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1.
Trends Plant Sci ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38692971

RESUMO

The predominant genetic defense mechanism against soybean cyst nematode (SCN) in 95% of the North America market is under threat by virulent SCN populations. Usovsky et al. identified GmSNAP02 as an SCN susceptibility gene through fine-mapping of unique bi-parental populations. Loss-of-function of GmSNAP02 confers enhanced resistance to more virulent SCN.

2.
Adv Sci (Weinh) ; : e2403227, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704731

RESUMO

To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before the cartilage damage can be repaired; this cannot be achieved with a single type of extracellular vesicles (EVs). Here, a hydrogel complex with logic-gates function is proposed that can spatiotemporally controlled release two types of EVs: interleukin 10 (IL-10)+ EVs to promote M2 polarization of macrophage, and SRY-box transcription factor 9 (SOX9)+ EVs to increase cartilage matrix synthesis. Following dose-of-action screening, the dual EVs are loaded into a matrix metalloporoteinase 13 (MMP13)-sensitive self-assembled peptide hydrogel (KM13E) and polyethylene glycol diacrylate/gelatin methacryloyl-hydrogel microspheres (PGE), respectively. These materials are mixed to form a "microspheres-in-gel" KM13E@PGE system. In vitro, KM13E@PGE abruptly released IL-10+ EVs after 3 days and slowly released SOX9+ EVs for more than 30 days. In vivo, KM13E@PGE increased the CD206+ M2 macrophage proportion in the synovial tissue and decreased the tumor necrosis factor-α and IL-1ß levels. The aggrecan and SOX9 expressions in the cartilage tissues are significantly elevated following inflammation subsidence. This performance is not achieved using anti-inflammatory or cartilage repair therapy alone. The present study provides an injectable, integrated delivery system with spatiotemporal control release of dual EVs, and may inspire logic-gates strategies for OA treatment.

3.
Neuroimage ; 294: 120640, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38719154

RESUMO

Attentional control, guided by top-down processes, enables selective focus on pertinent information, while habituation, influenced by bottom-up factors and prior experiences, shapes cognitive responses by emphasizing stimulus relevance. These two fundamental processes collaborate to regulate cognitive behavior, with the prefrontal cortex and its subregions playing a pivotal role. Nevertheless, the intricate neural mechanisms underlying the interaction between attentional control and habituation are still a subject of ongoing exploration. To our knowledge, there is a dearth of comprehensive studies on the functional connectivity between subsystems within the prefrontal cortex during attentional control processes in both primates and humans. Utilizing stereo-electroencephalogram (SEEG) recordings during the Stroop task, we observed top-down dominance effects and corresponding connectivity patterns among the orbitofrontal cortex (OFC), the middle frontal gyrus (MFG), and the inferior frontal gyrus (IFG) during heightened attentional control. These findings highlighting the involvement of OFC in habituation through top-down attention. Our study unveils unique connectivity profiles, shedding light on the neural interplay between top-down and bottom-up attentional control processes, shaping goal-directed attention.


Assuntos
Atenção , Eletroencefalografia , Habituação Psicofisiológica , Córtex Pré-Frontal , Humanos , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Atenção/fisiologia , Masculino , Feminino , Eletroencefalografia/métodos , Habituação Psicofisiológica/fisiologia , Adulto , Adulto Jovem , Teste de Stroop
4.
Adv Sci (Weinh) ; : e2310066, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38634211

RESUMO

Simple, sensitive, and accurate molecular diagnostics are critical for preventing rapid spread of infection and initiating early treatment of diseases. However, current molecular detection methods typically rely on extensive nucleic acid sample preparation and expensive instrumentation. Here, a simple, fully integrated, lab-in-a-magnetofluidic tube (LIAMT) platform is presented for "sample-to-result" molecular detection of virus. By leveraging magnetofluidic transport of micro/nano magnetic beads, the LIAMT device integrates viral lysis, nucleic acid extraction, isothermal amplification, and CRISPR detection within a single engineered microcentrifuge tube. To enable point-of-care molecular diagnostics, a palm-sized processor is developed for magnetofluidic separation, nucleic acid amplification, and visual fluorescence detection. The LIAMT platform is applied to detect SARS-CoV-2 and HIV viruses, achieving a detection sensitivity of 73.4 and 63.9 copies µL-1, respectively. Its clinical utility is further demonstrated by detecting SARS-CoV-2 and HIV in clinical samples. This simple, affordable, and portable LIAMT platform holds promise for rapid and sensitive molecular diagnostics of infectious diseases at the point-of-care.

