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Avian influenza viruses (AIVs) are the origin of multiple mammal influenza viruses. The genetic determinants of AIVs adapted to humans have been widely elucidated, however, the molecular mechanism of cross-species transmission and adaptation of AIVs to canines are still poorly understood. In this study, two H3N2 influenza viruses isolated from a live poultry market (A/environment/Guangxi/13431/2018, GX13431) and a swab sample from a canine (A/canine/Guangdong/0601/2019, GD0601) were used to investigate the possible molecular basis that determined H3N2 AIV adapting to canine. We found that GD0601 exhibited more robust polymerase activity in cells and higher pathogenicity in mice compared with its evolution ancestor H3N2 AIV GX13431. A series of reassortments of the ribonucleoprotein (RNP) complex showed that the PB2 subunit was the crucial factor that conferred high polymerase activity of GD0601, and the substitution of I714S in the PB2 subunit of GD0601 attenuated the replication and pathogenicity in mammal cells and the mouse model. Mechanistically, the reverse mutation of I714S in the PB2 polymerase subunit which was identified in AIV GX13431 reduced the nuclear import efficiency of PB2 protein and interfered with the interactions of PB2-PA/NP that affected the assembly of the viral RNP complex. Our study reveals amino acid mutation at the position of 714 in the nuclear localization signal (NLS) area in PB2 plays an important role in overcoming the barrier from poultry to mammals of the H3N2 canine influenza virus and provides clues for further study of mammalian adaptation mechanism of AIVs.
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Sous-type H3N2 du virus de la grippe A , Infections à Orthomyxoviridae , RNA replicase , Ribonucléoprotéines , Protéines virales , Animaux , Chiens , Sous-type H3N2 du virus de la grippe A/génétique , Sous-type H3N2 du virus de la grippe A/physiologie , Souris , Protéines virales/génétique , Protéines virales/métabolisme , RNA replicase/génétique , RNA replicase/métabolisme , Infections à Orthomyxoviridae/virologie , Humains , Ribonucléoprotéines/génétique , Ribonucléoprotéines/métabolisme , Transport nucléaire actif , Réplication virale , Mutation , Cellules rénales canines Madin-Darby , Maladies des chiens/virologie , Souris de lignée BALB C , Cellules HEK293 , Virus recombinants/génétiqueRÉSUMÉ
BACKGROUND: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. METHODS: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. RESULTS: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7. CONCLUSION: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.
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Psoriasis , Protéines plasmatiques de liaison au rétinol , Humains , Psoriasis/traitement médicamenteux , Psoriasis/sang , Psoriasis/immunologie , Protéines plasmatiques de liaison au rétinol/métabolisme , Mâle , Femelle , Adulte , Adulte d'âge moyen , Études prospectives , Résultat thérapeutique , Marqueurs biologiques/sang , Indice de gravité de la maladie , Courbe ROCRÉSUMÉ
BACKGROUND: Since its discovery, severe fever with thrombocytopenia syndrome (SFTS) has been characterized by rapid progression and poor prognosis, and no specific treatment is available. The aim of this study was to investigate the early warning indicators of mortality in SFTS patients. METHODS: This is a retrospective cross-sectional study. The study subjects were patients who were admitted to the hospital with a confirmed diagnosis of SFTS from January 2023 to October 2023, and their clinical symptoms and signs at the time of admission, as well as the laboratory indexes of the first blood collection after admission were collected, grouped according to the prognosis, and statistically analyzed. RESULTS: A total of 141 patients were collected, of which 27 patients died and 114 patients were in the survival group. Through statistical analysis, patients with combined hemorrhagic manifestations, disturbance of consciousness, lymphopenia, elevated lipase, and prolonged thrombin time on admission were independent risk factors for patients' death. By plotting the working characteristic curve of the subjects, as well as calculating the area under the curve, the results showed that the AUC of lymphopenia count was 0.670, 95% CI (0.563-0.776), P = 0.006; the AUC of elevated serum lipase index was 0.789, 95% CI (0.699-0.878), p < 0.001; the AUC of prolonged thrombin time was 0.749, 95% CI (0.645-0.854), p < 0.001. CONCLUSION: Patients with hemorrhagic manifestations, disturbance of consciousness, lymphocyte reduction, elevated serum lipase, and prolonged thrombin time on admission are more worthy of the clinician's attention, and require early and effective interventions to avoid further disease progression.
