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1.
Chem Mater ; 36(12): 6053-6061, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38947978

RESUMEN

Phase-pure polycrystalline Ba4RuMn2O10 was prepared and determined to adopt the noncentrosymmetric polar crystal structure (space group Cmc21) based on results of second harmonic generation, convergent beam electron diffraction, and Rietveld refinements using powder neutron diffraction data. The crystal structure features zigzag chains of corner-shared trimers, which contain three distorted face-sharing octahedra. The three metal sites in the trimers are occupied by disordered Ru/Mn with three different ratios: Ru1:Mn1 = 0.202(8):0.798(8), Ru2:Mn2 = 0.27(1):0.73(1), and Ru3:Mn3 = 0.40(1):0.60(1), successfully lowering the symmetry and inducing the polar crystal structure from the centrosymmetric parent compounds Ba4T3O10 (T = Mn, Ru; space group Cmca). The valence state of Ru/Mn is confirmed to be +4 according to X-ray absorption near-edge spectroscopy. Ba4RuMn2O10 is a narrow bandgap (∼0.6 eV) semiconductor exhibiting spin-glass behavior with strong magnetic frustration and antiferromagnetic interactions.

2.
Am J Transl Res ; 16(6): 2525-2532, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006285

RESUMEN

PURPOSE: To investigate the prevalence of occupational lower back pain (OLBP) among medical workers and identify the contributing factors. METHODS: An electronic questionnaire was distributed to medical workers at Yuebei People's Hospital to gather information on various factors, including gender, age, body mass index (BMI), length of employment, job role, education level, professional title, marital status, fertility status, frequency of night shift, weight lifting daily, duration of daily standing at work, frequency of bending, work-related stress, experience with low back protection training, and frequency of waist exercises. Univariate and multivariate logistic regression analyses were conducted to identify the factors associated with OLBP in medical workers. RESULTS: Out of the 98 medical workers surveyed, 67 experienced OLBP (68.37%). The results of multivariate logistic regression analysis revealed that working for more than 5 years, holding a nursing position, and lacking training in low back protection were significant risk factors for developing OLBP in medical workers (all P<0.05). CONCLUSION: OLBP is a prevalent issue among medical workers, and various factors such as length of employment, job role, and training in low back protection can influence its occurrence.

3.
Front Cell Infect Microbiol ; 14: 1399732, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006743

RESUMEN

Tigecycline serves as a last-resort antimicrobial agent against severe infections caused by multidrug-resistant bacteria. Tet(X) and its numerous variants encoding flavin-dependent monooxygenase can confer resistance to tigecycline, with tet(X4) being the most prevalent variant. This study aims to investigate the prevalence and characterize tigecycline resistance gene tet(X) in E. coli isolates from various origins in Yangzhou, China, to provide insights into tet(X) dissemination in this region. In 2022, we tested the presence of tet(X) in 618 E. coli isolates collected from diverse sources, including patients, pig-related samples, chicken-related samples, and vegetables in Yangzhou, China. The antimicrobial susceptibility of tet(X)-positive E. coli isolates was conducted using the agar dilution method or the broth microdilution method. Whole genome sequencing was performed on tet(X)-positive strains using Illumina and Oxford Nanopore platforms. Four isolates from pig or pork samples carried tet(X4) and exhibited resistance to multiple antimicrobial agents, including tigecycline. They were classified as ST542, ST10, ST761, and ST48, respectively. The tet(X4) gene was located on IncFIA8-IncHI1/ST17 (n=2), IncFIA18-IncFIB(K)-IncX1 (n=1), and IncX1 (n=1) plasmids, respectively. These tet(X4)-carrying plasmids exhibited high similarity to other tet(X4)-bearing plasmids with the same incompatible types found in diverse sources in China. They shared related genetic environments of tet(X4) associated with ISCR2, as observed in the first identified tet(X4)-bearing plasmid p47EC. In conclusion, although a low prevalence (0.65%) of tet(X) in E. coli strains was observed in this study, the horizontal transfer of tet(X4) among E. coli isolates mediated by pandemic plasmids and the mobile element ISCR2 raises great concerns. Thus, heightened surveillance and immediate action are imperative to curb this clinically significant resistance gene and preserve the efficacy of tigecycline.


