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Our previous study has verified that activation of group â metabotropic glutamate receptors (mGluRâ ) in the red nucleus (RN) facilitate the development of neuropathological pain. Here, we further discussed the functions and possible molecular mechanisms of red nucleus mGluR â ¡ (mGluR2 and mGluR3) in the development of neuropathological pain induced by spared nerve injury (SNI). Our results showed that mGluR2 and mGluR3 both were constitutively expressed in the RN of normal rats. At 2 weeks post-SNI, the protein expression of mGluR2 rather than mGluR3 was significantly reduced in the RN contralateral to the nerve lesion. Injection of mGluR2/3 agonist LY379268 into the RN contralateral to the nerve injury at 2 weeks post-SNI significantly attenuated SNI-induced neuropathological pain, this effect was reversed by mGluR2/3 antagonist EGLU instead of selective mGluR3 antagonist ß-NAAG. Intrarubral injection of LY379268 did not alter the PWT of contralateral hindpaw in normal rats, while intrarubral injection of EGLU rather than ß-NAAG provoked a significant mechanical allodynia. Further studies indicated that the expressions of nociceptive factors TNF-α and IL-1ß in the RN were enhanced at 2 weeks post-SNI. Intrarubral injection of LY379268 at 2 weeks post-SNI significantly suppressed the overexpressions of TNF-α and IL-1ß, these effects were reversed by EGLU instead of ß-NAAG. Intrarubral injection of LY379268 did not influence the protein expressions of TNF-α and IL-1ß in normal rats, while intrarubral injection of EGLU rather than ß-NAAG significantly boosted the expressions of TNF-α and IL-1ß. These findings suggest that red nucleus mGluR2 but not mGluR3 mediates inhibitory effect in the development of SNI-induced neuropathological pain by suppressing the expressions of TNF-α and IL-1ß. mGluR â ¡ may be potential targets for drug development and clinical treatment of neuropathological pain.
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Background: Studies based on observations have indicated potential associations between chronic gastrointestinal diseases and an increased risk of erectile dysfunction (ED). However, the causality of these connections remains ambiguous. Methods: Summary data for chronic gastrointestinal diseases were extracted from public data. Summary data on ED were extracted from three distinct sources. The genetic correlations between chronic gastrointestinal diseases and ED were explored using linkage disequilibrium score regression (LDSC). The causal associations between chronic gastrointestinal diseases and ED were evaluated using Mendelian randomization (MR) analysis, followed by a meta-analysis to determine the ultimate causal effect. Results: The LDSC results suggested significant genetic correlations between Crohn's disease (CD) and ED. Inflammatory bowel disease (IBD), ulcerative colitis (UC), and liver cirrhosis (LC) were found to have potential genetic correlations with ED. The combined multiple MR results indicate that IBD and CD have significant causal relationships with ED, while colorectal cancer (CRC) may have a potential causal effect on ED. Conclusion: This research provided evidence supporting a causal association between IBD, CD, CRC, and ED. The impact of chronic gastrointestinal diseases on ED warrants greater attention in clinical practice.
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The increasing prevalence of diabetic reproductive complications has prompted the development of innovative animal models. The use of the silkworm Bombyx mori as a model for diabetic reproductive damage shows potential as a valuable research tool. This study employed silkworms as a novel model to investigate diabetic reproductive damage. The silkworms were fed a high-glucose diet containing 10% glucose to induce a diabetic model. Subsequently, the study concentrated on assessing the influence of diabetes on the reproductive system of male silkworms. The results indicate that diabetes resulted in reduced luteinizing hormone (LH) and testosterone (T) levels, as well as elevated triglyceride (TG) levels in male silkworms. Moreover, diabetes mellitus was associated with pathological testicular damage in male silkworms, accompanied by decreased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels, along with increased malondialdehyde (MDA) levels in the testis. Additionally, diabetes mellitus reduced the expression of siwi1 and siwi2 genes in the testis of male silkworms. Overall, these results support using silkworms as a valuable model for studying diabetic reproductive damage.
