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1.
Nanoscale ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36723217

RESUMO

Magnetic resonance imaging (MRI)/nuclear medicine imaging (NMI) dual-modality imaging based on radiolabeled nanoparticles has been increasingly exploited for accurate diagnosis of tumor and cardiovascular diseases by virtue of high spatial resolution and high sensitivity. However, significant challenges exist in pursuing truly clinical applications, including massive preparation and rapid radiolabeling of nanoparticles. Herein, we report a clinically translatable kit for the convenient construction of MRI/NMI nanoprobes relying on the flow-synthesis and anchoring group-mediated radiolabeling (LAGMERAL) of iron oxide nanoparticles. First, homogeneous iron oxide nanoparticles with excellent performance were successfully obtained on a large scale by flow synthesis, followed by the surface anchoring of diphosphonate-polyethylene glycol (DP-PEG) to simultaneously render the underlying nanoparticles biocompatible and competent in robust labeling of radioactive metal ions. Moreover, to enable convenient and safe usage in clinics, the DP-PEG modified nanoparticle solution was freeze-dried and sterilized to make a radiolabeling kit followed by careful evaluations of its in vitro and in vivo performance and applicability. The results showed that 99mTc labeled nanoprobes are effectively obtained with a labeling yield of over 95% in 30 minutes after simply injecting Na[99mTcO4] solution into the kit. In addition, the Fe3O4 nanoparticles sealed in the kit can well stand long-term storage even for 300 days without deteriorating the colloidal stability and radiolabeling yield. Upon intravenous injection of the as-prepared radiolabeled nanoprobes, high-resolution vascular images of mice were obtained by vascular SPECT imaging and magnetic resonance angiography, demonstrating the promising clinical translational value of our radiolabeling kit.

2.
Microbiol Spectr ; : e0328822, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629433

RESUMO

The outer membrane vesicles (OMVs) produced by Porphyromonas gingivalis contain a variety of bioactive molecules that may be involved in the progression of periodontitis. However, the participation of P. gingivalis OMVs in the development of periodontitis has not been elucidated. Here, we isolated P. gingivalis OMVs and confirmed their participation in periodontitis both in vivo and in vitro. Microcomputed tomography (micro-CT) and histological analysis showed that under stimulation with P. gingivalis OMVs, the alveolar bone of rats was significantly resorbed in vivo. We found that P. gingivalis OMVs were taken up by human periodontal ligament cells ([hPDLCs]) in vitro, which subsequently resulted in apoptosis and inflammatory cytokine release, which was accomplished by the microRNA-size small RNA (msRNA) sRNA45033 in the P. gingivalis OMVs. Through bioinformatics analysis and screening of target genes, chromobox 5 (CBX5) was identified as the downstream target of screened-out sRNA45033. Using a dual-luciferase reporter assay, overexpression, and knockdown methods, sRNA45033 was confirmed to target CBX5 to regulate hPDLC apoptosis. In addition, CUT&Tag (cleavage under targets and tagmentation) analysis confirmed the mechanism that CBX5 regulates apoptosis through the methylation of p53 DNA. Collectively, these findings indicate that the role of P. gingivalis OMVs is immunologically relevant and related to bacterial virulence during the development of periodontitis. IMPORTANCE P. gingivalis is a bacterium often associated with periodontitis. This study demonstrates that (i) sRNA45033 in P. gingivalis OMVs targets CBX5, (ii) CBX5 regulates the methylation of p53 DNA and its expression, which is associated with apoptosis, and (iii) a novel mechanism of interaction between hosts and pathogens is mediated by OMVs in the occurrence of periodontitis.

