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1.
Foot Ankle Int ; : 10711007241250005, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722181

RESUMO

BACKGROUND: This study aims to evaluate the association of elevated blood glucose and postoperative complications among diabetic patients after surgical treatment of torsional ankle fracture. METHODS: This was a retrospective study of consecutive diabetic patients treated surgically for a torsional ankle injury between January 2017 and December 2021 at a large tertiary hospital. All patients who met inclusion and exclusion criteria were divided into a high-HbA1c group or a low-HbA1c group according to the HbA1c cutoff of 7.0% within 3 months of operation, then a propensity score match was performed to control potential confounding factors. The primary outcomes were postoperative complications, and secondary outcomes were unplanned secondary procedures. RESULTS: A matched cohort of 238 patients was finally included, with 119 patients with high HbA1c levels and 119 with low HbA1c levels. Patients with high HbA1c levels experienced more complications (31.1% vs 18.5%, P < .01) and more secondary procedures (22.7% and 8.4%, P < .01) than those with low HbA1c levels. Multivariate logistic regression indicated that patients with high HbA1c levels were significantly associated with higher proportions of any complications (OR 2.25, 95% CI 1.08-4.69; P = .03), superficial infection (OR 4.03, 95% CI 2.13-5.41; P < .01), deep infection (OR 1.42, 95% CI 1.23-2.02; P < .01), and any unplanned secondary operations (OR 3.72, 95% CI 1.62-8.52; P < .01) compared with those with low HbA1c levels after controlling for potential confounders. Multivariate linear regression showed that high HbA1c levels were significantly associated with a higher number of complications (ß = 4.61, 95% CI 2.63-18.18; P < .01) and a higher number of secondary procedures (ß = 4.44, 95% CI 2.79-10.87; P < .01). CONCLUSION: Patients with an HbA1c >7.0% within 3 months of operation are more likely to have a wound issue/infection and more likely to undergo a secondary procedure after surgical treatment of torsional ankle fractures in diabetic patients than patients with an HbA1c ≤7.0% within 3 months of operation. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

2.
Cereb Cortex ; 34(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38771238

RESUMO

Cognitive-control theories assume that the experience of response conflict can trigger control adjustments. However, while some approaches focus on adjustments that impact the selection of the present response (in trial N), other approaches focus on adjustments in the next upcoming trial (N + 1). We aimed to trace control adjustments over time by quantifying cortical noise by means of the fitting oscillations and one over f algorithm, a measure of aperiodic activity. As predicted, conflict trials increased the aperiodic exponent in a large sample of 171 healthy adults, thus indicating noise reduction. While this adjustment was visible in trial N already, it did not affect response selection before the next trial. This suggests that control adjustments do not affect ongoing response-selection processes but prepare the system for tighter control in the next trial. We interpret the findings in terms of a conflict-induced switch from metacontrol flexibility to metacontrol persistence, accompanied or even implemented by a reduction of cortical noise.


Assuntos
Cognição , Conflito Psicológico , Eletroencefalografia , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Cognição/fisiologia , Encéfalo/fisiologia , Adolescente
3.
Virus Genes ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568442

RESUMO

The tissue-specific characteristics have encouraged researchers to identify organ-specific lncRNAs as disease biomarkers. This study aimed to identify the clinical and functional roles of long non-coding RNA HLA-F antisense RNA 1 (HLA-F-AS1) in hepatitis B virus (HBV)-hepatocellular carcinoma (HCC). A total of 121 HBV-HCC, 81 chronic hepatitis B (CHB), and 85 normal liver tissues were evaluated in this study. Real-time quantitative PCR assay was used to evaluate the RNA expression levels. Performance in diagnosis was compared between alpha fetoprotein (AFP) and HLA-F-AS1 using Receiver Operating Characteristic (ROC) curves. Performance in post-hepatectomy prognosis with high or low HLA-F-AS1 was compared using Kaplan-Meier curves. Multi-variable analysis was used to determine the informative predictors. Downstream miRNAs for HLA-F-AS1 were predicted and miR-128-3p was confirmed by luciferase reporter assay and RNA pull-down assay. In vitro functional analysis was performed by MTS reagent for cell proliferation and transwell assay for cell migration. HLA-F-AS1 levels were significantly increased in the HBV-HCC compared to normal healthy tissue and CHB tissues. HLA-F-AS1 exhibited a well potential in making a distinction between HBV-HCC and health, as well as HBV-HCC and CHB. The survival analysis revealed that patients with high levels of HLA-F-AS1 tend to shorter overall survival times. The best prognostic performance was achieved by HLA-F-AS1 after multi-variable analysis (HR 2.290, 95% CI 1.191-4.403, p = 0.013). Functional analysis showed that HLA-F-AS1 promoted cell proliferation and migration via miR-128-3p. Up-regulation of HLA-F-AS1 could serve as a promising diagnostic and prognostic marker for HBV-HCC after surgery, maybe useful in the management of HBV-HCC patients. HLA-F-AS1 can promote the progression of HBV-HCC, may be useful in the targeting treatment of HBV-HCC patients.

