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1.
Clin Respir J ; 18(5): e13771, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38747117

RESUMEN

BACKGROUND: Hypertension is a main contributing factor of cardiovascular diseases; deregulated circular RNAs are involved in the pathogenesis of pulmonary arterial hypertension (PAH). Herein, we evaluated the function and mechanism of circST6GAL1 in PAH process. METHODS: Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic environment for functional analysis. The cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, and flow cytometry assays were used to investigate cell proliferation, migration, and apoptosis. qRT-PCR and Western blotting analyses were used for level measurement of genes and proteins. The binding between miR-509-5p and circST6GAL1 or multiple C2 and transmembrane domain containing 2 (MCTP2) was analyzed by dual-luciferase reporter, RNA immunoprecipitation, and pull-down assays. The monocrotaline (MCT)-induced PAH mouse models were established for in vivo assay. RESULTS: CircST6GAL1 was highly expressed in PAH patients and hypoxia-induced HPASMCs. Functionally, circST6GAL1 deficiency reversed hypoxia-induced proliferation and migration, as well as apoptosis arrest in HPASMCs. Mechanistically, circST6GAL1 directly targeted miR-509-5p, and MCTP2 was a target of miR-509-5p. Rescue assays showed that the regulatory effects of circST6GAL1 deficiency on hypoxia-induced HPASMCs were abolished. Moreover, forced expression of miR-509-5p suppressed HPASMC proliferation and migration and induced cell apoptosis under hypoxia stimulation, while these effects were abolished by MCTP2 overexpression. Moreover, circST6GAL1 silencing improved MCT-induced pulmonary vascular remodeling and PAH. CONCLUSION: CircST6GAL1 deficiency reversed hypoxia-induced proliferation and migration, as well as apoptosis arrest in HPASMCs, and alleviated pulmonary vascular remodeling in MCT-induced PAH mouse models through the miR-509-5p/MCTP2 axis, indicating a potential therapeutic target for PAH.


Asunto(s)
Apoptosis , Proliferación Celular , MicroARNs , Hipertensión Arterial Pulmonar , ARN Circular , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Ratones , Animales , ARN Circular/genética , ARN Circular/metabolismo , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/genética , Hipertensión Arterial Pulmonar/patología , Modelos Animales de Enfermedad , Miocitos del Músculo Liso/metabolismo , Masculino , Movimiento Celular/genética , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Células Cultivadas , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/patología
2.
ACS Pharmacol Transl Sci ; 7(5): 1335-1347, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38751628

RESUMEN

Prostate-specific membrane antigen (PSMA), a well-established biological marker for prostate cancer (PCa) imaging and therapy, is overexpressed on the surface of prostate cancer lesions. In this study, a triazole ring was introduced into the linker by click chemistry to generate a HYNIC-derived ligand (T), which exhibited good PSMA affinity (Ki = 2.23 nM). Eight stable 99mTc-labeled complexes, [99mTc]Tc-T-Mn (n = 1-8), with hydrophilic properties were synthesized by incorporating different coligands at high radiochemical yields and purities without purification. The radioligands were concentrated in the kidneys of healthy Kunming male mice and were significantly blocked by the PSMA inhibitor ZJ-43. The uptake of the optimized complex [99mTc]Tc-T-M2 was correlated with PSMA, and it had good PSMA affinity (Kd = 5.42 nM). [99mTc]Tc-T-M2 accumulated on LNCaP (PSMA++) tumors and was significantly blocked by ZJ-43 at 2 h p.i., indicating high PSMA specificity. Relatively suitable kidney uptake was beneficial for reducing kidneys exposure in patients. SPECT/CT imaging of [99mTc]Tc-T-M2 in LNCaP (PSMA++) or 22Rv1 (PSMA+) tumor-bearing mice revealed high tumor uptake, low background uptake (especially low kidney uptake (49.06 ± 9.20 %ID/g) at 2 h p.i.), and obvious inhibition by ZJ-43, whereas PC-3 (PSMA-) tumors were undetectable. A freeze-dried [99mTc]Tc-T-M2 kit was successfully developed (T-M2 kit). Preliminary clinical trials showed that [99mTc]Tc-T-M2 clearly identified small prostate cancer lesions and has potential for clinical application.