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Syndrome de fièvre sévère avec thrombocytopénie , Humains , Mâle , Femelle , Syndrome de fièvre sévère avec thrombocytopénie/mortalité , Syndrome de fièvre sévère avec thrombocytopénie/sang , Syndrome de fièvre sévère avec thrombocytopénie/virologie , Études rétrospectives , Adulte d'âge moyen , Études transversales , Sujet âgé , Pronostic , Facteurs de risque , Phlebovirus , Adulte , Sujet âgé de 80 ans ou plusRÉSUMÉ
The stannic oxide (SnO2) anode expands in volume during cycling causing a decrease in reversible capacity. In this work, we generated a spherical SnO2/Sn heterojunction with core-shell structure composites encapsulated by graphene (SnO2/Sn/G) in situ using a simple one-step hydrothermal and subsequent annealing process. SnO2/Sn heterojunction nanospheres dispersed in a porous graphene framework accelerate the diffusion kinetics of electrons and ions. In addition, the structure plays a key role in mitigating large volume changes and nanostructure agglomeration. As a result, SnO2/Sn/G exhibits excellent performance as an anode material for lithium-ion batteries (LIBs), maintaining a reversible specific capacity of 720.6 mA h g-1 even after 600 cycles at a current density of 0.5 A g-1.
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AIMS: To investigate the performance of a combined biomarker approach using the methylation status of the short stature homeobox 2 (SHOX2) and prostaglandin E2 receptor EP4 (PTGER4) genes, along with the serum levels of CYFRA21-1, for differential diganosis of malignant pleural mesothelioma (MPM) from benign reactive mesothelial hyperplasia (RMH). METHODS: We analysed 48 MPM tissue or pleural effusion cell block specimens and 42 cases with RMH. Real-time quantitative methylation-specific PCR was used to examine the methylation status of SHOX2, PTGER4, ras association domain family 1 isoform A, septin 9 gene and homeobox gene A9 genes. Additionally, we employed electrochemiluminescence immunoassay to measure nine serum tumour markers commonly used in pan-cancer screening tests. RESULTS: The receiver operating curve indicated that SHOX2, PTGER4 gene methylation and serum biomarker CYFRA21-1 exhibited good diagnostic performance in identifying MPM, with area under curves (AUCs) of 0.761, 0.904 and 0.847, respectively. The combination of SHOX2, PTGER4 methylation and CYFRA21-1 yielded an AUC value of 0.972. The diagnostic sensitivity and specificity of this panel in differentiating MPM from RMH were 91.3% (42/46) and 97.6% (41/42), respectively. Both tissue and cell block specimens can be used in the diagnostic process. Furthermore, elevated CYFRA21-1 levels were associated with poor prognosis (p<0.05). Hypermethylation level of PTGER4 may indicate an unfavourable prognosis of MPM, but the difference was not statistically significant. CONCLUSIONS: The combined detection of SHOX2 and PTGER4 methylation alongside serum CYFRA21-1 level significantly enhances the diagnosis of MPM. Additionally, CYFRA21-1 can serve as a prognostic indicator for MPM.
