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1.
PLoS Pathog ; 20(1): e1011949, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38285715

RESUMO

Schistosomes are flatworm parasites that undergo a complex life cycle involving two hosts. The regulation of the parasite's developmental processes relies on both coding RNAs and non-coding RNAs. However, the roles of non-coding RNAs, including long non-coding RNAs (lncRNAs) in schistosomes remain largely unexplored. Here we conduct advanced RNA sequencing on male and female S. japonicum during their pairing and reproductive development, resulting in the identification of nearly 8,000 lncRNAs. This extensive dataset enables us to construct a comprehensive co-expression network of lncRNAs and mRNAs, shedding light on their interactions during the crucial reproductive stages within the mammalian host. Importantly, we have also revealed a specific lncRNA, LNC3385, which appears to play a critical role in the survival and reproduction of the parasite. These findings not only enhance our understanding of the dynamic nature of lncRNAs during the reproductive phase of schistosomes but also highlight LNC3385 as a potential therapeutic target for combating schistosomiasis.


Assuntos
Parasitos , RNA Longo não Codificante , Schistosoma japonicum , Esquistossomose , Animais , Masculino , Feminino , Schistosoma japonicum/genética , RNA Longo não Codificante/genética , RNA Antissenso/genética , Esquistossomose/parasitologia , Parasitos/genética , Mamíferos
2.
J Biol Chem ; 300(7): 107369, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38750792

RESUMO

Phytochromes (Phys) are a diverse collection of photoreceptors that regulate numerous physiological and developmental processes in microorganisms and plants through photointerconversion between red-light-absorbing Pr and far-red light-absorbing Pfr states. Light is detected by an N-terminal photo-sensing module (PSM) sequentially comprised of Period/ARNT/Sim (PAS), cGMP-phosphodiesterase/adenylyl cyclase/FhlA (GAF), and Phy-specific (PHY) domains, with the bilin chromophore covalently-bound within the GAF domain. Phys sense light via the Pr/Pfr ratio measured by the light-induced rotation of the bilin D-pyrrole ring that triggers conformational changes within the PSM, which for microbial Phys reaches into an output region. A key step is a ß-stranded to α-helical reconfiguration of a hairpin loop extending from the PHY domain to contact the GAF domain. Besides canonical Phys, cyanobacteria express several variants, including a PAS-less subfamily that harbors just the GAF and PHY domains for light detection. Prior 2D-NMR studies of a model PAS-less Phy from Synechococcus_sp._JA-2-3B'a(2-13) (SyB-Cph1) proposed a unique photoconversion mechanism involving an A-pyrrole ring rotation while magic-angle-spinning NMR probing the chromophore proposed the prototypic D-ring flip. To help solve this conundrum, we determined the crystallographic structure of the GAF-PHY region from SyB-Cph1 as Pr. Surprisingly, this structure differs from canonical Phys by having a Pr ZZZsyn,syn,anti bilin configuration but shifted to the activated position in the binding pocket with consequent folding of the hairpin loop to α-helical, an architecture common for Pfr. Collectively, the PSM of SyB-Cph1 as Pr displayed a mix of dark-adapted and photoactivated features whose co-planar A-C pyrrole rings support a D-ring flip mechanism.


Assuntos
Proteínas de Bactérias , Fitocromo , Fitocromo/química , Fitocromo/metabolismo , Fitocromo/genética , Cristalografia por Raios X , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Cianobactérias/metabolismo , Luz , Domínios Proteicos , Modelos Moleculares , Conformação Proteica
3.
Plant J ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240190