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OBJECTIVE: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is considered to have the advantages of completely scarless, less postoperative pain, earlier flatus, and faster postoperative recovery. However, posterior myoma are relatively difficult to operate through vNOTES in the conventional lithotomy position. Thus, we innovated the application of prone position in the removal of posterior myoma in vNOTES. The aim of this study is the comparison of myomectomy outcomes of patient for single posterior myoma in prone and lithotomy position. DESIGN: A single-center, prospective study. SETTING: A university teaching hospital. PATIENTS: A total of 81 patients with posterior myoma who underwent myomectomy in vNOTES from January 2021 to December 2022. INTERVENTIONS: The patients underwent myomectomy in vNOTES in prone or lithotomy position. MEASUREMENTS AND MAIN RESULTS: Among the patients who underwent vNOTES myomectomy, 29 (35.8%) were in the lithotomy position group, and 52 (64.2%) in the prone position group. Of note, 4 (4.9%) patients underwent a conversion to LESS during the operation-3 in the lithotomy and 1 in the prone position group. And a patient in the lithotomy position group underwent resurgery for hemostasis due to postoperative pelvic bleeding. Compared with the lithotomy position, prone position significantly shortens the operation time (12.3, 95% CI: 6.811, 17.761. p = .009) without increasing the complications and postoperative discomfort of patients. CONCLUSION: Compared to the lithotomy position, the prone position provides greater convenience for operation and exhibits a lower rate of surgical conversion during the removal of single posterior myomas via vNOTES. Further, for patients selecting vNOTES, surgeons need to conduct sufficient preoperative evaluation, timely hemostasis during surgery, and timely surgical conversion if necessary to ensure patient safety.
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Cryptococcosis is a life-threatening invasive fungal infection with significantly increasing mortality worldwide, which is mainly caused by Cryptococcus neoformans and Cryptococcus gattii. These two species complexes have different epidemiological and clinical characteristics, indicating the importance of accurate differential diagnosis. However, the clinically used culture method and cryptococcal capsular antigen detection couldn't achieve the above goals. Herein, we established a novel duplex flap probe-based isothermal assay to identify the Cryptococcus neoformans and Cryptococcus gattii within 1 hour. This assay combined the highly sensitive nucleic acid isothermal amplification and highly specific fluorescence probe method, which could effectively distinguish the sequence differences of the two species complexes using two different fluorescence flap probes in a single reaction system. This novel method showed excellent detection performance with sensitivity (10 copies/µL each) and specificity (100%) compared to traditional culture and sequencing methods. Furthermore, we applied this method to spiked clinical samples, 30 cerebrospinal fluids and 30 bronchoalveolar lavage fluids, which kept good detection performance. This novel rapid duplex flap probe-based isothermal assay is a promising and robust tool for applications in differential diagnosis of the Cryptococcus neoformans and Cryptococcus gattii in clinical settings, especially when clinical suspicion for cryptococcal disease is high and epidemiological studies.
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Criptococosis , Cryptococcus gattii , Cryptococcus neoformans , Humanos , Cryptococcus neoformans/genética , Cryptococcus gattii/genética , Criptococosis/diagnóstico , Criptococosis/microbiología , Antígenos Fúngicos , Líquido del Lavado BronquioalveolarRESUMEN
At present, anti-cancer drug synergy therapy is one of the most important methods to overcome drug resistance and reduce drug toxicity in cancer treatment. High-throughput screening through deep learning can effectively improve the efficiency of discovering synergistic drugs. Nowadays, most of the existing deep learning algorithms for anti-cancer drug synergy prediction use deep neural networks and can only implicitly perform feature interaction. This study proposes a deep learning algorithm, named MolCross, which combines implicit feature interaction with explicit features to improve the accuracy of prediction of the anti-cancer drug synergy score. MolCross uses a deep autoencoder to extract features from high-dimensional input, uses the drug-specific subnetworks and cross-network to perform implicit feature interaction and explicit feature interaction respectively, and finally uses a synergy prediction network to combine the two feature interaction methods to obtain the final prediction results. We adopted a five-fold cross validation and compared MolCross with other four anti-cancer drug synergy prediction models. The results show that MolCross has better prediction performance than other models. MolCross also has good performance in terms of cross-cell line and cross-tissue type. Existing studies have demonstrated that cancer molecular subtypes have different sensitivities to targeted therapy. In this study, the features of cancer molecular subtype were introduced in the model using an embedding layer in MolCross to explore the effect of cancer molecular subtype on anti-cancer drug synergy. We also found that the cancer molecular subtype is one of the main factors affecting the synergy between drugs.
