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1.
Artigo em Inglês | MEDLINE | ID: mdl-38619440

RESUMO

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

2.
ACS Appl Mater Interfaces ; 16(13): 16340-16350, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38511525

RESUMO

As an additive for perovskites, in addition to functional groups, the steric configuration of molecules is worthy of consideration because it influences perovskite crystallization, thus determining whether defect passivation is effective without any side effects. In this work, the chiral molecules l- and d-pyroglutamic acid (l-PA and d-PA) were chosen as additives for perovskite passivators to reveal the reasons for the differences in passivation between amino acids with different steric configurations. Functional groups, such as the C═O groups and N-H groups of l-PA and d-PA, can passivate the perovskite defects. However, l-PA exhibited a more distorted steric configuration, while d-PA was more planar, leading to differences in the distances between the two C═O groups. Taking the Pb-Pb bond length as a reference, the shorter distance between the two C═O groups of l-PA distorts the perovskite lattice structure, which results in poor device stability. Conversely, the similar distance between the two C═O groups of d-PA promoted the preferred orientational growth of the perovskite. Finally, the d-PA-doped device accomplished an excellent efficiency of 24.11% with an improved open-circuit voltage of 1.17 V. Furthermore, the efficiency of the unencapsulated d-PA-doped device was maintained at 93% in N2 for more than 3000 h and 74% after 500 h of operation at maximum power point tracking under continuous illumination.

3.
J Org Chem ; 89(3): 2014-2023, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38241168

RESUMO

A Pd-catalyzed dual C-H carbonylation of commercially available diarylamines using Co2(CO)8 as a safe CO source has been developed. This methodology provides a facile approach for the synthesis of diversified acridones in moderate to good yields. The protocol features good functional group compatibility, operational safety, easy scale-up, and versatile transformations.

4.
J Am Chem Soc ; 146(1): 578-585, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38157440

RESUMO

Biofunctionalized conjugated polymers (i.e., carrying enzymes, antibodies, and nucleic acids) are of great interest for many biological applications, yet efficient biofunctionalization of conjugated polymers under biocompatible conditions is challenging. We report a facile strategy to make biofunctionalized conjugated polymers through thiol-ene chemistry with embedded latent disulfide functional groups. This is made possible through the design of a cyclic disulfide-containing dioxythiophene, which can be integrated into a series of conjugated polymers via acid-catalyzed chain-growth polymerization. The utility of such a biofunctionalized polymer with glucose oxidase has been examined in organic electrochemical transistors for the selective sensing of glucose. This work provides a venue for the creation of biofunctional organic semiconductors.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38047886

RESUMO

Nanozyme-induced reactive oxygen species (ROS)-dependent catalytic therapy has been developed into a powerful strategy against bacterial wound infections. However, the limited endogenous supply or instability of H2O2, the reliance on external stimuli for the generation of ROS, and the highly expressed glutathione (GSH) level make it a challenge to achieve high-performance therapeutic efficiency. In this work, a facile therapeutic strategy against bacterial infections with pristine CuFe layered double hydroxide (LDH) as the self-cascade nanoreactor is proposed without modification or additional energy input. CuFe LDH with an oxidase-like feature can catalyze the generation of multiple ROS, such as 1O2, ·O2-, and H2O2. And the self-generated H2O2 in the cascade nanoreactor could be further in situ transformed to ·OH owing to the peroxidase-like activity. As a result, the cell membrane of bacteria is destroyed, leading to death. Furthermore, its ultrahigh enzyme-like activity of CuFe LDH could effectively promote the breakdown of the biofilm structure. Additionally, the Cu2+-mediated GSH exhaustion of CuFe LDH further avoids the consumption of oxidized ROS and thereby significantly improves the sterilization effect. Finally, the as-prepared CuFe LDH with negligible side effects on normal tissues can be successfully used to eliminate the methicillin-resistant Staphylococcus aureus-infected wounds and accelerate their healing in the mouse model, which paves a new avenue as an antibacterial agent for clinical anti-infective treatment.