RESUMO

The lenticel is a channel-like structure that facilitates oxygen, carbon dioxide, and water vapor exchange on secondary growth tissue, such as a tree stem. Although the structure of lenticel has been described, there is limited understanding regarding the impact of this secondary structure on secondary growth as well as the cellular and metabolic processes underlying its formation. The study reveals the essential role of the lenticel in the process of tree secondary growth and the cellular and metabolic processes that take place during its formation. Under the stomata, lenticel development occurs when cells divide and differentiate into a structure of disconnected cells with air spaces between them. During lenticel formation, specific metabolic pathways and wax biosynthesis are activated. The SERK (somatic embryogenesis receptor kinase) gene controls lenticel density, and serk1serk3serk5 triple mutants enhance lenticel initiation. The findings shed light on the cellular and metabolic processes involved in lenticel formation, laying the groundwork for further mechanistic elucidation of their development, function, and genetic regulation in trees.

4.
Clin Infect Dis ; 78(4): 880-888, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38015658

RESUMO

BACKGROUND: Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster (HZ) and results in severe refractory neuropathic pain. This study aimed at evaluating the efficacy of premedication with duloxetine in the prevention of PHN. METHODS: The PROCESS trial is a multicenter, randomized, open-label, blinded-endpoint trial used a 1:1 duloxetine:control ratio. Adults 50 years or older with HZ who presented with vesicles within 72 hours were recruited. The primary outcome was the incidence of PHN at 12 weeks. PHN was defined as any pain intensity score other than 0 mm on the visual analog scale (VAS) at week 12 after the onset of the rash. The secondary outcomes were the number of participants with VAS >0 and VAS ≥3. The modified intention-to-treat (mITT) principle and per-protocol (PP) principle were used for the primary outcome analysis. RESULTS: A total of 375 participants were randomly assigned to the duloxetine group and 375 were assigned to the control group. There was no significant difference in the incidence of PHN in the duloxetine group compared with the control group in the mITT analysis (86 [22.9%] of 375 vs 108 [28.8%] of 375; P = .067). PP analysis produced similar results. However, there were significant differences between the 2 groups in the number of participants with VAS >0 and VAS ≥3 (P < .05 for all comparisons). CONCLUSIONS: Although absolute prevention of PHN does not occur, this trial found that premedication with duloxetine can reduce pain associated with HZ, and therefore can have clinically relevant benefits. Clinical Trials Registration. Clinicaltrials.gov, NCT04313335. Registered on 18 March 2020.


Assuntos
Herpes Zoster , Neuralgia Pós-Herpética , Adulto , Humanos , Neuralgia Pós-Herpética/tratamento farmacológico , Neuralgia Pós-Herpética/prevenção & controle , Neuralgia Pós-Herpética/epidemiologia , Cloridrato de Duloxetina/uso terapêutico , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Medição da Dor/efeitos adversos , Medição da Dor/métodos
5.
Mol Pain ; 20: 17448069241226960, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38172075

RESUMO

Repeated use of opioid analgesics may cause a paradoxically exacerbated pain known as opioid-induced hyperalgesia (OIH), which hinders effective clinical intervention for severe pain. Currently, little is known about the neural circuits underlying OIH modulation. Previous studies suggest that laterocapsular division of the central nucleus of amygdala (CeLC) is critically involved in the regulation of OIH. Our purpose is to clarify the role of the projections from infralimbic medial prefrontal cortex (IL) to CeLC in OIH. We first produced an OIH model by repeated fentanyl subcutaneous injection in male rats. Immunofluorescence staining revealed that c-Fos-positive neurons were significantly increased in the right CeLC in OIH rats than the saline controls. Then, we used calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) labeling and the patch-clamp recordings with ex vivo optogenetics to detect the functional projections from glutamate pyramidal neurons in IL to the CeLC. The synaptic transmission from IL to CeLC, shown in the excitatory postsynaptic currents (eEPSCs), inhibitory postsynaptic currents (eIPSCs) and paired-pulse ratio (PPR), was observably enhanced after fentanyl administration. Moreover, optogenetic activation of this IL-CeLC pathway decreased c-Fos expression in CeLC and ameliorated mechanical and thermal pain in OIH. On the contrary, silencing this pathway by chemogenetics exacerbated OIH by activating the CeLC. Combined with the electrophysiology results, the enhanced synaptic transmission from IL to CeLC might be a cortical gain of IL to relieve OIH rather than a reason for OIH generation. Scaling up IL outputs to CeLC may be an effective neuromodulation strategy to treat OIH.


