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1.
Small ; : e2407196, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39385656

ABSTRACT

The rational design of polysulfide electrocatalysts is of vital importance to achieve longevous Li─S batteries. Notwithstanding fruitful advances made in elevating electrocatalytic activity, efforts to regulate precatalyst phase evolution and protect active sites are still lacking. Herein, an in situ graphene-encapsulated bimetallic model catalyst (CoNi@G) is developed for striking a balance between electrocatalytic activity and stability for sulfur electrochemistry. The layer numbers of directly grown graphene can be dictated by tuning the synthetic duration. Exhaustive experimental and theoretical analysis comprehensively reveals that the tailored graphene chainmail boosts catalytic durability while guaranteeing moderate phase evolution, accordingly attaining a decorated surface sulfidation with advanced catalytic essence. Benefiting from the sustainable polysulfide electrocatalysis, CoNi@G enabled sulfur electrodes to harvest a capacity output of 1276.2 mAh g-1 at 0.2 C and a negligible capacity decay of 0.055% per cycle after 1000 cycles at 1.0 C. Such a maneuver can be readily extended to other metallic catalysts including NiFe, CoFe, or Co. The work elucidates the precatalyst phase evolution mechanism through a controllable graphene-armored strategy, offering meaningful guidance to realize durable electrocatalysts in Li─S batteries.

2.
Front Immunol ; 15: 1427124, 2024.
Article in English | MEDLINE | ID: mdl-39238647

ABSTRACT

Background: Ferroptosis, as a novel form of programmed cell death, plays a crucial role in the occurrence and development of bladder cancer (BCa). However, the regulatory mechanisms of ferroptosis in the tumor microenvironment (TME) of BCa remain to be elucidated. Methods: Based on single-cell RNA (scRNA) transcriptomic data of BCa, we employed non-negative matrix factorization (NMF) dimensionality reduction clustering to identify novel ferroptosis-related cell subtypes within the BCa TME, aiming to explore the biological characteristics of these TME cell subtypes. Subsequently, we conducted survival analysis and univariate Cox regression analysis to explore the prognostic significance of these cell subtypes. We investigated the relationship between specific subtypes and immune infiltration, as well as their implications for immunotherapy. Finally, we discovered a valuable and novel biomarker for BCa, supported by a series of in vitro experiments. Results: We subdivided cancer-associated fibroblasts (CAFs), macrophages, and T cells into 3-5 small subpopulations through NMF and further explored the biological features. We found that ferroptosis played an important role in the BCa TME. Through bulk RNA-seq analysis, we further verified that ferroptosis affected the progression, prognosis, and immunotherapy response of BCa by regulating the TME. Especially ACSL4+CAFs, we found that high-level infiltration of this CAF subtype predicted worse prognosis, more complex immune infiltration, and less response for immunotherapy. Additionally, we found that this type of CAF was associated with cancer cells through the PTN-SDC1 axis, suggesting that SDC1 may be crucial in regulating CAFs in cancer cells. A series of in vitro experiments confirmed these inferences: SDC1 promoted the progression of BCa. Interestingly, we also discovered FTH1+ macrophages, which were closely related to SPP1+ macrophages and may also be involved in the regulation of BCa TME. Conclusion: This study revealed the significant impact of ferroptosis on bladder cancer TME and identified novel ferroptosis-related TME cell subpopulations, ACSL4+CAFs, and important BCa biomarker SDC1.


Subject(s)
Disease Progression , Ferroptosis , Immunotherapy , Single-Cell Analysis , Transcriptome , Tumor Microenvironment , Urinary Bladder Neoplasms , Ferroptosis/genetics , Humans , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/pathology , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Immunotherapy/methods , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Prognosis , Cell Line, Tumor , Gene Expression Profiling , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/immunology , Cancer-Associated Fibroblasts/pathology
3.
Cell Death Discov ; 10(1): 391, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39223162