Asunto(s)
Antibacterianos , Infecciones por Escherichia coli , Escherichia coli , Pruebas de Sensibilidad Microbiana , Tigeciclina , Tigeciclina/farmacología , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , China , Antibacterianos/farmacología , Porcinos , Animales , Infecciones por Escherichia coli/microbiología , Humanos , Plásmidos/genética , Pollos/microbiología , Secuenciación Completa del Genoma , Farmacorresistencia Bacteriana Múltiple/genética , Verduras/microbiología , Proteínas de Escherichia coli/genética
4.
Life Sci ; 351: 122824, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38862061

RESUMEN

Inter-organ communication through hormones, cytokines and extracellular vesicles (EVs) has emerged to contribute to the physiological states and pathological processes of the human body. Notably, the liver coordinates multiple tissues and organs to maintain homeostasis and maximize energy utilization, with the underlying mechanisms being unraveled in recent studies. Particularly, liver-derived EVs have been found to play a key role in regulating health and disease. As an endocrine organ, the liver has also been found to perform functions via the secretion of hepatokines. Investigating the multi-organ communication centered on the liver, especially in the manner of EVs and hepatokines, is of great importance to the diagnosis and treatment of liver-related diseases. This review summarizes the crosstalk between the liver and distant organs, including the brain, the bone, the adipose tissue and the intestine in noticeable situations. The discussion of these contents will add to a new dimension of organismal homeostasis and shed light on novel theranostics of pathologies.


Asunto(s)
Vesículas Extracelulares , Hepatopatías , Hígado , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/fisiología , Hígado/metabolismo , Animales , Hepatopatías/metabolismo , Hepatopatías/patología , Hepatopatías/fisiopatología , Homeostasis/fisiología , Tejido Adiposo/metabolismo , Encéfalo/metabolismo , Citocinas/metabolismo , Huesos/metabolismo
5.
Nanoscale ; 16(27): 13171-13182, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38913445

RESUMEN

Rechargeable aluminum ion batteries (RAIBs) exhibit great potential for next-generation energy storage systems owing to the abundant resources, high theoretical volumetric capacity and light weight of the Al metal anode. However, the development of RAIBs based on Al metal anodes faces challenges such as dendrite formation, self-corrosion, and volume expansion at the anode/electrolyte interface, which needs the rational design of an aluminum anode for high-performance RAIBs. This work proposes a novel and low-cost strategy by utilizing an alloy electrodeposition method in a low-temperature molten salt system to fabricate an aluminum-tin (AlSn) alloy coating layer on copper foil as the anode for RAIBs, which successfully addresses the issues of dendrite formation and corrosion at the anode/electrolyte interface. The artificial AlSn alloy layer could enhance the active sites for metal Al homogeneous deposition and effectively retard the dendrite formation, which was verified by an in situ optical microscopy study. The symmetric AlSn@Cu cell demonstrates a low average overpotential of ∼38 mV at a current density of 0.5 mA cm-2 and a long-term lifespan of over 1100 h. Moreover, the AlSn@Cu//Mo6S8 full cells deliver a high capacity of 114.9 mA h g-1 at a current density of 100 mA g-1 and maintain ultra-stable cycling stability even over 1400 cycles with a ∼100% coulombic efficiency (CE) during the long-term charge/discharge processes. This facile alloy electrodeposition approach for designing high-performance Al-based anodes provides insights into the understanding of artificial interface chemistry on Al-based anodes and potentially accelerates the design of high-performance RAIBs.

6.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 605-610, 2024 Jun 15.
Artículo en Chino | MEDLINE | ID: mdl-38926377