3.
Exp Hematol Oncol ; 12(1): 7, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635765

RESUMO

BACKGROUND: Caspase-8 (Casp8) acts as an initiator in cell apoptosis signaling. However, the role of Casp8 in tuning the tumor immune microenvironment remains controversial due to the complicated crosstalk between immune-tolerogenic apoptotic cell death and immunogenic cell death cascades. METHODS: The Cancer Genome Atlas (TCGA) and publicly accessible immune checkpoint blockade (ICB)-treated cohorts were used to investigate the clinical relevance of Casp8. A tumor-bearing mouse model was used to characterize changes in the tumor microenvironment and to explore the efficacy of ICB treatment under Casp8 knockout conditions. RESULTS: By exploring TCGA datasets, we showed that the expression level of Casp8 was associated with an immuno-hot microenvironment across various solid tumor types. Casp8 deficiency leads to decreased CD8+ T cell infiltration and resistance to anti-PD-L1 therapy in a mouse model. Mechanistically, Casp8 deficiency or pharmacological disruption results in impaired ecto-calreticulin transition in tumor cells, which in turn hampers antigen presentation in draining lymph nodes. Furthermore, radiotherapy restored sensitivity to anti-PD-L1 treatment via elevated calreticulin surface expression. CONCLUSIONS: Our data revealed a causative role of Casp8 in modulating the immunogenicity of tumor cells and responsiveness to ICB immunotherapies and proposed radiotherapy as a salvage approach to overcome Casp8 deficiency-mediated ICB resistance.

4.
BMC Public Health ; 23(1): 64, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627582

RESUMO

BACKGROUND: People living with HIV(PLWH) are deemed more vulnerable to the SARS-CoV-2 infection than the uninfected population. Vaccination is an effective measure for COVID-19 control, yet, little knowledge exists about the willingness of men who have sex with men (MSM) living with HIV in China to be vaccinated. METHODS: This cross-sectional study evaluated the willingness of MSM living with HIV to receive COVID-19 vaccination in six cities of Guangdong, China, from July to September 2020. Factors associated with willingness to receive COVID-19 vaccination using multivariable logistic regression. RESULTS: In total, we recruited 944 HIV-positive MSM with a mean age of 29.2 ± 7.7 years. Of all participants, 92.4% of them were willing to receive the COVID-19 vaccine. Participants who were separated, divorced, or widowed (adjusted OR: 5.29, 95%CI: 1.02-27.48), had an annual income higher than 9,000 USD (adjusted OR: 1.70, 95%CI: 1.01-2.86), had ever taken an HIV self-test (adjusted OR: 1.78, 95%CI: 1.07-2.95), had ever disclosed sexual orientation to a doctor/nurse (adjusted OR: 3.16, 95%CI: 1.33-7.50), had ever disclosed sexual orientation to others besides their male partners (adjusted OR: 2.18, 95%CI: 1.29-3.69) were more willing to receive the vaccine. Sex with a female partner in the past six months decreased the likelihood of willingness to receive the vaccine (adjusted OR: 0.40, 95%CI: 0.17-0.95). Economic burden, worry that my health condition could not bear the risk of receiving COVID-19 vaccines, and concern that the vaccination would affect the immune status and antiretroviral therapy were the main reasons for unwillingness to receive vaccination. CONCLUSION: Our study showed that HIV-positive MSM had a high willingness to receive the COVID-19 vaccination. Targeted interventions such as health education should be conducted among MSM with HIV infection to enhance COVID-19 vaccine uptake.


Assuntos
COVID-19 , Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Homossexualidade Masculina , Vacinas contra COVID-19/uso terapêutico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Estudos Transversais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde , Inquéritos e Questionários , SARS-CoV-2 , Vacinação , China/epidemiologia
5.
Environ Int ; 172: 107759, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36696794