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Plants of the Meliaceae family have long attracted researchers' interest due to their various insecticidal activities, with triterpenes being the main active ingredients. In this paper, we discuss 93 triterpenoids with insecticidal activity from 37 insecticidal plant species of 15 genera (Munronia, Neobeguea, Pseudocedrela, Nymania, Quivisia, Ruagea, Dysoxylum, Soymida, Lansium, Sandoricum, Walsura, Trichilia, Swietenia, Turraea, and Xylocarpus) in the family Meliaceae. Among these genera, Trichilia deserves further research, with twelve species possessing insecticidal activity. The 93 insecticidal molecules included 27 ring-seco limonoids (comprising 1 ring A-seco group chemical, 1 ring B-seco group chemical, 5 ring D-seco group chemicals, 14 rings A,B-seco group chemicals, 5 rings B,D-seco group chemicals, and 1 rings A,B,D-seco group chemical), 22 ring-intact limonoids (comprising 5 cedrelone-class chemicals, 6 trichilin-class chemicals, 7 havanensin-class chemicals, 2 azadirone-class chemicals, 1 vilasinin-class chemical, and 1 other chemical), 33 2,30-linkage chemicals (comprising 25 mexicanolide-class chemicals and 8 phragmalin-class chemicals), 3 1,n-linkage-group chemicals, 3 onoceranoid-type triterpenoids, 2 apotirucallane-type terpenoids, 2 kokosanolide-type tetranortriterpenoids, and 1 cycloartane triterpene. In particular, 59 molecules showed antifeedant activity, 30 molecules exhibited poisonous effects, and 9 molecules possessed growth regulatory activity. Particularly, khayasin, beddomei lactone, 3ß,24,25-trihydroxycycloartane, humilinolides A-E and methyl-2-hydroxy-3ß-isobutyroxy-1-oxomeliac-8(30)-enate showed excellent insecticidal activities, which were comparable to that of azadirachtin and thus deserved more attention. Moreover, it was noteworthy that various chemicals (such as 12α-diacetoxywalsuranolide, 11ß,12α-diacetoxycedrelone, 1α,7α,12α-triacetoxy-4α-carbomethoxy-11ß-hydroxy-14ß,15ß-epoxyhavanensin, and 11-epi-21-hydroxytoonacilide, etc.) from Turraea showed excellent insecticidal activity. Specially, the insecticidal activity of khayasin from Neobeguea against the coconut leaf beetle were similar to that of rotenone. Therefore, it was a promising candidate insecticide for the control of the coconut leaf beetle.
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Insecticides , Meliaceae , Triterpènes , Meliaceae/composition chimique , Triterpènes/pharmacologie , Triterpènes/composition chimique , Insecticides/pharmacologie , Insecticides/composition chimique , Animaux , Limonines/pharmacologie , Limonines/composition chimique , Extraits de plantes/composition chimique , Extraits de plantes/pharmacologieRÉSUMÉ
Carboxymethyl Salix psammophila wood powder-imprinted membranes (CMSM-MIPs) were prepared by using wet spinning technology and molecular-imprinting technology for the selective removal of tetracycline from wastewater. Scanning electron microscopy, X-ray diffraction, thermogravimetry, and X-ray photoelectron spectroscopy characterizations demonstrate that CMSM-MIPs retain the membranous structure of Carboxymethyl Salix psammophila wood powder membranes, successfully encapsulate thin layers of imprinted polymers on the membrane surface, and exhibit excellent thermal stability. The adsorption results showed that CMSM-MIPs had the highest selective adsorption capacity for tetracycline, which was 253.8 mg/g. In addition, the adsorption capacities for oxytetracycline and chlortetracycline were 208.8 and 188 mg/g, respectively. It can be observed that CMSM-MIPs not only exhibit a high adsorption capacity for tetracycline but also demonstrate good adsorption capacities for oxytetracycline and chlortetracycline. The experimental results showed that CMSM-MIPs were best fitted with pseudo-second-order kinetics and most consistent with Freundlich fitting. The regeneration experiment showed that CMSM-MIPs still had good regeneration performance after 5 regeneration cycles. In conclusion, the CMSM-MIPs can not only have the natural adsorption performance of Salix psammophila wood powder but also give it higher selectivity through molecular imprinting, so as to achieve efficient removal of target organic pollutants in water.
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Salix , Tétracycline , Bois , Adsorption , Bois/composition chimique , Tétracycline/composition chimique , Tétracycline/isolement et purification , Salix/composition chimique , Poudres/composition chimique , Membrane artificielle , Polluants chimiques de l'eau/composition chimique , Polluants chimiques de l'eau/isolement et purification , Empreinte moléculaire/méthodes , Antibactériens/composition chimique , Antibactériens/isolement et purificationRÉSUMÉ
Gut Universe Database (GutUDB) provides a comprehensive, systematic, and practical platform for researchers, and is dedicated to the management, analysis, and visualization of knowledge related to intestinal diseases. Based on this database, eight major categories of omics data analyses are carried out to explore the genotype-phenotype characteristics of a certain intestinal disease. The first tool for comprehensive omics data research on intestinal diseases will help each researcher better understand intestinal diseases.