RESUMEN

OBJECTIVES: To investigate the expression of microRNA-142 (miR-142) in children with autoimmune thyroid disease (AITD) and its relationship with the imbalance of helper T cell 17 (Th17) and regulatory T cell (Treg). METHODS: A total of 89 children hospitalized for AITD from January 2019 to December 2022 were prospectively selected as the study subjects, including 48 children with Graves' disease (GD group) and 41 children with Hashimoto's thyroiditis (HT group). Additionally, 55 healthy children undergoing physical examinations during the same period were selected as the control group. The differences in serum miR-142, antithyroglobulin antibody (TGAb), antithyroperoxidase antibody (TPOAb), Th17/Treg, and interleukin-17 (IL-17) expression were compared among the groups. RESULTS: The expression of miR-142, TPOAb, TGAb, Th17, Th17/Treg, and IL-17 in the GD group and HT group was higher than that in the control group, while Treg was lower than that in the control group (P<0.05). Pearson correlation analysis revealed that in the GD group, miR-142 was positively correlated with TPOAb, TGAb, Th17, Th17/Treg, and IL-17 (r=0.711, 0.728, 0.785, 0.716, 0.709, respectively; P<0.001) and negatively correlated with Treg (r=-0.725, P<0.001); in the HT group, miR-142 was positively correlated with TPOAb and TGAb (r=0.752, 0.717, respectively; P<0.001). CONCLUSIONS: miR-142 is highly expressed in children with AITD, and its expression may be related to the Th17/Treg imbalance in children with GD.


Asunto(s)
Interleucina-17 , MicroARNs , Linfocitos T Reguladores , Células Th17 , Humanos , MicroARNs/sangre , Células Th17/inmunología , Niño , Masculino , Femenino , Linfocitos T Reguladores/inmunología , Interleucina-17/sangre , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/genética , Enfermedad de Hashimoto/sangre , Preescolar , Enfermedad de Graves/inmunología , Enfermedad de Graves/genética , Adolescente , Autoanticuerpos/sangre
7.
Integr Med Res ; 13(2): 101045, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38831890

RESUMEN

Background: Post-viral olfactory dysfunction (PVOD) is the common symptoms of long COVID, lacking of effective treatments. Traditional Chinese medicine (TCM) is claimed to be effective in treating olfactory dysfunction, but the evidence has not yet been critically appraised. We conducted a systematic review to evaluate the effectiveness and safety of TCM for PVOD. Methods: We searched eight databases to identified clinical controlled studies about TCM for PVOD. The Cochrane risk of bias tools and GRADE were used to evaluate the quality of evidence. Risk ratio (RR), mean differences (MD), and 95 % confidence interval (CI), were used for effect estimation and RevMan 5.4.1 was used for data analysis. Results: Six randomized controlled trials (RCTs) (545 participants), two non-randomized controlled trials (non-RCTs) (112 participants), and one retrospective cohort study (30 participants) were included. The overall quality of included studies was low. Acupuncture (n = 8) and acupoint injection (n = 3) were the mainly used TCM therapies. Five RCTs showed a better effect in TCM group. Four trials used acupuncture, and three trials used acupoint injection. The results of two non-RCTs and one cohort study were not statistically significant. Two trials reported mild to moderate adverse events (pain and brief syncope caused by acupuncture or acupoint injection). Conclusions: Limited evidence focus on acupuncture and acupoint injection for PVOD and suggests that acupuncture and acupoint injection may be effective in improving PVOD. More well-designed trials should focus on acupuncture to confirm the benefit. Protocol registration: The protocol of this review was registered at PROSPERO: CRD42022366776.

8.
Front Neurosci ; 18: 1416522, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38872941

RESUMEN

Background: Long term hypertension seriously promotes target organ damage in the brain and heart, and has increasingly become serious public health problem worldwide. The anti-hypertensive effects of capsaicin has been reported, however, the role and mechanism of capsaicin within the brain on salt-induced hypertension have yet to be elucidated. This study aimed to verify the hypothesis that capsaicin attenuates salt-induced hypertension via the AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus (PVN). Methods: Dahl salt-sensitive (Dahl S) rats were used as animal model for the present study. Rats were randomly divided into four groups based on their dietary regimen (0.3% normal salt diet and 8% high salt diet) and treatment methods (infusion of vehicle or capsaicin in the PVN). Capsaicin was chronically administered in the PVN throughout the animal experiment phase of the study that lasted 6 weeks. Results: Our results demonstrated that PVN pretreatment with capsaicin can slow down raise of the blood pressure elevation and heart rate (HR) of Dahl S hypertensive rats given high salt diet. Interestingly, the cardiac hypertrophy was significantly improved. Furthermore, PVN pretreatment with capsaicin induced decrease in the expression of mRNA expression of NADPH oxidase-2 (NOX2), inducible nitric oxide synthase (iNOS), NOX4, p-IKKß and proinflammatory cytokines and increase in number of positive cell level for Nrf2 and HO-1 in the PVN of Dahl S hypertensive rats. Additionally, the protein expressions of phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT) were decreased, phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were increased after the PVN pretreatment with capsaicin. Conclusion: Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/iNOS pathway in the PVN.

