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1.
Food Chem ; 451: 139464, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38704990

RESUMEN

Silver-metal organic framework (Ag@MOF) has exhibited outstanding antimicrobial activity in antimicrobial applications, and reducing the biotoxicity associated with silver has become a research priority. In this study, Ag@MOF was initially modified with sodium alginate (SA) to form SA-Ag@MOF. The results showed that SA could control the release of Ag+, reducing the release by about 8% at 24 h, and the biotoxicity was significantly reduced. Finally, SA-Ag@MOF was applied as an antimicrobial agent in citric acid-modified PVA film to develop a novel composite antimicrobial film. When added at 2 MIC, the CA3-M2 film can effectively inhibit the growth of E. coli and S. aureus, and the inhibition rate has reached 98%. For white radish packaging applications, CA3-M2 film inhibited the growth of surface microorganisms, while ensuring moisture and tissue hardness to extend shelf-life up to 7 days. Overall, the strategy conceived here can be a theoretical basis for novel antimicrobial packaging.

2.
Natl Sci Rev ; 11(5): nwae079, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38698901

RESUMEN

Virtual brain twins are personalized, generative and adaptive brain models based on data from an individual's brain for scientific and clinical use. After a description of the key elements of virtual brain twins, we present the standard model for personalized whole-brain network models. The personalization is accomplished using a subject's brain imaging data by three means: (1) assemble cortical and subcortical areas in the subject-specific brain space; (2) directly map connectivity into the brain models, which can be generalized to other parameters; and (3) estimate relevant parameters through model inversion, typically using probabilistic machine learning. We present the use of personalized whole-brain network models in healthy ageing and five clinical diseases: epilepsy, Alzheimer's disease, multiple sclerosis, Parkinson's disease and psychiatric disorders. Specifically, we introduce spatial masks for relevant parameters and demonstrate their use based on the physiological and pathophysiological hypotheses. Finally, we pinpoint the key challenges and future directions.

3.
Int J Mol Sci ; 25(9)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38732163

RESUMEN

The Chinese giant salamander (Andrias davidianus), listed as an endangered species under "secondary protection" in China, faces significant threats due to ecological deterioration and the expansion of human activity. Extensive field investigations are crucial to ascertain the current status in the wild and to implement effective habitat protection measures to safeguard this species and support its population development. Traditional survey methods often fall short due to the elusive nature of the A. davidianus, presenting challenges that are time-consuming and generally ineffective. To overcome these obstacles, this study developed a real-time monitoring method that uses environmental DNA (eDNA) coupled with recombinase polymerase amplification and lateral flow strip (RPA-LFD). We designed five sets of species-specific primers and probes based on mitochondrial genome sequence alignments of A. davidianus and its close relatives. Our results indicated that four of these primer/probe sets accurately identified A. davidianus, distinguishing it from other tested caudata species using both extracted DNA samples and water samples from a tank housing an individual. This method enables the specific detection of A. davidianus genomic DNA at concentrations as low as 0.1 ng/mL within 50 min, without requiring extensive laboratory equipment. Applied in a field survey across four sites in Huangshan City, Anhui Province, where A. davidianus is known to be distributed, the method successfully detected the species at three of the four sites. The development of these primer/probe sets offers a practical tool for field surveying and monitoring, facilitating efforts in population recovery and resource conservation for A. davidianus.


Asunto(s)
Urodelos , Animales , Urodelos/genética , China , Especies en Peligro de Extinción , ADN Ambiental/genética , ADN Ambiental/análisis , ADN Mitocondrial/genética , Genoma Mitocondrial
4.
Appl Opt ; 63(10): 2462-2468, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38568524