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Background: Wearable technology is used in healthcare to monitor the health of individuals. This study presents an updated systematic literature review of the use of wearable technology in promoting child and adolescent health, accompanied by recommendations for future research. Methods: This review focuses on studies involving children and adolescents aged between 2 and 18 years, regardless of their health condition or disabilities. Studies that were published from 2016 to 2024, and which met the inclusion criteria, were extracted from four academic databases (i.e. PubMed, Cochrane, Embase, and Web of Science) using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol. Data on intervention purposes, interventions deployed, intervention duration, measurements, and the main outcomes of the studies were collected. Results: A total of 53 studies involving 14,852 participants were reviewed. They focused on various aspects, including the ownership and use of wearable devices (n = 3), the feasibility (n = 22), effectiveness (n = 4), and adherence (n = 2) of intervention strategies, or a combination of multiple aspects (n = 22). Among the interventions deployed, Fitbit was the most frequently used, featuring in 26 studies, followed by ActiGraph (n = 11). In intervention studies, the majority of studies focused on pre-morbidity prevention (n = 26) and the treatment of illnesses (n = 20), with limited attention given to postoperative monitoring (n = 4). Conclusions: The use of wearable technology by children and adolescents has proven to be both feasible and effective for health promotion. This systematic review summarizes existing research by exploring the use of wearable technology in promoting health across diverse youth populations, including healthy and unhealthy individuals. It examines health promotion at various stages of the disease continuum, including pre-disease prevention, in-disease treatment, and postoperative monitoring. Additionally, the review provides directions for future research.
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Hydrogel strain sensors have received increasing attention due to their potential applications in human-machine interfaces and flexible electronics. However, they usually suffer from both mechanical and electrical hysteresis and poor water retention, which limit their practical applications. To address this challenge, a poly(acrylic acid-co-acrylamide) hydrogel crosslinked by silica nanoparticles is fabricated via photo polymerization and salting-out of hydrophilic ions for the strain sensor. The resulting hydrogel strain sensor possessed low electrical hysteresis (1.6%), low mechanical hysteresis (<7%), high cycle stability (>10 000 cycles), high durability, water retention and anti-freezing ability. Moreover, this strain sensor can be used as a wearable sensor for real-time control of robotic hands and hand gesture recognition. Finally, a sign language translation system has been demonstrated with the aid of machine learning, achieving recognition rates of over 98% for 15 different sign languages. This work offers a promising prospect for human-machine interfaces, smart wearable devices, and the Internet of Things.
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Hydrogels , Dispositifs électroniques portables , Humains , Hydrogels/composition chimique , Eau , Résines acryliques/composition chimique , Nanoparticules , Robotique/instrumentation , Robotique/méthodes , Silice/composition chimique , Congélation , Systèmes homme-machine , Apprentissage machineSujet(s)
Antigènes CD19 , Cellules dendritiques , Immunothérapie adoptive , Adulte , Humains , Adulte d'âge moyen , Antigènes CD19/immunologie , Vaccins anticancéreux/usage thérapeutique , Cellules dendritiques/immunologie , Immunothérapie adoptive/méthodes , Leucémie-lymphome lymphoblastique à précurseurs B/thérapie , Leucémie-lymphome lymphoblastique à précurseurs B/immunologie , Récepteurs chimériques pour l'antigène/immunologie , Récidive , Jeune adulte , Sujet âgéRÉSUMÉ
Exocytosis is a critical factor for designing efficient nanocarriers and determining cytotoxicity. However, the research on the exocytosis mechanism of nanoparticles, especially the role of long non-coding RNAs (lncRNAs), has not been reported. In this study, the exocytosis of AuNPs in the KYSE70 cells and the involved molecular pathways of exocytosis are analyzed. It demonstrates that nanoparticles underwent time-dependent release from the cells by exocytosis, and the release of ß-hexosaminidase confirms that AuNPs are excreted through lysosomes. Mechanistic studies reveal that lncRNA ESCCAL-1 plays a vital role in controlling the exocytosis of AuNPs through activation of the MAPK pathway, including the phosphorylation of ERK and JNK. The study implies that the ESCCAL-1-mediated pathway plays an important role in the exocytosis of AuNPs in KYSE70 cells. This finding has implications for the role of ESCCAL-1 on the drug resistance of esophagus cancer by controlling lysosome-mediated exocytosis.