ABSTRACT

Bladder cancer (BC) represents a prevalent and formidable malignancy necessitating innovative diagnostic and therapeutic strategies. Circular RNAs (circRNAs) have emerged as crucial regulators in cancer biology. In this study, we comprehensively evaluated ferroptosis levels in BC cells utilizing techniques encompassing lipid peroxidation assessment, transmission electron microscopy, and malondialdehyde (MDA) measurement. Additionally, we probed into the mechanistic intricacies by which circRNAs govern BC, employing RNA pull-down, RNA immunoprecipitation (RIP), and immunoprecipitation (IP) assays. Our investigation unveiled circSIRT5, which displayed significant downregulation in BC. Notably, circSIRT5 emerged as a promising prognostic marker, with diminished expression correlating with unfavorable clinical outcomes. Functionally, circSIRT5 was identified as an inhibitor of BC progression both in vitro and in vivo. Mechanistically, circSIRT5 exerted its tumor-suppressive activities through the formation of a ternary complex involving circSIRT5, SYVN1, and PHGDH. This complex enhanced the ubiquitination and subsequent degradation of PHGDH, ultimately promoting ferroptosis in BC cells. This ferroptotic process contributed significantly to the inhibition of tumor growth and metastasis in BC. In addition, FUS was found to accelerate the biogenesis of circSIRT5 in BC. These findings provide valuable insights into the pivotal role of circSIRT5 in BC pathogenesis, underscoring its potential as a diagnostic biomarker and therapeutic target for this malignancy.

4.
Adv Drug Deliv Rev ; 213: 115445, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39222795

ABSTRACT

Deformability is one of the critical attributes of nanoparticle (NP) drug carriers, along with size, shape, and surface properties. It affects various aspects of NP biotransport, ranging from circulation and biodistribution to interactions with biological barriers and target cells. Recent studies report additional roles of NP deformability in biotransport processes, including protein corona formation, intracellular trafficking, and organelle distribution. This review focuses on the literature published in the past five years to update our understanding of NP deformability and its effect on NP biotransport. We introduce different methods of modulating and evaluating NP deformability and showcase recent studies that compare a series of NPs in their performance in biotransport events at all levels, highlighting the consensus and disagreement of the findings. It concludes with a perspective on the intricacy of systematic investigation of NP deformability and future opportunities to advance its control toward optimal drug delivery.


Subject(s)
Nanoparticles , Nanoparticles/chemistry , Humans , Animals , Drug Carriers/chemistry , Drug Delivery Systems , Tissue Distribution , Biological Transport , Surface Properties
5.
Hum Genomics ; 18(1): 80, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014455

ABSTRACT

BACKGROUND: Keloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids. METHOD: Bulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids. RESULTS: In the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion. CONCLUSION: In summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment.


Subject(s)
Keloid , RNA-Seq , Keloid/genetics , Keloid/diagnosis , Keloid/pathology , Keloid/immunology , Keloid/drug therapy , Humans , Transcriptome/genetics , Gene Expression Profiling , Fibroblasts/metabolism , Fibroblasts/pathology , Fibroblasts/immunology , Gene Regulatory Networks , Tretinoin/pharmacology , Tretinoin/therapeutic use , Single-Cell Analysis/methods , Cell Differentiation/genetics , Sequence Analysis, RNA/methods , Machine Learning , Single-Cell Gene Expression Analysis
6.
J Cancer Res Clin Oncol ; 150(5): 264, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38767747

ABSTRACT

BACKGROUND: Bladder cancer (BCa) is among the most prevalent malignant tumors affecting the urinary system. Due to its highly recurrent nature, standard treatments such as surgery often fail to significantly improve patient prognosis. Our research aims to predict prognosis and identify precise therapeutic targets for novel treatment interventions. METHODS: We collected and screened genes related to the TGF-ß signaling pathway and performed unsupervised clustering analysis on TCGA-BLCA samples based on these genes. Our analysis revealed two novel subtypes of bladder cancer with completely different biological characteristics, including immune microenvironment, drug sensitivity, and more. Using machine learning classifiers, we identified SMAD6 as a hub gene contributing to these differences and further investigated the role of SMAD6 in bladder cancer in the single-cell transcriptome data. Additionally, we analyzed the relationship between SMAD6 and immune checkpoint genes. Finally, we performed a series of in vitro assays to verify the function of SMAD6 in bladder cancer cell lines. RESULTS: We have revealed two novel subtypes of bladder cancer, among which C1 exhibits a worse prognosis, lower drug sensitivity, a more complex tumor microenvironment, and a 'colder' immune microenvironment compared to C2. We identified SMAD6 as a key gene responsible for the differences and further explored its impact on the molecular characteristics of bladder cancer. Through in vitro experiments, we found that SMAD6 promoted the prognosis of BCa patients by inhibiting the proliferation and migration of BCa cells. CONCLUSION: Our study reveals two novel subtypes of BCa and identifies SMAD6 as a highly promising therapeutic target.