4.
Cancer Sci ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623968

RESUMO

Enhancing sensitivity to sorafenib can significantly extend the duration of resistance to it, offering substantial benefits for treating patients with hepatocellular carcinoma (HCC). However, the role of ferroptosis in influencing sorafenib sensitivity within HCC remains pivotal. The enhancer of zeste homolog 2 (EZH2) plays a significant role in promoting malignant progression in HCC, yet the relationship between ferroptosis, sorafenib sensitivity, and EZH2 is not entirely clear. Bioinformatic analysis indicates elevated EZH2 expression in HCC, predicting an unfavorable prognosis. Overexpressing EZH2 can drive HCC cell proliferation while simultaneously reducing ferroptosis. Further analysis reveals that EZH2 amplifies the modification of H3K27 me3, thereby influencing TFR2 expression. This results in decreased RNA polymerase II binding within the TFR2 promoter region, leading to reduced TFR2 expression. Knocking down EZH2 amplifies sorafenib sensitivity in HCC cells. In sorafenib-resistant HepG2(HepG2-SR) cells, the expression of EZH2 is increased. Moreover, combining tazemetostat-an EZH2 inhibitor-with sorafenib demonstrates significant synergistic ferroptosis-promoting effects in HepG2-SR cells. In conclusion, our study illustrates how EZH2 epigenetically regulates TFR2 expression through H3K27 me3, thereby suppressing ferroptosis. The combination of the tazemetostat with sorafenib exhibits superior synergistic effects in anticancer therapy and sensitizes the HepG2-SR cells to sorafenib, shedding new light on delaying and ameliorating sorafenib resistance.

5.
Dalton Trans ; 53(15): 6625-6630, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38517688

RESUMO

Applying molecular design to chiral organo-Zn2+ complexes, a new pair of chiral heteroleptic bis-pyrazolonate-Zn2+ enantiomers [Zn(PMBP)2(1R,2R-Chxn)] (R,R-Zn2+; HPMBP = 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone and 1R,2R-Chxn = (1R,2R)-cyclohexane-1,2-diamine) and [Zn(PMBP)2(1S,2S-Chxn)] (S,S-Zn2+; 1S,2S-Chxn = (1S,2S)-cyclohexane-1,2-diamine) have been synthesized and characterized in terms of photophysical and thermodynamic properties. In addition to a small Flack parameter (0.05(3)) associated with the solid-state elucidation of S,S-Zn2+, the circular dichroism (CD) and circularly polarized light (CPL) spectra for the chiral Zn2+ enantiomers show perfect mirror symmetry, establishing that the enantiopure 1,2-diamines successfully induce the optical isomerism of R,R-Zn2+ and S,S-Zn2+. As a result of the combined strong chiral induction capability of chiral 1,2-diamines and excellent photophysical properties of the pyrazolone ligand (PMBP)-, the two Zn2+ enantiomers exhibit high-quality pure blue fluorescence (ΦPL = 9-10%) and significant CPL activity (|glum| = 0.0065-0.0068). The heteroleptic strategy adopted in this study offers a new route to develop high-performance chiroptical luminophores.