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Tumeurs de l'oesophage , Carcinome épidermoïde de l'oesophage , Exocytose , Or , Nanoparticules métalliques , ARN long non codant , Exocytose/effets des médicaments et des substances chimiques , Humains , Or/composition chimique , Nanoparticules métalliques/composition chimique , Tumeurs de l'oesophage/métabolisme , Tumeurs de l'oesophage/anatomopathologie , Tumeurs de l'oesophage/génétique , Lignée cellulaire tumorale , Carcinome épidermoïde de l'oesophage/anatomopathologie , Carcinome épidermoïde de l'oesophage/métabolisme , Carcinome épidermoïde de l'oesophage/génétique , ARN long non codant/génétique , ARN long non codant/métabolisme , Lysosomes/métabolisme , Lysosomes/effets des médicaments et des substances chimiques , Système de signalisation des MAP kinases/effets des médicaments et des substances chimiques , Carcinome épidermoïde/anatomopathologie , Carcinome épidermoïde/métabolisme , Carcinome épidermoïde/génétiqueRÉSUMÉ
Dendritic cells (DCs), the most efficient antigen-presenting cells (APCs), bridge the innate and adaptive immune systems. As such, the turn-over of DCs is critical during autoimmune responses, and the dysregulation of DC apoptosis could cause severe immune destruction in the host. For example, reduction of immunogenic DCs by increased apoptosis could lead to immune tolerance to pathogen infection that might allow exposure of nuclear autoantigens, whereas reduced apoptosis could result in long-term lymphocyte activation to break the immune tolerance for the development of autoimmune disease. Thus, keeping a balance between survival and apoptosis of DCs is crucial to maintain immune homeostasis. In this review, we summarize the recent development on the factors inducing DC apoptosis and their underlying mechanisms to provide insights into the immunopathogenesis of some autoimmune diseases, which could lead to effective therapeutic interventions in the clinics.
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Apoptose , Maladies auto-immunes , Cellules dendritiques , Cellules dendritiques/immunologie , Humains , Maladies auto-immunes/immunologie , Apoptose/immunologie , Animaux , Tolérance immunitaire/immunologieRÉSUMÉ
OBJECTIVE: To examine the effectiveness of psychoeducational interventions on depression, anxiety, and health-related quality of life (HRQOL) for people undergoing maintenance hemodialysis (MHD). METHODS: This review used systematic review and meta-analysis as the research design. Nine databases, including PubMed, Web of Science, Embase, CINAHL Complete, Cochrane Library, CNKI, WanFang, VIP, and Chinese Biomedical Literature Database, were searched from the inception to the 8th of July 2023. Two reviewers independently identified randomized controlled trials (RCT) examining the effects of psychoeducational interventions on MHD patients. RESULTS: Fourteen studies involving 1134 MHD patients were included in this review. The results of meta-analyses showed that psychoeducational intervention had significant short-term (< 1 m) (SMD: -0.87, 95% CI: -1.54 to -0.20, p = 0.01, I2 = 91%; 481 participants), and medium-term (1-3 m) (SMD: -0.29, 95% CI: -0.50 to -0.08, p = 0.01, I2 = 49%; 358 participants) on anxiety in MHD patients, but the effects could not be sustained at longer follow-ups. Psychoeducational interventions can also have short-term (< 1 m) (SMD: -0.65, 95% CI: -0.91 to -0.38, p < 0.00001, I2 = 65%; 711 participants) and medium-term (1-3 m) (SMD: -0.42, 95% CI: -0.76 to -0.09, p = 0.01, I2 = 69%; 489 participants) effects in reducing depression levels in MHD patients. Psychoeducational interventions that use coping strategies, goal setting, and relaxation techniques could enhance the QOL in MHD patients in the short term (< 1 m) (SMD: 0.86, 95% CI: 0.42 to 1.30, p = 0.02, I2 = 86%; 241 participants). CONCLUSIONS: Psychoeducational interventions have shown great potential to improve anxiety, depression, and quality of life in patients with MHD at the short- and medium-term follow-ups.Trial registration number: CRD42023440561.