Assuntos
Analgésicos Opioides , Hiperalgesia , Ratos , Masculino , Animais , Hiperalgesia/metabolismo , Analgésicos Opioides/metabolismo , Ratos Sprague-Dawley , Tonsila do Cerebelo/metabolismo , Dor/metabolismo , Fentanila , Córtex Pré-Frontal/metabolismo
6.
Anal Chem ; 96(13): 5251-5257, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38512289

RESUMO

The electrochemiluminescence (ECL) intensity can be regulated by ionic current passing through the microchannel, which broadened the regulation of the ECL sensors. But in the early reported sensors, the electrostatic repulsion and steric hindrance caused few targets to approach the interface of the microchannel driven by concentration difference, which reduced the detection efficiency and prolonged the detection period. In this study, different accumulation strategies, such as a positive electric field and different polarity electric fields, were designed to accumulate targets in the microchannel. The interaction of azide groups and hydrogen sulfide served as a research model. Hydrogen sulfide can react with the negatively charged azide groups in the microchannel surface to produce positively charged amino groups, decreasing the negative charge density of the microchannel and thus altering the ionic current and ECL intensity. The accumulation of hydrogen sulfide at the microchannel tip can increase the collision probability with azide groups to improve the detection efficiency, and the integration of accumulation and reaction can shorten the detection period to 28 min. The hydrogen sulfide concentration on the microchannel tip accumulated by applying different polarity electric fields was 22.3-fold higher than that accumulated by applying a positive electric field. The selected research model broadened the application range of a microchannel-based ECL sensor and confirmed the universality of the microchannel-based ECL sensor.

7.
Anal Chem ; 96(33): 13710-13718, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39115804

RESUMO

Homogeneous electrochemiluminescence (ECL) has gained attention for its simplicity and stability. However, false positives due to solution background interference pose a challenge. To address this, magnetic ECL nanoparticles (Fe3O4@Ru@SiO2 NPs) were synthesized, offering easy modification, magnetic separation, and stable luminescence. These were utilized in an ECL sensor for miRNA-155 (miR-155) detection, with locked DNAzyme and substrate chain (mDNA) modified on their surface. The poor conductivity of long-chain DNA significantly impacts the conductivity and electron transfer capability of Fe3O4@Ru@SiO2 NPs, resulting in weaker ECL signals. Upon target presence, unlocked DNAzyme catalyzes mDNA cleavage, leading to shortened DNA chains and reduced density. In contrast, the presence of short-chain DNA has minimal impact on the conductivity and electron transfer capability of Fe3O4@Ru@SiO2 NPs. Simultaneously, the material surface's electronegativity decreases, weakening the electrostatic repulsion with the negatively charged electrode, resulting in the system detecting stronger ECL signals. This sensor enables homogeneous ECL detection while mitigating solution background interference through magnetic separation. Within a range of 100 fM to 10 nM, the sensor exhibits a linear relationship between ECL intensity and target concentration, with a 26.91 fM detection limit. It demonstrates high accuracy in clinical sample detection, holding significant potential for clinical diagnostics. Future integration with innovative detection strategies may further enhance sensitivity and specificity in biosensing applications.


