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1.
ACS Nano ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39268809

RESUMO

The development of a photosensitizer (PS) that induces pyroptosis could be a star for photodynamic therapy (PDT), particularly with type-I PSs that produce reactive oxygen species (ROS) in a hypoxic tumor microenvironment. Since pyroptosis is a recently characterized cell death pathway, it holds promise for advancing PDT in oncology, with PSs playing a critical role. Herein, we develop a PS named Th-M with aggregation-induced emission (AIE) characteristics for type-I PDT against tongue squamous cell carcinoma (TSCC). Th-M stands out for its exceptional mitochondrial-targeting ability, which triggers mitochondrial dysfunction and leads to Caspase-3 and Gasdermin E (GSDME) cleavage under white light irradiation, inducing pyroptosis in TSCC cells. Our studies verify the effectiveness of Th-M in destroying cancer cells in vitro and suppressing tumor growth in vivo while also demonstrating a favorable biosafety profile. This work pioneers the application of Th-M as a mitochondria-targeted, type-I PS that leverages the mechanism of pyroptosis, offering a potent approach for the treatment of TSSC with promising implications for future PDT of cancers.

2.
Natl Sci Rev ; 11(10): nwae248, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39301065

RESUMO

Two-dimensional (2D) non-layered materials in many aspects differ from their layered counterparts, and the exploration of their physical properties has produced many intriguing findings. However, due to challenges in applying existing experimental techniques to such nanoscale samples, their thermal properties have remained largely uncharacterized, hindering further exploration and device application using this promising material system. Here, we demonstrate an experimental study of thermal conduction in ß-In2S3, a typical non-layered 2D material, using a resonant nanoelectromechanical systems (NEMS) platform. We devise a new two-degrees-of-freedom technique, more responsive and sensitive than Raman spectroscopy, to simultaneously determine both the thermal conductivity to be 3.7 W m-1 K-1 and its interfacial thermal conductance with SiO2 as 6.4 MW m-2 K-1. Leveraging such unique thermal properties, we further demonstrate a record-high power-to-frequency responsivity of -447 ppm/µW in ß-In2S3 NEMS sensors, the best among drumhead NEMS-based bolometers. Our findings offer an effective approach for studying thermal properties and exploring potential thermal applications of 2D non-layered materials.

3.
Int Immunopharmacol ; 142(Pt B): 113215, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39326294

RESUMO

Psoriasis is a recurrent autoimmune disease characterized by seasonal and latitudinal variations. Double-stranded DNA (dsDNA) is a crucial component of nucleic acids and nucleosomes that provoke innate immune responses. Given the potential influence of climate on immunity and the development of autoimmune diseases, a comprehensive quantitative analysis of dsDNA levels in the population is warranted. In this case-control study conducted from 2016 to 2020, 10,110 psoriasis patients and matched controls from 12 regions in China were included. This study examined variations in serum dsDNA levels based on season and latitude. The results revealed significant associations between geographical location, climatic conditions, and season with serum dsDNA concentration. Individuals residing in Northern China exhibited significantly higher serum dsDNA levels compared to those in the South (1.00 vs. 0.96 ng/ml), and those in medium latitude regions had higher levels than their counterparts in areas with extreme latitudes (0.98 vs. 0.96 ng/ml). Furthermore, individuals in regions with low to medium ultraviolet exposure demonstrated higher serum dsDNA concentrations than those in areas with high ultraviolet levels (1.03 vs. 0.93 ng/ml), and individuals in winter showed higher levels than those in summer (1.03 vs. 0.92 ng/ml). Factors such as sex, UV index, humidity, and sunshine duration were inversely related to serum dsDNA levels, while age and daylight hours showed a positive association. These findings suggest that meteorological and climatic factors play a role in influencing serum dsDNA levels.