RESUMEN

In this paper, the green upconversion (UC) fluorescence emission from E r 3+/Y b 3+/H o 3+ tri-doped tellurite glass is investigated for temperature sensing. The doping of H o 3+ ions not only enhances the chance of energy level transition but also avoids the influence of the thermal effect caused by the proximity of 2 H 11/2 and 4 S 3/2 energy levels. The luminescence characteristics at different Y b 3+ and H o 3+ ion concentration doping molar ratios were investigated, and the strongest luminescence characteristics were exhibited when the Y b 3+ ion concentration was at 5 mol% and H o 3+ at 0.2 mol%. Based on this, a tri-doped T e O 2-Z n O-B i 2 O 3 (TZB) no-core fiber was fabricated and connected with multimode fibers (MMFs) to form a temperature sensor. The temperature sensing performance of the tri-doped TZB temperature sensor was evaluated in detail over the temperature range of 255-365 K. The repeatability and stability of the temperature sensor was experimentally verified. The E r 3+/Y b 3+/H o 3+ tri-doped sensor can be used for noninvasive optical temperature sensing in the fields of environmental monitoring, biological sensing, and industrial process temperature control, etc.

5.
J Int Med Res ; 52(3): 3000605241236276, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38506348

RESUMEN

OBJECTIVE: To explore the levels of expression and clinical role of peroxiredoxin 6 (PRDX6) in lung adenocarcinoma. METHODS: This retrospective study used a series of bioinformatics methods to detect the levels of expression of and mutations in the PRDX6 gene in a range of cancers and lung adenocarcinoma. Immunohistochemistry was used to verify the levels of expression of PRDX6 protein in samples of lung adenocarcinoma compared with normal adjacent tissue. The effect of PRDX6 gene knockdown on the in vitro proliferation of a lung adenocarcinoma cell line was measured. Bioinformatics methods were used to determine the diagnostic value and impact on survival of the PRDX6 gene in patients with lung adenocarcinoma. RESULTS: The results showed that the PRDX6 gene was highly expressed in lung adenocarcinoma and there were five mutations at different sites on the gene. PRDX6 promoted the proliferation of the lung adenocarcinoma cell line. The survival duration of lung adenocarcinoma patients with high levels of PRDX6 gene expression was significantly shorter than that of patients with low PRDX6 gene expression. CONCLUSION: PRDX6 is highly expressed in lung adenocarcinoma and higher levels of expression of the PRDX6 gene were associated with a poorer prognosis.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Peroxiredoxina VI/genética , Peroxiredoxina VI/metabolismo , Estudios Retrospectivos , Adenocarcinoma del Pulmón/genética , Línea Celular , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología
6.
J Med Virol ; 96(3): e29528, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38501378

RESUMEN

The emerging Omicron subvariants have a remarkable ability to spread and escape nearly all current monoclonal antibody (mAb) treatments. Although the virulence of SARS-CoV-2 has now diminished, it remains a significant threat to public health due to its high transmissibility and susceptibility to mutation. Therefore, it is urgent to develop broad-acting and potent therapeutics targeting current and emerging Omicron variants. Here, we identified a panel of Omicron BA.1 spike receptor-binding domain (RBD)-targeted nanobodies (Nbs) from a naive alpaca VHH library. This panel of Nbs exhibited high binding affinity to the spike RBD of wild-type, Alpha B.1.1.7, Beta B.1.351, Delta plus, Omicron BA.1, and BA.2. Through multivalent Nb construction, we obtained a subpanel of ultrapotent neutralizing Nbs against Omicron BA.1, BA.2, BF.7 and even emerging XBB.1.5, and XBB.1.16 pseudoviruses. Protein structure prediction and docking analysis showed that Nb trimer 2F2E5 targets two independent RBD epitopes, thus minimizing viral escape. Taken together, we obtained a panel of broad and ultrapotent neutralizing Nbs against Omicron BA.1, Omicron BA.2, BF.7, XBB.1.5, and XBB.1.16. These multivalent Nbs hold great promise for the treatment against SARS-CoV-2 infection and could possess a superwide neutralizing breadth against novel omicron mutants or recombinants.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos de Dominio Único , Humanos , Anticuerpos de Dominio Único/genética , Anticuerpos Monoclonales , Epítopos , Anticuerpos Neutralizantes , Anticuerpos Antivirales
7.
Eur J Pharmacol ; 970: 176492, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38503401

RESUMEN

Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by remodeling of the pulmonary vasculature and elevated pulmonary arterial pressure, ultimately leading to right heart failure and death. Despite its clinical significance, the precise molecular mechanisms driving PAH pathogenesis warrant confirmation. Compelling evidence indicates that during the development of PAH, pulmonary vascular cells exhibit a preference for energy generation through aerobic glycolysis, known as the "Warburg effect", even in well-oxygenated conditions. This metabolic shift results in imbalanced metabolism, increased proliferation, and severe pulmonary vascular remodeling. Exploring the Warburg effect and its interplay with glycolytic enzymes in the context of PAH has yielded current insights into emerging drug candidates targeting enzymes and intermediates involved in glucose metabolism. This sheds light on both opportunities and challenges in the realm of antiglycolytic therapy for PAH.