RESUMO

BACKGROUND: Bisphenol A (BPA), a ubiquitous environmental endocrine disruptor, has been extensively demonstrated to be associated with metabolic disorders, including obesity and type 2 diabetes mellitus. However, the underlying mechanism underpinning the environmental etiology of chronic metabolic disorders has not been sufficiently elucidated. OBJECTIVES: This study is designed to explore the toxicological pathogenesis of chronic inflammation in BPA exposure during obesity. METHODS: We investigated the role of IL-17A in the association of BPA exposure and obesity from human cross-sectional study to animal models, including genetically modified IL-17A-/- mice. RESULTS: Here, our work started from case-control observation that BPA exposure was significantly associated with risk of obesity (odds ratio = 4.72, 95%CI: 3.18 - 11.18, P < 0.01), metabolic disorder and levels of interleukin-17A (IL-17A) in human adipose (estimated changes ß = 0.46, 95%CI: 0.15 - 1.01, P < 0.01) with bariatric surgery. Animal model fed with high-fat diet (HFD) confirmed that BPA exposure aggravated body weight gain and insulin resistance, concurrent with much heightened inflammatory responses in the adipose tissue including increase in IL-17A and macrophage polarization towards M1 stage. Genetically modified IL-17A ablated mice (IL-17A-/-) showed reversed adipose tissue inflammation response, improved macrophage polarization homeostasis, along with insulin sensitivity in both HFD group alone or much more significantly the HFD + BPA group. Moreover, mediation analysis in human epidemiological investigation demonstrated that plasma IL-17A attributed up to 30.01% mediating role in the associations between BPA exposure and obesity risk. DISCUSSION: This research paradigm from human to animal provides strong evidence for the elucidation of IL-17A moderating inflammation and insulin resistance in obesity. Such findings reiterate the obesogenic role of environmental endocrine disruptor BPA in metabolic disorders and unveils the potential toxicological mechanisms underpinning such effect.

6.
ACS Nano ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700840

RESUMO

An electron-transport layer with appropriate energy alignment and enhanced charge transfer is critical for perovskite solar cells (PSCs). In addition, interface stress and lattice distortion are inevitable during the crystallization process of perovskite. Herein, IT-4F is introduced into PSCs at the buried SnO2 and perovskite interface, which assists in releasing the residual stress in the perovskite layer. Meanwhile, the work function of SnO2/IT-4F is lower than that of SnO2, which facilitates charge transfer from perovskite to ETL and consequently leads to a significant improvement in the power conversion efficiency (PCE) to 23.73%. The VOC obtained is as high as 1.17 V, corresponding to a low voltage deficit of 0.38 V for a 1.55 eV bandgap. Consequently, the device based on IT-4F maintains 94% of the initial PCE over 2700 h when stored in N2 and retains 87% of the initial PCE after operation for 1000 h.

7.
Nat Commun ; 14(1): 426, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702841

RESUMO

Pyroelectricity originates from spontaneous polarization variation, promising in omnipresent non-static thermodynamic energy harvesting. Particularly, changing spontaneous polarization via out-of-plane uniform heat perturbations has been shown in solar pyroelectrics. However, these approaches present unequivocal inefficiency due to spatially coupled low temperature change and duration along the longitudinal direction. Here we demonstrate unconventional giant polarization ripples in transverse pyroelectrics, without increasing the total energy input, into electricity with an efficiency of 5-fold of conventional longitudinal counterparts. The non-uniform graded temperature variation arises from decoupled heat localization and propagation, leading to anomalous in-plane heat perturbation (29-fold) and enhanced thermal disequilibrium effects. This in turn triggers an augmented polarization ripple, fundamentally enabling unprecedented electricity generation performance. Notably, the device generates a power density of 38 mW m-2 at 1 sun illumination, which is competitive with solar thermoelectrics and ferrophotovoltaics. Our findings provide a viable paradigm, not only for universal practical pyroelectric heat harvesting but for flexible manipulation of transverse heat transfer towards sustainable energy harvesting and management.