6.
bioRxiv ; 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38106138

RESUMO

Histone deacetylase inhibitors (HDIs) modulate ß cell function in preclinical models of diabetes; however, the mechanisms underlying these beneficial effects have not been determined. In this study, we investigated the impact of the HDI sodium butyrate (NaB) on ß cell function and calcium (Ca2+) signaling using ex vivo and in vitro models of diabetes. Our results show that NaB significantly improved glucose-stimulated insulin secretion in islets from human organ donors with type 2 diabetes and in cytokine-treated INS-1 ß cells. Consistently, NaB partially rescued glucose-stimulated Ca2+ oscillations in mouse islets treated with proinflammatory cytokines. Because the oscillatory phenotype of Ca2+ in the ß cell is governed by changes in endoplasmic reticulum (ER) Ca2+ levels, next we explored the relationship between NaB and store-operated calcium entry (SOCE), a rescue mechanism that acts to refill ER Ca2+ levels through STIM1-mediated gating of plasmalemmal Orai channels. We found that NaB treatment preserved basal ER Ca2+ levels and restored SOCE in IL-1ß-treated INS-1 cells. Furthermore, we linked these changes with the restoration of STIM1 levels in cytokine-treated INS-1 cells and mouse islets, and we found that NaB treatment was sufficient to prevent ß cell death in response to IL-1ß treatment. Mechanistically, NaB counteracted cytokine-mediated reductions in phosphorylation levels of key signaling molecules, including AKT, ERK1/2, glycogen synthase kinase-3α (GSK-3α), and GSK-3ß. Taken together, these data support a model whereby HDI treatment promotes ß cell function and Ca2+ homeostasis under proinflammatory conditions through STIM1-mediated control of SOCE and AKT-mediated inhibition of GSK-3.

7.
J Dermatolog Treat ; 34(1): 2279899, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38010938

RESUMO

Immunoglobulin gamma (IgG) type 4-related disease (IgG4-RD) is a chronic immunologic systemic disorder that could affect multiple organs, which may cause irreversible organ damage or even death. Skin involvement is rare and associated especially with systemic disease. The dermatologist must be equipped to recognize IgG4-RD to prevent delayed identification and treatment. This case reports a very rare case of IgG4-related skin disease (IgG4-RSD) presenting with a generalized angiolymphoid hyperplasia with eosinophilia (ALHE)-like lesions in a middle-aged male patient with no other organ involvement. He was treated with oral glucocorticoid and cyclophosphamide, which resulted in complete remission. No relapse and disease progression were seen with a follow-up for 8 years.


Assuntos
Hiperplasia Angiolinfoide com Eosinofilia , Doença Relacionada a Imunoglobulina G4 , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Angiolinfoide com Eosinofilia/patologia , Hiperplasia Angiolinfoide com Eosinofilia/terapia , Ciclofosfamida/uso terapêutico , Seguimentos , Glucocorticoides/uso terapêutico , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/complicações
8.
Zhongguo Zhong Yao Za Zhi ; 48(18): 5068-5077, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37802849

RESUMO

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.


Assuntos
Isoflavonas , Micelas , Ratos , Animais , Distribuição Tecidual , Cromatografia Líquida , Espectrometria de Massas em Tandem , Ratos Endogâmicos SHR , Isoflavonas/farmacologia
9.
Front Pharmacol ; 14: 1236656, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601055

RESUMO

Background: The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD). Methods: A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug-metabolite-target-disease (BMTD) network and a protein-protein interaction (PPI) network, and the predictions were validated using an FD rat model. Results: A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE). Conclusion: Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings.

10.
Angew Chem Int Ed Engl ; 62(36): e202304699, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37409373

RESUMO

Developing new reactive pathway to activate inert C(sp3 )-H bonds for valuable oxygenated products remains a challenge. We prepared a series of triazine conjugated organic polymers to photoactivate C-H into aldehyde/ketone via O2 →H2 O2 →⋅OH→Cl⋅→Cl2 ⋅- . Experiment results showed Cl2 ⋅- could successively activate C(sp3 )-H more effectively than Cl⋅ to generate unstable dichlorinated intermediates, increasing the kinetic rate ratio of dichlorination to monochlorination by a factor of 2,000 and thus breaking traditional dichlorination kinetic constraints. These active intermediates were hydrolyzed into aldehydes or ketones easily, when compared with typical stable dichlorinated complexes, avoiding chlorinated by-product generation. Moreover, an integrated two-phase system in an acid solution strengthened the Cl2 ⋅- mediated process and inhibited product overoxidation, where the conversion rate of toluene reached 16.94 mmol/g/h and the selectivity of benzaldehyde was 99.5 %. This work presents a facile and efficient approach for selective conversion of inert C(sp3 )-H bonds using Cl2 ⋅- .