4.
Langmuir ; 40(37): 19396-19403, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39226526

RESUMO

The design and preparation of anode materials with structural stability, fast ion transmission, and low open-circuit voltage are critical to the development of magnesium ion batteries (MIBs). The feasibility of the unique phase Haeckelite MoS2 (Hae-MoS2) monolayer with Haeckelite structure as a potential anode material for MIBs was investigated using density functional theory (DFT) calculations. The Hae-MoS2 monolayer exhibits excellent structural stability and semimetallic characteristics with a Dirac cone located at the Gamma point of band structure. Mg ion is easily adsorbed on the Hae-MoS2 monolayer surface with an adsorption energy of -2.06 eV and can diffuse rapidly with a low diffusion energy barrier (0.3 eV), indicating excellent charge and discharge rates. Most importantly, the Hae-MoS2 monolayer exhibits a suitable open-circuit voltage, which falls within the desired voltage range and ensures the safety of battery performance. These exceptional properties indicate that the Hae-MoS2 monolayer can be proposed as a candidate for anode material for MIBs.

5.
Front Bioeng Biotechnol ; 12: 1414323, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267906

RESUMO

In the quest to tackle stress urinary incontinence (SUI), the synthesis of cutting-edge biomaterials and regenerative materials has emerged as a promising frontier. Briefly, animal models like vaginal distension and bilateral ovariectomy serve as crucial platforms for unraveling the intricacies of SUI, facilitating the evaluation of innovative treatments. The spotlight, however, shines on the development and application of novel biomaterials-ranging from urethral bulking agents to nano-gel composites-which aim to bolster urethral support and foster tissue regeneration. Furthermore, the exploration of stem cell therapies, particularly those derived from adipose tissues and urine, heralds a new era of regenerative medicine, offering potential for significant improvements in urinary function. This review encapsulates the progress in biomaterials and regenerative strategies, highlighting their pivotal role in advancing the treatment of SUI, thereby opening new avenues for effective and minimally invasive solutions.

6.
Curr Opin Plant Biol ; 82: 102625, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39236592

RESUMO

The specialized metabolism of St. John's wort, Hypericum perforatum L., is a key focus in medicinal plant research due to its hallmark bioactive compounds hyperforin and hypericin. Known for its traditional medicinal uses dating back to ancient times, St. John's wort is currently used for mild depression therapy. Recent research works have shed light on the biosynthesis of various metabolites in this plant, such as flavonoids, xanthones, hyperforin, and hypericin. The elucidation of these pathways, along with the discovery of novel enzymes like hyperforin synthase, support the pharmaceutical research by enabling scalable production of bioactive compounds for the development of new drugs. Elucidation of the hyperforin biosynthesis based on single-cell RNA-seq is an approach that will be expanded and accelerate the gene discovery and full pathway reconstitution of plant specialized metabolites.

8.
Acta Pharm Sin B ; 14(8): 3476-3492, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39234615

RESUMO

Owing to their limited accuracy and narrow applicability, current antimicrobial peptide (AMP) prediction models face obstacles in industrial application. To address these limitations, we developed and improved an AMP prediction model using Comparing and Optimizing Multiple DEep Learning (COMDEL) algorithms, coupled with high-throughput AMP screening method, finally reaching an accuracy of 94.8% in test and 88% in experiment verification, surpassing other state-of-the-art models. In conjunction with COMDEL, we employed the phage-assisted evolution method to screen Sortase in vivo and developed a cell-free AMP synthesis system in vitro, ultimately increasing AMPs yields to a range of 0.5-2.1 g/L within hours. Moreover, by multi-omics analysis using COMDEL, we identified Lactobacillus plantarum as the most promising candidate for AMP generation among 35 edible probiotics. Following this, we developed a microdroplet sorting approach and successfully screened three L. plantarum mutants, each showing a twofold increase in antimicrobial ability, underscoring their substantial industrial application values.

9.
J Int Med Res ; 52(9): 3000605241275375, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39344813

RESUMO

Pulmonary actinomycosis is a rare pulmonary infectious disease that is often challenging to diagnose early and has a high misdiagnosis rate. In some cases, it can be particularly difficult to distinguish pulmonary actinomycosis from lung cancer. We herein report a rare case of pulmonary actinomycosis in which the preoperative examinations strongly suggested lung cancer, leading to the patient undergoing right upper lung resection and bronchoplasty. The patient had a good postoperative recovery; however, the postoperative pathology report indicated pulmonary actinomycosis. In this report, we summarize the key aspects of the diagnosis and treatment of pulmonary actinomycosis to aid clinicians in reducing the likelihood of misdiagnosis.