Subject(s)
Machine Learning , Smad6 Protein , Tumor Microenvironment , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/metabolism , Prognosis , Smad6 Protein/genetics , Smad6 Protein/metabolism , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , Cell Proliferation , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic
7.
ACS Nano ; 18(15): 10642-10652, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38560784

ABSTRACT

Considerable attention has been by far paid to stabilizing metallic Zn anodes, where side reactions and dendrite formation still remain detrimental to their practical advancement. Electrolyte modification or protected layer design is widely reported; nonetheless, an effective maneuver to synergize both tactics has been rarely explored. Herein, we propose a localized electrolyte optimization via the introduction of a dual-functional biomass modificator over the Zn anode. Instrumental characterization in conjunction with molecular dynamics simulation indicates local solvation structure transformation owing to the limitation of bound water with intermolecular hydrogen bonds, effectively suppressing hydrogen evolutions. Meanwhile, the optimized nucleation throughout the protein membrane allows uniform Zn deposition. Accordingly, the symmetric cell exhibits an elongated lifespan of 3280 h at 1.0 mA cm-2/1.0 mAh cm-2, while the capacity retention of the full cell sustains 91.1% after 2000 cycles at 5.0 A g-1. The localized electrolyte tailoring via protein membrane introduction might offer insights into operational metal anode protection.

8.
J Colloid Interface Sci ; 663: 577-590, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38428115

ABSTRACT

Photodynamic therapy (PDT) is limited in tumor therapy due to the mature antioxidant barrier of tumor microenvironment (TME) and phototoxicity/easy-degradation characteristics of photosensitizers. Therefore, we prepared Cu2+-doped hollow carbon nanoparticles (CHC) to protect the loaded photosensitizers and sensitize TME by glutathione-depletion and peroxidase (POD)-like activity for enhanced PDT. CHC significantly increased the maximum speed of POD-like reaction (Vm) of 8.4 times. By coating with hyaluronic acid (HA), the active sites on CHC were temporarily masked with low catalytic property, and restored in response to the overexpressed hyaluronidase in TME. Meanwhile, due to the excellent photothermal conversion efficiency (32.5 %) and hollow structure of CHC, the loaded photosensitizers were well protected from sunlight activation-induced unwanted phototoxicity and rapid degradation under the near-infrared light irradiation. In-vivo anti-tumor experiments demonstrated that the combination of photothermal-photodynamic effect achieved the best anti-tumor effect (tumor inhibition rate at 87.8 %) compared with any monotherapy. In addition, the combination of photothermal and photodynamic effect could efficiently suppress the cell migration, manifesting the reduced number of lung metastasized nodules by 74 %. This work provides an integrated platform for photosensitizers protection and TME sensitization for enhanced PDT.


Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Humans , Photosensitizing Agents/chemistry , Carbon/pharmacology , Tumor Microenvironment , Neoplasms/drug therapy , Catalysis , Cell Line, Tumor , Nanoparticles/chemistry , Hydrogen Peroxide
9.
Ophthalmic Res ; 67(1): 248-256, 2024.
Article in English | MEDLINE | ID: mdl-38527448