5.
Angew Chem Int Ed Engl ; 63(20): e202403123, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38516796

RESUMO

The CRISPR-Cas12a system has emerged as a powerful tool for next-generation nucleic acid-based molecular diagnostics. However, it has long been believed to be effective only on DNA targets. Here, we investigate the intrinsic RNA-enabled trans-cleavage activity of AsCas12a and LbCas12a and discover that they can be directly activated by full-size RNA targets, although LbCas12a exhibits weaker trans-cleavage activity than AsCas12a on both single-stranded DNA and RNA substrates. Remarkably, we find that the RNA-activated Cas12a possesses higher specificity in recognizing mutated target sequences compared to DNA activation. Based on these findings, we develop the "Universal Nuclease for Identification of Virus Empowered by RNA-Sensing" (UNIVERSE) assay for nucleic acid testing. We incorporate a T7 transcription step into this assay, thereby eliminating the requirement for a protospacer adjacent motif (PAM) sequence in the target. Additionally, we successfully detect multiple PAM-less targets in HIV clinical samples that are undetectable by the conventional Cas12a assay based on double-stranded DNA activation, demonstrating unrestricted target selection with the UNIVERSE assay. We further validate the clinical utility of the UNIVERSE assay by testing both HIV RNA and HPV 16 DNA in clinical samples. We envision that the intrinsic RNA targeting capability may bring a paradigm shift in Cas12a-based nucleic acid detection and further enhance the understanding of CRISPR-Cas biochemistry.


Assuntos
Proteínas Associadas a CRISPR , Sistemas CRISPR-Cas , RNA , Humanos , Proteínas Associadas a CRISPR/metabolismo , Proteínas Associadas a CRISPR/genética , Sistemas CRISPR-Cas/genética , Desoxirribonucleases/metabolismo , Endodesoxirribonucleases/metabolismo , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/química , RNA/metabolismo , RNA/química , RNA/genética
6.
Sci Total Environ ; 912: 168736, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-37996034

RESUMO

There is growing evidence that the interactions between sulfur dioxide (SO2) and organic peroxides (POs) in aerosol and clouds play an important role in atmospheric sulfate formation and aerosol aging, yet the reactivity of POs arising from anthropogenic precursors toward SO2 remains unknown. In this study, we investigate the multiphase reactions of SO2 with secondary organic aerosol (SOA) formed from the photooxidation of toluene, a major type of anthropogenic SOA in the atmosphere. The reactive uptake coefficient of SO2 on toluene SOA was determined to be on the order of 10-4, depending strikingly on aerosol water content. POs contribute significantly to the multiphase reactivity of toluene SOA, but they can only explain a portion of the measured SO2 uptake, suggesting the presence of other reactive species in SOA that also contribute to the particle reactivity toward SO2. The second-order reaction rate constant (kII) between S(IV) and toluene-derived POs was estimated to be in the range of the kII values previously reported for commercially available POs (e.g., 2-butanone peroxide and 2-tert-butyl hydroperoxide) and the smallest (C1-C2) and biogenic POs. In addition, unlike commercial POs that can efficiently convert S(IV) into both inorganic sulfate and organosulfates, toluene-derived POs appear to mainly oxidize S(IV) to inorganic sulfate. Our study reveals the multiphase reactivity of typical anthropogenic SOA and POs toward SO2 and will help to develop a better understanding of the formation and evolution of atmospheric secondary aerosol.

7.
Biomedicines ; 11(12)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38137541

RESUMO

(1) Background: Diabetic cardiomyopathy (DCM) is a unique form of cardiomyopathy that develops as a consequence of diabetes and significantly contributes to heart failure in patients. Esaxerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has demonstrated potential in reducing the incidence of cardiovascular and renal events in individuals with chronic kidney and diabetes disease. However, the exact protective effects of esaxerenone in the context of DCM are still unclear. (2) Methods: The DCM model was successfully induced in mice by administering streptozotocin (55 mg/kg per day) for five consecutive days. After being fed a normal diet for 16 weeks, echocardiography was performed to confirm the successful establishment of the DCM model. Subsequent sequencing and gene expression analysis revealed significant differences in gene expression in the DCM group. These differentially expressed genes were identified as potential targets for DCM. By utilizing the Swiss Target Prediction platform, we employed predictive analysis to identify the potential targets of esaxerenone. A protein-protein-interaction (PPI) network was constructed using the common targets of esaxerenone and DCM. Enrichment analysis was conducted using Metascape. (3) Results: Compared to the control, the diabetic group exhibited impaired cardiac function and myocardial fibrosis. There was a total of 36 common targets, with 5 key targets. Enrichment analysis revealed that the chemokine and PI3K-Akt signaling pathway was considered a crucial pathway. A target-pathway network was established, from which seven key targets were identified. All key targets exhibited good binding characteristics when interacting with esaxerenone. (4) Conclusion: The findings of this study suggest that esaxerenone exhibits a favorable therapeutic effect on DCM, primarily by modulating the chemokine and PI3K-Akt signaling pathway.