9.
Front Pharmacol ; 15: 1383831, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863976

RESUMEN

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

10.
Anal Chem ; 96(24): 9961-9968, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38838250

RESUMEN

In this study, a novel europium dual-ligand metal-organic gel (Eu-D-MOGs) with high-efficient anodic annihilation electrochemiluminescence (ECL) was synthesized as an ECL emitter to construct a biosensor for ultrasensitive detection of microRNA-221 (miR-221). Impressively, compared to the ECL signal of europium single-ligand metal-organic gels (Eu-S-MOGs), the ECL signal of Eu-D-MOGs was significantly improved since the two organic ligands could jointly replace the H2O and coordinate with Eu3+, which could remarkably reduce the nonradiative vibrational energy transfer caused by the coordination between H2O and Eu3+ with a high coordination demand. In addition, Eu-D-MOGs could be electrochemically oxidized to Eu-D-MOGs•+ at 1.45 V and reduced to Eu-D-MOGs•- at 0.65 V to achieve effective annihilation of ECL, which overcame the side reaction brought by the remaining emitters at negative potential. This benefited from the annihilation ECL performance of the central ion Eu3+ caused by its redox in the electrochemical process. Furthermore, the annihilation ECL signal of Eu3+ could be improved by sensitizing Eu3+ via the antenna effect. In addition, combined with the improved rolling circle amplification-assisted strand displacement amplification strategy (RCA-SDA), a sensitive biosensor was constructed for the sensitive detection of miR-221 with a low detection limit of 5.12 aM and could be successfully applied for the detection of miR-221 in the lysate of cancer cells. This strategy offered a unique approach to synthesizing metal-organic gels as ECL emitters without a coreactant for the construction of ECL biosensing platforms in biomarker detection and disease diagnosis.


Asunto(s)
Técnicas Electroquímicas , Electrodos , Europio , Geles , Mediciones Luminiscentes , MicroARNs , Europio/química , MicroARNs/análisis , Técnicas Electroquímicas/métodos , Ligandos , Geles/química , Técnicas Biosensibles/métodos , Límite de Detección , Humanos
11.
Biomed Chromatogr ; 38(8): e5943, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38890009

RESUMEN

In this study, a targeted nanocarrier was developed by functionalizing graphene oxide with polyethyleneimine and folic acid, intended for loading oridonin. The nanocarrier was successfully synthesized and characterized using an ultraviolet spectrum, Fourier transform infrared spectroscopy and scanning electron microscopy. The nanocarrier demonstrated a remarkable oridonin loading capacity, reaching 424.8 µg/mg, as determined by ultra-high performance liquid chromatography. In vitro drug release experiments exhibited a pH-dependent release profile, with a higher cumulative release in an acidic environment. The release mechanism followed the Ritger-Peppas equation model. Cytotoxicity assays indicated minimal toxicity of the nanocarrier. Enhanced cellular uptake by MCF7 cells was observed for carriers functionalized with folate and polyethyleneimine. These findings highlight the potential of functionalized graphene oxide as a promising carrier for oridonin delivery in biomedical applications.


Asunto(s)
Neoplasias de la Mama , Diterpenos de Tipo Kaurano , Portadores de Fármacos , Grafito , Grafito/química , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/farmacología , Humanos , Células MCF-7 , Portadores de Fármacos/química , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Antineoplásicos/farmacología , Antineoplásicos/química , Liberación de Fármacos , Supervivencia Celular/efectos de los fármacos , Ácido Fólico/química , Nanopartículas/química , Cromatografía Líquida de Alta Presión/métodos
12.
Opt Lett ; 49(11): 3226-3229, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824369

RESUMEN

We propose and demonstrate a data fragment multipath transmission scheme to achieve a secure optical communication based on polarization regulation. A dual-polarization Mach-Zehnder modulator (DPMZM) is driven by digital signals which are scattered by field-programmable gate array (FPGA) and transmitted in multiple paths. By utilizing two orthogonal polarization states, we have achieved a signal transmission under different optical parameters, and the transmission rate of the two paths can reach over 10 Gbps through a 20 km fiber with 2.5 Gbps hopping rate. In addition, we establish a theoretical model to analyze the security of the system and simulate brute force cracking; the probability of cracking the minimum information unit is 1.53 × 10-53. This proves that it is difficult to obtain a user data even using the fastest computers. Our scheme has provided, to our knowledge, a new approach for physical layer security.