3.
Plant Cell Environ ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38752443

RESUMEN

Bamboo cultivation, particularly Moso bamboo (Phyllostachys edulis), holds significant economic importance in various regions worldwide. Bamboo shoot degradation (BSD) severely affects productivity and economic viability. However, despite its agricultural consequences, the molecular mechanisms underlying BSD remain unclear. Consequently, we explored the dynamic changes of BSD through anatomy, physiology and the transcriptome. Our findings reveal ruptured protoxylem cells, reduced cell wall thickness and the accumulation of sucrose and reactive oxygen species (ROS) during BSD. Transcriptomic analysis underscored the importance of genes related to plant hormone signal transduction, sugar metabolism and ROS homoeostasis in this process. Furthermore, BSD appears to be driven by the coexpression regulatory network of senescence-associated gene transcription factors (SAG-TFs), specifically PeSAG39, PeWRKY22 and PeWRKY75, primarily located in the protoxylem of vascular bundles. Yeast one-hybrid and dual-luciferase assays demonstrated that PeWRKY22 and PeWRKY75 activate PeSAG39 expression by binding to its promoter. This study advanced our understanding of the molecular regulatory mechanisms governing BSD, offering a valuable reference for enhancing Moso bamboo forest productivity.

4.
Photodiagnosis Photodyn Ther ; : 104093, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38641030

RESUMEN

BACKGROUND: Dermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. METHODS: This study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. RESULTS: 5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. CONCLUSIONS: The findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence.

5.
J Asthma Allergy ; 17: 391-397, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38681237

RESUMEN

Objective: This study aimed to explore whether saliva pepsin concentration (SPC) could be regarded as a risk factor for the occurrence and unfavorable control of asthma in children with allergic rhinitis. Methods: A prospective study was conducted on a group of 20 consecutive children newly diagnosed with allergic rhinitis and asthma (referred to as the asthma group). All these children underwent fractional exhaled nitric oxide (FeNO) measurement, lung function tests, and assessment of asthma control using the 7-item Childhood Asthma Control Test (C-ACT) score. Simultaneously, a control group consisting of 20 children with simple allergic rhinitis, matched for baseline characteristics, was included. SPC measurement was performed in the two groups. Results: The SPC value was significantly higher in the asthma group than that in the control group (165.0 ± 82.8 ng/mL vs 68.4 ± 34.5 ng/mL) (P < 0.001). In the asthma group, SPC was independently associated with FeNO, the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), and forced expiratory flow at 50% and 75% of FVC (FEF50 and FEF75) (all P < 0.05). The severity of nasal symptoms evaluated by the visual analogue scale (N-VAS) was independently associated with FEF75, the maximal mid-expiratory flow (MMEF), and C-ACT score (P < 0.05). Conclusion: Direct pepsin exposure and uncontrolled nasal symptoms may play crucial roles in the pathogenesis and progression of childhood allergic asthma. The SPC value can be considered as a risk factor for asthma in children with allergic rhinitis.

6.
Medicine (Baltimore) ; 103(16): e37831, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38640322

RESUMEN

Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is still unclear. The OSCC datasets GSE74530 and GSE85195 configuration files were downloaded from the Gene Expression Omnibus (GEO) database and were derived from platforms GPL570 and GPL6480. Differentially expressed genes (DEGs) were screened. The weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEGs. A total of 1756 DEGs were identified. According to Gene Ontology (GO) analysis, they were predominantly enriched in processes related to organic acid catabolic metabolism, centromeric, and chromosomal region condensation, and oxidoreductase activity. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DEGs were mainly concentrated in metabolic pathways, P53 signaling pathway, and PPAR signaling pathway. Weighted gene co-expression network analysis was performed with a soft-thresholding power set at 9, leading to the identification of 6 core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1). The gene expression heatmap revealed that core genes (CDK1, CCNA2) were highly expressed in OSCC samples. Comparative Toxicogenomics Database analysis demonstrated associations between the 6 genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) and oral tumors, precancerous lesions, inflammation, immune system disorders, and tongue tumors. The associated miRNAs for CDK1 gene were hsa-miR-203a-3p.2, while for CCNA2 gene, they were hsa-miR-6766-3p, hsa-miR-4782-3p, and hsa-miR-219a-5p. CDK1 and CCNA2 are highly expressed in OSCC. The higher the expression of CDK1 and CCNA2, the worse the prognosis.