8.
Medicine (Baltimore) ; 102(1): e32622, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607879

RESUMO

BACKGROUND: Acupotomy as well as Juanbi decoction has been used in the treatment of lumbar disc herniation. However, there is no study on ultrasound-guided acupotomy combined with Juanbi decoction in the treatment of lumbar disc herniation. METHOD: This study was supported by the Sichuan Provincial Administration of Traditional Chinese Medicine [grant number: 2020LC0163] and the Science and Technology Department of Sichuan Province [grant number: 2022YFS0418]. This study was 3 center, open, randomized, controlled trial, and was carried out from December 2020 to December 2022. A total of 60 eligible patients with LDH were split into group A and group B at random. The group B received Juanbi Decoction 3 times daily for 2 weeks along with an acupotomy assisted by ultrasound. The acupotomy was administered once a week. The same protocol was used with the group A, but the Juanbi Decoction was replaced with normal saline. OBSERVATION INDEX: Visual analogue scale (VAS) score on 1 day and 1 week after treatment, VAS score, Japanese orthopedic association low back pain score(JOA) rate, Oswestry Disability Index (ODI), and low back outcome scale (LBOS) at 1, 3, 6, and 12 months after treatment in 2 groups. RESULTS: There were no significant differences in general information, VAS score before treatment, JOA, ODI, and LBOS between the 2 groups (P > .05). Intra-group comparison: VAS score, JOA rate, ODI, and LBOS were compared before and after treatment in both groups, and the differences were statistically significant (P < .05). There were significant differences in VAS and LBOS between the 2 groups at 3 and 6 months after treatment, and there were statistically significant differences in ODI and JOA rates at 3, 6, and 12 months after treatment between the 2 groups. CONCLUSION: Acupotomy aided by ultrasound combined with Juanbi Decoction significantly relieves lumbar pain and can improve lumbar function in patients with LDH, and the clinical efficacy lasts for about 6 months.


Assuntos
Terapia por Acupuntura , Deslocamento do Disco Intervertebral , Dor Lombar , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/terapia , Vértebras Lombares/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia de Intervenção
9.
Sci Adv ; 9(2): eadf5701, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36638175

RESUMO

Flexible thermoelectric harvesting of omnipresent spatial thermodynamic energy, though promising in low-grade waste heat recovery (<100°C), is still far from industrialization because of its unequivocal cost-ineffectiveness caused by low thermoelectric efficiency and power-cost coupled device topology. Here, we demonstrate unconventional upcycling of low-grade heat via physics-guided rationalized flexible thermoelectrics, without increasing total heat input or tailoring material properties, into electricity with a power-cost ratio (W/US$) enhancement of 25.3% compared to conventional counterparts. The reduced material usage (44%) contributes to device power-cost "decoupling," leading to geometry-dependent optimal electrical matching for output maximization. This offers an energy consumption reduction (19.3%), electricity savings (0.24 kWh W-1), and CO2 emission reduction (0.17 kg W-1) for large-scale industrial production, fundamentally reshaping the R&D route of flexible thermoelectrics for techno-economic sustainable heat harvesting. Our findings highlight a facile yet cost-effective strategy not only for low-grade heat harvesting but also for electronic co-design in heat management/recovery frontiers.

10.
Langenbecks Arch Surg ; 408(1): 51, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662263

RESUMO

BACKGROUND: Recently, indocyanine green (ICG) fluorescence imaging has been increasingly used in laparoscopic anatomic liver resection. The aim of this study was to investigate the efficacy of ICG-guided laparoscopic anatomic liver resection in hepatocellular carcinoma (HCC) compared with traditional laparoscopic anatomic liver resection. METHODS: A retrospective study was performed on patients with pathologically diagnosed HCC who successfully underwent laparoscopic anatomical liver resection from January 2019 to December 2021. The outcomes were compared between the two groups before and after the propensity score matching (PSM). RESULTS: A total of 110 patients were included in this study, including 50 patients in the ICG-guided group and 60 patients in the traditional group. Compared with the traditional group, the ICG-guided group had a shorter operative duration (P = 0.040), less intraoperative blood loss (P = 0.044), a lower incidence of postoperative complications (P = 0.023), and a shorter postoperative hospitalisation (P < 0.001). After PSM, significant differences remained between the two groups for the duration of postoperative hospitalisation (P = 0.018) and postoperative complications (P = 0.042). There was no significant difference in the recurrence rate between the two groups before and after PSM. CONCLUSION: Laparoscopic anatomic liver resection guided by ICG fluorescence imaging can reduce the duration of postoperative hospitalisation for patients and the incidence of postoperative complications. However, it has no impact on the long-term outcome of patients.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Verde de Indocianina , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Hepatectomia/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Imagem Óptica/métodos
11.
Aging Clin Exp Res ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656506