ABSTRACT

INTRODUCTION: This study aimed to determine the interchangeability of bilateral anterior chamber depth (ACD) in intraocular lens (IOL) power calculations for cataractous eyes and refractive outcomes using the unaffected fellow eye's ACD in subluxated crystalline lenses. METHODS: The predicted postoperative spherical equivalent (SE) calculated using the Kane formula with and without fellow eye's ACD in 202 cataract patients was compared. Refractive outcomes of the newer formulas (the Kane, Barrett Universal II [BUII], and Pearl-DGS formulas) with affected eye's ACD and with unaffected fellow eye's ACD were compared in 33 eyes with lens subluxation (the affected eye) undergoing in-the-bag IOL implantation. The SD of the prediction error (PE) was assessed using the heteroscedastic method. RESULTS: In 202 paired cataractous eyes, no marked ACD difference was found bilaterally; the predicted SE obtained without the fellow eye's ACD was comparable with that calculated with the fellow eye one (p = 0.90), with a mean absolute difference of 0.03 ± 0.03 D. With the affected eye AL, keratometry, and ACD, the median absolute error (MedAE) was 0.38-0.64 D, and the percentage of PE within ±0.50 D was 30.30-57.58%. The unaffected eye's ACD improved the results (MedAE, 0.35-0.49 D; the percentage of PE within ±0.50 D, 54.55-63.64%). The SDs of the BUII (0.82 D) and Pearl-DGS formulas (0.87 D) with the affected eye's ACD were significantly larger than those of the Kane and Pearl-DGS formulas (both 0.69 D) with the unaffected eye's ACD. CONCLUSION: Bilateral ACD was interchangeable in IOL power calculation for cataractous eyes when using the Kane formula. Unaffected eye's ACD in lieu of affected eye's ACD can enhance the accuracy of newer formulas in patients with unilateral subluxated lenses undergoing in-the-bag IOL implantation.


Subject(s)
Anterior Chamber , Lens Subluxation , Lenses, Intraocular , Refraction, Ocular , Humans , Male , Female , Aged , Refraction, Ocular/physiology , Middle Aged , Lens Subluxation/surgery , Lens Subluxation/diagnosis , Lens Subluxation/physiopathology , Adult , Visual Acuity , Retrospective Studies , Optics and Photonics , Lens Implantation, Intraocular/methods , Biometry/methods , Aged, 80 and over
10.
Heliyon ; 10(1): e23398, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38226271

ABSTRACT

Objective: To systematically evaluate the effectiveness and safety of integrated Chinese and Western medicine in the treatment of acute myeloid leukaemia (AML) in elderly people. Method: The Cochrane Library, PubMed, Web of Science, Excerpta Medica Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Data and VIP Data databases were systematically searched from database inception to 30 June 2023 to identify cases of AML treatment with and without integrated Chinese and Western medicine. Fixed- and random-effect models were used to pool the main results, and the pooled risk ratio (RR) with a 95 % confidence interval (CI) was used as the effect indicator. Results: Eleven randomized controlled trial (RCT) involving 828 patients were finally included. The meta-analysis results showed that the overall response efficiency of integrated Chinese and Western medicine in treating myeloid leukaemia in elderly people was better than that of Western medicine alone (RR = 1.23, 95 % CI: 1.13, 1.33, p < 0.001). There was significant difference in the complete remission rate between the two groups (RR = 1.38, 95 % CI: 1.15, 1.65, p < 0.001). The incidence of myelosuppression (RR = 0.49, 95 % CI: 0.32, 0.75, p = 0.001), hepatic and renal insufficiency (RR = 0.43, 95 % CI: 0.29, 0.66, p < 0.001), infection (RR = 0.26, 95 % CI: 0.17, 0.40, p < 0.001) and gastrointestinal discomfort (RR = 0.31, 95 % CI: 0.22, 0.46, p < 0.001) of integrated Chinese and Western medicine were significantly lower than that of Western medicine alone. Conclusion: Compared with Western medicine alone, the application of integrated traditional Chinese and Western medicine can improve the total clinical remission rate and reduce adverse effects following chemotherapy. However, more high-quality results of randomised controlled trials and analysis are needed to confirm the findings.

11.
Cancer Lett ; 582: 216515, 2024 02 01.
Article in English | MEDLINE | ID: mdl-38056687

ABSTRACT

Bladder cancer (BC) is a common malignancy in males, and currently lacks ideal therapeutic approaches. Exploring emerging therapeutic targets from the perspective of endogenous peptides to improve the prognosis of bladder cancer patients holds promise. In this study, we have identified CTSGDP-13, a novel endogenous peptide, which demonstrates potential anti-cancer effects in BC. Our findings reveal that CTSGDP-13 can promote ferroptosis in BC cells, both in vitro and in vivo, leading to the inhibition of BC progression. Furthermore, we have identified TRIM25 as a downstream regulatory target of CTSGDP-13. The expression of TRIM25 is significantly upregulated in BC, and its inhibition of ferroptosis promotes BC progression. Mechanistic studies have shown that CTSGDP-13 promotes the ubiquitination and subsequent degradation of TRIM25 by disrupting its interaction with the deubiquitinase USP7. Further investigations indicate that CTSGDP-13 promotes ferroptosis in BC by regulating the USP7/TRIM25/KEAP1 axis. The elucidation of the functional mechanisms of natural CTSGDP-13 and TRIM25 holds promise in providing valuable therapeutic targets for BC diagnosis and treatment.