8.
Cell Biol Toxicol ; 39(6): 2551-2568, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37957486

RESUMO

BACKGROUND: The current study probed into how tumor cell-derived exosomes (Exos) mediated hsa_circ_0001739/lncRNA AC159540.1 to manipulate microRNA (miR)-218-5p/FTO-N6-methyladenosine (m6A)/MYC signal axis in liver metastasis in colorectal cancer (CRC). METHODS: hsa_circ_0001739 and lncRNA AC159540.1 were identified as the upstream regulator of miR-218-5p using ENCORI and LncBase databases. Expression patterns of miR-218-5p, hsa_circ_0001739, lncRNA AC159540.1, FTO, and MYC were detected, accompanied by loss-and-gain-of function assays to examine their effects on CRC cell biological functions. SW480 cells-derived Exos were purified, followed by in vitro studies to uncover the effect of hsa_circ_0001739/lncRNA AC159540. RESULTS: miR-218-5p was downregulated while hsa_circ_0001739/lncRNA AC159540.1 was upregulated in CRC tissues and cells. Silencing of hsa_circ_0001739/lncRNA AC159540.1 restrained the malignant phenotypes of CRC cells. Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 competitively inhibited miR-218-5p to elevate FTO and MYC. The inducing role of Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 in CRC was also validated in vivo. CONCLUSION: Conclusively, Exos-mediated circ_0001739/lncRNA AC159540.1 regulatory network is critical for CRC, offering a theoretical basis for CRC treatment.


Assuntos
Neoplasias Colorretais , Exossomos , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Exossomos/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Neoplasias Colorretais/genética , Proliferação de Células/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato
9.
Front Med (Lausanne) ; 10: 1206577, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37881631

RESUMO

Recently, the application of the amniotic membrane (AM) in ophthalmology is gradually expanding from the anterior to the posterior segment of the eye. Its characteristics of anti-inflammation, anti-bacterial, anti-vascularization, immune regulation, anti-fibrosis, pro-epithelialization, and so forth have made it a hot topic in ophthalmic research. AM has been confirmed to repair photoreceptors, restore normal retinal structures, and close the abnormal structures in the optic disc. Currently, the application areas mainly include retinal hole, retinal detachment, optic disc pit, retinal degenerative diseases, and choroidal hole. This article reviews the current literature applying AM transplantation in the treatment of various posterior segment diseases while comparing the clinical outcomes with other techniques.

10.
Environ Sci Technol ; 57(41): 15558-15570, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37797208

RESUMO

Organic peroxides (POs) are ubiquitous in the atmosphere and particularly reactive toward dissolved sulfur dioxide (SO2), yet the reaction kinetics between POs and SO2, especially in complex inorganic-organic mixed particles, remain poorly constrained. Here, we report the first investigation of the multiphase reactions between SO2 and POs in monoterpene-derived secondary organic aerosol internally mixed with different inorganic salts (ammonium sulfate, ammonium bisulfate, or sodium nitrate). We find that when the particles are phase-separated, the PO-S(IV) reactivity is consistent with that measured in pure SOA and depends markedly on the water content in the organic shell. However, when the organic and inorganic phases are miscible, the PO-S(IV) reactivity varies substantially among different aerosol systems, mainly driven by their distinct acidities (not by ionic strength). The second-order PO-S(IV) rate constant decreases monotonically from 5 × 105 to 75 M-1 s-1 in the pH range of 0.1-5.6. Both proton catalysis and general acid catalysis contribute to S(IV) oxidation, with their corresponding third-order rate constants determined to be (6.4 ± 0.7) × 106 and (6.9 ± 4.6) × 104 M-2 s-1 at pH 2-6, respectively. The measured kinetics imply that the PO-S(IV) reaction in aerosol is an important sulfate formation pathway, with the reaction kinetics dominated by general acid catalysis at pH > 3 under typical continental atmospheric conditions.