Assuntos
DNA , Técnicas Eletroquímicas , Medições Luminescentes , MicroRNAs , Dióxido de Silício , MicroRNAs/análise , Técnicas Eletroquímicas/métodos , DNA/química , Dióxido de Silício/química , Humanos , Técnicas Biossensoriais/métodos , Propriedades de Superfície , DNA Catalítico/química , DNA Catalítico/metabolismo , Nanopartículas de Magnetita/química , Limite de Detecção , Rutênio/química
8.
Anal Chem ; 96(10): 4290-4298, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38427621

RESUMO

Halide perovskites have emerged as a highly promising class of photoelectric materials. However, the application of lead-based perovskites has been hindered by their toxicity and relatively weak stability. In this work, a composite material comprising a lead-free perovskite cesium copper iodide (CsCu2I3) nanocrystal and a metal-organic framework (MOF-801) has been synthesized through an in situ growth approach. The resulting composite material, denoted as CsCu2I3/MOF-801, demonstrates outstanding stability and exceptional optoelectronic characteristics. MOF-801 may serve a dual role by acting as a protective barrier between CsCu2I3 nanocrystals and the external environment, as well as promoting the efficient transfer of photogenerated charge carriers, thereby mitigating their recombination. Consequently, CsCu2I3/MOF-801 demonstrates its utility by providing both stability and a notably high initial photocurrent. Leveraging the inherent reactivity between H2S and the composite material, which results in the formation of Cu2S and structural alteration, an exceptionally sensitive photoelectrochemical sensor for H2S detection has been designed. This sensor exhibits a linear detection range spanning from 0.005 to 100 µM with a remarkable detection limit of 1.67 nM, rendering it highly suitable for precise quantification of H2S in rat brains. This eco-friendly sensor significantly broadens the application horizon of perovskite materials and lays a robust foundation for their future commercialization.

9.
Ecol Appl ; 34(1): e2811, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36708137

RESUMO

Biological invasions have become a worldwide problem, and measures to efficiently prevent and control invasions are still in development. Like many other parts of the world, China is undergoing a dramatic increase in plant invasions. Most of the currently 933 established (i.e., naturalized) plant species, of which 214 are categorized as invasive, have been introduced into China for cultivation. It is likely that many of those species are still being traded, particularly online, by plant nurseries. However, studies assessing whether naturalized and invasive species are currently being traded more or less than nonnaturalized aliens are rare. We extracted online-trade information for 13,718 cultivated alien plant taxa on 1688.com, the largest website for domestic B2B in China. We analyzed how the presence in online-nursery catalogs, the number of online nurseries that offerred the species for sale, and the product type (i.e., seeds, live plants and vegetative organs) differed among nonnaturalized, naturalized noninvasive, and invasive species. Compared to nonnaturalized taxa, naturalized noninvasive and invasive taxa were 3.7-5.2 times more likely to be available for purchase. Naturalized noninvasive and invasive taxa were more frequently offered as seeds by online nurseries, whereas nonnaturalized taxa were more frequently offered as live plants. Based on these findings, we propose that, to reduce the further spread of invasive and potentially invasive plants, implementation of plant-trade regulations and a monitoring system of the online horticultural supply chain will be essential.


Assuntos
Espécies Introduzidas , Plantas , Sementes , Comércio , China
10.
J Org Chem ; 89(12): 8878-8887, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38845522

RESUMO

A one-pot approach has been developed for the synthesis of α-ketothioamide derivatives from sulfur ylides, nitrosobenzenes, and thioacetic acid. This protocol is carried out under mild reaction conditions in generally moderate to excellent yields without any precious catalysts, affording the derivatives with structural diversity. Additionally, a possible mechanism for this chemical transformation is proposed.

11.
J Cardiovasc Pharmacol ; 84(1): 45-57, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38922585

RESUMO

ABSTRACT: Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein cholesterol is the primary goal in preventing and treating AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in regulating low-density lipoprotein cholesterol metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20( S )-protopanaxatriol (20( S )-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20( S )-PPT were investigated in vivo and in vitro by Western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and other assays. The in vitro experiments revealed that 20( S )-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low-density lipoprotein receptor protein levels, promoted low-density lipoprotein uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of forkhead box O3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20( S )-PPT upregulated aortic α-smooth muscle actin expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol diet in ApoE -/- mice (high-cholesterol diet-fed group). Additionally, 20( S )-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the high-cholesterol diet-fed group. The study revealed that 20( S )-PPT inhibited low-density lipoprotein receptor degradation via PCSK9 to alleviate AS.