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Antineoplásicos , Aprendizaje Profundo , Sinergismo Farmacológico , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Algoritmos , Redes Neurales de la ComputaciónRESUMEN
Hepatitis C remains a global health problem, especially in poverty-stricken areas. A rapid and sensitive point-of-care (POC) diagnostic tool is critical for the early detection and timely treatment of hepatitis C virus (HCV) infection. Here, for the first time, we reported a novel molecular diagnostic assay, termed reverse transcription multiple cross displacement amplification integrated with a gold-nanoparticle-based lateral flow biosensor (RT-MCDA-AuNPs-LFB), which was developed for rapid, sensitive, specific, and visual identification of HCV. HCV-RT-MCDA induced rapid isothermal amplification through a specific primer set targeting the 5'untranslated region gene from the major HCV genotypes 1b, 2a, 3b, 6a, and 3a that are prevalent in China. The optimal reaction temperature and time for RT-MCDA-AuNPs-LFB were 68°C and 25 min, respectively. The limit of detection of the assay was 10 copies per test, and the specificity was 100% for the experimental strains. The whole detection procedure, including crude nucleic acid isolation (~5 min), RT-MCDA (68°C, 25 min), and visual AuNPs-LFB result confirmation (less than 2 min), was performed within 35 min. The preliminary results indicated that the HCV-RT-MCDA-AuNPs-LFB assay could be a valuable tool for sensitive, specific, visual, cost-saving, and rapid detection of HCV and has potential as a POC diagnostic platform for field screening and early clinical detection of HCV infection.
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Técnicas Biosensibles , Hepatitis C , Nanopartículas del Metal , Humanos , Hepacivirus/genética , Sensibilidad y Especificidad , Técnicas de Amplificación de Ácido Nucleico/métodos , Oro , Hepatitis C/diagnóstico , Técnicas Biosensibles/métodosRESUMEN
Neutrophil-to-lymphocyte ratio (NLR), a novel inflammatory marker, is strongly associated with the risk of sarcopenia. Notably, being overweight has been found to accelerate the loss of skeletal muscle mass and function in chronic kidney disease (CKD) patients. However, the effect of overweight status on the relationship between NLR and sarcopenia risk has been poorly studied. We conducted a cross-sectional study at a hemodialysis center in Chengdu, China, from September to December 2022. The prevalence of sarcopenia was determined according to the Asian Working Group for Sarcopenia (AWGS). Participants were stratified based on body mass index (BMI) categories for the Asian population (non-overweight < 23 kg/m2 and overweight ≥ 23 kg/m2). 272 participants aged 18-85 years were included, with 144 being male. The overall prevalence of sarcopenia was 32.72% (89/272). After adjusting for covariates, NLR was significantly associated with sarcopenia risk in overweight participants (OR 1.60, 95% CI 1.15-2.24, p = 0.006), whereas it was not significant in the non-overweight group (OR 0.88, 95% CI 0.70-1.10, p = 0.254). Moreover, subgroup analysis showed a significant interactive association between NLR and overweight status with respect to sarcopenia. These findings emphasize the potential significance of regular screening of NLR for the early detection of sarcopenia in overweight patients undergoing maintenance hemodialysis.
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Sarcopenia , Humanos , Masculino , Femenino , Sarcopenia/epidemiología , Sarcopenia/etiología , Sarcopenia/diagnóstico , Sobrepeso/complicaciones , Neutrófilos , Estudios Transversales , Diálisis Renal/efectos adversos , Linfocitos , Prevalencia , Fuerza de la Mano/fisiologíaRESUMEN
OBJECTIVES: In the current study, for the first time, we reported a novel HCV molecular diagnostic approach termed reverse transcription loop-mediated isothermal amplification integrated with a gold nanoparticles-based lateral flow biosensor (RT-LAMP-AuNPs-LFB), which we developed for rapid, sensitive, specific, simple, and visual identification of HCV. METHODS: A set of LAMP primer was designed according to 5'untranslated region (5'UTR) gene from the major HCV genotypes 1b, 2a, 3b, 6a, and 3a, which are prevalent in China. The HCV-RT-LAMP-AuNPs-LFB assay conditions, including HCV-RT-LAMP reaction temperature and time were optimized. The sensitivity, specificity, and selectivity of our assay were evaluated in the current study. The feasibility of HCV-RT-LAMP-AuNPs-LFB was confirmed through clinical serum samples from patients with suspected HCV infections. RESULTS: An unique set of HCV-RT-LAMP primers were successfully designed targeting on the 5'UTR gene. The optimal detection process, including crude nucleic acid extraction (approximately 5 min), RT-LAMP reaction (67â, 30 min), and visual interpretation of AuNPs-LFB results (~ 2 min), could be performed within 40 min without specific instruments. The limit of detection was determined to be 20 copies per test. The HCV-RT-LAMP-AuNPs-LFB assay exhibited high specificity and anti-interference. CONCLUSIONS: These preliminary results confirmed that the HCV-RT-LAMP-AuNPs-LFB assay is a sensitive, specific, rapid, visual, and cost-saving assay for identification of HCV. This diagnostic approach has great potential value for point-of-care (POC) diagnostic of HCV, especially in resource-challenged regions.