Subject(s)
Ferroptosis , Urinary Bladder Neoplasms , Male , Humans , Kelch-Like ECH-Associated Protein 1 , Micropeptides , Ubiquitin-Specific Peptidase 7 , NF-E2-Related Factor 2 , Urinary Bladder Neoplasms/pathology
12.
Int J Pharm ; 649: 123665, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38048889

ABSTRACT

Recently, cylindrical granules have been applied in pharmaceutical fields and their aspect ratio (AR) is considered an important factor in the manufacturing process. However, the relationships between AR and the tableting process were seldom reported. This study aims to clarify the role of AR in the tableting process of cylindrical granules. First, mesalazine cylindrical granules with different AR were extruded, and their physical attributes were then comprehensively characterized. Subsequently, their compression behaviors and tableting performances were systematically assessed. Notably, it was found that the cylindrical granules with high AR possessed good anti-deformation capacity and favorable tabletability. Finally, the dissolution test suggested that tablets compressed from cylindrical granules with higher AR showed lower dissolution rates. Collectively, findings in this study identified that the AR of cylindrical granules was a critical factor in the tableting process and provided valuable guidance for the application of these granules in oral solid formulations.


Subject(s)
Mesalamine , Drug Compounding/methods , Tablets , Particle Size , Tensile Strength
13.
Adv Mater ; 36(9): e2306992, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37917072

ABSTRACT

Potassium metal battery is an appealing candidate for future energy storage. However, its application is plagued by the notorious dendrite proliferation at the anode side, which entails the formation of vulnerable solid electrolyte interphase (SEI) and non-uniform potassium deposition on the current collector. Here, this work reports a dual-modification design of aluminum current collector to render dendrite-free potassium anodes with favorable reversibility. This work achieves to modulate the electronic structure of the designed current collector and accordingly attain an SEI architecture with robust inorganic-rich constituents, which is evidenced by detailed cryo-EM inspection and X-ray depth profiling. The thus-produced SEI manages to expedite ionic conductivity and guide homogeneous potassium deposition. Compared to the potassium metal cells assembled using typical aluminum current collector, cells based on the designed current collector realize improved rate capability (maintaining 400 h under 50 mA cm-2 ) and low-temperature durability (stable operation at -50 °C). Moreover, scalable production of the current collector allows for the sustainable construction of high-safety potassium metal batteries, with the potential for reducing the manufacturing cost.

14.
Small ; 20(5): e2305533, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37786306

ABSTRACT

CO2 capture and conversion technology are highly promising technologies that definitely play a part in the journey towards carbon neutrality. Releasing CO2 by mild stimulation and the development of high efficiency catalytic processes are urgently needed. The magnetic field, as a thermodynamic parameter independent of temperature and pressure, is vital in the enhancement of CO2 capture and conversion process. In this review, the recent progress of magnetic field-enhanced CO2 capture and conversion is comprehensively summarized. The theoretical fundamentals of magnetic field on CO2 adsorption, release and catalytic reduction process are discussed, including the magnetothermal, magnetohydrodynamic, spin selection, Lorentz forces, magnetoresistance and spin relaxation effects. Additionally, a thorough review of the current progress of the enhancement strategies of magnetic field coupled with a variety of fields (including thermal, electricity, and light) is summarized in the aspect of CO2 related process. Finally, the challenges and prospects associated with the utilization of magnetic field-assisted techniques in the construction of CO2 capture and conversion systems are proposed. This review offers a reference value for the future design of catalysts, mechanistic investigations, and practical implementation for magnetic field enhanced CO2 capture and conversion.