Assuntos
Peróxidos , Dióxido de Enxofre , Sulfatos/química , Atmosfera/química , Aerossóis
11.
Mol Plant ; 16(12): 1882-1884, 2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-37865821
12.
Biosens Bioelectron ; 242: 115751, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37839349

RESUMO

In the field of oil refining, the presence of excessive residual phosphorus in crude oil can significantly impact its quality, thereby emphasizing the necessity for compact and convenient testing equipment. This study primarily focuses on developing of self-powered biosensor (SPB) using immobilizing Choline Oxidase with a photoactive ternary nanocomposite complex (CHOx-BiOI-rGO-Fe3O4 NPs-ITO) as the anode and utilizing a Pt electrode as the cathode. The successful preparation of the ternary composite photoelectrode for the anode was confirmed through a range of characterization techniques, including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), N2 absorption/desorption, Dynamic light scattering (DLS), and Ultraviolet-visible diffuse reflection spectrometer (UV-vis DRS). The electrochemical and photoelectrochemical properties were assessed using an electrochemical workstation, revealing a significant enhancement photoelectrical responsiveness attributed to the formation of heterojunction structures. The SPB exhibited a remarkable linear relationship between the instantaneous photocurrent and phosphatidylcholine (PC) concentration, with a regression equation of I (µA) = 39.62071C (mM) + 3.47271. The linear range covered a concentration range of 0.01-10 mM, and the detection limit (S/N = 3) was determined to be 0.008 mM. It demonstrated excellent reproducibility and storage stability, positioning it a promising alternative to High-performance liquid chromatography (HPLC) for accurate quantification of PC content in rhodotorula glutinis oil. The standard recovery PC content ranged from 98.48% to 103.53%, with a relative standard deviation (RSD) ranging from 1.4% to 2.4%. This research presents a convenient and precise detection device that has the potential to address the issue of lagging detection in the oil refining process.


Assuntos
Técnicas Biossensoriais , Nanocompostos , Fosfolipídeos , Reprodutibilidade dos Testes , Técnicas Biossensoriais/métodos , Nanocompostos/química
13.
Materials (Basel) ; 16(19)2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37834667

RESUMO

CoCrNi alloys exhibit excellent strength and ductility. In this work, the CoCrNiV multi-principal alloy with single-phase fine grained (FG) structure was prepared by rolling and heat treatment. The characteristics of deformation microstructures and mechanical properties were systematically investigated by scanning electron microscope (SEM) and transmission electron microscope (TEM). The results indicate that the CoCrNiV alloy successfully attains a yield strength of 1060 MPa while maintaining a uniform elongation of 24.1%. The enhanced strength originates from FG structure and severe lattice distortion induced by V addition. Meanwhile, the exceptional ductility arises from the stable strain-hardening ability facilitated by dislocations and stacking faults. The deformation mechanisms and the optimization strategies for attaining both strength and ductility are thoroughly discussed.

14.
Sens Actuators B Chem ; 3902023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37303825

RESUMO

Alpha-fetoprotein (AFP) is an important protein biomarker of liver cancer, as its serum levels are highly correlated with the progression of disease. Conventional immunoassays for AFP detection rely on enzyme-linked immunosorbent assay analyses with expensive and bulky equipment. Here, we developed a simple, affordable, and portable CRISPR-powered personal glucose meter biosensing platform for quantitative detection of the AFP biomarker in serum samples. The biosensor takes advantage of the excellent affinity of aptamer to AFP and the collateral cleavage activity of CRISPR-Cas12a, enabling sensitive and specific CRISPR-powered protein biomarker detection. To enable point-of-care testing, we coupled invertase-catalyzed glucose production with the glucose biosensing technology to quantify AFP. Using the developed biosensing platform, we quantitatively detected AFP biomarker in spiked human serum samples with a detection sensitivity of down to 10 ng/mL. Further, we successfully applied the biosensor to detect AFP in clinical serum samples from patients with liver cancer, achieving comparable performance to the conventional assay. Therefore, this novel CRISPR-powered personal glucose meter biosensor provides a simple yet powerful alternative for detecting AFP and potentially other tumor biomarkers at the point of care.