6.
ACS Pharmacol Transl Sci ; 7(3): 630-640, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38481681

RESUMO

Melanocortin-4 receptor (MC4R) functions as a crucial neuroendocrine G protein-coupled receptor (GPCR) in the central nervous system of mammals, displaying agonist-independent constitutive activity that is mainly determined by its N-terminal domain. We previously reported that zebrafish MC4R exhibited a much higher basal cAMP level in comparison to mammalian MC4Rs. However, the functional evolution of constitutive activities in chordate MC4Rs remains to be elucidated. Here we cloned and compared the constitutive activities of MC4Rs from nine vertebrate species and showed that the additive action of the N-terminus with the extracellular region or transmembrane domain exhibited a combined pharmacological effect on the MC4R constitutive activity. In addition, we demonstrated that four residues of F149, Q156, V163, and K164 of the second intracellular loop played a vital role in determining MC4R constitutive activity. This study provided novel insights into functional evolution and identified a key motif essential for constitutive modulation of MC4R signaling.

7.
Emerg Microbes Infect ; 13(1): 2324078, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38407218

RESUMO

Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a heterogeneous disease with a diverse spectrum of clinical phenotypes. No studies have demonstrated the relationship between underlying endotypes and clinical phenotypes as well as prognosis about this disease. Thus, we conducted a multicentre prospective longitudinal study on children hospitalized for MPP between June 2021 and March 2023, with the end of follow-up in August 2023. Blood samples were collected and processed at multiple time points. Multiplex cytokine assay was performed to characterize serum cytokine profiles and their dynamic changes after admission. Cluster analysis based on different clinical phenotypes was conducted. Among the included 196 patients, the levels of serum IL-17A and IL-6 showed remarkable variabilities. Four cytokine clusters based on the two cytokines and four clinical groups were identified. Significant elevation of IL-17A mainly correlated with diffuse bronchiolitis and lobar lesion by airway mucus hypersecretions, while that of IL-6 was largely associated with lobar lesion which later developed into lung necrosis. Besides, glucocorticoid therapy failed to inhibit IL-17A, and markedly elevated IL-17A and IL-6 levels may correlate with lower airway obliterans. Our study provides critical relationship between molecular signatures (endotypes) and clustered clinical phenotypes in paediatric patients with MPP.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Criança , Mycoplasma pneumoniae/genética , Interleucina-6 , Interleucina-17/genética , Estudos Prospectivos , Estudos Longitudinais , Citocinas
8.
Adv Mater ; 36(19): e2313056, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38315828

RESUMO

Conventional 3D organic-inorganic halide perovskite materials have shown substantial potential in the field of optoelectronics, enabling the power conversation efficiency of solar cells beyond 26%. A key challenge limiting the further commercial application of 3D perovskite solar cells is their inherent instability over outer oxygen, humidity, light, and heat. By contrast, 2D Ruddlesden-Popper (2DRP) perovskites with bulky organic cations can effectively stabilize the inorganic slabs, yielding excellent environmental stability. However, the efficiencies of 2DRP perovskite solar cells are much lower than those of the 3D counterparts due to poor charge carrier transporting property of insulating bulky organic cations. Their inner structural, dielectric, optical, and excitonic properties remain to be primarily studied. In this review, the main reasons for the low efficiency of 2DRP perovskite solar cells are first analyzed. Next, a detailed description of various strategies for improving the charge carrier transporting of 2DRP perovskites is provided, such as bandgap regulation, perovskite crystal phase orientation and distribution, energy level matching, interfacial modification, etc. Finally, a summary is given, and the possible future research directions and methods to achieve high-efficiency and stable 2DRP perovskite solar cells are rationalized.

9.
Small ; : e2309218, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38258343

RESUMO

Low-dimensional Ruddlesden-Popper phase (LDRP) perovskites are widely studied in the field of photovoltaics due to their tunable energy-band properties, enhanced photostability, and improved environmental stability compared to the 3D perovskites. However, the insulating spacers with weak intramolecular interaction used in LDRP materials limit the out-of-plane charge transport, leading to poor device performance of LDRP perovskite solar cells (PSCs). Here, a functional ligand, 3-guanidinopropanoic acid (GPA), which is capable of forming strong intramolecular hydrogen bonds through the carboxylic acid group, is employed as an organic spacer for LDRP PSCs. Owing to the strong interaction between GPA molecules, high-quality LDRP (GPA)2 (MA)n-1 Pbn I3n+1 film with promoted formation of n = 5 phase, improved crystallinity, preferential vertical growth orientations, reduced trap-state density, and prolonged carrier lifetime is achieved using GPAI as the dimensionality regulator compared to butylamine hydroiodide (BAI). As a result, GPA-based LDRP PSC exhibits a champion power conversion efficiency of 18.16% that is much superior to the BA-based LDRP PSC (15.43%). Importantly, the optimized GPA-based LDRP PSCs without encapsulation show enhanced illumination, thermal, storage, and humidity stability compared to BA-based ones. This work provides new insights into producing high n value LDRP films and their efficient and stable PSCs.