13.
Clin Pharmacol Drug Dev ; 13(7): 819-827, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38757472

RESUMEN

Dysregulated lysophosphatidic acid receptor 1 (LPAR1) signaling is implicated in fibrotic diseases, including systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Fipaxalparant (HZN-825) is a small molecule acting as a negative allosteric modulator of LPAR1 and is in phase 2 clinical evaluations for treating diffuse cutaneous SSc and IPF. This open-label, phase 1 study examined the pharmacokinetics (PKs), food effect, and safety of fipaxalparant in healthy volunteers. Dose proportionality was evaluated for fipaxalparant single doses of 150, 300, and 450 mg under fasted conditions. Food effect was tested with a 450-mg single dose under fasted conditions or with a high-fat meal. Multiple-dose PKs for twice-daily dosing of either 300 or 450 mg with low- or high-fat meals was also assessed. Fipaxalparant was safe and well tolerated in healthy volunteers (n = 36) under all conditions. Fipaxalparant exposure increased in a less than dose-proportional manner from 150 to 450 mg. At 450 mg, a high-fat meal increased the maximum observed concentration and area under the curve by approximately 1.9- and 2.1-fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies.


Asunto(s)
Interacciones Alimento-Droga , Voluntarios Sanos , Receptores del Ácido Lisofosfatídico , Humanos , Adulto , Masculino , Femenino , Persona de Mediana Edad , Regulación Alostérica , Adulto Joven , Relación Dosis-Respuesta a Droga , Ayuno , Área Bajo la Curva
14.
Biomed Pharmacother ; 175: 116694, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38713943

RESUMEN

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP's natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases.


Asunto(s)
Aterosclerosis , Diabetes Mellitus , Quempferoles , Enfermedad del Hígado Graso no Alcohólico , Obesidad , Humanos , Quempferoles/farmacología , Quempferoles/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Animales , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/metabolismo , Transducción de Señal/efectos de los fármacos
15.
Cell Rep Med ; 5(5): 101573, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38776874

RESUMEN

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.


Asunto(s)
Anticuerpos Monoclonales , Epítopos , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Humanos , Herpesvirus Humano 4/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Anticuerpos Monoclonales/inmunología , Epítopos/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Ratones , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Proteínas Virales/inmunología , Linfocitos B/inmunología
16.
J Multidiscip Healthc ; 17: 2359-2370, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774623

RESUMEN

Objective: The aim of this study is to examine the diagnostic significance of using handgrip dynamometry and diaphragmatic ultrasound in intensive care unit-acquired weakness (ICU-AW). Methods: This study included patients who received mechanical ventilation in the ICU at the Fourth Hospital of Hebei Medical University from July to December 2020. We collected comprehensive demographic data and selected conscious patients for muscle strength and ICU-AW assessments. The evaluation comprised grip strength measurement and bedside ultrasound for diaphragmatic excursion (DE) and thickening fraction (DTF). Results were documented for comparative analysis between patient groups, focusing on the diagnostic efficacy of grip strength, DE, DTF, and their combined application in diagnosing ICU-AW. Results: A total of 95 patients were initially considered for inclusion in this study. Following the exclusion of 20 patients, a final cohort of 75 patients were enrolled, comprising of 32 patients (42.6%) diagnosed with ICU-AW and 43 patients (57.4%) classified as non-ICU-AW. Comparative analysis revealed that grip strength, DE, and DTF were significantly lower in the ICU-AW group (P < 0.05). Subgroup analysis specific to male patients demonstrated a noteworthy decrease in grip strength, DE, and DTF within the ICU-AW group (P < 0.05). Receiver operating characteristic curve analysis indicated statistically significant diagnostic value for ICU-AW with grip strength, DE, DTF, and grip strength and diaphragmatic ultrasound (P < 0.01). Furthermore, it was observed that the amalgamation of grip strength and diaphragmatic ultrasound significantly enhanced the diagnostic accuracy of ICU-AW in patients who are critically ill. Conclusion: Grip strength, DE, DTF, and the combined use of grip strength with diaphragm ultrasound demonstrated diagnostic efficacy in ICU-AW. Notably, the integration of grip strength with diaphragm ultrasound exhibited a heightened capacity to enhance the diagnostic value specifically in patients diagnosed who are critically ill with ICU-AW.