Asunto(s)
Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Pulmonar Primaria Familiar , Glucólisis , Pulmón/metabolismo , Arteria Pulmonar/metabolismo , Remodelación Vascular
8.
New Phytol ; 242(2): 507-523, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38362849

RESUMEN

Polyploidization is a major event driving plant evolution and domestication. However, how reshaped epigenetic modifications coordinate gene transcription to generate phenotypic variations during wheat polyploidization is currently elusive. Here, we profiled transcriptomes and DNA methylomes of two diploid wheat accessions (SlSl and AA) and their synthetic allotetraploid wheat line (SlSlAA), which displayed elongated root hair and improved root capability for nitrate uptake and assimilation after tetraploidization. Globally decreased DNA methylation levels with a reduced difference between subgenomes were observed in the roots of SlSlAA. DNA methylation changes in first exon showed strong connections with altered transcription during tetraploidization. Homoeolog-specific transcription was associated with biased DNA methylation as shaped by homoeologous sequence variation. The hypomethylated promoters showed significantly enriched binding sites for MYB, which may affect gene transcription in response to root hair growth. Two master regulators in root hair elongation pathway, AlCPC and TuRSL4, exhibited upregulated transcription levels accompanied by hypomethylation in promoter, which may contribute to the elongated root hair. The upregulated nitrate transporter genes, including NPFs and NRTs, also are significantly associated with hypomethylation, indicating an epigenetic-incorporated regulation manner in improving nitrogen use efficiency. Collectively, these results provided new insights into epigenetic changes in response to crop polyploidization and underscored the importance of epigenetic regulation in improving crop traits.


Asunto(s)
Metilación de ADN , Tetraploidía , Metilación de ADN/genética , Triticum/genética , Epigénesis Genética , Transcriptoma , Regulación de la Expresión Génica de las Plantas
9.
Int J Biol Macromol ; 263(Pt 1): 130336, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38387631

RESUMEN

This study focused on the preparation, functionality, and application of smart food packaging films based on polyvinyl alcohol (PVA) and anthocyanins (ACNs) -loaded sodium alginate-chitosan quaternary ammonium salt (HACC-SA) nanocomplexes. The average encapsulation rate of anthocyanins-loaded nanocomplexes reached 62.51 %, which improved the hydrophobicity and water vapor barrier of the PVA film. FTIR confirmed that the nanocomplexes were immobilized in the PVA film matrix by hydrogen bonding, which improved the mechanical properties of the film. The SEM and XRD results demonstrated that the HACC-SA-ACNs nanocomplexes were uniformly distributed in the film matrix and the crystallinity of PVA was decreased. The P/HACC-SA-ACNs film showed a significant response to buffers of pH 2-13 and high color stability after 21 days of storage compared to the P/ACNs film. Furthermore, the color of the composite film changed from purple to red as the milk freshness decreased during 72 h of milk freshness monitoring, indicating that the P/HACC-SA-ACNs films were suitable and promising for application as smart packaging materials.