Asunto(s)
Proteína Quinasa CDC2 , Carcinoma de Células Escamosas , Ciclina A2 , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proteína Quinasa CDC2/genética , Proteína Quinasa CDC2/metabolismo , Biología Computacional , Ciclina A2/genética , Ciclina A2/metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética , Redes Reguladoras de Genes , Neoplasias de Cabeza y Cuello/genética , MicroARNs/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología
7.
Sci Rep ; 14(1): 8057, 2024 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580650

RESUMEN

The potential of adverse events (AEs) after thoracic endovascular aortic repair (TEVAR) in patients with type B aortic dissection (TBAD) has been reported. To avoid the occurrence of AEs, it is important to recognize high-risk population for prevention in advance. The data of 261 patients with TBAD who received TEVAR between June 2017 and June 2021 at our medical center were retrospectively reviewed. After the implementation of exclusion criteria, 172 patients were finally included, and after 2.8 years (range from 1 day to 5.8 years) of follow up, they were divided into AEs (n = 41) and non-AEs (n = 131) groups. We identified the predictors of AEs, and a prediction model was constructed to calculate the specific risk of postoperative AEs at 1, 2, and 3 years, and to stratify patients into high-risk (n = 78) and low-risk (n = 94) group. The prediction model included seven predictors: Age > 75 years, Lower extremity malperfusion (LEM), NT-proBNP > 330 pg/ml, None distal tear, the ratio between the diameter of the ascending aorta and descending aorta (A/D ratio) > 1.2, the ratio of the area of the false lumen to the total aorta (FL ratio) > 64%, and acute TEVAR, which exhibited excellent predictive accuracy performance and discriminatory ability with C statistic of 82.3% (95% CI 77.3-89.2%). The prediction model was contributed to identify high-risk patients of postoperative AEs, which may serve to achievement of personalized treatment and follow-up plans for patients.


Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Anciano , Reparación Endovascular de Aneurismas , Implantación de Prótesis Vascular/efectos adversos , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/etiología , Estudios Retrospectivos , Procedimientos Endovasculares/efectos adversos , Resultado del Tratamiento , Factores de Tiempo , Aorta Torácica/cirugía , Disección Aórtica/cirugía , Factores de Riesgo
8.
Angew Chem Int Ed Engl ; 63(17): e202316907, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38436539

RESUMEN

The efficient ethanol electrosynthesis from CO2 is challenging with low selectivity at high CO2 electrolysis rates, due to the competition with H2 and other reduction products. Copper-based bimetallic electrocatalysts are potential candidates for the CO2-to-ethanol conversion, but the secondary metal has mainly been focused on active components (such as Ag, Sn) for CO2 electroreduction, which also promote selectivity of ethylene or other reduction products rather than ethanol. Limited attention has been given to alkali-earth metals due to their inherently active chemical property. Herein, we rationally synthesized a (111) facet-oriented nano Cu2Mg (designated as Cu2Mg(111)) intermetallic compound with high-density ordered Cu3-Mg sites. The in situ Raman spectroscopy and density function theory calculations revealed that the Cu3 - δ $_{^{\rm{{\rm \delta} }} }$ --Mg- δ $_{^{\rm{{\rm \delta} }} }$ + active sites allowed to increase *CO surface coverage, decrease reaction energy for *CO-CO coupling, and stabilize *CHCHOH intermediates, thus promoting the ethanol formation pathway. The Cu2Mg(111) catalyst exhibited a high FEC2H5OH of 76.2±4.8 % at 600 mA⋅cm-2, and a peak value of |jC2H5OH| of 720±34 mA⋅cm-2, almost 4 times of that using conventional Cu2Mg with (311) facets, comparable to the best reported values for the CO2-to-ethanol electroreduction.