17.
Research (Wash D C) ; 7: 0355, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694202

RESUMEN

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.

18.
Front Neurol ; 15: 1375383, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694772

RESUMEN

Background: Postoperative delirium (POD) is a common postoperative neurological complication that can lead to a variety of postoperative complications. At present, the pathogenesis of POD is unclear. This study aims to explore the relationship between serum prealbumin and serum albumin and POD and whether serum prealbumin and serum albumin influence POD through POD core pathology. Objective: We enrolled 500 Chinese Han patients between September 2020 to January 2023. We analyzed the risk and protective factors of POD using the multivariate logistic regression. We also assessed the predictive power of serum prealbumin, serum albumin, and both in combination with CSF POD biomarkers. We used Stata MP16.0. to examine whether the association between serum prealbumin and serum albumin and POD was mediated by CSF POD biomarkers, and conducted an internal validation study to verify the accuracy of the combination of serum prealbumin + serum albumin + CSF POD biomarkers for predicting POD. The model was visualized using ROC curve and decision curve analysis (DCA). DynNom and Shiny packages were used to create an online calculator. Ten patients who had POD occurring from February 2023 to October 2023 were selected for internal verification. Results: Finally, a total of 364 patients were included in our study. Levels of serum prealbumin, serum albumin in the POD group were lower than those in the NPOD group. The lever of serum prealbumin, serum albumin were protective factors for POD. The relationship between serum prealbumin, serum albumin and POD was partially mediated by T-tau (12.28%) and P-tau (20.61%). The model combining serum prealbumin and serum albumin and POD biomarkers exhibited a relatively better discriminatory ability to predict POD. DCA also showed that the combination of serum prealbumin and serum albumin and POD biomarkers brought high predictive benefits to patients. The dynamic online calculator can accurately predict the occurrence of POD in the internal validation study. Conclusion: Preoperative low serum prealbumin and serum albumin levels were the preoperative risk factors for POD, which is partly mediated by T-tau and P-tau. The model combining serum prealbumin and serum albumin and CSF POD biomarkers can accurately predict the occurrence of POD. Clinical trial registration: http://www.clinicaltrials.gov, identifier ChiCTR2000033439.

19.
Front Pharmacol ; 15: 1360633, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38716236

RESUMEN

Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. Systematic Review Registration: INPASY202350066.

20.
Integr Med Res ; 13(2): 101039, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38746044

RESUMEN

Background: Chronic fatigue is a predominant symptom of post COVID-19 condition, or long COVID. We aimed to evaluate the efficacy and safety of Traditional, Complementary and Integrative Medicine (TCIM) for fatigue post COVID-19 infection. Methods: Ten English and Chinese language databases and grey literature were searched up to 12 April 2023 for randomized controlled trials (RCTs). Cochrane "Risk of bias" (RoB) tool was applied. Evidence certainty was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Effect estimates were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Results: Thirteen RCTs with 1632 participants were included. One RCT showed that Bufei Huoxue herbal capsules reduced fatigue (n=129, MD -14.90, 95%CI -24.53 to -5.27), one RCT reported that Ludangshen herbal liquid lowered fatigue (n=184, MD -1.90, 95%CI -2.38 to -1.42), and the other one RCT shown that fatigue disappearance rate was higher with Ludangshen herbal liquid (n=184, RR 4.19, 95%CI 2.06 to 8.53). Compared to traditional Chinese medicine rehabilitation (TCM-rahab) alone, one RCT showed that fatigue symptoms were lower following Qingjin Yiqi granules plus TCM-rehab (n=388, MD -0.48, 95%CI -0.50 to -0.46). Due to concerns with RoB and/or imprecision, the certainty in this evidence was low to very low. No serious adverse events was reported. Conclusions: Limited evidence suggests that various TCIM interventions might reduce post COVID-19 fatigue. Larger, high quality RCTs of longer duration are required to confirm these preliminary findings. Study Registration: The protocol of this review has been registered at PROSPERO: CRD42022384136.

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