15.
Sci Total Environ ; 914: 169582, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38154646

ABSTRACT

Metals are rarely found as free ions in natural and anthropogenic environments, but they are often associated with organic matter and minerals. Under the context of circular economy, metals should be recycled, yet they are difficult to extract for their complex forms in real situations. Based on the protocols of review methodology and the analysis of VOS viewer, there are few reviews on the properties of metal-organic complexes, decomplexation methods, the effect of coexisting ions, the pH influence, and metal recovery methods for the increasingly complicated metal-organic complexes wastewater. Conventional treatment methods such as flocculation, adsorption, biological degradation, and ion exchange fail to decompose metal-organic complexes completely without causing secondary pollution in wastewater. To enhance comprehension of the behavior and morphology exhibited by metal-organic complexes within aqueous solutions, we presented the molecular structure and properties of metal-organic complexes, the decomplexation mechanisms that encompassed both radical and non-radical oxidizing species, including hydroxyl radical (OH), sulfate radical (SO˙4-), superoxide radical (O˙2-), hydrogen peroxide (H2O2), ozone (O3), and singlet oxygen (1O2). More importantly, we reviewed novel aspects that have not been covered by previous reviews considering the impact of operational parameters and coexisting ions. Finally, the potential avenues and challenges were proposed for future research.

16.
Invest Ophthalmol Vis Sci ; 64(15): 6, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38051262

ABSTRACT

Purpose: Oxidative stress and cellular senescence are risk factors for age-related cataract. Heme oxygenase 1 (HO-1) is a critical antioxidant enzyme and related to autophagy. Here, we investigate the crosstalk among HO-1, oxidative stress, and cellular senescence in mouse lens epithelial cells (LECs). Methods: The gene expression of HO-1, p21, LC3, and p62 was measured in human samples. The protective properties of HO-1 were examined in hydrogen peroxide (H2O2)-damaged LECs. Autophagic flux was examined by Western blot and mRFP-GFP-LC3 assay. Western blotting and lysotracker staining were used to analyze lysosomal function. Flow cytometry was used to detect intracellular reactive oxygen species and analyze cell cycle. Senescence-associated ß-galactosidase assay was used to determine cellular senescence. The crosstalk between HO-1 and transcription factor EB (TFEB) was further observed in TFEB-knockdown cells. The TFEB binding site in the promoter region of Hmox1 was predicted by the Jasper website and was confirmed by chromatin immunoprecipitation assay. Results: HO-1 gene expression decreased in LECs of patients with age-related nuclear cataract, whereas mRNA expression levels of p21, LC3, and p62 increased. Upon H2O2-induced oxidative stress, LECs showed the characteristics of autophagic flux blockade, lysosomal dysfunction, and premature senescence. Interestingly, HO-1 significantly restored the impaired autophagic flux and lysosomal function and delayed cellular senescence. TFEB gene silencing greatly reduced the HO-1-mediated autophagic restoration, leading to a failure to prevent LECs from oxidative stress and premature senescence. Conclusions: We demonstrated HO-1 effects on restoring autophagic flux and delaying cellular senescence under oxidative stress in LECs, which are dependent on TFEB.


Subject(s)
Cataract , Hydrogen Peroxide , Animals , Humans , Mice , Autophagy , Cataract/prevention & control , Cataract/metabolism , Cellular Senescence , Epithelial Cells/metabolism , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Hydrogen Peroxide/toxicity , Hydrogen Peroxide/metabolism , Oxidative Stress
17.
Cancer Sci ; 114(11): 4157-4171, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37702269

ABSTRACT

Metastasis is an important factor affecting the prognosis of hormone receptor-positive breast cancer (BC). However, the molecular basis for migration and invasion of tumor cells remains poorly understood. Here, we identify that bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1), which plays an important role in innate immunity, is significantly elevated in breast cancer and associated with lymph node metastasis. High expression of BPIFB1 and its coding mRNA are significantly associated with poor prognosis of hormone receptor-positive BC. Using enrichment analysis and constructing immune infiltration evaluation, we predict the potential ability of BPIFB1 to promote macrophage M2 polarization. Finally, we demonstrate that BPIFB1 promotes the metastasis of hormone receptor-positive BC by stimulating the M2-like polarization of macrophages via the establishment of BC tumor cells/THP1 co-culture system, qPCR, Transwell assay, and animal experiments. To our knowledge, this is the first report on the role of BPIFB1 as a tumor promoter by activating the macrophage M2 polarization in hormone receptor-positive breast carcinoma. Together, these results provide novel insights into the mechanism of BPIFB1 in BC.