9.
Sci Total Environ ; 924: 171581, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38461973

RESUMEN

Nitrogen (N) fertilization is crucial for maintaining plant productivity. Clonal plants can share resources between connected ramets through clonal integration influencing microbial communities and regulating soil biogeochemical cycling, especially in the rhizosphere. However, the effect of various N fertilization practices on microbial communities in the rhizosphere of clonal ramets remain unknown. In this study, clonal fragments of Moso bamboo (Phyllostachys edulis), consisting of a parent ramet, an offspring ramet, and an interconnecting rhizome, were established in the field. NH4NO3 solution was applied to the parent, offspring ramets or rhizomes to investigate the effect of fertilization practices on the structure and function of rhizosphere microbial communities. The differences in N availability, microbial biomass and community composition, and abundance of nitrifying genes among rhizosphere soils of ramets gradually decreased during the rapid growth of Moso bamboo, irrespective of fertilization practice. The soil N availability variation, particularly in NO3-, caused by fertilization practices altered the rhizosphere microbial community. Soil N availability and stable microbial biomass N in parent fertilization were the highest, being 9.0 % and 18.7 %, as well as 60.8 % and 90.4 % higher than rhizome and offspring fertilizations, respectively. The microbial network nodes and links in rhizome fertilization were 1.8 and 7.5 times higher than in parent and offspring fertilization, respectively. However, the diversity of bacterial community and abundance of nitrifying and denitrifying genes were the highest in offspring fertilization among three practices, which may be associated with increased N loss. Collectively, the rhizosphere microbial community characteristics depended on fertilization practices by altering the clonal integration of N in Moso bamboo. Parent and rhizome fertilization were favorable for N retention in plant-soil system and resulted in more stable microbial functions than offspring fertilization. Our findings provide new insights into precision fertilization for the sustainable Moso bamboo forest management.


Asunto(s)
Microbiota , Nitrógeno , Rizoma , Poaceae , Microbiología del Suelo , Suelo , Fertilización
10.
Small ; : e2309568, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38461520

RESUMEN

Wounds in harsh environments can face long-term inflammation and persistent infection, which can slow healing. Wound spray is a product that can be rapidly applied to large and irregularly dynamic wounds, and can quickly form a protective film in situ to inhibit external environmental infection. In this study, a biodegradable A and B combined multi-functional spray hydrogel is developed with methacrylate-modified chitosan (CSMA1st ) and ferulic acid (FA) as type A raw materials and oxidized Bletilla striata polysaccharide (OBSP) as type B raw materials. The precursor CSMA1st -FA/OBSP (CSOB-FA1st ) hydrogel is formed by the self-cross-linking of dynamic Schiff base bonds, the CSMA-FA/OBSP (CSOB-FA) hydrogel is formed quickly after UV-vis light, so that the hydrogel fits with the wound. Rapid spraying and curing provide sufficient flexibility and rapidity for wounds and the hydrogel has good injectability, adhesive, and mechanical strength. In rats and miniature pigs, the A and B combined spray hydrogel can shrink wounds and promote healing of infected wounds, and promote the enrichment of fibrocyte populations. Therefore, the multifunctional spray hydrogel combined with A and B can protect irregular dynamic wounds, prevent wound infection and secondary injury, and be used for safe and effective wound treatment, which has a good prospect for development.

11.
Nature ; 627(8002): 101-107, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38418886

RESUMEN

Li-ion batteries (LIBs) for electric vehicles and aviation demand high energy density, fast charging and a wide operating temperature range, which are virtually impossible because they require electrolytes to simultaneously have high ionic conductivity, low solvation energy and low melting point and form an anion-derived inorganic interphase1-5. Here we report guidelines for designing such electrolytes by using small-sized solvents with low solvation energy. The tiny solvent in the secondary solvation sheath pulls out the Li+ in the primary solvation sheath to form a fast ion-conduction ligand channel to enhance Li+ transport, while the small-sized solvent with low solvation energy also allows the anion to enter the first Li+ solvation shell to form an inorganic-rich interphase. The electrolyte-design concept is demonstrated by using fluoroacetonitrile (FAN) solvent. The electrolyte of 1.3 M lithium bis(fluorosulfonyl)imide (LiFSI) in FAN exhibits ultrahigh ionic conductivity of 40.3 mS cm-1 at 25 °C and 11.9 mS cm-1 even at -70 °C, thus enabling 4.5-V graphite||LiNi0.8Mn0.1Co0.1O2 pouch cells (1.2 Ah, 2.85 mAh cm-2) to achieve high reversibility (0.62 Ah) when the cells are charged and discharged even at -65 °C. The electrolyte with small-sized solvents enables LIBs to simultaneously achieve high energy density, fast charging and a wide operating temperature range, which is unattainable for the current electrolyte design but is highly desired for extreme LIBs. This mechanism is generalizable and can be expanded to other metal-ion battery electrolytes.

