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Cartilage repair and regeneration have become a global issue that millions of patients from all over the world need surgical intervention to repair the articular cartilage annually due to the limited self-healing capability of the cartilage tissues. Cartilage tissue engineering has gained significant attention in cartilage repair and regeneration by integration of the chondrocytes (or stem cells) and the artificial scaffolds. Recently, polysaccharide-protein based scaffolds have demonstrated unique and promising mechanical and biological properties as the artificial extracellular matrix of natural cartilage. In this review, we summarize the modification methods for polysaccharides and proteins. The preparation strategies for the polysaccharide-protein based hydrogel scaffolds are presented. We discuss the mechanical, physical and biological properties of the polysaccharide-protein based scaffolds. Potential clinical translation and challenges on the artificial scaffolds are also discussed.
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Cartilage articulaire , Polyosides , Régénération , Ingénierie tissulaire , Structures d'échafaudage tissulaires , Structures d'échafaudage tissulaires/composition chimique , Humains , Polyosides/composition chimique , Régénération/effets des médicaments et des substances chimiques , Ingénierie tissulaire/méthodes , Animaux , Cartilage articulaire/physiologie , Protéines/composition chimique , Hydrogels/composition chimique , Chondrocytes/cytologie , Chondrocytes/effets des médicaments et des substances chimiques , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/pharmacologie , Cartilage/physiologie , Cicatrisation de plaie/effets des médicaments et des substances chimiquesRÉSUMÉ
Basophils, rare granulocytes, have long been acknowledged for their roles in type 2 immune responses. However, the mechanisms by which basophils adapt their functions to diverse mammalian microenvironments remain unclear. Recent advancements in specific research tools and single-cell-based technologies have greatly enhanced our understanding of basophils. Several studies have shown that basophils play a role in maintaining homeostasis but can also contribute to pathology in various tissues and organs, including skin, lung, and others. Here, we provide an overview of recent basophil research, including cell development, characteristics, and functions. Based on an increasing understanding of basophil biology, we suggest that the precise targeting of basophil features might be beneficial in alleviating certain pathologies such as asthma, atopic dermatitis (AD), and others.
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Granulocytes basophiles , Différenciation cellulaire , Granulocytes basophiles/immunologie , Humains , Animaux , Différenciation cellulaire/immunologie , Eczéma atopique/immunologie , Asthme/immunologie , Homéostasie/immunologieRÉSUMÉ
Heterotopic brain tissue is rare and has not been reported. Our center made the first report. 4 years and 2 months old Girl presented with a cystic mass in the right adrenal gland 2 weeks after right upper abdominal pain. The operation was successful, and the diagnosis was confirmed by postoperative pathology. 6 months after the procedure, the incision healed well without recurrence. This case report has a detailed diagnosis and treatment process and satisfactory examination results. It can provide a reference for diagnosing and treating clinical HBT and reduce the risk of misdiagnosis and mistreatment.
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Glandes surrénales , Choristome , Enfant , Femelle , Humains , Nourrisson , Glandes surrénales/imagerie diagnostique , Glandes surrénales/chirurgie , Choristome/chirurgie , Choristome/anatomopathologie , Douleur abdominale/étiologie , Tête/anatomopathologieRÉSUMÉ
OBJECTIVE: Prostate cancer (PC) is a significant disease affecting men's health worldwide. More than 60% of patients over 65 years old and more than 80% are diagnosed with localized PC. The current choice of treatment modalities for localized PC and whether overtreatment is controversial. Therefore, we wanted to construct a nomogram to predict the risk factors associated with cancer-specific survival (CSS) and overall survival (OS) in elderly patients with localized PC while assessing the survival differences in surgery and radiotherapy for elderly patients with localized PC. METHODS: Data of patients with localized PC over 65 years were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models were used to determine independent risk factors for CSS and OS. Nomograms predicting CSS and OS were built using multivariate Cox regression models. The consistency index (C-index), the area under the subject operating characteristic curve (AUC), and the calibration curve were used to test the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to test the potential clinical value of this model. RESULTS: A total of 90,434 patients over 65 years and diagnosed with localized PC from 2010 to 2018 were included in the study. All patients were randomly assigned to the training set (n = 63,328) and the validation set (n = 27,106). Univariate and multivariate Cox regression model analysis showed that age, race, marriage, T stage, surgical, radiotherapy, prostate-specific antigen (PSA), and Gleason score (GS) were independent risk factors for predicting CSS in elderly patients with localized PC. Age, race, marriage, surgery, radiotherapy, PSA, and GS were independent risk factors for predicting OS in elderly patients with localized PC. The c-index of the training and validation sets for the predicted CSS is 0.802(95%CI:0.788-0.816) and 0.798(95%CI:0.776-0.820, respectively). The c-index of the training and validation sets for predicting OS is 0.712(95%:0.704-0.720) and 0.724(95%:0.714-0.734). It shows that the nomograms have excellent discriminatory ability. The AUC and the calibration curves also show good accuracy and discriminability. CONCLUSION: We have developed new nomograms to predict CSS and OS in elderly patients with localized PC. After internal validation and external temporal validation with reasonable accuracy, reliability and potential clinical value, the model can be used for clinically assisted decision-making.