Assuntos
Actinomicose , Erros de Diagnóstico , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Actinomicose/diagnóstico , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Diagnóstico Diferencial , Pneumopatias/diagnóstico , Pneumopatias/microbiologia , Pneumopatias/cirurgia , Pneumopatias/patologia , Pulmão/patologia , Pulmão/microbiologia , Pulmão/diagnóstico por imagem , Pulmão/cirurgia
10.
Biomater Sci ; 12(19): 5063-5075, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39212588

RESUMO

3D bioprinting, a significant advancement in biofabrication, is renowned for its precision in creating tissue constructs. Collagen, despite being a gold standard biomaterial, faces challenges in bioink formulations due to its unique physicochemical properties. This study introduces a novel, neutral-soluble, photocrosslinkable collagen maleate (ColME) that is ideal for 3D bioprinting. ColME was synthesized by chemically modifying bovine type I collagen with maleic anhydride, achieving a high substitution ratio that shifted the isoelectric point to enhance solubility in physiological pH environments. This modification was confirmed to preserve the collagen's triple-helix structure substantially. Bioprinting parameters for ColME were optimized, focusing on adjustments to the bioink concentration, extrusion pressure, nozzle speed, and temperature. Results demonstrated that lower temperatures and smaller nozzle sizes substantially improved the print quality of grid structures. Additionally, the application of intermittent photo-crosslinking facilitated the development of structurally robust 3D multilayered constructs, enabling the stable fabrication of complex tissues. Cell viability assays showed that encapsulated cells within the ColME matrix maintained high viability after printing. When compared to methacrylated gelatin, ColME exhibited superior mechanical strength, resistance to enzymatic digestion, and overall printability, positioning it as an outstanding bioink for the creation of durable, bioactive 3D tissues.


Assuntos
Bioimpressão , Maleatos , Impressão Tridimensional , Animais , Maleatos/química , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Colágeno/química , Reagentes de Ligações Cruzadas/química , Processos Fotoquímicos , Engenharia Tecidual , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Tinta , Alicerces Teciduais/química , Humanos , Colágeno Tipo I/química
11.
Cell Genom ; 4(8): 100627, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39096913

RESUMO

Excision repair cross-complementation group 2 (ERCC2) encodes the DNA helicase xeroderma pigmentosum group D, which functions in transcription and nucleotide excision repair. Point mutations in ERCC2 are putative drivers in around 10% of bladder cancers (BLCAs) and a potential positive biomarker for cisplatin therapy response. Nevertheless, the prognostic significance directly attributed to ERCC2 mutations and its pathogenic role in genome instability remain poorly understood. We first demonstrated that mutant ERCC2 is an independent predictor of prognosis in BLCA. We then examined its impact on the somatic mutational landscape using a cohort of ERCC2 wild-type (n = 343) and mutant (n = 39) BLCA whole genomes. The genome-wide distribution of somatic mutations is significantly altered in ERCC2 mutants, including T[C>T]N enrichment, altered replication time correlations, and CTCF-cohesin binding site mutation hotspots. We leverage these alterations to develop a machine learning model for predicting pathogenic ERCC2 mutations, which may be useful to inform treatment of patients with BLCA.