RESUMO

PURPOSE: This study aimed to explore the correlation between nutritional status screening using the MNA-SF and stroke-associated infections (SAI) in older adults. METHODS: A retrospective study of patients aged over 70 years with acute stroke was conducted. The patients were divided into normal nutritional status, malnutrition risk, and malnutrition groups depending on their baseline MNA-SF scores. The correlation between nutritional status and SAI was identified using multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to demonstrate the predicted value of MNA-SF. RESULTS: 497 patients were included, 101 (20.32%) developed SAI. 32.29% of patients with malnutrition developed SAI, while 25.14% of those with malnutrition risk developed SAI. Malnutrition (aOR 4.58, 95% CI 2.34-8.96, p < 0.001) and risk of malnutrition (aOR 3.70, 95%CI 2.01-6.85, p < 0.001) were independent risk factors for SAI in older stroke patients. The area under the curve (AUC) value of MNA-SF was 0.713. CONCLUSION: MNA-SF is a simple and effective nutritional screening tool for predicting the occurrence of SAI in older patients with acute stroke.

12.
iScience ; 26(1): 105761, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36594012

RESUMO

The light-harvesting complex II of Bryopsis corticulans (B-LHCII), a green alga, differs from that of spinach (S-LHCII) in chlorophyll (Chl) and carotenoid (Car) compositions. We investigated ultrafast excitation dynamics of B-LHCII with visible-to-near infrared time-resolved absorption spectroscopy. Absolute fluorescence quantum yield (Φ FL) of LHCII and spectroelectrochemical (SEC) spectra of Chl a and b were measured to assist the spectral analysis. Red-light excitation at Chl Qy-band, but not Car-band, induced transient features resembling the characteristic SEC spectra of Chl a ⋅+ and Chl b ⋅-, indicating ultrafast photogeneration of Chl-Chl charge transfer (CT) species; Φ FL and 3Car∗ declined whereas CT species increased upon prolonging excitation wavelength, showing positive correlation of 1Chl∗ deactivation with Chl-Chl CT formation. Moreover, ultrafast Chl b-to-Chl a and Car-to-Chl singlet excitation transfer were illustrated. The red-light induction of Chl-Chl CT species, as also observed for S-LHCII, is considered a general occurrence for LHCIIs in light-harvesting form.

13.
Reprod Sci ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694081

RESUMO

Embryo implantation and decidualization are key steps in establishing a successful pregnancy. Defects in embryo implantation and decidualization can cause a series of adverse chain reactions which can contribute to harmful pregnancy outcomes, such as embryo growth retardation, preeclampsia, miscarriage, premature birth, and so on. Approximately 75% of failed pregnancies are considered to be due to embryo implantation failure or defects. Decidualization, characterized by proliferation and differentiation of uterine stromal cells, is one of the essential conditions for blastocyst implantation, placental formation, and maintenance of pregnancy and is indispensable for the establishment of pregnancy in many species. Embryo implantation and decidualization are closely regulated by estrogen and progesterone secreted by the ovaries. Many cellular events and molecular signaling network pathways are involved in this process. This article reviews the recent advances in the molecular mechanisms of estrogen- and progesterone-regulating uterine receptivity establishment, blastocyst implantation, and decidualization, in order to better understand the underlying molecular mechanisms of hormonal regulation of embryo implantation and to develop new strategies for preventing or treating embryo implantation defects and improving the pregnancy rate of women.

14.
Psychiatry Res ; 321: 115073, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36716553

RESUMO

Nicotine addiction is a neuropsychiatric disorder with dysfunction in cortices as well as white matter (WM). The nature of the functional alterations in WM remains unclear. The small-world model can well characterize the structure and function of the human brain. In this study, we utilized the small-world model to compare the WM functional connectivity between 62 nicotine addiction participants (called the discovery sample) and 66 matched healthy controls (called the control sample). We also recruited an independent sample comprising 32 nicotine addicts (called the validation sample) for clinical application. The WM functional network data at the network level showed that the nicotine addiction group revealed decreased small-worldness index (σ) and normalized clustering coefficient (γ) compared with healthy controls. For clinical application, the small-world topology of WM functional connectivity could distinguish nicotine addicts from healthy controls (classification accuracy=0.59323, p = 0.0464). We trained abnormal small-world properties on the discovery sample to identify the severity of nicotine addiction, and the identification was successfully applied to the validation sample (classification accuracy=0.65625, p = 0.0106). Our neuroimaging findings provide direct evidence for WM functional changes in nicotine addiction and suggest that the small-world properties of WM function could be qualified as potential biomarkers in nicotine addiction.