11.
Diabetes ; 72(10): 1433-1445, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37478155

RESUMO

Altered endoplasmic reticulum (ER) Ca2+ signaling has been linked with ß-cell dysfunction and diabetes development. Store-operated Ca2+ entry replenishes ER Ca2+ through reversible gating of plasma membrane Ca2+ channels by the ER Ca2+ sensor, stromal interaction molecule 1 (STIM1). For characterization of the in vivo impact of STIM1 loss, mice with ß-cell-specific STIM1 deletion (STIM1Δß mice) were generated and challenged with high-fat diet. Interestingly, ß-cell dysfunction was observed in female, but not male, mice. Female STIM1Δß mice displayed reductions in ß-cell mass, a concomitant increase in α-cell mass, and reduced expression of markers of ß-cell maturity, including MafA and UCN3. Consistent with these findings, STIM1 expression was inversely correlated with HbA1c levels in islets from female, but not male, human organ donors. Mechanistic assays demonstrated that the sexually dimorphic phenotype observed in STIM1Δß mice was due, in part, to loss of signaling through the noncanonical 17-ß estradiol receptor (GPER1), as GPER1 knockdown and inhibition led to a similar loss of expression of ß-cell maturity genes in INS-1 cells. Together, these data suggest that STIM1 orchestrates pancreatic ß-cell function and identity through GPER1-mediated estradiol signaling. ARTICLE HIGHLIGHTS: Store-operated Ca2+ entry replenishes endoplasmic reticulum (ER) Ca2+ through reversible gating of plasma membrane Ca2+ channels by the ER Ca2+ sensor, stromal interaction molecule 1 (STIM1). ß-Cell-specific deletion of STIM1 results in a sexually dimorphic phenotype, with ß-cell dysfunction and loss of identity in female but not male mice. Expression of the noncanonical 17-ß estradiol receptor (GPER1) is decreased in islets of female STIM1Δß mice, and modulation of GPER1 levels leads to alterations in expression of ß-cell maturity genes in INS-1 cells.


Assuntos
Canais de Cálcio , Proteínas de Membrana , Animais , Camundongos , Feminino , Humanos , Proteínas de Membrana/metabolismo , Canais de Cálcio/metabolismo , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo , Cálcio/metabolismo , Receptores de Estradiol/metabolismo , Receptor alfa de Estrogênio/metabolismo , Sinalização do Cálcio , Proteínas de Ligação ao GTP/metabolismo
12.
Ultrason Sonochem ; 95: 106411, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37098312

RESUMO

Ag2S quantum dots (QDs) have aroused extensive concerns in intravital imaging field due to their merits of narrow bandgap, low biological toxicity and decent fluorescence emission properties in the second near-infrared (NIR-II) window. However, low quantum yield (QY) and poor uniformity of Ag2S QDs are still main obstacles for its application. In this work, a novel strategy of utilizing ultrasonic field is presented, which can enhance the microdroplet-based interfacial synthesis of Ag2S QDs. The ultrasound increases the presence of ions at the reaction sites by enhancing the ion mobility in the microchennels. Therefore, the QY is enhanced from 2.33 % (optimal QY without ultrasound) to 8.46 %, which is the highest value of Ag2S ever reported without ion-doping. Also, the decrease of the corresponding full width at half maximum (FWHM) from 312 nm to 144 nm indicates the obvious uniformity improvement of the obtained QDs. Further mechanism exploration illustrates that ultrasonic cavitation significantly increases the interfacial reaction sites by splitting the droplets. Meanwhile, the acoustic flow field strengthens the ion renewal at the droplet interface. Consequently, the mass transfer coefficient increases by more than 500 %, which is favorable to improve both the QY and quality of Ag2S QDs. This work serves both fundamental research and practical production for the synthesis of Ag2S QDs.