Asunto(s)
Quitosano , Materiales Inteligentes , Animales , Antocianinas , Leche , Embalaje de Alimentos , Alginatos , Alcohol Polivinílico , Compuestos de Amonio Cuaternario , Concentración de Iones de Hidrógeno
10.
Biomed Pharmacother ; 172: 116229, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38330708

RESUMEN

Reperfusion stands as a pivotal intervention for ischemic heart disease. However, the restoration of blood flow to ischemic tissue always lead to further damage, which is known as myocardial ischemia/reperfusion injury (MIRI). Ramelteon is an orally administered drug used to improve sleep quality, which is famous for its high bioadaptability and absence of notable addictive characteristics. However, the specific mechanism by which it improves MIRI is still unclear. Sirtuin-3 (Sirt3), primarily located in mitochondria, is crucial in mitigating many cardiac diseases, including MIRI. Based on the structure of Sirt3, we simulated molecular docking and identified several potential amino acid binding sites between it and ramelteon. Therefore, we propose a hypothesis that ramelteon may exert cardioprotective effects by activating the Sirt3 signaling pathway. Our results showed that the activation levels and expression level of Sirt3 were significantly decreased in MIRI tissue and H2O2 stimulated H9C2 cells, while ramelteon treatment upregulated Sirt3 activity and expression. After treat with 3-TYP, a classic Sirt3 activity inhibitor, we constructed myocardial ischemia/reperfusion surgery in vivo and induced H9C2 cells with H2O2 in vitro. The results showed that the myocardial protection and anti-apoptotic effects of ramelteon were antagonized by 3-TYP, indicating that the activation of Sirt3 is a key mechanism for ramelteon to exert myocardial protection. In summary, our results confirm a novel mechanism by which ramelteon improves MIRI by activating Sirt3 signaling pathway, providing strong evidence for the treatment of MIRI with ramelteon.


Asunto(s)
Indenos , Isquemia Miocárdica , Daño por Reperfusión Miocárdica , Sirtuina 3 , Humanos , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Peróxido de Hidrógeno , Simulación del Acoplamiento Molecular , Miocitos Cardíacos , Apoptosis
11.
Front Med (Lausanne) ; 11: 1308299, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38343639

RESUMEN

This report described three cases with long-term severe dysmenorrhea, and these cases were referred to our department for medical help. The diagnosis of accessory cavitated uterine malformation (ACUM) was considered based on symptoms and ultrasound/MRI findings. Moreover, a combined approach involving hysteroscopic surgery and laparoscopic surgery was undertaken, and no complications occurred during surgery and in the post-operative period. It is important to consider ACUM in patients with severe dysmenorrhea that does not respond to medical management. Surgery is the most effective treatment for this anomaly.

12.
Am J Otolaryngol ; 45(3): 104229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38422555

RESUMEN

PURPOSE: This multicenter, prospective study is designed to investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the Middle Ear Effusion (MEE) of patients developing Otitis Media with Effusion (OME) subsequent to an Omicron infection. The objective is to elucidate any potential association between the virus and the condition. METHODS: This study, conducted from January to June 2023, spanned the Otolaryngology departments of two medical institutions in Eastern China. Patients manifesting OME subsequent to Omicron infection from both hospitals were subjected to comprehensive otolaryngological assessments, including pure-tone audiometry (PTA), tympanometry, otoscopic examination, and nasopharyngolaryngoscopy. Subsequently, MEE samples extracted from these patients were analyzed through RT-PCR to detect SARS-CoV-2. RESULTS: In this study, 23 patients (32-84 years; 57.5 ± 14.8 mean age; 47.8 % male) presented OME in 25 ears post-Omicron infection, with 21 (91.3 %) exhibiting unilateral symptoms. The median duration from infection to MEE sampling was 21 days (IQR: 25-46; range: 11-150). Predominantly, 64.0 % exhibited Type B tympanograms, and fluid accumulation was observed in 88.0 % of ears. SARS-CoV-2 was detected in 3 MEE samples (12.0 %), with cycle threshold values ranging between 25.65 and 33.30. CONCLUSIONS: Our study highlights the potential effects of COVID-19 on the middle ear, suggesting a link between SARS-CoV-2 and OME onset. The virus, a significant contributor to OME, is detectable in the MEE nearly a month post-Omicron infection, indicating a potential alteration in OME treatment strategies and a risk of recurrence, emphasizing the necessity for otolaryngologist vigilance.