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Técnicas Biosensibles , Hepatitis C , Nanopartículas del Metal , Humanos , Hepacivirus/genética , Oro , Sensibilidad y Especificidad , Regiones no Traducidas 5' , Hepatitis C/diagnóstico , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Diagnóstico Molecular/métodos , Técnicas Biosensibles/métodosRESUMEN
OBJECTIVES: This study aimed to appraise clinical practice guidelines (CPGs) for the treatment of carbapenem-resistant Gram-negative Bacilli (CRGNB) infections and to summarise the recommendations. METHODS: A systematic search of the literature published from January 2012 to March 2023 was undertaken to identify CPGs related to CRGNB infections treatment. The methodological and reporting quality of eligible CPGs were assessed using six domains of the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and seven domains of the Reporting Items for practice Guidelines in HealThcare (RIGHT) checklist. Basic information and recommendations of included CPGs were extracted and compared. RESULTS: A total of 21 CPGs from 7953 relevant articles were included. The mean overall AGREE II score was 62.7%, and was highest for "clarity of presentation" (90.2%) and lowest for "stakeholder involvement" (44.8%). The overall reporting quality of all of the CPGs was suboptimal, with the proportion of eligible items ranging from 45.7 to 85.7%. The treatment of CRGNB infections is related to the type of pathogen, the sensitivity of antimicrobial agents, and the site of infection. In general, the recommended options mainly included novel ß-lactam/ ß-lactamase inhibitors, cefiderocol, ampicillin-sulbactam (mainly for carbapenem-resistant Acinetobacter baumannii [CRAB]), and combination therapy, involving polymyxin B/colistin, tigecycline (except for carbapenem-resistant Pseudomonas aeruginosa), aminoglycosides, carbapenems, fosfomycin, and sulbactam (mainly for CRAB). CONCLUSIONS: The methodological and reporting quality of CPGs for the treatment of CRGNB infections are generally suboptimal and need further improvement. Both monotherapy with novel drugs and combination therapy play important roles in the treatment.
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Antibacterianos , Carbapenémicos , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Guías de Práctica Clínica como Asunto , Humanos , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Carbapenémicos/uso terapéutico , Carbapenémicos/farmacología , Cefiderocol , Fosfomicina/uso terapéutico , Fosfomicina/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Pruebas de Sensibilidad Microbiana/normas , Sulbactam/uso terapéutico , Sulbactam/farmacología , Tigeciclina/uso terapéutico , Tigeciclina/farmacologíaRESUMEN
Epstein-Barr virus (EBV) is a ubiquitous gamma herpesvirus that maintains a lifelong latent association with B lymphocytes. Here, a rapid and reliable diagnosis platform for detecting EBV infection, employing loop-mediated isothermal amplification (LAMP) combined with a gold nanoparticles-based lateral flow biosensors (AuNPs-LFB) (termed LAMP Amplification Mediated AuNPs-LFB Detection, LAMAD), was developed in the current study. A set of specific LAMP primers targeting the Epstein-Barr nuclear antigen (EBNA) leader protein (EBNA-LP) gene was designed and synthesized. Subsequently, these templates extracted from various pathogens and whole blood samples were used to optimize and evaluate the EBV-LAMAD assay. As a result, the limit of detection (LoD) of the EBV-LAMAD assay was 45 copies/reaction. The EBV-LAMAD assay can detect all representative EBV pathogens used in the study, and of note, no cross-reactions were observed with other non-EBV organisms. Moreover, the whole workflow of the EBV-LAMAD assay can be completed within 70 min, including rapid EBV template preparation, EBV-LAMP amplification, and AuNPs-LFB-mediated detection. Taken together, the EBV-LAMAD assay targeting the EBNA-LP gene is a rapid, simplified, sensitive, reliable, and easy-to-use detection protocol that can be used as a competitive potential diagnostic/screening tool for EBV infection in clinical settings, especially in basic laboratories in resource-limited regions. KEY POINTS: ⢠A novel, simplified, and easy-to-use AuNPs-LFB biosensor was designed and prepared. ⢠LAMP combined with an AuNPs-LFB targeting the novel EBNA-LP gene was established. ⢠EBV-LAMAD is a rapid, sensitive, and reliable detection protocol for EBV infection.