12.
J Med Chem ; 67(4): 3190-3202, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38320123

RESUMEN

Fibroblast activation protein (FAP), which is expressed on the cell membranes of fibroblasts in most solid tumors, has become an important target for tumor diagnosis and treatment. However, previously reported 99mTc-labeled FAPI-04 complexes have high blood uptake, limiting their use in the clinic. In this work, six 99mTc-labeled FAPI-46 derivatives with different linkers (different amino acids, peptides, or polyethylene glycol) were prepared and evaluated. They had good in vitro stability, hydrophilicity, and good specificity for FAP. The biodistribution and MicroSPECT images revealed that they all had high specific tumor uptake for FAP, and their blood uptake was significantly decreased. Among them, [99mTc]Tc-6-1 exhibited the highest target-to-nontarget ratios (tumor/blood: 6.06 ± 1.19; tumor/muscle: 10.26 ± 0.44) and good tumor uptake (16.15 ± 0.83%ID/g), which also had significantly high affinity for FAP, good in vivo stability, and safety. Therefore, [99mTc]Tc-6-1 holds great potential as a promising molecular tracer for FAP tumor imaging.


Asunto(s)
Quinolinas , Transporte Biológico , Línea Celular Tumoral , Radiofármacos/química , Distribución Tisular , Tecnecio/química
13.
Photodiagnosis Photodyn Ther ; 45: 103979, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38242189

RESUMEN

BACKGROUND: Keloids are aggressive fibroproliferative disorders that cause aesthetic and functional damage. Photodynamic therapy (PDT) has shown promise as a novel treatment for keloids. However, the limited penetration of 5-aminolevulinic acid (ALA) and unsatisfactory outcomes in dense scars hinder its effectiveness as a monotherapy. The objective of this study is to assess the efficacy and safety of fractional CO2 laser followed by 5-ALA PDT for keloids. METHODS: A total of 12 patients with keloid were included in our study. Each lesion was pretreated by fractional CO2 laser with 26-28 W to create microthermal zones. After topical application of 5-ALA solution, an irradiation of 635 nm red light with 120 J/cm2 was performed. The treatment was repeated at least every 2 weeks. Efficacy and safety were evaluated using the Vancouver Scar Scale (VSS), the Visual Analogue Scale (VAS) for keloid-related symptoms and documentation of postoperative complications. Statistical analysis was performed to compare VSS and keloid-related symptom VAS scores of the baseline and final treatment sessions. RESULTS: The final treatment resulted in a statistically significant decrease in all parameters of VSS and VAS for pruritus and pain compared to the baseline. Except for postoperative hyperpigmentation, no infections, scar aggravation, or recurrence were observed during at least 6 months of follow-up. Overall, patients expressed a high level of satisfaction with the treatment outcome. CONCLUSIONS: Fractional CO2 laser followed by 5-ALA PDT is a promising method for treating keloids. However, its synergetic effects need to be validated through clinical trials involving larger patient cohorts.


Asunto(s)
Queloide , Láseres de Gas , Fotoquimioterapia , Humanos , Queloide/tratamiento farmacológico , Ácido Aminolevulínico/uso terapéutico , Dióxido de Carbono , Láseres de Gas/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos
14.
Int J Mol Sci ; 25(2)2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38256119

RESUMEN

To develop a novel 99mTc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5-9) with different carbon linkers were designed, synthesized and radiolabeled with the [99mTc]Tc(I)+ core, [99mTc][Tc(I)(CO)3(H2O)3]+ core and [99mTc][Tc(V)N]2+ core. All the complexes are hydrophilic, maintain good stability and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [99mTc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio. SPECT imaging study of [99mTc]Tc-CN5UBI 29-41 in bacterial infection mice showed that there was a clear accumulation in the infection site, suggesting that this radiotracer could be a potential radiotracer for bacterial infection imaging.