Asunto(s)
COVID-19 , Otitis Media con Derrame , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/diagnóstico , Otitis Media con Derrame/virología , Otitis Media con Derrame/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Pruebas de Impedancia Acústica/métodos
13.
Chin Med ; 19(1): 28, 2024 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-38369521

RESUMEN

BACKGROUND: To investigate the effec of the herb-partitioned moxibustion on T-lymphocyte activity in immunosuppressed rats through differential modulation of the immune checkpoint molecules CD28 and CTLA-4. METHODS: Forty-eight Sprague‒Dawley rats were randomly divided into the normal group (NG), the cyclophosphamide model group (CTX), the herb-partitioned moxibustion group (HPM), the CD28 inhibitor + herb-partitioned moxibustion group (aCD28 + HPM), the CTLA-4 inhibitor + herb-partitioned moxibustion group (aCTLA-4 + HPM), and the levamisole group (LEV) (8 rats per group). The immunosuppression model was prepared using cyclophosphamide. HPM treatments was performed via herb-partitioned moxibustion at 4 acupoints, Zhongwan (CV12), Shenque (CV8), Guanyuan (CV4), and Zusanli (ST36). Subsequently, the moxa floss was made into a conical moxa cone, which was then placed on the herbal cake and ignited. Five consecutive moxibustion strokes were performed daily for 10 consecutive days. In addition to the same moxibustion, each rat in the aCD28 + HPM group was injected intraperitoneally with 0.5 mg/kg of CD28 inhibitor per rat on the first day of treatment, and 100 µL of CTLA-4 inhibitor was injected into the aCTLA-4 + HPM group on Days 1, 4, and 7. For the positive control, levamisole (LEV) was administered by gavage at a dose of 2 mg/kg once daily for 10 days. RESULTS: Compared with those in CTX model rats, the WBC counts in the HPM and other groups were significantly higher. The immobility time of EPM in the HPM group was significantly lower than that of the CTX group. The HE stainin results also showed that after treatment, the the marginal zone area of the spleen tissue in the HPM increased, the number of lymphatic sheath lymphocytes around the small central artery of the spleen increased, and the amount of red pulp containing a small amount of pigmentation was partially reduced. Compared with those in the CTX group, the serum levels of CD28, CTLA-4, B7-1, and B7-2 were significantly lower, and the levels of α-MSH, TrkB, and BDNF were significantly greater in the HPM group. The results of the flow cytometry assay showed a significant increase in the number of CD8 + T lymphocytes after treatment with HPM or other agents compared to that in the CTX group. The immunofluorescence results showed that the levels of CD28 and CTLA-4 lower in spleen tissues than in control tissues, and the binding ability of CD28 to B7-1 and B7-2 was weakened after treatment with HPM and other treatments compared with CTX rats, PCR for CD28, CTLA-4 and B7-1 showed similar results. CONCLUSION: In the immunosuppressive rat model induced by cyclophosphamide, HPM upregulated the expression of α-MSH, TrkB, and BDNF, and downregulated the expression of CD28 and CTLA-4, thereby enhancing the activity of CD8+ T lymphocytes, restoring spleen function, improving the immunosuppressive state, restoring immune function, and effectively alleviating depressive symptoms.

14.
Medicine (Baltimore) ; 103(6): e37068, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38335425

RESUMEN

This study aims to investigate the relationship between the human papillomavirus (HPV) infection and the altered vaginal microecological environment of patients. Initially, HPV genotyping and microecological detection were performed in 1281 subjects in the Department of Obstetrics and Gynecology of The First Hospital of Qinhuangdao (Qinhuangdao, China). The relationship between the enzymes of vaginal microecology, that is, proline aminopeptidase and acetylglucosaminidase, and vaginal inflammatory diseases, as well as the prognosis of HPV infection, was analyzed. The experimental findings indicated a close relationship between the expression of positive prolyl aminopeptidase and trichomonas vaginitis, as well as bacterial vaginitis. In addition, the expression of acetylglucosaminidase is closely associated with trichomonas vaginitis and vulvovaginal candidiasis. Furthermore, the observations indicated that positive prolyl aminopeptidase and acetylglucosaminidase could increase the risk of various subtypes of HPV infection in patients. The receiver operating characteristic curve analysis presented that the expression of prolyl aminopeptidase and acetylglucosaminidase could offer exceptional diagnostic efficacy, indicating their association with persistent HPV infection. In summary, our results highlighted that the expression of positive prolyl aminopeptidase and acetylglucosaminidase in the vaginal microecology could be substantially correlated to the occurrence and the development of vaginal inflammatory diseases, as well as the outcome and the risk of persistent HPV infection.