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Nomogrammes , Tumeurs de la prostate , Sujet âgé , Mâle , Humains , Pronostic , Antigène spécifique de la prostate , Reproductibilité des résultats , Tumeurs de la prostate/radiothérapie , Tumeurs de la prostate/chirurgieRÉSUMÉ
BACKGROUND: Pancreatic cancer, referred to as the "monarch of malignancies," is a neoplastic growth mostly arising from the epithelial cells of the pancreatic duct and acinar cells. This particular neoplasm has a highly unfavorable prognosis due to its marked malignancy, inconspicuous initial manifestation, challenging early detection, rapid advancement, and limited survival duration. Cellular immunotherapy is the ex vivo culture and expansion of immune effector cells, granting them the capacity to selectively target malignant cells using specialized techniques. Subsequently, these modified cells are reintroduced into the patient's organism with the purpose of eradicating tumor cells and providing therapeutic intervention for cancer. PRESENT SITUATION: Presently, the primary cellular therapeutic modalities employed in the treatment of pancreatic cancer encompass CAR T-cell therapy, TCR T-cell therapy, NK-cell therapy, and CAR NK-cell therapy. AIM OF REVIEW: This review provides a concise overview of the mechanisms and primary targets associated with various cell therapies. Additionally, we will explore the prospective outlook of cell therapy in the context of treating pancreatic cancer.
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Antimicrobial peptides (AMPs) exhibit mighty antibacterial properties without inducing drug resistance. Achieving much higher selectivity of AMPs towards bacteria and normal cells has always been a continuous goal to be pursued. Herein, a series of sulfonium-based polypeptides with different degrees of branching and polymerization were synthesized by mimicking the structure of vitamin U. The polypeptide, G2 -PM-1H+ , shows both potent antibacterial activity and the highest selectivity index of 16000 among the reported AMPs or peptoids (e.g., the known index of 9600 for recorded peptoid in "Angew. Chem. Int. Ed., 2020, 59, 6412."), which can be attributed to the high positive charge density of sulfonium and the regulation of hydrophobic chains in the structure. The antibacterial mechanisms of G2 -PM-1H+ are primarily ascribed to the interaction with the membrane, production of reactive oxygen species (ROS), and disfunction of ribosomes. Meanwhile, altering the degree of alkylation leads to selective antibacteria against either gram-positive or gram-negative bacteria in a mixed-bacteria model. Additionally, both in vitro and in vivo experiments demonstrated that G2 -PM-1H+ exhibited superior efficacy against methicillin-resistant Staphylococcus aureus (MRSA) compared to vancomycin. Together, these results show that G2 -PM-1H+ possesses high biocompatibility and is a potential pharmaceutical candidate in combating bacteria significantly threatening human health.
Sujet(s)
Staphylococcus aureus résistant à la méticilline , Peptoïdes , Vitamine U , Humains , Vitamine U/pharmacologie , Peptides/composition chimique , Antibactériens/pharmacologie , Antibactériens/composition chimique , Vancomycine/pharmacologie , Peptoïdes/composition chimique , Bactéries , Peptides antimicrobiens , Tests de sensibilité microbienneRÉSUMÉ
Background: Hamartoma is a mass formed by the proliferation and disorder of two or more kinds of cells inherent in normal organs or anatomical parts, which can occur in any part of the body. The most common hamartoma are kidney hamartoma, spleen hamartoma, liver hamartoma, and lung hamartoma. Urethral hamartoma is extremely rare in clinical practice. Case report: Combined with literature review, the diagnosis and treatment process of a child with posterior urethral hamartoma and hypospadias in our hospital were analyzed. The patient was cured after surgical treatment, the lesion was completely removed, the appearance was satisfactory, and there was no recurrence, urethral stricture, urethral fistula, and other complications. The pathological results of this case support the histological diagnosis of hamartoma, which provides reference for the clinical diagnosis and treatment of congenital malformation and tumor of urogenital in children. Conclusion: When a child has posterior urethral hamartoma, the symptoms may not be very typical, and it is often combined with urethral malformation. Therefore, it is necessary to perform careful physical examination combined with pathological examination to be able to make an accurate diagnosis. Under normal circumstances, the prognosis of urethral hamartoma is good. However, more cases are needed to be observed for verification, and a long-term effective follow-up after surgery is needed.