Assuntos
Mutação , Neoplasias da Bexiga Urinária , Proteína Grupo D do Xeroderma Pigmentoso , Humanos , Neoplasias da Bexiga Urinária/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Prognóstico
12.
J Orthop Surg (Hong Kong) ; 32(2): 10225536241277604, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39155598

RESUMO

OBJECTIVES: Platelet-rich plasma treatment delays the need for total knee replacement in patients with knee osteoarthritis. However, its use and preparation remain controversial. The aim of this study was to investigate the relationship between anticoagulant use in the preparation of platelet-rich plasma and post-treatment pain in patients with knee osteoarthritis. Additionally, we explored the efficacy of platelet-rich plasma over medium- and long-term follow-up periods and identified other factors that may affect treatment outcomes. METHODS: In this retrospective study, 225 patients with knee osteoarthritis, who underwent knee platelet-rich plasma treatment from June 2021 to January 2022, were examined at three study centres. Patients were categorised, based on the type and amount of anticoagulant used during platelet-rich plasma preparation, into 4% sodium citrate (SC) 0.6 mL, 4% SC 1 mL, 4% SC 2 mL, heparin 0.1 mL, and heparin 0.2 mL groups. We analysed the patients' basic information, pain after treatment, and inflammatory markers (i.e., interleukin 6, tumour necrosis factor-α, and hypersensitive C-reactive protein) in the joint fluid via enzyme-linked immunosorbent assay and joint fluid crystallisation. Additionally, we assessed the patients' Western Ontario and McMaster University scores and minimal clinically significant differences after treatment. RESULTS: Patients in the 4% SC 0.6 mL and heparin 0.1 mL groups experienced less pain after platelet-rich plasma treatment than did patients in the high-dose anticoagulant group. The joint fluid of patients with pain in these groups had lower levels of inflammatory markers. Patients treated with SC had slightly better medium- and long-term therapeutic outcomes than did patients treated with heparin. Patients with poorly controlled hyperuricemia also experienced pain after platelet-rich plasma treatment. CONCLUSIONS: The results suggest that platelet-rich plasma prepared using high-dose anticoagulants or administered to patients with poorly controlled hyperuricaemia may lead to moderate-to-severe knee pain and joint effusion after joint puncture therapy. Platelet-rich plasma had a therapeutic effect on knee osteoarthritis; however, its efficacy gradually decreased over time. SC anticoagulant is more suitable for platelet-rich plasma preparation than is heparin. Further studies are needed to understand the safety and the various factors influencing platelet-rich plasma therapy.


Assuntos
Anticoagulantes , Hiperuricemia , Osteoartrite do Joelho , Plasma Rico em Plaquetas , Humanos , Estudos Retrospectivos , Masculino , Feminino , Osteoartrite do Joelho/terapia , Anticoagulantes/administração & dosagem , Idoso , Hiperuricemia/terapia , Hiperuricemia/complicações , Pessoa de Meia-Idade , Artralgia/etiologia , Artralgia/terapia , Artralgia/diagnóstico , Heparina/administração & dosagem , Citrato de Sódio/administração & dosagem , Injeções Intra-Articulares , Medição da Dor
13.
Anal Chem ; 96(32): 13174-13184, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39093925

RESUMO

The small molecule epiberberine (EPI) is a natural alkaloid with versatile bioactivities against several diseases including cancer and bacterial infection. EPI can induce the formation of a unique binding pocket at the 5' side of a human telomeric G-quadruplex (HTG) sequence with four telomeric repeats (Q4), resulting in a nanomolar binding affinity (KD approximately 26 nM) with significant fluorescence enhancement upon binding. It is important to understand (1) how EPI binding affects HTG structural stability and (2) how enhanced EPI binding may be achieved through the engineering of the DNA binding pocket. In this work, the EPI-binding-induced HTG structure stabilization effect was probed by a peptide nucleic acid (PNA) invasion assay in combination with a series of biophysical techniques. We show that the PNA invasion-based method may be useful for the characterization of compounds binding to DNA (and RNA) structures under physiological conditions without the need to vary the solution temperature or buffer components, which are typically needed for structural stability characterization. Importantly, the combination of theoretical modeling and experimental quantification allows us to successfully engineer Q4 derivative Q4-ds-A by a simple extension of a duplex structure to Q4 at the 5' end. Q4-ds-A is an excellent EPI binder with a KD of 8 nM, with the binding enhancement achieved through the preformation of a binding pocket and a reduced dissociation rate. The tight binding of Q4 and Q4-ds-A with EPI allows us to develop a novel magnetic bead-based affinity purification system to effectively extract EPI from Rhizoma coptidis (Huang Lian) extracts.