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Anxiété , Dépression , Éducation du patient comme sujet , Qualité de vie , Dialyse rénale , Humains , Dialyse rénale/psychologie , Éducation du patient comme sujet/méthodes , Anxiété/prévention et contrôle , Anxiété/étiologie , Dépression/psychologie , Dépression/étiologie , Dépression/prévention et contrôle , Dépression/thérapie , Essais contrôlés randomisés comme sujet , Détresse psychologique , Défaillance rénale chronique/thérapie , Défaillance rénale chronique/psychologieRÉSUMÉ
Obesity presents a significant global health challenge, increasing the susceptibility to chronic conditions such as diabetes, cardiovascular disease, and hypertension. Within the context of obesity, lipid metabolism, adipose tissue formation, and inflammation are intricately linked to endoplasmic reticulum stress (ERS). ERS modulates metabolism, insulin signaling, inflammation, as well as cell proliferation and death through the unfolded protein response (UPR) pathway. Serving as a crucial nexus, ERS bridges the functionality of adipose tissue and the inflammatory response. In this review, we comprehensively elucidate the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, aiming to offer insights into targeting ERS for ameliorating metabolic dysregulation in obesity-associated chronic diseases such as hyperlipidemia, hypertension, fatty liver, and type 2 diabetes.
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Diabète de type 2 , Hypertension artérielle , Humains , Diabète de type 2/métabolisme , Stress du réticulum endoplasmique/physiologie , Obésité/métabolisme , Tissu adipeux/métabolisme , Inflammation/métabolismeRÉSUMÉ
Mechanically robust hydrogel fibers have demonstrated great potential in energy dissipation and shock-absorbing applications. However, developing such materials that are recyclable, energy-efficient, and environmentally friendly remains an enormous challenge. Herein, inspired by spider silk, a continuous and scalable method is introduced for spinning a polyacrylamide hydrogel microfiber with a hierarchical sheath-core structure under ambient conditions. Applying pre-stretch and twist in the as-spun hydrogel microfibers results in a tensile strength of 525 MPa, a toughness of 385 MJ m-3, and a damping capacity of 99%, which is attributed to the reinforcement of hydrogen-bond nanoclusters within the microfiber matrix. Moreover, it maintains both structural and mechanical stability for several days, and can be directly dissolved in water, providing a sustainable spinning dope for re-spinning into new microfibers. This work provides a new strategy for the spinning of robust and recyclable hydrogel-based fibrous materials.
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OBJECTIVES: Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy. METHODS AND RESULTS: Univariate analyses unveiled significant associations between two specific single nucleotide polymorphisms rs1057910 in CYP2C9 and rs9923231 in VKORC1 and stable warfarin dosage ( P â <â 0.001). Further, employing multivariate logistic regression analysis adjusted for age, sex and height, the investigation revealed that patients harboring at least one variant allele in CYP2C9 exhibited a heightened risk of bleeding events compared to those with the wild-type genotype (odds ratioâ =â 2.16, P â =â 0.04). Moreover, a meta-analysis conducted to consolidate findings confirmed the associations of both CYP2C9 (rs1057910) and VKORC1 (rs9923231) with stable warfarin dosage. Notably, CYP2C9 variant genotypes were significantly linked to an increased risk of hemorrhagic complications ( P â <â 0.00001), VKORC1 did not demonstrate a similar association. CONCLUSION: The associations found between specific genetic variants and both stable warfarin dosage and bleeding risk might be the potential significance of gene detection in optimizing warfarin therapy for improving patient efficacy and safety.