16.
J Environ Manage ; 328: 117200, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36608456

RESUMO

A novel electromagnetic induction low temperature thermal desorption treatment (EMI LTTD) for petroleum hydrocarbons contaminated soil was introduced in this work. The removal rate of total petroleum hydrocarbons (TPH) under various factors, the morphology changes of soils as well as removal mechanism were investigated. Results suggested that increasing the heating temperature significantly increased the removal rate of TPH. At the beginning of 20 min, most of hydrocarbons (93.44-96.91 wt%) was removed with the temperature ranged from 200 °C to 300 °C. Besides, the initial contaminants concentration, particle size and thickness of soil slightly influenced the removal rate of TPH. Desorption kinetic study demonstrated that first-order model was well-described for desorption behavior. Response surface methodology analysis showed the temperature of 216 °C, the residence time of 21 min and the moisture content of 18% was an optimum condition recommended for potentially practical application. Under this condition, the results for the composition of hydrocarbons based on carbon number fractions indicated that the fractions of C10∼C16, C17∼C22 still existed in soil, while C23∼C28 was not detected after EMI LTTD treatment. Proposed mechanism was both hydrocarbons removed by evaporation at any temperature, while parts of heavy hydrocarbons was cracked within the soil close to induction medium, resulting in re-adsorption of light hydrocarbons. A buckwheat germination and growth test indicated that soil treated by EMI LTTD was potential in reutilization for planting.


Assuntos
Poluição por Petróleo , Petróleo , Poluentes do Solo , Petróleo/análise , Solo/química , Poluentes do Solo/análise , Hidrocarbonetos/química , Poluição por Petróleo/análise , Biodegradação Ambiental
17.
J Enzyme Inhib Med Chem ; 38(1): 2169682, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36688444

RESUMO

A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The in vitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC50 values of 1.3 µM and 0.81 µM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1ß and NO. In addition, compound 3f presented significant neuroprotective effect on Aß25-35-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes in vitro and plasma. Furthermore, compound 3f could improve AlCl3-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.


Assuntos
Doença de Alzheimer , Hidroxiquinolinas , Fármacos Neuroprotetores , Quinolinas , Animais , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Carbamatos/farmacologia , Peixe-Zebra , Inibidores da Colinesterase/farmacologia , Quinolinas/farmacologia , Desenho de Fármacos , Acetilcolinesterase/metabolismo , Relação Estrutura-Atividade , Estrutura Molecular
18.
Pain Res Manag ; 2023: 7088004, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36686371

RESUMO

Objective: The purpose of the present study (a randomized clinical trial) was to evaluate the preemptive analgesic effects of pregabalin combined with celecoxib in total knee arthroplasty (TKA). Methods: From January 2019 to June 2021, we enrolled 149 patients who underwent TKA and divided them into four groups: the placebo group (n = 36), celecoxib group (n = 38), pregabalin group (n = 38), and combination group (n = 37). Each group was given the corresponding preemptive analgesia regimen at 12 and 2 hours before surgery. The pain score at rest and upon movement, cumulative dosage of sufentanil, knee range of motion (ROM), high-sensitivityC-reactive protein (hs-CRP) level, and adverse effects were evaluated after TKA to compare the effects of the preemptive analgesia regimens among the four groups. Results: The pain scores upon movement were significantly lower in the combination group than in the other three groups at 6, 12, 24, and 48 hours after surgery (P < 0.05). The cumulative dose of sufentanil within 48 hours after surgery was lowest in the combined group among the four groups (P < 0.05). Hs-CRP, ROM, and postoperative nausea and vomiting (PONV) were within 72 hours after surgery significantly improved in the combination group compared with those of the three other groups (P < 0.05). Conclusion: The preemptive analgesia regimen of pregabalin combined with celecoxib had positive effects on improving acute pain and reducing the cumulative dose of opioids after TKA. This trial is registered with ChiCTR2100041595.