Asunto(s)
Infecciones por Papillomavirus , Vaginitis por Trichomonas , Femenino , Embarazo , Humanos , Infecciones por Papillomavirus/epidemiología , Acetilglucosaminidasa , Vagina/microbiología , Virus del Papiloma Humano
15.
PeerJ ; 12: e16686, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38188153

RESUMEN

Background: The Cangshan National Nature Reserve of Dali City was adopted as the research object to clarify the vertical distribution characteristics of soil organic carbon (SOC) and vegetation types at different elevations in western Yunnan. Methods: The contents of SOC, light fraction organic carbon (LFOC), heavy fraction organic carbon (HFOC), and water-soluble organic carbon (WSOC) in the 0-30 cm soil layer at different elevations (2,400, 2,600, 2,800, 3,000, 3,200, 3,400, and 3,600 m) were determined, and the above-ground vegetation types at different elevations were investigated. Results: Results showed that the SOC content was the highest in 0-20 cm surface soil and gradually decreased with the deepening of the soil layer. It increased then decreased with the increase in elevation, and it peaked at 3,000 m. The LFOC content was between 1.28 and 7.3515 g kg-1. It exhibited a decreasing trend and little change in profile distribution. The HFOC content ranged between 12.9727 and 23.3708 g kg-1; it increased then decreased with the increase in profile depth. The WSOC content was between 235.5783 and 392.3925 mg kg-1, and the response sensitivity to elevation change was weak. With the increase in elevation, WSOC/SOC and LFOC/SOC showed a similar trend, whereas HFOC presented an opposite trend. This observation indicates that the active organic carbon content at 3,600 m was lower than that at 2,400 m, and the middle elevation was conducive to the storage of active organic carbon. Meanwhile, the physical and chemical properties of soil affected the distribution of organic carbon to a certain extent. The vegetation type survey showed that the above-ground dominant species within 2,400-2,800 m were Pinus yunnanensis and Pinus armandii. Many evergreen and mixed coniferous broadleaf forests were distributed from 3,000 m to 3,200 m. Species of Abies delavayi were mainly distributed from 3,400 m to 3,600 m. This research serves as a reference for the study of forest soil carbon stability in high-elevation areas and plays an important role in formulating reasonable land use management policies, protecting forest soil, reducing organic carbon loss, and investigating the carbon sequestration stability of forest ecosystems.


Asunto(s)
Carbono , Pinus , Ecosistema , Suelo , China , Carbón Orgánico , Agua
16.
Int Immunopharmacol ; 126: 111285, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38061118

RESUMEN

OBJECTIVES: HWH486 inhibits Bruton's tyrosine kinase and therefore shows promise as a treatment against rheumatoid arthritis and chronic spontaneous urticaria. This phase I trial assessed tolerability, safety, pharmacokinetics and pharmacodynamics of a single oral dose of HWH486 capsules in healthy adults. METHODS: A single-center, randomized, double-blind, placebo-controlled, dose-escalation study from 10 to 800 mg was conducted in 96 healthy Chinese adults, of whom 80 received HWH486 and 16 received placebo. RESULTS: A total of 96 subjects were enrolled, and all completed the study. In the HWH486 group, mean Tmax ranged from 1.03 to 2.00 h, and mean T1/2 ranged from 0.85 to 8.67 h across the dose range from 10 to 800 mg. Mean Cmax increased linearly with dose, while mean AUC0-t increased non-linearly. Occupancy of Bruton's tyrosine kinase peaked within 0.50-4.00 h after administration across the dose groups, and the delay until peak occupancy decreased with increasing dose. Twenty-five subjects (31.25 %) in the HWH486 group experienced 35 treatment-emergent adverse events, while four subjects (25.00 %) in the placebo group experienced eight such events. CONCLUSIONS: HWH486 is well tolerated and safe in healthy adults, in whom it can strongly bind Bruton's tyrosine kinase. These findings justify clinical studies of HWH486 efficacy against autoimmune diseases.