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Anticoagulants , Asiatiques , Cytochrome P-450 CYP2C9 , Polymorphisme de nucléotide simple , Vitamin K epoxide reductases , Warfarine , Humains , Cytochrome P-450 CYP2C9/génétique , Vitamin K epoxide reductases/génétique , Warfarine/effets indésirables , Warfarine/administration et posologie , Femelle , Mâle , Adulte d'âge moyen , Anticoagulants/effets indésirables , Anticoagulants/administration et posologie , Sujet âgé , Asiatiques/génétique , Hémorragie/induit chimiquement , Hémorragie/génétique , Chine , Adulte , Génotype , Études d'associations génétiques , Peuples d'Asie de l'EstRÉSUMÉ
Peptides present an alternative modality to immunoglobulin domains or small molecules for developing therapeutics to either agonize or antagonize cellular pathways associated with diseases. However, peptides often suffer from poor chemical and physical stability, limiting their therapeutic potential. Disulfide-constrained peptides (DCP) are naturally occurring and possess numerous desirable properties, such as high stability, that qualify them as drug-like scaffolds for peptide therapeutics. DCPs contain loop regions protruding from the core of the molecule that are amenable to peptide engineering via direct evolution by use of phage display technology. In this study, we have established a robust platform for the discovery of peptide therapeutics using various DCPs as scaffolds. We created diverse libraries comprising seven different DCP scaffolds, resulting in an overall diversity of 2 x 1011. The effectiveness of this platform for functional hit discovery has been extensively evaluated, demonstrating a hit rate comparable to that of synthetic antibody libraries. By utilizing chemically synthesized and in vitro folded peptides derived from selections of phage displayed DCP libraries, we have successfully generated functional inhibitors targeting the HtrA1 protease. Through affinity maturation strategies, we have transformed initially weak binders against Notch2 with micromolar Kd values to high-affinity ligands in the nanomolar range. This process highlights a viable hit-to-lead progression. Overall, our platform holds significant potential to greatly enhance the discovery of peptide therapeutics.
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Disulfures , Peptides , Peptides/pharmacologie , Peptides/composition chimique , Banque de peptides , Peptide hydrolasesRÉSUMÉ
Botanical insecticides are considered an environmentally friendly approach to insect control because they are easily biodegraded and cause less environmental pollution compared to traditional chemical pesticides. In this study, we reported the insecticidal activities of the ingredients from Taiwania flousiana Gaussen (T. flousiana). Five compounds, namely helioxanthin (C1), taiwanin E (C2), taiwanin H (C3), 7,4'-dimethylamentoflavone (C4), and 7,7â³-di-O-methylamentoflavone (C5), were isolated and tested against the second, third, and fourth instar larvae of Aedes aegypti. Our results indicated that all five compounds showed insecticidal activities, and helioxanthin, which is an aryltetralin lignan lactone, was the most effective with LC50 values of 0.60, 2.82, and 3.12 mg/L, respectively, 48 h after application, with its activity against the second instar larvae similar to that of pyrethrin and better than that of rotenone. Further studies found that helioxanthin accumulated in the gastric cecum and the midgut and caused swelling of mitochondria with shallow matrices and fewer or disappeared crista. Additionally, our molecular mechanisms studies indicated that the significantly differentially expressed genes (DEGs) were mainly associated with mitochondria and the cuticle, among which the voltage-dependent anion-selective channel (VDAC) gene was the most down-regulated by helioxanthin, and VDAC is the potential target of helioxanthin by binding to specific amino acid residues (His 122 and Glu 147) via hydrogen bonds. We conclude that aryltetralin lignan lactone is a potential class of novel insecticides by targeting VDAC.
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Aedes , Insecticides , Lignanes , Animaux , Insecticides/composition chimique , Simulation de docking moléculaire , Lignanes/pharmacologie , Extraits de plantes/composition chimique , LarveRÉSUMÉ
The available interventions for androgenic alopecia (AGA), the most common type of hair loss worldwide, remain limited. The insulin growth factor (IGF) system may play an important role in the pathogenesis of AGA. However, the exact role of IGF binding protein-related protein 1 (IGFBP-rP1) in hair growth and AGA has not been reported. In this study, we first found periodic variation in IGFBP-rP1 during the hair cycle transition in murine hair follicles (HFs). We further demonstrated that IGFBP-rP1 levels were lower in the serum and scalp HFs of individuals with AGA than in those of healthy controls. Subsequently, we verified that IGFBP-rP1 had no cytotoxicity to human outer root sheath cells (HORSCs) and that IGFBP-rP1 reversed the inhibitory effects of DHT on the migration of HORSCs in vitro. Finally, a DHT-induced AGA mouse model was created. The results revealed that the expression of IGFBP-rP1 in murine HFs was downregulated after DHT treatment and that subcutaneous injection of IGFBP-rP1 delayed catagen occurrence and prolonged the anagen phase of HFs in mice with DHT-induced AGA. The present work shows that IGFBP-rP1 is involved in hair cycle transition and exhibits great therapeutic potential for AGA.