Subject(s)
Macrophages , Tumor Microenvironment , Animals , Macrophages/metabolism , Lymphatic Metastasis/pathology , Prognosis , Coculture Techniques , Cell Line, Tumor
18.
Plant Direct ; 7(8): e517, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37577137

ABSTRACT

AT-HOOK MOTIF NUCLEAR LOCALIZED (AHL) proteins occur in all sequenced plant species. They bind to the AT-rich DNA sequences in chromosomes and regulate gene transcription related to diverse biological processes. However, the molecular mechanism underlying how AHL proteins regulate gene transcription is poorly understood. In this research, we used root hair production as a readout to study the function of two Arabidopsis AHL proteins, AHL17, and its closest homolog AHL28. Overexpression of AHL17 or AHL28 greatly enhanced root hair production by increasing the transcription of an array of genes downstream of RHD6. RHD6 is a key transcription factor that regulates root hair development. Mutation of RHD6 completely suppressed the overproduction of root hairs by blocking the transcription of AHL17-activated genes. The overexpression of AHL17 or AHL28, however, neither affected the transcription of RHD6 nor the accumulation of RHD6 protein. These two AHL proteins also did not directly interact with RHD6. Furthermore, we found that three members of the Heat Shock Protein70 family, which have been annotated as the subunits of the plant Mediator complex, could form a complex with both AHL17 and RHD6. Our research might reveal a previously unrecognized mechanism of how AHL proteins regulate gene transcription.

19.
Math Biosci Eng ; 20(6): 10495-10513, 2023 Apr 10.
Article in English | MEDLINE | ID: mdl-37322945

ABSTRACT

For constrained image-based visual servoing (IBVS) of robot manipulators, a model predictive control (MPC) strategy tuned by reinforcement learning (RL) is proposed in this study. First, model predictive control is used to transform the image-based visual servo task into a nonlinear optimization problem while taking system constraints into consideration. In the design of the model predictive controller, a depth-independent visual servo model is presented as the predictive model. Next, a suitable model predictive control objective function weight matrix is trained and obtained by a deep-deterministic-policy-gradient-based (DDPG) RL algorithm. Then, the proposed controller gives the sequential joint signals, so that the robot manipulator can respond to the desired state quickly. Finally, appropriate comparative simulation experiments are developed to illustrate the efficacy and stability of the suggested strategy.


Subject(s)
Robotics , Learning , Algorithms , Computer Simulation
20.
J Ophthalmol ; 2023: 4032011, 2023.
Article in English | MEDLINE | ID: mdl-37124064

ABSTRACT

Purpose: To evaluate refractive outcomes, intraocular lens (IOL) power calculation, and IOL position following a novel conjunctiva-sparing transscleral fixation technique. Methods: Forty-one eyes of 40 patients managed with a flapless transscleral-sutured technique were included. Preoperative and postoperative refractive errors (spherical equivalents, SE) were compared. IOL position was assessed on the Scheimpflug images. IOL power was calculated by SRK/T, Holladay 1, and Hoffer Q formulas. Results: The mean age was 57.39 ± 14.83 years (range: 26 to 79 years), and the mean follow-up was 7.46 ± 6.42 months (range: 1 to 24 months). Surgical indications were aphakia (n = 14), subluxated lenses (n = 3), and IOL dislocation (n = 24). The SE was 4.50 ± 6.38 diopter (D) (range: -3.75 to 13.75 D) preoperatively and -1.68 ± 1.57 D (range: -5.50 to 1.13 D) postoperatively (P < 0.001). The mean tilt angle and decentration were 2.90° ± 1.93° (range: 0.39° to 9.10°) and 0.23 ± 0.19 mm (range: 0.02 to 0.94 mm) vertically, and 1.75° ± 1.41° (range: 0.24° to 7.65°) and 0.18 ± 0.19 mm (range: 0.02 to 1.06 mm) horizontally, which were clinically insignificant. All three IOL formulas produced myopic errors (range: -0.29 to -0.50 D). The SRK/T had the lowest median absolute error (0.55 D), followed by the Holladay 1 (0.70 D) and the Hoffer Q (0.74 D). The three formulas had the same percentage of prediction errors (PEs) within ±0.5 D (43.48%), while the Hoffer Q had the highest percentage of PEs within ±1.0 D (82.61%). Conclusion: The present technique can serve as an alternative approach for transscleral IOL fixation and refractive correction in eyes with compromised capsular support, ensuring the stability of IOLs and reasonable IOL power calculation accuracy.

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