13.
Diabetes ; 72(6): 746-757, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36913741

RESUMO

The transcriptional activity of Pdx1 is modulated by a diverse array of coregulatory factors that govern chromatin accessibility, histone modifications, and nucleosome distribution. We previously identified the Chd4 subunit of the nucleosome remodeling and deacetylase complex as a Pdx1-interacting factor. To identify how loss of Chd4 impacts glucose homeostasis and gene expression programs in ß-cells in vivo, we generated an inducible ß-cell-specific Chd4 knockout mouse model. Removal of Chd4 from mature islet ß-cells rendered mutant animals glucose intolerant, in part due to defects in insulin secretion. We observed an increased ratio of immature-to-mature insulin granules in Chd4-deficient ß-cells that correlated with elevated levels of proinsulin both within isolated islets and from plasma following glucose stimulation in vivo. RNA sequencing and assay for transposase-accessible chromatin with sequencing showed that lineage-labeled Chd4-deficient ß-cells have alterations in chromatin accessibility and altered expression of genes critical for ß-cell function, including MafA, Slc2a2, Chga, and Chgb. Knockdown of CHD4 from a human ß-cell line revealed similar defects in insulin secretion and alterations in several ß-cell-enriched gene targets. These results illustrate how critical Chd4 activities are in controlling genes essential for maintaining ß-cell function. ARTICLE HIGHLIGHTS: Pdx1-Chd4 interactions were previously shown to be compromised in ß-cells from human donors with type 2 diabetes. ß-Cell-specific removal of Chd4 impairs insulin secretion and leads to glucose intolerance in mice. Expression of key ß-cell functional genes and chromatin accessibility are compromised in Chd4-deficient ß-cells. Chromatin remodeling activities enacted by Chd4 are essential for ß-cell function under normal physiological conditions.


Assuntos
Cromatina , Diabetes Mellitus Tipo 2 , Camundongos , Animais , Humanos , Cromatina/genética , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/genética , Diabetes Mellitus Tipo 2/genética , DNA Helicases/genética , Camundongos Knockout , Expressão Gênica , Glucose
14.
Biomater Adv ; 149: 213390, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36963249

RESUMO

The development of fascinating materials with functional properties has revolutionized the humankind with materials comfort, stopped the spreading of diseases, relieving the environmental pollution pressure, economized government research funds, and prolonged their serving life. The outbreak of Coronavirus Disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered great global public health concern. Face masks are crucial tools to impede the spreading of SARS-CoV-2 from human to human. However, current face masks exhibit in a variety of colors (opaque), like blue, black, red, etc., leading to a communication barrier between the doctor and the deaf-mute patient when wearing a mask. High optical transparency filters can be utilized for both personal protection and lip-reading. Thus, shaping face air filter into a transparent appearance is an urgent need. Electrospinning technology, as a mature technology, is commonly used to form nanofiber materials utilizing high electrical voltage. With the alteration of the diameters of nanofibers, and proper material selection, it would be possible to make the transparent face mask. In this article, the research progress in the transparent face air filter is reviewed with emphasis on three parts: mechanism of the electrospinning process and light transmission, preparation of transparent face air filter, and their innovative potential. Through the assessment of classic cases, the benefits and drawbacks of various preparation strategies and products are evaluated, to provide general knowledge for the needs of different application scenarios. In the end, the development directions of transparent face masks in protective gear, particularly their novel functional applications and potential contributions in the prevention and control of the epidemic are also proposed.


Assuntos
Filtros de Ar , COVID-19 , Nanofibras , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Filtração
15.
Zhongguo Zhong Yao Za Zhi ; 48(3): 579-587, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36872220

RESUMO

Traditional Chinese medicine(TCM) has a long history and abundant experience in external therapy, which marks human wisdom. In the early history of human, people found that fumigation, coating, and sticking of some tree branches and herb stems can help alleviate scabies and remove parasites in productive labor, which indicates the emergence of external therapy. Pathogen usually enters the body through the surface, so external therapy can be used to treat the disease. External therapy is among the major characteristic of surgery of TCM. As one of the external therapies in TCM, external application to acupoints smooths the zang-fu organs through meridians and collaterals, thereby harmonizing yin and yang. This therapy emerged in the early society, formed the Spring and Autumn Period and the Warring States Period, improved in the Song and Ming dynasties, and matured in the Qing dynasty. With the efforts of experts in history, it has had a mature theory. According to modern research, it can avoid the first-pass effect of liver and the gastrointestinal irritation and improve the bioavailability of Chinese medicine. Based on the effect of Chinese medicine and the theory of meridian and collateral, it can stimulate the acupoints, exert regulatory effect on acupoints, and give full play to the efficacy of TCM and the interaction of the two. Thereby, it can regulate qi and blood and balance yin and yang, thus being widely used in the treatment of diseases. In this paper, the use of external application to acupoints, the effect on skin immunity, the regulation of neuro-inflammatory mechanism, the relationship between acupoint application and human circulation network, and the development of its dosage form were summarized through literature review. On this basis, this study is expected to lay a foundation for further research.