10.
Sci China Life Sci ; 67(4): 817-828, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38217639

RESUMO

The Convention on Biological Diversity seeks to conserve at least 30% of global land and water areas by 2030, which is a challenge but also an opportunity to better preserve biodiversity, including flowering plants (angiosperms). Herein, we compiled a large database on distributions of over 300,000 angiosperm species and the key functional traits of 67,024 species. Using this database, we constructed biodiversity-environment models to predict global patterns of taxonomic, phylogenetic, and functional diversity in terrestrial angiosperms and provide a comprehensive mapping of the three diversity facets. We further evaluated the current protection status of the biodiversity centers of these diversity facets. Our results showed that geographical patterns of the three facets of plant diversity exhibited substantial spatial mismatches and nonoverlapping conservation priorities. Idiosyncratic centers of functional diversity, particularly of herbaceous species, were primarily distributed in temperate regions and under weaker protection compared with other biodiversity centers of taxonomic and phylogenetic facets. Our global assessment of multifaceted biodiversity patterns and centers highlights the insufficiency and unbalanced conservation among the three diversity facets and the two growth forms (woody vs. herbaceous), thus providing directions for guiding the future conservation of global plant diversity.


Assuntos
Magnoliopsida , Filogenia , Biodiversidade , Plantas , Ecossistema , Conservação dos Recursos Naturais
11.
J Pineal Res ; 76(1): e12927, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38018267

RESUMO

The pineal gland has evolved from a photoreceptive organ in fish to a neuroendocrine organ in mammals. This study integrated multiple daytime single-cell RNA-seq datasets from the pineal glands of zebrafish, rats, and monkeys, providing a detailed examination of the evolutionary transition at single-cell resolution. We identified key factors responsible for the anatomical and functional transformation of the pineal gland. We retrieved and integrated daytime single-cell transcriptomic datasets from the pineal glands of zebrafish, rats, and monkeys, resulting in a total of 22 431 cells after rigorous quality filtering. Comparative analysis was then conducted to elucidate the evolution of pineal cells, their photosensitivity, their role in melatonin production, and the signaling processes within the glands of these species. Our analysis identified distinct cellular compositions of the pineal gland in zebrafish, rats, and monkeys. Zebrafish photoreceptors exhibited comprehensive phototransduction gene expression, while specific genes, including transducin (Gngt1, Gnb3, and Gngt2) and phosducin (Pdc), were consistently present in mammalian pinealocytes. We found transcriptional similarities between the pineal gland and retina, underscoring shared evolutionary and functional pathways. Zebrafish displayed unique light-responsive circadian gene activity compared to rats and monkeys. Key ligand-receptor interactions were identified, especially involving MDK and PTN, influencing melatonin synthesis across species. Furthermore, we observed species-specific GPCR (G protein-coupled receptors) expressions related to melatonin synthesis and their alignment with retinal expressions. Our findings also highlighted specific transcription factors (TFs) and regulatory networks associated with pineal gland evolution and function. Our study provides a detailed analysis of the pineal gland's evolution from fish to mammals. We identified key transcriptional changes and controls that highlight the gland's functional diversity. Notably, we found significant ligand-receptor interactions influencing melatonin synthesis and demonstrated parallels between pineal and retinal expressions. These insights enhance our understanding of the pineal gland's role in phototransduction, melatonin production, and circadian rhythms in vertebrates.