Assuntos
Aorta , Doenças da Aorta , Aterosclerose , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Placa Aterosclerótica , Pró-Proteína Convertase 9 , Receptores de LDL , Sapogeninas , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Aterosclerose/genética , Sapogeninas/farmacologia , Pró-Proteína Convertase 9/metabolismo , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Receptores de LDL/metabolismo , Humanos , Masculino , Doenças da Aorta/patologia , Doenças da Aorta/prevenção & controle , Doenças da Aorta/metabolismo , Doenças da Aorta/genética , Doenças da Aorta/tratamento farmacológico , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Proteólise/efeitos dos fármacos , Células Hep G2 , Inibidores de PCSK9 , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Camundongos , Dieta Hiperlipídica , Apolipoproteínas E
12.
Analyst ; 149(3): 815-823, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38117163

RESUMO

The constrained enzymatic activity and aggregation challenges encountered by small-sized nanozymes pose obstacles to their practical utility, necessitating a strategy to mitigate aggregation and boost enzymatic catalytic efficiency. In this work, a negatively charged Eu MOF was utilized as the encapsulation matrix, encapsulating the small-sized nanozymes FeNCDs into the Eu MOF to synthesize an FeNCDs@Eu MOF. The dispersibility of the encapsulated FeNCDs was increased, and owing to the negative charge of the FeNCDs@Eu MOF, electrostatic pre-concentration of the positively charged target molecule tetracycline (TC) was facilitated, thereby amplifying the enzymatic catalytic efficiency of the FeNCDs. The response of the FeNCDs to TC increased by nearly 6 times upon encapsulation. The TC detection limit (LOD) of the FeNCDs@Eu MOF-based sensor is as low as 11.63 nM. The incorporation of fluorescence detection expanded the linear range of the sensor, rendering it more suitable for practical sample detection.


Assuntos
Colorimetria , Európio , Tetraciclina , Antibacterianos , Corantes Fluorescentes , Espectrometria de Fluorescência
13.
Headache ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39193836

RESUMO

OBJECTIVE: To explore the efficacy and safety of 5% lidocaine-medicated plaster (LMP) in patients with trigeminal neuralgia (TN). BACKGROUND: TN is an excruciatingly painful type of neuropathic facial pain. Anti-epileptics are the first-line treatment for TN; however, these oral drugs alone sometimes fail to achieve satisfactory analgesic effects. Two retrospective studies have shown that LMP can be an effective and safe treatment option for some patients with TN. No other high-quality clinical studies have explored the effect and safety of LMP in patients with TN. METHODS: The PATCH trial is an enriched enrollment with randomized withdrawal, double-blind, vehicle-controlled, parallel-group trial performed at five study centers. Eligible patients with TN received LMP during a 3-week initial open-label phase. Patients who met the response criteria entered the double-blind treatment phase and were randomly assigned for treatment with either LMP (LMP group) or vehicle patches (control group) at a 1:1 ratio. Patients who met the criteria for treatment failure were withdrawn from the double-blind treatment phase, and treatment was continued in the remaining patients for up to 28 days. The primary outcome was the number of treatment failures. The secondary endpoints were the time to loss of therapeutic response (LTR) in the double-blind phase and the weekly mean pain severity in both the open-label phase and the double-blind phase of the study. RESULTS: The first patient was enrolled in this study on May 1, 2021, and the enrollment of the last patient was completed on August 26, 2022. A total of 307 patients were initially screened, 226 (74.0%) of whom entered the open-label phase. Of the 226 respondents, 124 (55.0%) were randomized to the double-blind phase. In the double-blind phase, 62 patients were assigned to the LMP group, and 62 were assigned to the control group. For the primary endpoint, 16 (26.0%) patients with LMP and 36 (58.0%) patients with vehicle patches met the treatment failure criteria during the double-blind phase (relative risk, 0.48; 95% confidence interval [CI], 0.31 to 0.75; p < 0.001). The survival curve of the LTR showed that the LTR of LMP was significantly longer than that of the vehicle patches (hazard ratio, 0.275; 95% CI, 0.15 to 0.50; log-rank p < 0.001). LMP also significantly reduced the weekly mean pain severity in the double-blind phase of the study (p = 0.007). CONCLUSIONS: LMP produced partial relief of pain symptoms in some patients with TN. For responders, LMP may be used as an add-on therapy in a multidrug treatment protocol.