Assuntos
Pontos de Acupuntura , Meridianos , Humanos , Disponibilidade Biológica , Fumigação , Medicina Tradicional Chinesa
16.
Food Chem Toxicol ; 175: 113743, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36972840

RESUMO

Sunitinib (SNT)-induced cardiotoxicity is associated with abnormal calcium regulation caused by phosphoinositide 3 kinase inhibition in the heart. Berberine (BBR) is a natural compound that exhibits cardioprotective effects and regulates calcium homeostasis. We hypothesized that BBR ameliorates SNT-induced cardiotoxicity by normalizing the calcium regulation disorder via serum and glucocorticoid-regulated kinase 1 (SGK1) activation. Mice, neonatal rat cardiomyocytes (NRVMs), and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to study the effects of BBR-mediated SGK1 activity on the calcium regulation disorder caused by SNT as well as the underlying mechanism. BBR offered prevention against SNT-induced cardiac systolic dysfunction, QT interval prolongation, and histopathological changes in mice. After the oral administration of SNT, the Ca2+ transient and contraction of cardiomyocytes was significantly inhibited, whereas BBR exhibited an antagonistic effect. In NRVMs, BBR was significantly preventive against the SNT-induced reduction of calcium transient amplitude, prolongation of calcium transient recovery, and decrease in SERCA2a protein expression; however, SGK1 inhibitors resisted the preventive effects of BBR. In hiPSC-CMs, BBR pretreatment significantly prevented SNT from inhibiting the contraction, whereas coincubation with SGK1 inhibitors antagonized the effects of BBR. These findings indicate that BBR attenuates SNT-induced cardiac dysfunction by normalizing the calcium regulation disorder via SGK1 activation.


Assuntos
Berberina , Cardiopatias , Ratos , Camundongos , Humanos , Animais , Sunitinibe/metabolismo , Sunitinibe/farmacologia , Cálcio/metabolismo , Berberina/farmacologia , Cardiotoxicidade/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Cardiopatias/induzido quimicamente , Cardiopatias/prevenção & controle , Cardiopatias/metabolismo , Miócitos Cardíacos
17.
AAPS PharmSciTech ; 24(2): 69, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36792796

RESUMO

In order to better promote the application of the polymeric mixed micelles (PMMs) in oral delivery, in addition to focusing on the improvement of micellar structural stability, it is necessary to obtain the absorption characteristics of the intact micellar particles. In this work, the transport behavior across Caco-2 cells of FS/PMMs composed of Pluronic F127 and Solutol HS15 was tracked by encapsulating an environment-responsive probe into the particles. The specific property of the probe is the water-initiated aggregation-caused quenching (ACQ) ability, by which integral particles can be identified accurately. The influence of polymeric ratios (FS) on the transcellular behavior of FS/PMMs was explored and the single pass intestinal perfusion experiment was used to further illustrate it. Moreover, pharmacokinetics parameters were detected to analyze the relationship among FS ratios, transport behavior, and pharmacokinetic parameters. FS ratios were found to hardly affect the endocytosis pathways and intracellular itinerary of FS/PMMs, but do affect the proportion of each path. FS/PMMs with high HS15 content, namely System-I, were found to primarily undergo receptor-mediated endocytosis pathway and be less susceptible to lysosomal degradation, which would lead to more absorption and higher Cmax and AUC than drug suspension. In contrast, despite System-II with high F127 content cannot contribute to drug plasma concentration, it can prolong the in vivo retention time. These findings provided evidence for the role of polymeric ratios in modulating the transcellular absorption and pharmacokinetic parameters of the drug-loaded PMMs, and would be a step forward in helping PMMs' design to enhance oral drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Micelas , Humanos , Células CACO-2 , Polímeros/química , Poloxâmero/química , Transcitose , Portadores de Fármacos/química
18.
RSC Adv ; 13(5): 3193-3203, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36756419

RESUMO

Sulfate radical-based technology has been considered as an efficient technology to remove pharmaceuticals and personal care products (PPCPs) with heterogeneous metal-mediated catalysts for the activation of peroxymonosulfate (PMS). In this study, La2CoO4+δ perovskite with Ruddlesden-Popper type structure was synthesised by the sol-gel method, which was employed in PMS activation. Different characteriazation technologies were applied for the characterization of La2CoO4+δ , such as SEM-EDX, XRD, and XPS technologies. A common organic compound, bisphenol A (BPA), is used as a target contaminant, and the effect impactors were fully investigated and explained. The results showed that when the dosage of La2CoO4+δ was 0.5 g L-1 and the concentration of PMS was 1.0 mM in neutral pH solution, about 91.1% degradation efficiency was achieved within 25 minutes. Quenching experiments were introduced in the system to verify the catalytic mechanism of PMS for the BPA degradation, proving the existence of superoxide, hydroxyl radicals and sulfate radicals, which are responsible for the catalytic degradation of BPA. Moreover, the reusability and stability of the catalyst were also conducted which showed good stability during the reaction. This work would improve the applications of A2BO4-type perovskites for activating PMS to degrade BPA.