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Técnicas Biosensibles , Infecciones por Virus de Epstein-Barr , Nanopartículas del Metal , Técnicas de Diagnóstico Molecular , Humanos , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/diagnóstico , Oro , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas Biosensibles/métodos , Sensibilidad y EspecificidadRESUMEN
1-Methylcytosine (1mCyt) is the base for nucleoside N1-methylpseudodeoxycytidine of Hachimoji nucleic acids and a frequently used model compound for theoretical studies on excited states of cytosine nucleosides. However, there is little experimental characterization of spectra and photo-dynamic properties of 1mCyt. Herein, we report a comprehensive investigation into excited state dynamics and effects of solvents on fluorescence dynamics of 1mCyt in both water and acetonitrile. The study employed femtosecond broadband time-resolved fluorescence, transient absorption, and steady-state spectroscopy, along with density functional theory and time-dependent density functional theory calculations. The results obtained provide the first experimental evidence for identifying a dark-natured â¼5.7 ps lifetime nπ* state in the ultrafast non-radiative deactivation with 1mCyt in aqueous solution. This study also demonstrates a significant effect of the solvent on 1mCyt's fluorescence emission, which highlights the crucial role of solute-solvent hydrogen bonding in altering structures and reshaping the radiative as well as nonradiative dynamics of the 1mCyt's ππ* state in the aprotic solvent compared to the protic solvent. The solvent effect exhibited by 1mCyt is distinctive from that known for deoxycytidine, indicating the need for caution in using 1mCyt for modelling the ultrafast dynamics of Cyt nucleosides in solvents with varying properties. Overall, our study unveils a deactivation mechanism that confers a high degree of photo-stability for 1mCyt in solution, shedding light on the molecular basis for solvent-induced effects on the excited state dynamics of nucleobases and derivatives.
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OBJECTIVE: Artificial hip arthroplasty (AHA) is widely accepted in elderly patients with femoral neck fractures, but it is associated with high risk of death and various postoperative complications due to old age and accompanying chronic diseases. Therefore, this study aimed to explore the risk factors for death in elderly patients with femoral neck fractures after AHA and to establish a nomogram risk prediction model, which is expected to reveal high-risk patients and improve the postoperative quality of life and survival rate of patients. METHODS: Elderly patients who underwent AHA for femoral neck fractures in our hospital from September 2014 to May 2021were retrospectively analyzed. These patients were divided into a survival group and a death group according to their clinical outcomes. The following clinical data were recorded for the patients in the two groups: sex, age, underlying diseases, smoking and drinking history, preoperative nutritional risk score (NRS) and American Society of Anesthesiologists (ASA) score, as well as relevant indicators about the operation. These data were subject to univariate analysis and then logistic analysis to determine the risk factors of death. Subsequently, a nomogram risk prediction model was established and further validated with the receiver operating characteristic curve (ROC) and the Hosmer-Lemeshow test. Finally, the effects of predictive risk factors were analyzed using the Kaplan-Meier survival curve. RESULTS: Follow-up was completed by 260 patients, including 206 patients in the survival group and 54 patients in the death group; the overall death rate was 20.77%, and the follow-up time, age, postoperative 1, 3 and 5-year death rates were 3.47 ± 1.93 years, 75.32 ± 9.12 years, 5.77%, 12.51%, and 25.61%, respectively. The top three causes of death in 54 patients were respiratory disease, cerebrocardiovascular disease, and digestive disease, respectively. The logistic analysis indicated that elderly patients with femoral neck fractures, the risk factors for death after AHA were age ≥ 80 years, preoperative NRS ≥ 4, HB ≤ 90 g/L, CR ≥ 110 umol/L, and ASA score ≥ 3, as well as postoperative albumin ≤ 35 g/L, the nomogram was established, and then its predictive performance was successfully validated using the ROC curve (AUC = 0.814, 95% confidence interval = 0.749-0.879) and the Hosmer-Lemeshow test (p = 0.840). Furthermore, Kaplan-Meier survival curve analysis revealed that the abovementioned six indicators were correlated with the post-AHA survival time of elderly patients with femoral neck fractures (pLog Rank < 0.05). CONCLUSION: Old age, preoperatively high NRS and ASA score, anemia, poor renal function, and postoperative hypoproteinemia are the major risk factors for death in elderly patients with femoral neck fractures after AHA; they are also associated with postoperative survival. Early identification and effective interventions for optimization of modifiable risk factors are recommended to improve the postoperative quality of life and survival rates.