Assuntos
Berberina , Quadruplex G , Berberina/química , Berberina/análogos & derivados , Berberina/farmacologia , Humanos , DNA/química , Ácidos Nucleicos Peptídicos/química
14.
Mol Plant ; 17(9): 1439-1457, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39135343

RESUMO

Hyperforin is the compound responsible for the effectiveness of St. John's wort (Hypericum perforatum) as an antidepressant, but its complete biosynthetic pathway remains unknown. Gene discovery based on co-expression analysis of bulk RNA-sequencing data or genome mining failed to discover the missing steps in hyperforin biosynthesis. In this study, we sequenced the 1.54-Gb tetraploid H. perforatum genome assembled into 32 chromosomes with the scaffold N50 value of 42.44 Mb. By single-cell RNA sequencing, we identified a type of cell, "Hyper cells", wherein hyperforin biosynthesis de novo takes place in both the leaves and flowers. Through pathway reconstitution in yeast and tobacco, we identified and characterized four transmembrane prenyltransferases (HpPT1-4) that are localized at the plastid envelope and complete the hyperforin biosynthetic pathway. The hyperforin polycyclic scaffold is created by a reaction cascade involving an irregular isoprenoid coupling and a tandem cyclization. Our findings reveal how and where hyperforin is biosynthesized, enabling synthetic-biology reconstitution of the complete pathway. Thus, this study not only deepens our comprehension of specialized metabolism at the cellular level but also provides strategic guidance for elucidation of the biosynthetic pathways of other specializied metabolites in plants.


Assuntos
Hypericum , Floroglucinol , Terpenos , Hypericum/metabolismo , Hypericum/genética , Floroglucinol/análogos & derivados , Floroglucinol/metabolismo , Terpenos/metabolismo , Análise de Célula Única , Antidepressivos/metabolismo , Antidepressivos/farmacologia , Vias Biossintéticas , Análise de Sequência de RNA , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Folhas de Planta/metabolismo
15.
Adv Mater ; 36(39): e2407750, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39115352

RESUMO

Thin endometrium (TE) is closely associated with infertility in reproductive medicine. Estrogen therapy gains unsatisfactory outcomes. In this study, an artificial mucus based on dopamine (L-DOPA)-modified hyaluronic acid combining phytoestrogen cajaninstilbene acid and rat urinary exosomes (CUEHD) is constructed for TE treatment using a rat TE model. In the rat TE model, the dominant elastic behavior and adhesive properties of CUEHD guarantee adequate retention, rendering superior synergistic treatment efficacy and favorable biosafety characteristics. CUEHD treatment significantly increases endometrial thickness and promotes receptivity and fertility. Mechanistically, estrogen homeostasis, inflammation inhibition, and endometrial regeneration are achieved through the crosstalk between ER-NLRP3-IL1ß and Wnt-ß catenin-TGFß-smad signaling pathways. Moreover, the therapeutic potential of exosomes from human urine and adipose tissue-derived stem cells (ADSCs) and rat ADSCs are also demonstrated, indicating extensive use of the artificial mucus system. Thus, this study illustrates a platform combining phytoestrogen and exosomes with promising implications for TE treatment.


Assuntos
Dopamina , Endométrio , Exossomos , Ácido Hialurônico , Muco , Fitoestrógenos , Animais , Ácido Hialurônico/química , Feminino , Exossomos/metabolismo , Exossomos/química , Endométrio/metabolismo , Endométrio/efeitos dos fármacos , Endométrio/citologia , Ratos , Humanos , Muco/metabolismo , Dopamina/urina , Dopamina/metabolismo , Fitoestrógenos/química , Fitoestrógenos/farmacologia , Ratos Sprague-Dawley
16.
Int Immunopharmacol ; 141: 112987, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39182267