Asunto(s)
Proteínas Ribosómicas , Infecciones Estafilocócicas , Animales , Ratones , Distribución Tisular , Infecciones Estafilocócicas/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Cianuros , Inflamación/diagnóstico por imagen
15.
Int J Biol Macromol ; 254(Pt 1): 127761, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38287598

RESUMEN

Ulcerative colitis (UC) is a chronic disease with diffuse mucosal inflammation limited to the colon. A topical drug delivery system that could be facilely performed and efficiently retained at colon are attractive for clinical ulcerative colitis treatment. Herein, a novel platform for rectal administration of thermosensitive hydrogel co-loaded with nanoparticles to treat ulcerative colitis was developed. Thiolated-hyaluronic acid was synthesized, and prepared nanoparticles with zein and Puerarin. And the Bletilla striata polysaccharide with colonic mucosa repair effect was oxidized, and mixed with chitosan and ß-sodium glycerophosphate to prepare thermosensitive hydrogel. Thermosensitive hydrogels were combined with nanoparticles to investigate their mucosal adhesion, retention, and permeability, as well as their therapeutic effects on ulcerative colitis. Thiolated-hyaluronic acid nanoparticles had good stability, and could be quickly converted into hydrogel at body temperature when combined with thermosensitive hydrogel. The nanoparticles-loaded thermosensitive hydrogel also was excellent at mucosal penetration, enhancing the retention time of drugs in colon, and effectively controlling drug release. In vivo ulcerative colitis treatment revealed that the nanoparticles-loaded hydrogel significantly repaired the colonic mucosa and inhibit colonic inflammation. Therefore, the thermosensitive hydrogel co-loaded nanoparticles will have a promising application in effective treatment of ulcerative colitis by topical administration.


Asunto(s)
Quitosano , Colitis Ulcerosa , Nanopartículas , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Quitosano/uso terapéutico , Hidrogeles/uso terapéutico , Ácido Hialurónico/uso terapéutico , Sistemas de Liberación de Medicamentos , Polisacáridos/uso terapéutico , Inflamación/tratamiento farmacológico
16.
Artículo en Inglés | MEDLINE | ID: mdl-38265907

RESUMEN

In our daily lives, people frequently consider daily schedule to meet their needs, such as going to a barbershop for a haircut, then eating in a restaurant, and finally shopping in a supermarket. Reasonable activity location or point-of-interest (POI) and activity sequencing will help people save a lot of time and get better services. In this article, we propose a reinforcement learning-based deep activity factor balancing model to recommend a reasonable daily schedule according to user's current location and needs. The proposed model consists of a deep activity factor balancing network (DAFB) and a reinforcement learning framework. First, the DAFB is proposed to fuse multiple factors that affect daily schedule recommendation (DSR). Then, a reinforcement learning framework based on policy gradient is used to learn the parameters of the DAFB. Further, on the feature storage based on the matrix method, we compress the feature storage space of the candidate POIs. Finally, the proposed method is compared with seven benchmark methods using two real-world datasets. Experimental results show that the proposed method is adaptive and effective.

17.
Int J Biol Macromol ; 254(Pt 3): 128015, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37951426

RESUMEN

Bletilla striata polysaccharide (BSP) is a naturally occurring polysaccharide that demonstrates notable biocompatibility and biodegradability. Additionally, BSP possesses therapeutic attributes, including anti-inflammatory and reparative actions. Herein, we report a novel BSP hydrogel prepared using 1,4-butanediol diglycidyl ether (BDDE) as a cross-linking agent. The hydrogel was synthesized via condensation of the hydroxyl group in the BSP molecule with the epoxy group in BDDE. This technique of preparation preserves BSP's natural properties while avoiding any potentially hazardous or adverse effects that may occur during the chemical alteration. Compared with BSP before crosslinking, BSP hydrogel has distinct advantages, such as a three-dimensional network structure, improved water retention, enhanced swelling capacity, greater thermal stability, and superior mechanical properties. Experiments on in vitro cytotoxicity, hemolysis, and degradation revealed that BSP hydrogel had good biocompatibility and biodegradability. Finally, we evaluated the in vivo wound repair effect of BSP hydrogel, and the results showed that BSP hydrogel had a significant wound-healing effect. Furthermore, the BSP hydrogel promoted the polarization of M1-type macrophages towards the M2-type and reduced the inflammatory response during the wound healing phase. Because of its ease of production, safety, efficacy, and environmental friendliness, BSP hydrogel is considered a highly promising material for wound dressings.