Assuntos
Melatonina , Glândula Pineal , Animais , Ratos , Glândula Pineal/metabolismo , Melatonina/metabolismo , Peixe-Zebra/genética , Ligantes , Ritmo Circadiano/genética , Mamíferos/metabolismo
12.
Biology (Basel) ; 12(11)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37997972

RESUMO

In the context of the intensification of global urbanization, how urbanization (urban heat island effect and air pollution) affects urban tree growth is not fully understood. In this paper, the radial growth and xylem anatomical characteristics of three different tree species (Quercus mongolica, Fraxinus mandshurica, and Pinus sylvestris var. mongolica) in urban and rural areas of Harbin were compared by means of tree-ring anatomy. The results showed that there were significant differences in the growth of both broadleaf trees and conifers between urban and rural areas. The vessel number, cumulative area of vessels, and theoretical hydraulic conductivity of all tree species in rural areas were higher than those in urban areas, indicating that urbanization may have the effect of slowing down growth. However, broadleaf trees in urban areas had higher vessel density and a greater percentage of a conductive area within xylem and theoretical xylem-specific hydraulic conductivity. The thickness of cell walls and cell wall reinforcement index of P. sylvestris var. mongolica were strongly reduced by air pollution, implying that it may be more sensitive to urbanization. Compared to Q. mongolica, F. mandshurica showed less sensitivity to urbanization. Warming and drying climate in Harbin may be an important factor affecting tree growth.

13.
Phys Chem Chem Phys ; 25(46): 32100-32109, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37982601

RESUMO

In order to further clarify the effect of sulfur doping on the laser damage threshold of potassium dihydrogen phosphate (KDP), the properties of sulfur substituting for phosphorus doping defects (SP) in KDP crystals with paraelectric (PE) and ferroelectric (PE) phases are studied in this article. More accurate defect transition levels were obtained by band edge correction, and the band edge corrected values were 1.28 eV and 1.88 eV for the PE and FE phases, respectively. The defect formation energies with four different defect charges (0, +1, +2, and-1) were obtained using the finite size correction scheme. The stable defect charge states were (+2 charge state) (+1 charge state) and (-1 charge state) in turn when the Fermi level moved from the valence band maximum (VBM) to the conduction band minimum (CBM). Moreover, by considering the electron-phonon coupling, the optical absorption and emission spectra were obtained. The absorption peak for the state of the PE phase at 4.63 eV was close to the experimental value. We predicted that the absorption peak at 4.50 eV belongs to the state with the FE phase. The emission peaks at 0.10 eV and 1.36 eV were related to the PE and FE phases, accordingly. The absorption may affect the application of S-KDP crystals and reduce the laser damage threshold.

14.
Microbiol Spectr ; : e0185823, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37754782

RESUMO

Public health threats posed by emerging respiratory infections are a significant concern, particularly in children and infants. Traditional culture-based detection methods are time-consuming and typically require 1-3 days. Herein, we developed and evaluated a 23-plex common respiratory pathogen mass spectrometry assay that enables the simultaneous detection of 18 common respiratory pathogens in children. This assay combines matrix-assisted laser desorption/ionization time of flight mass spectrometry with multiplex reverse transcription-PCR and targets 11 bacterial and 7 viral pathogens (including 10 subtypes), and two internal controls. The detection limit of the common respiratory pathogen mass spectrometry assay was as low as 1 copy/µL, with no cross-reactivity with other organisms. We assessed the clinical performance of the common respiratory pathogen mass spectrometry assay using respiratory samples from 450 children. The total 450 clinical specimens underwent analysis via matrix-assisted laser desorption/ionization time of flight mass spectrometry, and the outcomes were juxtaposed with those derived from real-time reverse-transcriptase PCR conducted concurrently. The concordance between these methods was 96.0%, and the multiple infection identification rate was 7.1%. This innovative approach enables the simultaneous analysis of numerous outcomes from a solitary examination across 192 specimens within a timeframe of approximately 7 hours, with a dramatically reduced sample use and cost. In summary, the common respiratory pathogen mass spectrometry assay is a sensitive, accurate, and cost-effective method for detecting common respiratory pathogens in children and has the potential to revolutionize the diagnosis of respiratory tract infections. IMPORTANCE This study aimed to present and evaluate a novel co-detection method that enables the simultaneous identification of 11 bacterial and 7 viral pathogens in about 7 hours using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Our approach utilizes a combination of multiplex reverse transcription-PCR and matrix-assisted laser desorption/ionization time of flight mass spectrometry, which overcomes the limitations of conventional assays, which include a long assessment time, technical difficulty, and high costs. As a screening method for common respiratory pathogens in children, common respiratory pathogen mass spectrometry assay has the potential to revolutionize the diagnosis of respiratory tract infections by providing an accurate etiological diagnosis. The common respiratory pathogen mass spectrometry assay is expected to be a critical tool for the diagnosis of respiratory infections in children, offering a more efficient, cost-effective, and accurate approach for the detection of common respiratory pathogens.

