulching (M) and no-mulching, and the secondary experimental factors included no fertilizer application (CK), organic fertilizer substituting chemical fertilizer at 0% (T0, 0.00 kg·hm-2 organic fertilizer and 225.00 kg·hm-2 chemical fertilizer), 25% (T25, 56.25 kg·hm-2 organic fertilizer and 168.75 kg·hm-2 chemical fertilizer), 50% (T50, 112.50 kg·hm-2 organic fertilizer and 112.50 kg·hm-2 chemical fertilizer), 75% (T75, 168.75 kg·hm-2 organic fertilizer and 56.25 kg·hm-2 chemical fertilizer), and 100% (T100, 225.00 kg·hm-2 organic fertilizer and 0.00 kg·hm-2 chemical fertilizer), for a total of 12 treatments. The results showed as follows:1 both mulching and fertilizer application (with or without mulching) factors significantly increased soil N2O and CO2 emissions and reduced soil uptake of CH4(P<0.05). Compared to chemical fertilizer treatments, the organic fertilizer treatments reduced soil N2O emission by 11.8% to 52.6% and 14.1% to 68.0% and increased soil CO2 emission by 5.1% to 24.1% and 15.1% to 48.7% under mulching and no-mulching conditions, respectively (P<0.05). Compared to that under no-mulching, the global warming potential (GWP) under mulching increased by 140.7% to 206.6%. Compared to that in the CK treatment, the GWP of fertilized treatments increased by 36.6% to 67.6% and 31.2% to 89.1% under mulching and no-mulching conditions (P<0.05), respectively. Combined with the yield factor, the greenhouse gas intensity (GHGI) under the mulching condition increased by 103.4% to 166.2% compared to that under the no-mulching condition. Therefore, GHG emissions could be reduced by increasing yields. 2 The mulching treatments increased maize yield by 8.4% to 22.4% and WUE by 4.8% to 24.9% (P<0.05). Fertilizer application significantly increased maize yield and WUE. The organic fertilizer treatments increased yield by 2.6% to 8.5% and WUE 13.5% to 23.2% under the mulching condition compared to that in the MT0 treatment and increased yield by 3.9% to 14.3% and WUE 4.5% to 18.2% under the no-mulching condition compared to that in the T0 treatment. 3 In the 0-40 cm soil layer, the total nitrogen content of mulching treatments was increased by 2.4% to 24.7% compared with that of the no-mulching treatments. Fertilizer application treatments increased the total nitrogen content by 18.1% to 48.9% and 15.4% to 49.7% under the mulching and no-mulching conditions, respectively. Mulching and fertilizer application promoted nitrogen accumulation and nitrogen fertilizer use efficiency in maize plants (P<0.05). Compared to that in chemical fertilizer treatments, the organic fertilizer treatments increased nitrogen fertilizer use efficiency by 2.6% to 8.5% and 3.9% to 14.3% under mulching and no-mulching conditions, respectively. Combining ecological and economic benefits, the MT50 under mulching conditions and T75 under no-mulching conditions can be recommended as planting models to guarantee stable yield and achieve green and sustainable agricultural production.


Subject(s)
Greenhouse Gases , Farms , Zea mays , Carbon Dioxide , Fertilizers , Nitrogen , Soil , Water
19.
Sensors (Basel) ; 23(11)2023 May 28.
Article in English | MEDLINE | ID: mdl-37299872

ABSTRACT

A number of textile-based fiber optic sensors have recently been proposed for the continuous monitoring of vital signs. However, some of these sensors are likely unsuitable for conducting direct measurements on the torso as they lack elasticity and are inconvenient. This project provides a novel method for creating a force-sensing smart textile by inlaying four silicone-embedded fiber Bragg grating sensors into a knitted undergarment. The applied force was determined within 3 N after transferring the Bragg wavelength. The results show that the sensors embedded in the silicone membranes achieved enhanced sensitivity to force, as well as flexibility and softness. Additionally, by assessing the degree of FBG response to a range of standardized forces, the linearity (R2) between the shift in the Bragg wavelength and force was found to be above 0.95, with an ICC of 0.97, when tested on a soft surface. Furthermore, the real-time data acquisition could facilitate the adjustment and monitoring of force during the fitting processes, such as in bracing treatment for adolescent idiopathic scoliosis patients. Nevertheless, the optimal bracing pressure has not yet been standardized. This proposed method could help orthotists to adjust the tightness of brace straps and the location of padding in a more scientific and straightforward way. The output of this project could be further extended to determine ideal bracing pressure levels.


Subject(s)
Textiles , Elasticity , Pressure , Silicones , Reproducibility of Results
20.
Front Bioeng Biotechnol ; 11: 1219460, 2023.
Article in English | MEDLINE | ID: mdl-37388768

ABSTRACT

Background: Fracture or bone defect caused by accidental trauma or disease is a growing medical problem that threats to human health.Currently, most orthopedic implant materials must be removed via follow-up surgery, which requires a lengthy recovery period and may result in bacterial infection. Building bone tissue engineering scaffolds with hydrogel as a an efficient therapeutic strategy has outstanding bionic efficiency.By combining some bionic inorganic particles and hydrogels to imitate the organic-inorganic characteristics of natural bone extracellular matrix, developing injectable multifunctional hydrogels with bone tissue repair effects and also displaying excellent antibacterial activity possesses attractive advantages in the field of minimally invasive therapy in clinical. Methods: In the present work, a multifunctional injectable hydrogel formed by photocrosslinking was developed by introducing hydroxyapatite (HA) microspheres to Gelatin Methacryloyl (GelMA) hydrogel. Results: The composite hydrogels exhibited good adhesion and bending resistance properties due to the existence of HA. In addition, when the concentration of GelMA is 10% and the concentration of HA microspheres is 3%, HA/GelMA hydrogel system displayed increased microstructure stability, lower swelling rate, increased viscosity, and improved mechanical properties. Furthermore, the Ag-HA/GelMA demonstrated good antibacterial activity against Staphylococcus aureus and Escherichia coli, which could signifificantly lower the risk of bacterial infection following implantation. According to cell experiment, the Ag-HA/GelMA hydrogel is capable of cytocompatibility and has low toxicity to MC3T3 cell. Conclusion: Therefore, the new photothermal injectable antibacterial hydrogel materials proposed in this study will provide a promising clinical bone repair strategy and is expected to as a minimally invasive treatment biomaterial in bone repair fields.

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