RESUMO

Rheumatoid arthritis (RA) is an enduring autoimmune inflammatory condition distinguished by continual joint inflammation, hyperplasia of the synovium, erosion of bone, and deterioration of cartilage.Fibroblast-like synoviocytes (FLSs) exhibiting "tumor-like" traits are central to this mechanism.ADP-ribosylation factor-like 4c (ARL4C) functions as a Ras-like small GTP-binding protein, significantly impacting tumor migration, invasion, and proliferation.However, it remains uncertain if ARL4C participates in the stimulation of RA FLSs exhibiting "tumor-like" features, thereby fostering the advancement of RA. In our investigation, we unveiled, for the inaugural instance, via the amalgamated scrutiny of single-cell RNA sequencing (scRNA-seq) and Bulk RNA sequencing (Bulk-seq) datasets, that activated fibroblast-like synoviocytes (FLSs) showcase high expression of ARL4C, and the ARL4C protein expression in FLSs derived from RA patients significantly surpasses that observed in individuals with osteoarthritis (OA) and traumatic injury (trauma).Silencing of the ARL4C gene markedly impeded the proliferation of RA FLSs by hindered the transition of cells from the G0/G1 phase to the S phase, and intensified cell apoptosis and diminished the migratory and invasive capabilities. Co-culture of ARL4C gene-silenced RA FLSs with monocytes/macrophages significantly inhibited the polarization of monocytes/macrophages toward M1 and the repolarization of M2 to M1.Furthermore, intra-articular injection of shARL4C significantly alleviated synovial inflammation and cartilage erosion in collagen-induced arthritis (CIA) rats. In conclusion, our discoveries propose that ARL4C assumes a central role in the synovial inflammation, cartilage degradation, and bone erosion associated with RA by triggering the PI3K/AKT and MAPK signaling pathways within RA FLSs.ARL4C holds promise as a prospective target for the development of pharmaceutical agents targeting FLSs, with the aim of addressing RA.


Assuntos
Fatores de Ribosilação do ADP , Artrite Reumatoide , Macrófagos , Sinoviócitos , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Humanos , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Fatores de Ribosilação do ADP/metabolismo , Fatores de Ribosilação do ADP/genética , Animais , Macrófagos/imunologia , Macrófagos/metabolismo , Ratos , Análise de Célula Única , Progressão da Doença , Proliferação de Células , Células Cultivadas
17.
Eur J Med Chem ; 277: 116745, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39106659

RESUMO

In response to the escalating threat of microbial resistance, a series of novel pleuromutilin derivatives, conjugated with phenyl-sulfide and boron-containing moieties, were designed and synthesized. Most derivatives, especially 14b and 16b, demonstrated significant efficacy against Gram-positive bacteria, including multidrug-resistant strains, as well as pleuromutilin-resistant strains. Compound 16b showed high stability in the liver microsomes of rats and humans, along with acceptable tolerance in vitro and in vivo. Additionally, compound 16b exhibited promising efficacy in MRSA-infected mouse models. Our data highlight the potential of conjugated pleuromutilin derivatives as valuable agents against drug-resistant bacteria.


Assuntos
Antibacterianos , Diterpenos , Testes de Sensibilidade Microbiana , Pleuromutilinas , Compostos Policíclicos , Compostos Policíclicos/química , Compostos Policíclicos/farmacologia , Compostos Policíclicos/síntese química , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Animais , Humanos , Camundongos , Ratos , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Boro/química , Boro/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Microssomos Hepáticos/química
18.
Front Pharmacol ; 15: 1427318, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39101139