14.
Environ Sci Technol ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264176

RESUMO

As regulatory standards for per- and polyfluoroalkyl substances (PFAS) become increasingly stringent, innovative water treatment technologies are urgently demanded for effective PFAS removal. Reported sorbents often exhibit limited affinity for PFAS and are frequently hindered by competitive background substances. Recently, fluorinated sorbents (abbreviated as fluorosorbents) have emerged as a potent solution by leveraging fluorine-fluorine (F···F) interactions to enhance selectivity and efficiency in PFAS removal. This review delves into the designs and applications of fluorosorbents, emphasizing how F···F interactions improve PFAS binding affinity. Specifically, the existence of F···F interactions results in removal efficiencies orders of magnitude higher than other counterpart sorbents, particularly under competitive conditions. Furthermore, we provide a detailed analysis of the fundamental principles underlying F···F interactions and elucidate their synergistic effects with other sorption forces, which contribute to the enhanced efficacy and selectivity. Subsequently, we examine various fluorosorbents and their synthesis and fluorination techniques, underscore the importance of accurately characterizing F···F interactions through advanced analytical methods, and emphasize the significance of this interaction in developing selective sorbents. Finally, we discuss challenges and opportunities associated with employing advanced techniques to guide the design of selective sorbents and advocate for further research in the development of sustainable and cost-effective treatment technologies leveraging F···F interactions.

15.
BMC Cardiovasc Disord ; 24(1): 147, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448835

RESUMO

OBJECTIVE: Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate whether there is an effective sedative that can prevent postoperative delirium while also examining the safety of using sedatives during the perioperative period. METHODS: The net-meta analysis was used to compare the incidence of postoperative delirium among four sedatives: sevoflurane, propofol, dexmedetomidine, and midazolam. Interventions were ranked according to their surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 41 RCT studies involving 6679 patients were analyzed. Dexmedetomidine can effectively reduce the incidence of postoperative delirium than propofol (OR 0.47 95% CI 0.25-0.90), midazolam (OR 0.42 95% CI 0.17-1.00), normal saline (OR 0.42 95% CI 0.33-0.54) and sevoflurane (OR 0.39 95% CI 0.18-0.82). The saline group showed a significantly lower incidence of bradycardia compared to the group receiving dexmedetomidine (OR 0.55 95% CI 0.37-0.80). In cardiac surgery, midazolam (OR 3.34 95%CI 2.04-5.48) and normal saline (OR 2.27 95%CI 1.17-4.39) had a higher rate of postoperative delirium than dexmedetomidine, while in non-cardiac surgery, normal saline (OR 1.98 95%CI 1.44-2.71) was more susceptible to postoperative delirium than dexmedetomidine. CONCLUSION: Our analysis suggests that dexmedetomidine is an effective sedative in preventing postoperative delirium whether in cardiac surgery or non-cardiac surgery. The preventive effect of dexmedetomidine on postoperative delirium becomes more apparent with longer surgical and extubation times. However, it should be administered with caution as it was found to be associated with bradycardia.