Asunto(s)
Hidrogeles , Compuestos Orgánicos , Hidrogeles/farmacología , Compuestos Orgánicos/farmacología , Polisacáridos/química , Cicatrización de Heridas
18.
Small ; 20(15): e2308004, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37992242

RESUMEN

In the electrochemical CO2 reduction reaction (CO2RR), the coverages of *CO and *H intermediates on a catalyst surface are critical for the selective generation of C1 or C2 products. In this work, we have synthesized several CuxZnyMnz ternary alloy electrocatalysts, including Cu8ZnMn, Cu8Zn6Mn, and Cu8ZnMn2, by varying the doping compositions of Zn and Mn, which are efficient in binding *CO and *H adsorbates in the CO2 electroreduction process, respectively. The increase of *H coverage allows to promotion of the CH4 and H2 formation, while the increase of the *CO coverage facilitates the production of C2H4 and CO. As a result, the Cu8ZnMn catalyst presented a high CO2-to-CH4 partial current density (-418 ± 22 mA cm-2) with a Faradaic efficiency of 55 ± 2.8%, while the Cu8Zn6Mn catalyst exhibited a CO2-to-C2H4 partial current density (-440 ± 41 mA cm-2) with a Faradaic efficiency of 58 ± 4.5%. The study suggests a useful strategy for rational design and fabrication of Cu electrocatalysts with different doping for tailoring the reduction products.

19.
J Environ Sci (China) ; 138: 585-596, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38135422

RESUMEN

We developed a single-particle optical particle counter with polarization detection (SOPC) for the real-time measurement of the optical size and depolarization ratio (defined as the ratio of the vertical component to the parallel component of backward scattering) of atmospheric particles, the polarization ratio (DR) value can reflect the irregularity of the particles. The SOPC can detect aerosol particles with size larger than 500 nm and the maximum particle count rate reaches ∼1.8 × 105 particles per liter. The SOPC uses a modulated polarization laser to measure the optical size of particles according to forward scattering signal and the DR value of the particles by backward S and P signal components. The sampling rate of the SOPC was 106 #/(sec·channel), and all the raw data were processed online. The calibration curve was obtained by polystyrene latex spheres with sizes of 0.5-10 µm, and the average relative deviation of measurement was 3.96% for sub 3 µm particles. T-matrix method calculations showed that the DR value of backscatter light at 120° could describe the variations in the aspect ratio of particles in the above size range. We performed insitu observations for the evaluation of the SOPC, the mass concentration constructed by the SOPC showed good agreement with the PM2.5 measurements in a nearby state-controlled monitoring site. This instrument could provide useful data for source appointment and regulations against air pollution.


Asunto(s)
Contaminación del Aire , Monitoreo del Ambiente , Monitoreo del Ambiente/métodos , Tamaño de la Partícula , Luz , Microesferas
20.
Int J Nanomedicine ; 18: 7759-7784, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38144510

RESUMEN

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation, eventually leading to severe disability and premature death. At present, the treatment of RA is mainly to reduce inflammation, swelling, and pain. Commonly used drugs are non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs). These drugs lack specificity and require long-term, high-dose administration, which can cause serious adverse effects. In addition, the oral, intravenous, and intra-articular injections will reduce patient compliance, resulting in high cost and low bioavailability. Due to these limitations, microneedles (MNs) have emerged as a new strategy to efficiently localize the drugs in inflamed joints for the treatment of RA. MNs can overcome the cuticle barrier of the skin without stimulating nerves and blood vessels. Which can increase patient compliance, improve bioavailability, and avoid systemic circulation. This review summarizes and evaluates the application of MNs in RA, especially dissolving MNs (DMNs). We encourage the use of MNs to treat RA, by describing the general properties of MNs, materials, preparation technology, drug release mechanism, and advantages. Furthermore, we discussed the biological safety, development prospects, and future challenges of MNs, hoping to provide a new strategy for the treatment of RA.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Humanos , Administración Cutánea , Piel , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Inflamación/tratamiento farmacológico , Sistemas de Liberación de Medicamentos
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