RESUMO

Background: Statins, which are medications that lower lipid levels, are extensively used to decrease cardiovascular disease risk. Recently, the use of statins in cancer prevention has attracted considerable interest. However, it is still unclear whether the use of statins has a causal effect on bladder cancer. Methods: The two-sample Mendelian Randomization (MR) was performed to infer the causal relationship between statin therapy (atorvastatin, simvastatin, and rosuvastatin) and bladder cancer. Single-nucleotide polymorphisms (SNP)-based genome-wide association studies (GWAS) of statins (atorvastatin, simvastatin, and rosuvastatin) were gathered from the UK Biobank, involving 462,933 participants. We acquired summary-level genetic data on bladder cancer from a European cohort of 175,121 individuals. The inverse variance weighted (IVW) method was the main analytical technique used, supplemented by MR-Egger, weighted median, weighted mode, and simple mode to estimate causal effects. Additionally, sensitivity analyses were conducted to verify the robustness and reliability of our findings. Results: Based on the IVW analysis, we identified a significant causal association between rosuvastatin use and a decreased risk of bladder cancer, with genetic analysis inferring the substantial reduction in odds (OR = 3.52E-19, 95% CI: 5.48E-32-2.26E-06, p = 0.005). In contrast, the IVW results did not reveal a statistically significant relationship between the genetically estimated use of atorvastatin (OR = 7.42E-03, 95% CI: 6.80E-06-8.084, p = 0.169) or simvastatin (OR = 0.135, 95% CI: 0.008-2.330, p = 0.168) and bladder cancer risk. Conclusion: We investigated the causal link between statin therapy (atorvastatin, simvastatin, and rosuvastatin) and bladder cancer using a two-sample Mendelian Randomization analysis among the European population. Our findings indicated that genetically predicted use of rosuvastatin was associated with a decreased risk of bladder cancer, whereas no significant genetically predicted causal effects were observed for atorvastatin and simvastatin use.

19.
Sensors (Basel) ; 24(15)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39123999

RESUMO

Wireless sensing is a crucial technology for building smart cities, playing a vital role in applications such as human monitoring, route planning, and traffic management. Analyzing the data provided by wireless sensing enables the formulation of more scientific decisions. The wireless sensing of dynamic events is a significant branch of wireless sensing. Sensing the specific times and durations of dynamic events is a challenging problem due to the dynamic event information is concealed within static environments. To effectively sense the relevant information of event occurrence, we propose a wireless sensing method for dynamic events based on RSSI, named RSSI-WSDE. RSSI-WSDE utilizes variable-length sliding windows and statistical methods to process original RSSI time series, amplifying the differences between dynamic events and static environments. Subsequently, z-score normalization is employed to enhance the comparability of the sensing effects for different dynamic events. Furthermore, by setting the adaptive threshold, the occurrence of dynamic event is sensed and the relevant information is marked on the original RSSI time series. In this study, the sensing performance of RSSI-WSDE was tested in indoor corridors and outdoor urban road environments. The wireless sensing of dynamic events, including walking, running, cycling, and driving, was conducted. The experimental results demonstrate that RSSI-WSDE can accurately sense the occurrence of dynamic events, marking the specific time and duration with millisecond-level precision. Moreover, RSSI-WSDE exhibits robust performance in wireless sensing of dynamic events in both indoor and outdoor environments.

20.
Langmuir ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137090

RESUMO

Although precise regulation of the crystalline structures of metal oxides is an effective method to improve their antibacterial activities, the corresponding mechanisms involved in this process are still unclear. In this study, three kinds of cuprous oxide (Cu2O) samples with different structures of cubes, octahedra, and rhombic dodecahedra (c-Cu2O, o-Cu2O, and r-Cu2O) have been successfully synthesized and their antibacterial activities are compared. The antibacterial activities follow the order of r-Cu2O > o-Cu2O > c-Cu2O, revealing the significant dependence of the antibacterial activities on the crystalline structures of Cu2O. Quenching experiments, as well as the NBT and DPD experiments indicate that ≡CuII─OO• superoxo and ≡CuII─OOH peroxo, instead of •OH, O2•-, and H2O2, are the primary oxidizing species in the oxidative damage to E. coli. Raman analysis further confirms the presence of both ≡CuII─OO• superoxo and ≡CuII─OOH peroxo on the surface of r-Cu2O. On the other hand, the NCP experiment reveals that Cu+, instead of Cu2+, also contributes to the antibacterial process. This study provides new insight into the antibacterial mechanisms of Cu2O.

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