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Artroplastia de Reemplazo de Cadera , Fracturas del Cuello Femoral , Humanos , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Nomogramas , Estudios Retrospectivos , Calidad de Vida , Fracturas del Cuello Femoral/cirugía , Fracturas del Cuello Femoral/etiología , Factores de RiesgoRESUMEN
Glial cell-mediated neuroinflammation and neuronal attrition are highly correlated with cognitive impairment in Alzheimer's disease. YKL-40 is a secreted astrocytic glycoprotein that serves as a diagnostic biomarker of Alzheimer's disease. High levels of YKL-40 are associated with either advanced Alzheimer's disease or the normal aging process. However, the functional role of YKL-40 in Alzheimer's disease development has not been firmly established. In a 5xFAD mouse model of Alzheimer's disease, we observed increased YKL-40 expression in the cerebrospinal fluid of 7-month-old mice and was correlated with activated astrocytes. In primary astrocytes, Aß1-42 upregulated YKL-40 in a dose-dependent manner and was correlated with PI3-K signaling pathway activation. Furthermore, primary neurons treated with YKL-40 and/or Aß1-42 resulted in significant synaptic degeneration, reduced dendritic complexity, and impaired electrical parameters. More importantly, astrocyte-specific knockout of YKL-40 over a period of 7 days in symptomatic 5xFAD mice could effectively reduce amyloid plaque deposition in multiple brain regions. This was also associated with attenuated glial activation, reduced neuronal attrition, and restored memory function. These biological phenotypes could be explained by enhanced uptake of Aß1-42 peptides, increased rate of Aß1-42 degradation and acidification of lysosomal compartment in YKL-40 knockout astrocytes. Our results provide new insights into the role of YKL-40 in Alzheimer's disease pathogenesis and demonstrate the potential of targeting this soluble biomarker to alleviate cognitive defects in symptomatic Alzheimer's disease patients.
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Enfermedad de Alzheimer , Animales , Humanos , Lactante , Ratones , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Astrocitos/metabolismo , Biomarcadores/metabolismo , Proteína 1 Similar a Quitinasa-3/metabolismo , Modelos Animales de Enfermedad , Ratones TransgénicosRESUMEN
Developing self-assembled biomedical materials based on insect proteins is highly desirable due to their advantages of green, rich, and sustainable characters as well as excellent biocompatibility, which has been rarely explored. Herein, salt-induced controllable self-assembly, antibacterial performance, and infectious wound healing performance of an insect cuticle protein (OfCPH-2) originating from the Ostrinia furnacalis larva head capsule are investigated. Interestingly, the addition of salts could trigger the formation of beaded nanofibrils with uniform diameter, whose length highly depends on the salt concentration. Surprisingly, the OfCPH-2 nanofibrils not only could form functional films with broad-spectrum antibacterial abilities but also could promote infectious wound healing. More importantly, a possible wound healing mechanism was proposed, and it is the strong abilities of OfCPH-2 nanofibrils in promoting vascular formation and antibacterial activity that facilitate the process of infectious wound healing. Our exciting findings put forward instructive thoughts for developing innovative bioinspired materials based on insect proteins for wound healing and related biomedical fields.