15.
Water Res ; 239: 120061, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37201375

RESUMO

The widespread use of antibiotics has created an antibiotic resistance genes (ARGs)-enriched environment, which causes high risks on human and animal health. Although antibiotics can be partially adsorbed and degraded in wastewater treatment processes, striving for a complete understanding of the microbial adaptive mechanism to antibiotic stress remains urgent. Combined with metagenomics and metabolomics, this study revealed that anammox consortia could adapt to lincomycin by spontaneously changing the preference for metabolite utilization and establishing interactions with eukaryotes, such as Ascomycota and Basidiomycota. Specifically, quorum sensing (QS) based microbial regulation and the ARGs transfer mediated by clustered regularly interspaced short palindromic repeats (CRISPR) system and global regulatory genes were the principal adaptive strategies. Western blotting results validated that Cas9 and TrfA were mainly responsible for the alteration of ARGs transfer pathway. These findings highlight the potential adaptative mechanism of microbes to antibiotic stress and fill gaps in horizontal gene transfer pathways in the anammox process, further facilitating the ARGs control through molecular and synthetic biology techniques.


Assuntos
Sistemas CRISPR-Cas , Percepção de Quorum , Animais , Humanos , Lincomicina/farmacologia , Multiômica , Oxidação Anaeróbia da Amônia , Antibacterianos/farmacologia
16.
Anal Chim Acta ; 1262: 341258, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37179057

RESUMO

CRISPR technology has recently emerged as a powerful biosensing tool for sensitive and specific nucleic acid detection when coupled with isothermal amplification (e.g., recombinase polymerase amplification (RPA)). However, it remains a challenge to incorporate isothermal amplification into CRISPR detection in a one-pot system due to their poor compatibility. Here, we developed a simple CRISPR gel biosensing platform for human immunodeficiency virus (HIV) RNA detection by combining reverse transcription-recombinase polymerase amplification (RT-RPA) reaction solution with a CRISPR gel. In our CRISPR gel biosensing platform, CRISPR-Cas12a enzymes are embedded into the agarose gel, providing a spatially separated but connected reaction interface with the RT-RPA reaction solution. During isothermal incubation, the RT-RPA amplification occurs initially on the CRISPR gel. When RPA products are sufficiently amplified and reach the CRISPR gel, the CRISPR reaction occurs in the whole tube. With the CRISPR gel biosensing platform, we successfully detected down to 30 copies of HIV RNA per test within 30 min. Furthermore, we validated its clinical utility by detecting HIV clinical plasma samples, achieving superior performance compared with the real-time RT-PCR method. Thus, our one-pot CRISPR gel biosensing platform demonstrates great potential for rapid and sensitive molecular detection of HIV and other pathogens at the point of care.


Assuntos
Infecções por HIV , Transcrição Reversa , Humanos , Sensibilidade e Especificidade , RNA Viral/genética , Recombinases/genética , Infecções por HIV/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos
17.
Environ Sci Pollut Res Int ; 30(26): 69486-69498, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37140858

RESUMO

Liquid exfoliation of bulk g-C3N5 was applied to synthesize g-C3N5 nanosheets. In order to characterize the samples, X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectra (FT-IR), X-ray photoelectron spectra (XPS), UV-Vis absorption spectra (UV-Vis), and photoluminescence spectra (PL) were examined. g-C3N5 nanosheets exhibited enhanced performance in the inactivation of Escherichia coli (E. coli) with visible light irradiation relative to bulk g-C3N5 and promoted complete inactivation of E. coli within 120 min. h+ and •O2- were the principal reactive species in the antibacterial process. In the early stages, SOD and CAT played a defensive role in resisting oxidative damage of active species. With the prolonged light exposure time, the antioxidant protection system was overwhelmed leading to the destruction of the cell membrane. The leakage of cell contents such as K+, protein, and DNA caused bacterial apoptosis ultimately. The enhanced photocatalytic antibacterial performance of g-C3N5 nanosheets is ascribed to the stronger redox property by the upward shift of CB and downward shift of VB compared with bulk g-C3N5. On the other hand, larger specific surface area and better separation efficiency of photoinduced carriers are helpful to the improved photocatalytic performance. This study systematically revealed the inactivation process toward E. coli and expanded the application range of g-C3N5-based materials with abundant solar energy.