Assuntos
Analgesia , Artroplastia do Joelho , Humanos , Celecoxib/uso terapêutico , Pregabalina/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Sufentanil , Estudos Prospectivos , Proteína C-Reativa , Analgésicos Opioides/uso terapêutico , Dor/etiologia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Método Duplo-Cego
19.
World J Clin Cases ; 11(1): 92-103, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36687184

RESUMO

BACKGROUND: In recently diagnosed patients with thyroid cancer, papillary thyroid cancer (PTC), as the most common histological subtype, accounts for 90% of all cases. Although PTC is known as a relatively adolescent malignant disease, there still is a high possibility of recurrence in PTC patients with a poor prognosis. Therefore, new biomarkers are necessary to guide more effective stratification of PTC patients and personalize therapy to avoid overtreatment or inadequate treatment. Accumulating evidence demonstrates that microRNAs (miRNAs) have broad application prospects as diagnostic biomarkers in cancer. AIM: To explore novel markers consisting of miRNA-associated signatures for PTC prognostication. METHODS: We obtained and analyzed the data of 497 PTC patients from The Cancer Genome Atlas. The patients were randomly assigned to either a training or testing cohort. RESULTS: We discovered 237 differentially expressed miRNAs in tumorous thyroid tissues compared with normal tissues, which contained 172 up-regulated and 65 down-regulated miRNAs. The evaluation of differently expressed miRNAs was conducted using our risk score model. We then successfully generated a four-miRNA potential prognostic signature [risk score = (-0.001 × hsa-miR-181a-2-3p) + (0.003 × hsa-miR-138-5p) + (-0.018 × hsa-miR-424-3p) + (0.284 × hsa-miR-612)], which reliably distinguished patients from high and low risk with a significant difference in the overall survival (P < 0.01) and was effective in predicting the five-year disease survival rate with the area under the receiver operating characteristic curve of 0.937 and 0.812 in the training and testing cohorts, respectively. Additionally, there was a trend indicated that high-risk patients had shorter relapse-free survival, although statistical significance was not reached (P = 0.082) in our sequencing cohort. CONCLUSION: Our results indicated a four-miRNA signature that has a robust predictive effect on the prognosis of PTC. Accordingly, we would recommend more radical therapy and closer follow-ups for high-risk groups.

20.
Am J Trop Med Hyg ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36689943

RESUMO

Malaria is a parasitic disease caused by Plasmodium, and Anopheles sinensis is a vector of malaria. Although malaria is no longer indigenous to China, a high risk remains for local transmission of imported malaria. This study aimed to identify the risk distribution of vector An. sinensis and malaria transmission. Using data collected from routine monitoring in Shanghai from 2010 to 2020, online databases for An. sinensis and malaria, and environmental variables including climate, geography, vegetation, and hosts, we constructed 10 algorithms and developed ensemble models. The ensemble models combining multiple algorithms (An. sinensis: area under the curve [AUC] = 0.981, kappa = 0.920; malaria: AUC = 0.959, kappa = 0.800), with the best out-of-sample performance, were used to identify important environmental predictors for the risk distributions of An. sinensis and malaria transmission. For An. sinensis, the most important predictor in the ensemble model was moisture index, which reflected degree of wetness; the risk of An. sinensis decreased with higher degrees of wetness. For malaria transmission, the most important predictor in the ensemble model was the normalized differential vegetation index, which reflected vegetation cover; the risk of malaria transmission decreased with more vegetation cover. Risk levels for An. sinensis and malaria transmission for each district of Shanghai were presented; however, there was a mismatch between the risk classification maps of An. sinensis and malaria transmission. Facing the challenge of malaria transmission in Shanghai, in addition to precise An. sinensis monitoring in risk areas of malaria transmission, malaria surveillance should occur even in low-risk areas for An. sinensis.

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