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Cicatrización de Heridas , Infección de Heridas , Animales , Materiales Biocompatibles , Antibacterianos/farmacología , Proteínas de Insectos/farmacología , Insectos , HidrogelesRESUMEN
Epstein-Barr virus (EBV), a double-stranded DNA virus belonging to the family Herpesviridae, infects more than 95% of healthy adults by attacking the host immune system. Here, a novel detection protocol, utilizing the modified multiple cross displacement amplification (MCDA) technique combined with a gold nanoparticles-based lateral flow biosensors (AuNPs-LFB), was devised and developed to detect EBV infection (termed EBV-MCDA-LFB assay). Ten MCDA primers targeting the EBNA-LP gene were designed, including CP1* primers modified with 6-carboxyfluorescein (FAM) and D1* primers modified with biotin. Then, nucleic acid templates extracted from various pathogens and whole blood samples were used to optimize and evaluate the EBV-MCDA-LFB assay. As a result, the lowest concentration of EBNA-plasmids, which can be detected by MCDA-LFB assay with an optimal reaction condition of 67°C for 30 min, was 10 copies/reaction. Here, the MCDA-LFB assay can detect all EBV pathogens used in the study, and no cross-reactions with non-EBV organisms were observed. Meanwhile, the entire detection workflow of the EBV-MCDA-LFB assay for whole blood samples, including DNA template preparation (25 min), EBV-MCDA amplification (30 min), and AuNPs-LFB-mediated validation (2-5 min), can be completed within 1 h. Taken together, the EBV-MCDA-LFB assay established in the current study is a rapid, simplified, sensitive, specific, and easy-to-obtain technique that can be used as a screening or diagnostic tool for EBV infection in clinical applications, especially in resource-poor regions.
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4-Hydroxyphenylpyruvate dioxygenase (HPPD) plays a crucial role in the synthesis of nutrients needed to maintain optimal plant growth. Its level is closely linked to the extent of abiotic stress experienced by plants. Moreover, it is also the target of commercial herbicides. Therefore, labeling of HPPD in plants not only enables visualization of its tissue distribution and cellular uptake, it also facilitates assessment of abiotic stress of plants and provides information needed for the development of effective environmentally friendly herbicides. In this study, we created a method for fluorescence labeling of HPPD that avoids interference with the normal growth of plants. In this strategy, a perylene-linked dibenzyl-cyclooctyne undergoes strain-promoted azide-alkyne cycloaddition with an azide-containing HPPD ligand. The activation-based labeling process results in a significant emission enhancement caused by the change in the fluorescent forms from an excimer to a monomer. Notably, this activated bioorthogonal strategy is applicable to visualizing HPPD in Arabidopsis thaliana, and assessing its response to multiple abiotic stresses. Also, it can be employed to monitor in vivo levels and locations of HPPD in crops. Consequently, the labeling strategy will be a significant tool in investigations of HPPD-related abiotic stress mechanisms, discovering novel herbicides, and uncovering unknown biological functions.
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4-Hidroxifenilpiruvato Dioxigenasa , Herbicidas , Azidas , Fluorescencia , Productos Agrícolas , Inhibidores EnzimáticosRESUMEN
To analyze the clinical manifestations of children with Kawasaki disease (KD), and risk factors of coronary artery lesion (CAL). A total of 223 patients admitted to Anhui Children Hospital from January 2017 to December 2019 were enrolled. According to the clinical data, the children with KD were divided into complete Kawasaki disease (CKD) and incomplete Kawasaki disease (IKD) groups. According to the results of the cardiac color ultrasound, the children were divided into the CAL and nCAL groups. The clinical symptoms of children with KD were compared between the CKD and IKD groups. The risk factors of CAL were analyzed by univariate and binary logistic regression analyses. The incidence constituent ratio of KD increased annually from 2017 to 2019 (P < .05). The proportion of fever duration no longer than 10 days, chapped lips, fingertip decrustation, perianal desquamation, and fever combined with rash in the CKD group was significantly higher compared to the IKD group (P < .05), while intravenous immunoglobulin non-response and CAL were significantly lower than those in the IKD group (P < .05). The proportion of males, age <1 year, fever duration longer than 10 days, and IKD in the CAL group were significantly higher compared to the nCAL group, while hemoglobin levels were significantly lower than that in the nCAL group (P < .05). Sex, age, fever duration, atypical KD, and hemoglobin levels were risk factors for CAL in children with KD. Persistent fever, conjunctival hyperemia, chapped lips, and rash were common clinical symptoms in children with KD. The risk of CAL was relatively higher in children with low hemoglobin levels and IKD, whose ages were <1 year old and whose fever time was more than 10 days, which requires high clinical vigilance.