19.
ACS Appl Mater Interfaces ; 15(3): 4113-4121, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36642933

RESUMO

Electrochromic (EC) devices show promising prospects with the increasing demand for energy-efficient and sustainable technologies. Multifunctionality integration is an inevitable characteristic for EC devices to adapt to changing environments. Herein, a dual-mode temperature-dependent EC device is demonstrated for the first time. Combined with the transparent PVA/EG-ZnCl2 organohydrogel electrolyte, the devices exhibit good EC performances over a wide temperature range (-40 to 40 °C). The evolutions of ion/electron transport kinetics-related indicators with temperature are further explored and simulated to reveal the mechanism of the temperature dependence of EC devices. Significantly, the optimized tungsten oxide-based EC device shows high performances at the extremely low temperature of -40 °C with a large transmittance modulation (80.8% @660 nm) and outstanding optical memory effects (97.3% retention of the initial transmittance modulation after 32 h) without electrical energy consumption. Furthermore, with a perovskite quantum dot photoluminescence film serving as the backlight, the device can switch display modes between emissive and reflective to realize its functionality in bright or dark conditions. This work provides a broad application prospect for EC devices in diverse environments of light (bright/dark) and temperature (hot/cold).

20.
mBio ; 14(1): e0301022, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36537811

RESUMO

Diffusible signal factor (DSF) represents a family of widely conserved quorum-sensing (QS) signals which regulate virulence factor production and pathogenicity in numerous Gram-negative bacterial pathogens. We recently reported the identification of a highly potent DSF-quenching bacterial isolate, Pseudomonas nitroreducens HS-18, which contains an operon with four DSF-inducible genes, digABCD, or digA-D, that are responsible for degradation of DSF signals. However, the regulatory mechanisms that govern the digA-D response to DSF induction have not yet been characterized. In this study, we identified a novel transcriptional regulator we designated RdmA (regulator of DSF metabolism) which negatively regulates the expression of digA-D and represses DSF degradation. In addition, we found that a gene cluster located adjacent to rdmA was also negatively regulated by RdmA and played a key role in DSF degradation; this cluster was hence named dmg (DSF metabolism genes). An electrophoretic mobility shift assay and genetic analysis showed that RdmA represses the transcriptional expression of the dmg genes in a direct manner. Further studies demonstrated that DSF acts as an antagonist and binds to RdmA, which abrogates RdmA binding to the target promoter and its suppression on transcriptional expression of the dmg genes. Taken together, the results from this study have unveiled a central regulator and a gene cluster associated with the autoinduction of DSF degradation in P. nitroreducens HS-18, and this will aid in the understanding of the genetic basis and regulatory mechanisms that govern the quorum-quenching activity of this potent biocontrol agent. IMPORTANCE DSF family quorum-sensing (QS) signals play important roles in regulation of bacterial physiology and virulence in a wide range of plant and human bacterial pathogens. Quorum quenching (QQ), which acts by either degrading QS signals or blocking QS communication, has proven to be a potent disease control strategy, but QQ mechanisms that target DSF family signals and associated regulatory mechanisms remain largely unknown. Recently, we identified four autoinduced DSF degradation genes (digABCD) in P. nitroreducens HS-18. By using a combination of transcriptome and genetic analysis, we identified a central regulator that plays a key role in autoinduction of dig expression, as well as a new gene cluster (dmgABCDEFGH) involved in DSF degradation. The significance of our study is in unveiling the autoinduction mechanism that governs DSF signal quorum quenching for the first time, to our knowledge, and in identification of new genes and enzymes responsible for DSF degradation. The findings from this study shed new light on our understanding of the DSF metabolism pathway and the regulatory mechanisms that modulate DSF quorum quenching and will provide useful clues for design and development of a new generation of highly potent QQ biocontrol agents against DSF-mediated bacterial infections.


Assuntos
Pseudomonas , Percepção de Quorum , Humanos , Percepção de Quorum/genética , Pseudomonas/genética , Pseudomonas/metabolismo , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
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