15.
Int J Biol Macromol ; 253(Pt 2): 126857, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37703973

RESUMO

The development of sustainable and well-performing food packaging materials takes on critical significance, whereas it is still challenging. To overcome the shortcomings of polyvinyl alcohol (PVA) as a degradable packaging material, in this work, hydrophobic quaternary ammonium salt (QAS) modified cellulose nanofibers (CNF) and tannic acid­iron ion coordination complexes (TA-Fe) were adopted for the preparation of functional PVA films. The modified CNF (CNF-QAS) not only improved the mechanical properties and water resistance of PVA, but also endowed it with antibacterial ability. In addition, the synergistic antibacterial capability with CNF-QAS was achieved using TA-Fe with photothermal therapy. As a result, the modulus, elongation at break, tensile strength, and water contact angle of the prepared PVA films were examined as 88 MPa, 200 %, 11.7 MPa, and 94.8°, respectively. Furthermore, with the assistance of CNF-QAS and TA-Fe, the films inhibited the growth of E. coli and S. aureus by 99.8 % and 99.7 %, respectively, and they exhibited high cell viability of 90.5 % for L929 fibroblasts. Based on the above encouraging properties, the functional PVA films could significantly extend the shelf life of oranges for over two weeks, proving the excellent application prospects in the food packaging field.


Assuntos
Complexos de Coordenação , Nanofibras , Álcool de Polivinil/química , Embalagem de Alimentos , Nanofibras/química , Escherichia coli , Staphylococcus aureus , Celulose/farmacologia , Celulose/química , Compostos de Amônio Quaternário/farmacologia , Antibacterianos/farmacologia , Água
16.
Cell Res ; 33(12): 940-951, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37674011

RESUMO

Members of the solute carrier organic anion transporting polypeptide (OATPs) family function as transporters for a large variety of amphipathic organic anions including endogenous metabolites and clinical drugs, such as bile salts, steroids, thyroid hormones, statins, antibiotics, antivirals, and anticancer drugs. OATP1B1 plays a vital role in transporting such substances into the liver for hepatic clearance. FDA and EMA recommend conducting in vitro testing of drug-drug interactions (DDIs) involving OATP1B1. However, the structure and working mechanism of OATPs still remains elusive. In this study, we determined cryo-EM structures of human OATP1B1 bound with representative endogenous metabolites (bilirubin and estrone-3-sulfate), a clinical drug (simeprevir), and a fluorescent indicator (2',7'-dichlorofluorescein), in both outward- and inward-open states. These structures reveal major and minor substrate binding pockets and conformational changes during transport. In combination with mutagenesis studies and molecular dynamics simulations, our work comprehensively elucidates the transport mechanism of OATP1B1 and provides the structural basis for DDI predictions involving OATP1B1, which will greatly promote our understanding of OATPs.


Assuntos
Transportador 1 de Ânion Orgânico Específico do Fígado , Humanos , Transporte Biológico , Microscopia Crioeletrônica , Fígado/metabolismo , Transportador 1 de Ânion Orgânico Específico do Fígado/química , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Transportadores de Ânions Orgânicos/química , Hormônios Tireóideos/metabolismo
17.
Int J Biol Macromol ; 244: 125353, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37330076

RESUMO

With the trend of sustainable development and the complex medical environment, there is a strong demand for multimodal antibacterial cellulose wound dressing (MACD) with photothermal therapy (PTT). Herein, a novel MACD fabrication strategy with PTT was proposed and implemented through graft polymerization of an imidazolium ionic liquid monomer containing iron complex anion structure. The fabricated hydrogels exhibited excellent antibacterial properties because of the efficient photothermal conversion ability (68.67 %) of ionic liquids and the intrinsic structural characteristic of quaternary ammonium salts. The antibacterial ratio of cellulosic hydrogel dressings to S. aureus and E. coli could reach 99.57 % and 99.16 %, respectively. Additionally, the fabricated hydrogels demonstrated extremely low hemolysis rates (<5 %) and excellent cell viability (~>85 %). Furthermore, in vivo antibacterial experimental results proved that the fabricated antibacterial dressings could significantly accelerate wound healing. Therefore, the proposed strategy would provide a new method of designing and preparing high-performance cellulose wound dressings.