Assuntos
Anestésicos , Delírio do Despertar , Hipnóticos e Sedativos , Humanos , Anestésicos/uso terapêutico , Bradicardia , Dexmedetomidina , Delírio do Despertar/prevenção & controle , Hipnóticos e Sedativos/uso terapêutico , Midazolam , Propofol , Solução Salina , Sevoflurano , Metanálise em Rede
16.
Bioorg Chem ; 148: 107450, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761704

RESUMO

Here, a series of 3-(6-aminopyridin-3-yl) benzamide derivatives were designed and synthesized. Cell viability assay indicated that most compounds exhibited potent antiproliferative activity against all the tested cancer cells. Among them, compound 7l displayed the best antiproliferative activity particularly in A549 cells, with an IC50 value of 0.04 ± 0.01 µM. RNA-seq analysis was employed to explore the potential pathways related to the antiproliferative activity of compound 7l. The data revealed that 7l exerted antiproliferative activity mainly by regulating cell cycle, DNA replication and p53 signaling pathway. Indeed, compound 7l induced G2/M phase arrest by AURKB transcription inhibition and resulted in cell apoptosis via p53 signaling pathway. Most importantly, compound 7l demonstrated potent antitumor activity in A549 xenograft tumor model. Collectively, 7l might be a promising lead compound for the development of new therapeutic agents for AURKB overexpressed or mutated cancers.


Assuntos
Antineoplásicos , Apoptose , Benzamidas , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Benzamidas/síntese química , Benzamidas/química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Animais , Camundongos , Camundongos Nus , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Transcrição Gênica/efeitos dos fármacos , Camundongos Endogâmicos BALB C
17.
Metab Brain Dis ; 39(6): 1109-1115, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39017967

RESUMO

This study aims to investigate the causal relationship between primary Sjögren's syndrome (SS) and multiple sclerosis (MS) using a two-sample Mendelian randomization (MR) analysis to provide insights into their common mechanisms and implications for therapeutic strategies. We utilized data from Genome-Wide Association Studies (GWAS) for primary SS (1,290 cases and 213,145 controls) and MS (4,888 cases and 10,395 controls), restricted to European ancestry. Instrumental variables (IVs) were selected based on genetic variants associated with primary SS. The primary MR method was Inverse Variance Weighted (IVW), supplemented by MR Egger, Weighted Median, Simple Mode, and Weighted Mode algorithms to assess the bidirectional causal relationships between MS and primary SS. Sensitivity analyses, including MR-PRESSO and leave-one-out analysis, were conducted to ensure the robustness of our findings. After excluding SNPs with pleiotropic effects, 42 and 5 SNPs were identified as robust IVs for primary SS and MS, respectively. Our analysis revealed a significant protective effect of MS on primary SS, with IVW showing an OR of 0.896 (95% CI: 0.841-0.954, P = 0.001). No significant heterogeneity or horizontal pleiotropy was detected, supporting the reliability of the results. Our findings suggest a potential protective effect of MS against primary SS, indicating a negative causal association between these two autoimmune diseases. This adds valuable genetic evidence to the understanding of the complex interplay between primary SS and MS, offering new avenues for research and therapeutic interventions.


Assuntos
Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Esclerose Múltipla , Polimorfismo de Nucleotídeo Único , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/genética , Esclerose Múltipla/genética , Predisposição Genética para Doença/genética
18.
BMC Health Serv Res ; 24(1): 541, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678273