Asunto(s)
Artritis Reumatoide , Enfermedades Autoinmunes , Adulto , Humanos , Agammaglobulinemia Tirosina Quinasa , Área Bajo la Curva , Método Doble Ciego , Artritis Reumatoide/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Voluntarios Sanos
17.
Int J Biol Macromol ; 256(Pt 1): 128014, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37951439

RESUMEN

In order to cope with the increasingly severe food contamination and safety problems, a powerful sterilization of food packaging material is urgently needed. Chitosan (CS) has potential applications in food packaging due to its good film-forming properties, but its antibacterial activity is not sufficient to meet the needs in practical applications. Silver nanoparticles (AgNPs) have the problem of weak immediate antibacterial activity as a broad-spectrum antibacterial agent. Therefore, in this study, AgNPs@GA@Cur-POTS (AGCP) composite antibacterial system was prepared by combining AgNPs with antibacterial photodynamic therapy using gallic acid (GA) as a reducing agent, curcumin (Cur) as a photosensitizer and perfluorosilane (POTS) for surface modification. The results showed that AGCP could produce a large number of reactive oxygen species under blue light irradiation, killing >90 % of E. coli and S. aureus within 2 h. Subsequently, the composite film of CS loaded with AGCP (CS/AGCP) was prepared by the flow-delay method. The CS/AGCP composite film exhibited excellent barrier properties and antioxidant activity, while its antibacterial rates against E. coli and S. aureus reached 98.44 ± 1.27 % and 99.11 ± 0.24 %, respectively, while the OD630 values of the two groups of bacteria treated with it showed no significant increase in incubation for up to 132 h, exhibiting remarkable and sustained antibacterial effects. Taken together, this work will provide a new strategy for antibacterial food packaging.


Asunto(s)
Quitosano , Curcumina , Nanopartículas del Metal , Plata , Curcumina/farmacología , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacología , Embalaje de Alimentos/métodos
18.
Clin Microbiol Infect ; 30(2): 206-210, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37805032

RESUMEN

BACKGROUND: Bats have garnered increased attention in the field of life sciences for their typical biological characteristics of carrying a variety of zoonotic viruses without disease, long lifespans, low tumorigenesis rates, and high metabolism. When it was found that bats can carry the rabies virus, over 60 years of research revealed that bats host over 4100 distinct viruses, including Ebola virus and SARS-CoV. OBJECTIVES: This paper primarily reviews the profiles of zoonotic viruses carried by bats across various regions globally. The review aims to provide a foundation and reference for future research on monitoring zoonotic viruses in diverse global regions and bat species, exploring the coevolutionary relationship between bats and viruses, understanding the tolerance mechanisms of bat B cells, prevention, and treatment of zoonotic diseases caused by bats. SOURCES: The search used 'bat', 'bats', 'rabies virus', 'Dengue virus', 'West Nile virus', 'Zika virus', 'St. Louis encephalitis virus', 'Japanese encephalitis virus', 'Hantavirus', 'Novel hantavirus', 'Rift Valley fever virus', 'Crimean Congo hemorrhagic fever virus', 'Paramyxovirus', 'Nipah virus', 'Hendra virus', 'Menangle virus', 'Tioman virus', 'Marburg Virus', 'Bombali virus', 'Ebola virus', 'Influenza A virus', 'coronavirus', 'Hepatitis B virus', and 'Hepatitis E virus' as text in PubMed. CONTENT: A total of 147 references were obtained. Surveys on severe zoonotic virus carriage have been limited to only 83 bat species belonging to nine families, which are distributed all over the world. We also briefly describe the antibody responses and B-cell molecules in bats. IMPLICATIONS: Several viruses have been found in different species of bats. This suggests that bats may be important hosts for future viral infectious diseases. Particularly in recent years, the close correlation between human infection pandemics caused by coronaviruses and bats highlights the pressing need to comprehend the species, tolerance, and coevolutionary mechanisms of zoonotic viruses carried by different bat species.