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The cytochrome P450 (CYP) AspB is involved in the biosynthesis of the diketopiperazine (DKP) aspergilazine A. Tryptophan-linked dimeric DKP alkaloids are a large family of natural products that are found in numerous species and exhibit broad and often potent bioactivity. The proposed mechanisms for C-N bond formation by AspB, and similar C-C bond formations by related CYPs, have invoked the use of a ferryl-intermediate as an oxidant to promote substrate dimerization. Here, the parallel application of steady-state and transient kinetic approaches reveals a very different mechanism that involves a ferric-superoxide species as a primary oxidant to initiate DKP-assembly. Single turnover kinetic isotope effects and a substrate analog suggest the probable nature and site for abstraction. The direct observation of CYP-superoxide reactivity rationalizes the atypical outcome of AspB and reveals a new reaction manifold in heme enzymes.
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Fer , Superoxydes , Dimérisation , Cytochrome P-450 enzyme system , Oxydants , Pipérazinediones , Dipeptides , Électrolytes , CatalyseRÉSUMÉ
Giant fibroepithelial polyp (FP) of the scrotum in infants is a rare disease. We reported the first case of FP in China. The child was only 9 months and 12 days old and was admitted to the hospital due to rapid growth and rupture of the scrotal mass. The patient underwent scrotal exploration under general anesthesia, and the mass was cystic-solid with clear boundaries. The tumor did not invade the sarcolemma of the scrotum and testicular tissue. The intraoperative pathological frozen section tended to be benign, and the scrotum's tumor and subcutaneous pedicle tissue were removed entirely after 0.5â cm from the boundary of the mass. The operation was successful. The mass was confirmed as FP by postoperative pathology. 6 months after the operation, the incision healed well without recurrence. This case report has a detailed diagnosis and treatment process and adequate examination results. It can provide a reference for diagnosing and treating FP in infants and reduce the risk of misdiagnosis and mistreatment.
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Rationale: Accumulating evidence illustrated that the reprogramming of the super-enhancers (SEs) landscape could promote the acquisition of metastatic features in pancreatic cancer (PC). Given the anatomy-based TNM staging is limited by the heterogeneous clinical outcomes in treatment, it is of great clinical significance to tailor individual stratification and to develop alternative therapeutic strategies for metastatic PC patients based on SEs. Methods: In our study, ChIP-Seq analysis for H3K27ac was performed in primary pancreatic tumors (PTs) and hepatic metastases (HMs). Bootstrapping and univariate Cox analysis were implemented to screen prognostic HM-acquired, SE-associated genes (HM-SE genes). Then, based on 1705 PC patients from 14 multicenter cohorts, 188 machine-learning (ML) algorithm integrations were utilized to develop a comprehensive super-enhancer-related metastatic (SEMet) classifier. Results: We established a novel SEMet classifier based on 38 prognostic HM-SE genes. Compared to other clinical traits and 33 published signatures, the SEMet classifier possessed robust and powerful performance in predicting prognosis. In addition, patients in the SEMetlow subgroup owned dismal survival rates, more frequent genomic alterations, and more activated cancer immunity cycle as well as better benefits in immunotherapy. Remarkably, there existed a tight correlation between the SEMetlow subgroup and metastatic phenotypes of PC. Among 18 SEMet genes, we demonstrated that E2F7 may promote PC metastasis through the upregulation of TGM2 and DKK1. Finally, after in silico screening of potential compounds targeted SEMet classifier, results revealed that flumethasone could enhance the sensitivity of metastatic PC to routine gemcitabine chemotherapy. Conclusion: Overall, our study provided new insights into personalized treatment approaches in the clinical management of metastatic PC patients.