RESUMO

BACKGROUND: Research on health resource allocation trends in ethnic minority and impoverished areas in China is limited since the 2009 Medical Reform. This study aimed to investigate the variations and inequalities in health resource distribution among ethnic minority, poverty-stricken, and non-minority regions in Sichuan Province, a multi-ethnic province in Southwest China, from 2009 to 2019. METHODS: The numbers of beds, doctors and nurses were retrospectively sourced from the Sichuan Health Statistics Yearbook between 2009 and 2019. All the 181 counties in Sichuan Province were categorized into five groups: Yi, Zang, other ethnic minority, poverty-stricken, and non-minority county. The Theil index, adjusted for population size, was used to evaluate health resource allocation inequalities. RESULTS: From 2009 to 2019, the number of beds (Bedp1000), doctors (Docp1000), and nurses (Nurp1000) per 1000 individuals in ethnic minority and poverty-stricken counties consistently remained lower than non-minority counties. The growth rates of Bedp1000 in Yi (140%) and other ethnic minority counties (127%) were higher than in non-minority counties (121%), while the growth rates of Docp1000 in Yi (20%) and Zang (11%) counties were lower than non-minority counties (61%). Docp1000 in 33% and 50% of Yi and Zang ethnic counties decreased, respectively. Nurp1000 in Yi (240%) and other ethnic minority (316%) counties increased faster than non-minority counties (198%). The Theil index for beds and nurses declined, while the index for doctors increased. Key factors driving increases in bed allocation include preferential policies and economic development levels, while health practitioner income, economic development levels and geographical environment significantly influence doctor and nurse allocation. CONCLUSIONS: Preferential policies have been successful in increasing the number of beds in health facilities, but not healthcare workers, in ethnic minority regions. The ethnic disparities in doctor allocation increased in Sichuan Province. To increase the number of doctors and nurses in ethnic minority and poverty-stricken regions, particularly in Yi counties, more preferential policies and resources should be introduced.


Assuntos
Disparidades em Assistência à Saúde , Humanos , China/etnologia , Etnicidade/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/tendências , Grupos Minoritários/estatística & dados numéricos , Enfermeiras e Enfermeiros/estatística & dados numéricos , Médicos/estatística & dados numéricos , Médicos/provisão & distribuição , Pobreza/estatística & dados numéricos , Alocação de Recursos , Estudos Retrospectivos , Povo Asiático
19.
Multivariate Behav Res ; 59(2): 229-250, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37776890

RESUMO

Forced-choice questionnaires involve presenting items in blocks and asking respondents to provide a full or partial ranking of the items within each block. To prevent involuntary or voluntary response distortions, blocks are usually formed of items that possess similar levels of desirability. Assembling forced-choice blocks is not a trivial process, because in addition to desirability, both the direction and magnitude of relationships between items and the traits being measured (i.e., factor loadings) need to be carefully considered. Based on simulations and empirical studies using item pairs, we provide recommendations on how to construct item pairs matched by desirability. When all pairs contain items keyed in the same direction, score reliability is improved by maximizing within-block loading differences. Higher reliability is obtained when even a small number of pairs consist of unequally keyed items.


Assuntos
Reprodutibilidade dos Testes , Psicometria , Inquéritos e Questionários
20.
J Environ Manage ; 360: 121207, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38788408

RESUMO

Sludge is an inevitable waste product of sewage treatment with a high water content and large volume, it poses a significant threat of secondary pollution to both water and the atmosphere without proper disposal. In this regard, dewatering has emerged as an attractive method in sludge treatment, as it can reduce the sludge volume, enhance its transportability and calorific value, and even decrease the production of landfill leachate. In recent years, physical conditioning methods including non-chemical conditioners or energy input alone, have been extensively researched for their potential to enhance sludge dewatering efficiency, such as thermal treatment, freeze-thaw, microwave, ultrasonic, skeleton builders addition, and electro-dewatering, as well as combined methods. The main objective of this paper is to comprehensively evaluate the dewatering capacity of various physical conditioning methods, and identify key factors affecting sludge dewatering efficiency. In addition, future research anticipated directions and outlooks are proposed. This work is expected to provide valuable insights for developing efficient, eco-friendly, and low-energy consumption techniques for deep sludge dewatering.


Assuntos
Esgotos , Eliminação de Resíduos Líquidos , Eliminação de Resíduos Líquidos/métodos , Água/química
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