Assuntos
Celulose , Líquidos Iônicos , Celulose/farmacologia , Hidrogéis/farmacologia , Escherichia coli , Staphylococcus aureus , Polímeros , Antibacterianos/farmacologia , Cicatrização
18.
Carbohydr Polym ; 315: 121001, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37230624

RESUMO

With the increasing requirements for sustainable development and environmental protection, the design and development of bio-adsorbent based on the widely sourced cellulose have attracted widespread attention. In this study, a polymeric imidazolium satls (PIMS) functionalized cellulose foam (CF@PIMS) was conveniently fabricated. It was then employed to efficiently remove ciprofloxacin (CIP). Three imidazolium salts containing phenyl groups that can lead to multiple interactions with CIP were elaborately designed and then screened through a combination of molecular simulation and removal experiments to acquire the most significant binding ability of CF@PIMS. Besides, the CF@PIMS retained the well-defined 3D network structure as well as high porosity (90.3 %) and total intrusion volume (6.05 mL g-1) as the original cellulose foam (CF). Therefore, the adsorption capacity of CF@PIMS reached an astonishing value of 736.9 mg g-1, nearly 10 times that of the CF. Furthermore, the pH-affected and ionic strength-affected adsorption experiments confirmed that the non-electrostatic interaction took on a critical significance in the adsorption. The reusability experiments showed that the recovery efficiency of CF@PIMS was higher than 75 % after 10 adsorption cycles. Thus, a high-potential method was proposed in terms of the design and preparation of functionalized bio-adsorbent to remove waste matters from samples of the environment.


Assuntos
Ciprofloxacina , Poluentes Químicos da Água , Ciprofloxacina/química , Sais , Celulose/química , Adsorção , Poluentes Químicos da Água/química , Cinética
19.
J Econ Entomol ; 116(3): 993-1001, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37177893

RESUMO

The tomato pest Phthorimaea absoluta Meyrick is highly invasive but has not yet invaded North America. However, several morphologically similar species are already present, making detection of P. absoluta presence and invasion challenging. We designed a quantitative PCR molecular diagnostic to differentiate P. absoluta, P. operculella (Zeller), or Keiferia lycopersicella (Walsingham) (Lepidoptera: Gelechiidae) DNA. Additionally, we developed an RPA-Cas12a molecular diagnostic that allows for the isothermal detection of P. absoluta DNA, eliminating the need for a thermocycler. The results of the RPA-Cas12a diagnostic can be visualized simply using a UV light source and cell phone camera. We expect these diagnostics to improve quarantine and prevention measures against this serious agricultural threat.


Assuntos
Lepidópteros , Mariposas , Solanum lycopersicum , Animais , Mariposas/genética , Solanum lycopersicum/genética , Sistemas CRISPR-Cas , Patologia Molecular , Reação em Cadeia da Polimerase
20.
Clin Immunol ; 250: 109322, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37024023

RESUMO

NK cells are one of key immune components in neuroblastoma (NB) surveillance and eradication. Glucose metabolism as a major source of fuel for NK activation is exquisitely regulated. Our data revealed a diminished NK activation and a disproportionally augmented CD56bright subset in NB. Further study showed that NK cells in NB presented with an arrested glycolysis accompanied by an elevated expression of the long noncoding RNA (lncRNA) EPB41L4A-AS1, a known crucial participant in glycolysis regulation, in the CD56bright NK subset. The inhibitory function of lncRNA EPB41L4A-AS1 was recapitulated. Interestingly, our study demonstrated that exosomal lncRNA EPB41L4A-AS1 was transferrable from CD56bright NK to CD56dim NK and was able to quench the glycolysis of target NK. Our data demonstrated that an arrested glycolysis in patient NK cells was associated with an elevated lncRNA in CD56bright NK subset and a cross-talk between heterogeneous NK subsets was achieved by transferring metabolic inhibitory lncRNA through exosomes.


Assuntos
Exossomos , Neuroblastoma , RNA Longo não Codificante , Humanos , Antígeno CD56 , Exossomos/metabolismo , Glicólise , Células Matadoras Naturais , Neuroblastoma/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
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