Asunto(s)
Exantema , Síndrome Mucocutáneo Linfonodular , Insuficiencia Renal Crónica , Lactante , Masculino , Humanos , Niño , Recién Nacido , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/epidemiología , Vasos Coronarios/diagnóstico por imagen , Factores de Riesgo , Fiebre/epidemiología , Fiebre/etiología , HemoglobinasRESUMEN
Neuroinflammation is considered to have a prominent role in the pathogenesis of Alzheimer's disease (AD). Microglia are the resident macrophages of the central nervous system, and modulating microglia activation is a promising strategy to prevent AD. Essential oil of Jasminum grandiflorum L. flowers is commonly used in folk medicine for the relief of mental pressure and disorders, and analyzing the volatile compound profiles and evaluating the inhibitory effects of J. grandiflorum L. essential oil (JGEO) on the excessive activation of microglia are valuable for its application. This study aims to explore the potential active compounds in JGEO for treating AD by inhibiting microglia activation-integrated network pharmacology, molecular docking, and the microglia model. A headspace solid-phase microextraction combined with the gas chromatography-mass spectrometry procedure was used to analyze the volatile characteristics of the compounds in J. grandiflorum L. flowers at 50°C, 70°C, 90°C, and 100°C for 50 min, respectively. A network pharmacological analysis and molecular docking were used to predict the key compounds, key targets, and binding energies based on the detected compounds in JGEO. In the lipopolysaccharide (LPS)-induced BV-2 cell model, the cells were treated with 100 ng/mL of LPS and JGEO at 7.5, 15.0, and 30 µg/mL, and then, the morphological changes, the production of nitric oxide (NO) and reactive oxygen species, and the expressions of tumor necrosis factor-α, interleukin-1ß, and ionized calcium-binding adapter molecule 1 of BV-2 cells were analyzed. A total of 34 compounds with significantly different volatilities were identified. α-Hexylcinnamaldehyde, nerolidol, hexahydrofarnesyl acetone, dodecanal, and decanal were predicted as the top five key compounds, and SRC, EGFR, VEGFA, HSP90AA1, and ESR1 were the top five key targets. In addition, the binding energies between them were less than -3.9 kcal/mol. BV-2 cells were activated by LPS with morphological changes, and JGEO not only could clearly reverse the changes but also significantly inhibited the production of NO and reactive oxygen species and suppressed the expressions of tumor necrosis factor-α, interleukin-1ß, and ionized calcium-binding adapter molecule 1. The findings indicate that JGEO could inhibit the overactivation of microglia characterized by decreasing the neuroinflammatory and oxidative stress responses through the multi-compound and multi-target action modes, which support the traditional use of JGEO in treating neuroinflammation-related disorders.
RESUMEN
Conjugated diyne derivatives are important scaffolds in modern organic synthetic chemistry. Using the Glaser reaction involves the coupling of terminal alkynes which can efficiently produce conjugated diyne derivatives, while the use of a stoichiometric amount of copper salts, strong inorganic base, and excess oxidants is generally needed. Developing an environmentally friendly and effective method for the construction of symmetrical 1,3-diynes compounds by Glaser coupling is still highly desirable. In this study, we present an economical method for the production of symmetric diynes starting from various terminal acetylenes in a Glaser reaction. A simple and practical bis-N-heterocyclic carbene ligand has been introduced as efficient ligands for the Cu-catalyzed Glaser reaction. High product yields were obtained at 100 °C for a variety of substrates including aliphatic and aromatic terminal alkynes and differently substituted terminal alkynes including the highly sterically hindered substrate 2-methoxy ethynylbenzene or 2-trifluoromethyl ethynylbenzene and a series of functional groups, such as trifluoromethyl group, ester group, carboxyl group, and nitrile group. The established protocol is carried out in air under base-free condition and is operationally simple. These research work suggest that bis-N-heterocyclic carbene could also an appealing ligand for Glaser reaction and provide a reference for the preparation of symmetric 1,3-diynes in industrial filed.