Assuntos
Escherichia coli , Luz , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Microscopia Eletrônica de Transmissão
18.
ACS Appl Mater Interfaces ; 15(14): 17742-17756, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37006134

RESUMO

Reactive oxygen species (ROS) produced by noble metallic nanoparticles under visible light is an effective way to combat drug-resistant bacteria colonized on the wound. However, the photocatalytic efficiency of noble metallic nanoparticles is limited by its self-aggregation in water media. Moreover, the fast release of noble metallic ions from nanoparticles might engender cellular toxicity and hazardous environmental issues. Herein, we chose AgNPs, the most common plasmonic noble metallic nanoparticles, as an example, modifying the surface of AgNPs with oleic acid and n-butylamine and imbedded them into calcium alginate (CA) hydrogel that holds tissue adhesion, rapid hemostatic, sunlight-sensitive antibacterial and anti-inflammatory abilities, and thus effectively promotes the healing of wounds. Unlike conventional AgNP-based materials, the constrain of colloids and hydrogel networks hinders the leach of Ag+. Nonetheless, the CA/Ag hydrogels exhibit on-demand photodynamic antibacterial efficacy due to the generation of ROS under visible light. In addition, the CA/Ag hydrogel can effectively stop the hemorrhage in a mouse liver bleeding model due to their skin-adaptive flexibility and tissue adhesiveness. The potent sunlight-responsive antibacterial activity of the CA/Ag hydrogel can effectively kill multidrug-resistant bacteria both in vitro (>99.999%) and in vivo (>99.9%), while the diminished Ag+ release guarantees its biocompatibility. The CA/Ag hydrogel significantly promotes the wound healing process by the downregulation of proinflammatory cytokines (TNF-α and IL-6) in a rodent full-thickness cutaneous wound model. Overall, the proposed multifunctional CA/Ag nanocomposite hydrogel has excellent prospects as an advanced wound dressing.


Assuntos
Hemostáticos , Nanopartículas Metálicas , Animais , Camundongos , Hidrogéis/farmacologia , Hemostáticos/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Cicatrização , Antibacterianos/farmacologia , Nanopartículas Metálicas/uso terapêutico
19.
Pharmaceutics ; 15(4)2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37111561

RESUMO

The evaluation of bioequivalence (BE) for topical dermatological drug products is challenging, and there has been significant interest from regulatory authorities in developing new BE methodologies in recent years. Currently, BE is demonstrated by comparative clinical endpoint studies; these are costly and time-consuming and often lack sensitivity and reproducibility. Previously, we reported excellent correlations between in vivo Confocal Raman Spectroscopy in human subjects and in vitro skin permeation testing (IVPT) with the human epidermis for skin delivery of ibuprofen and a number of excipients. The aim of the present proof-of-concept study was to evaluate CRS as a method to assess BE of topical products. Two commercially available formulations, Nurofen Max Strength 10% Gel and Ibuleve Speed Relief Max Strength 10% Gel, were selected for evaluation. Delivery of ibuprofen (IBU) to the skin was determined in vitro and in vivo by IVPT and CRS, respectively. The formulations examined were found to deliver comparable amounts of IBU across the skin over 24 h in vitro (p > 0.05). Additionally, the formulations resulted in similar skin uptake values measured with CRS in vivo, either at 1 h or 2 h after application (p > 0.05). This is the first study to report the capability of CRS for the demonstration of BE of dermal products. Future studies will focus on the standardisation of the CRS methodology for a robust and reproducible pharmacokinetic (PK)-based evaluation of topical BE.

20.
Molecules ; 28(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37049847

RESUMO

In this paper, a novel S-scheme CuS/Bi5O7I heterojunction was successfully constructed using a two-step approach comprising the alkaline hydrothermal method and the adsorption-deposition method, and it consisted of Bi5O7I microrods with CuS particles covering the surface. The photocatalytic antibacterial effects on Escherichia coli (E. coli) were systematically examined with visible light exposure. The results suggested that the 3%-CuS/Bi5O7I composite showed the optimal antibacterial activity, completely inactivating E. coli (5 × 108 cfu/mL) in 180 min of irradiation. Moreover, the bacterial inactivation process was scientifically described. •O2- and h+ were the major active species for the inactivation of the bacteria. In the early stages, SOD and CAT initiated the protection system to avoid the oxidative destruction of the active species. Unfortunately, the antioxidant protection system was overwhelmed thereafter, which led to the destruction of the cell membrane, as evidenced by the microstructure changes in E. coli cells. Subsequently, the leakage of intracellular components including K+, proteins, and DNA resulted in the unavoidable death of E. coli. Due to the construction of the S-scheme heterojunction, the CuS/Bi5O7I composite displayed the boosted visible light harvesting, the high-efficiency separation of photogenerated electrons and holes, and a great redox capacity, contributing to an outstanding photocatalytic disinfection performance. This work offers a new opportunity for S-scheme Bi5O7I-based heterojunctions with potential application in water disinfection.


Assuntos
Desinfecção , Escherichia coli , Escherichia coli/efeitos da radiação , Desinfecção/métodos , Catálise , Luz , Antibacterianos
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