Asunto(s)
Quirópteros , Infecciones por Coronavirus , Coronavirus , Ebolavirus , Virus ARN , Infección por el Virus Zika , Virus Zika , Animales , Humanos , Zoonosis/epidemiología , Virus ARN/genética , Coronavirus/genética
19.
Clin Exp Rheumatol ; 42(1): 30-38, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38019149

RESUMEN

OBJECTIVES: Increased serum uric acid (SUA) levels are well known to be concomitant of cardiovascular and kidney diseases, and have been proposed to be implicated in the development of arteriolar damage. The aim of the present study was to assess the association between SUA levels, renal damage and its implication for outcome in patients with lupus nephritis (LN). METHODS: This retrospective study included 194 cases with biopsy proven LN at the Affiliated Hospital of Qingdao University between January 2013 and June 2021. We reviewed clinical, laboratory and histologic data of patients and analysed the correlation between SUA levels, renal damage and the primary outcome (death or ESRD). Biopsy-proven arteriolar damage was defined by the presence of arteriolar hyalinosis and/or intimal thickening. RESULTS: Compared to LN patients without hyperuricemia, LN patients with hyperuricaemia presented with higher BP, hyperlipidaemia, lower eGFR, lower haemoglobin, lower serum albumin, worse renal arteriolar damage and proteinuria, and also higher SLEDAI score, activity index and chronicity index (p<0.05). At logistic regression analysis, SUA was independently related to the presence of arteriolar damage. For each 100 µmol/L increase in SUA levels the risk for arteriolar damage raised by 53.8% (hazard ratio [HR] =1.538; 95% CI: 1.147-2.063; p=0.004) after adjustment for haemoglobin, serum creatinine and erythrocyte sedimentation rate. Cox regression analysis showed that female (HR=3.180; 95% CI: 1.216-8.313; p=0.018), white blood cell count (HR=1.111; 95% CI: 1.027-1.202; p=0.009), SUA (HR=1.100; 95% CI: 1.023-1.253; p=0.035), serum creatinine (HR=1.800; 95% CI: 1.348-2.404; p<0.001), and renal arteriolar damage (HR=3.117; 95% CI: 1.022-9.511; p=0.046) was significantly associated with development of ESRD or death in patients with LN after adjustment for several potential confounding factors. Furthermore, for each 100 µmol/L increase in SUA levels, the risk of ESRD or death increased by 10%. CONCLUSIONS: SUA levels are directly associated with renal arteriolar damage and poor prognosis in LN patients. Hyperuricaemia is an important predictor for poor prognosis in patients with LN.


Asunto(s)
Hiperuricemia , Fallo Renal Crónico , Nefritis Lúpica , Humanos , Femenino , Nefritis Lúpica/complicaciones , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/patología , Ácido Úrico , Hiperuricemia/complicaciones , Hiperuricemia/diagnóstico , Estudios Retrospectivos , Creatinina , Riñón/patología , Hemoglobinas , Factores de Riesgo
20.
Bioelectrochemistry ; 156: 108599, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37988979

RESUMEN

The accurate determination of organophosphorus pesticide residues is of great importance for human disease monitoring and environmental safety. Numerous detection methods exist, among which sensitive monitoring of organophosphorus compounds using electrochemical sensors has gradually become a research hotspot. This paper used acetylcholinesterase (AChE) as an indicator anchored on a zinc oxide-reduced graphene oxide (ZnO-rGO) composite rich in active sites, in which green non-toxic zinc oxide (ZnO) nanomaterials were uniformly distributed on the reduced graphene for rapid detection of organophosphorus. The effects of different ratios of ZnO to reduced graphene on the performance of ZnO-rGO nanocomposites were investigated. The AChE/ZnO-rGO biosensor detects organophosphorus by electrochemical inhibition of acetylcholinesterase in the presence of organophosphorus. The developed electrochemical biosensor has high selectivity and good linearity, and the ZnO-rGO nanocomposite as a matrix for immobilization of acetylcholinesterase and detection of organophosphorus has the potential for highly sensitive pesticide detection.


Asunto(s)
Técnicas Biosensibles , Grafito , Plaguicidas , Óxido de Zinc , Humanos , Óxido de Zinc/química , Grafito/química , Compuestos Organofosforados , Acetilcolinesterasa/química , Técnicas Biosensibles/métodos
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