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Tumeurs du pancréas , Humains , Tumeurs du pancréas/traitement médicamenteux , Tumeurs du pancréas/génétique , , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Études de cohortesRÉSUMÉ
Small cell carcinoma of the bladder (SCCB) is a rare urological tumor. The prognosis of SCCB is abysmal. Therefore, this study aimed to construct nomograms that predict overall survival (OS) and cancer-specific survival (CSS) in SCCB patients. Information on patients diagnosed with SCCB during 2004-2018 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models analyzed Independent risk factors affecting patients' OS and CSS. Nomograms predicting the OS and CSS were constructed based on the multivariate Cox regression model results. The calibration curve verified the accuracy and reliability of the nomograms, the concordance index (C-index), and the area under the curve (AUC). Decision curve analysis (DCA) assessed the potential clinical value. 975 patients were included in the training set (N = 687) and the validation set (N = 288). Multivariate COX regression models showed that age, marital status, AJCC stage, T stage, M stage, surgical approach, chemotherapy, tumor size, and lung metastasis were independent risk factors affecting the patients' OS. However, distant lymph node metastasis instead AJCC stage is the independent risk factor affecting the CSS in the patients. We successfully constructed nomograms that predict the OS and CSS for SCCB patients. The C index of the training set and the validation set of the OS were 0.747 (95% CI 0.725-0.769) and 0.765 (95% CI 0.736-0.794), respectively. The C index of the CSS were 0.749 (95% CI 0.710-0.773) and 0.786 (95% CI 0.755-0.817), respectively, indicating that the predictive models of the nomograms have excellent discriminative power. The calibration curve and the AUC also show good accuracy and discrimination of the nomograms. To sum up, We established nomograms to predict the OS and CSS of SCCB patients. The nomograms have undergone internal cross-validation and show good accuracy and reliability. The DCA shows that the nomograms have an excellent clinical value that can help doctors make clinical-assisted decision-making.
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Carcinome à petites cellules , Tumeurs du poumon , Carcinome pulmonaire à petites cellules , Tumeurs de la vessie urinaire , Humains , Pronostic , Études rétrospectives , Intelligence artificielle , Reproductibilité des résultats , Tumeurs de la vessie urinaire/diagnostic , Tumeurs de la vessie urinaire/épidémiologie , Nomogrammes , Tumeurs du poumon/diagnostic , Programme SEERRÉSUMÉ
Polymer coatings with improved surface antibacterial properties are of great importance for the application and development of implantable medical devices. Herein, we report the design, preparation, and antibacterial properties of a series of brush polymers (Dex-KEs) with hydrophilic dextran main-chains and mixed-charge polypeptide (KE) side-chains. Dex-KEs showed higher bactericidal activity and antifouling and antibiofilm properties than maleic acid modified dextran (Dex-Ma), KE, Dex-Ma/KE blend coatings, and brush polymer coatings with hydrophobic main-chains (AcDex-KEs). They also showed negligible in vitro cytotoxicity toward different mammalian cells and good in vivo biocompatibility. Dex-KE-coated implants exhibited potent in vivo resistance to bacterial infection before or after implantation.
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Dextrane , Polymères , Animaux , Polymères/pharmacologie , Dextrane/pharmacologie , Staphylococcus aureus , Matériaux revêtus, biocompatibles/pharmacologie , Antibactériens/pharmacologie , MammifèresRÉSUMÉ
Objective: To investigate the effects of white blood cell (WBC) count on fetal fraction (FF), which is an essential quality control for obtaining reliable results, and on the rate of screen failures in noninvasive prenatal screening (NIPS). Methods: Noninvasive prenatal screening, serum lipid and liver enzyme level measurements, and WBC count were performed for 4,281 pregnancies with male fetuses. After adjusting for confounders, including the maternal characteristics and alanine aminotransferase (ALT) levels, the effect of WBC count on FF and test failure rate was measured by linear and logistic regression analyses. Results: Fetal fraction was negatively associated with BMI, ALT, IVF conceptions, and WBC count and positively correlated with gestational age in the multivariate linear regression model. Moreover, WBC count was the most important factor affecting FF after BMI according to the standardization coefficient analysis. In the 4,281 pregnancy samples with male fetuses, FF decreased with WBC count from 11.45% at ≤8 to 9.02% at >12, and FF markedly decreased to 7.40% in pregnancies with a higher WBC count (>12) and higher BMI (≥25 kg/m2). Meanwhile, the test failure rates were significantly higher in the WBC count > 12 group (4.29%) than in the WBC count ≤ 8 group (0.89%). Notably, when the BMI of pregnancies with a WBC count of >12 was >25, the rate reached 7.53%. Subsequently, multivariate logistic regression analysis further confirmed that an increased BMI and WBC count were independently and significantly associated with the test failure rates. Conclusion: An increased WBC count was associated with lower FF and higher test failure rates, suggesting that these important factors should be carefully considered during genetic counseling in pregnant women who decide to undergo blood collection or resampling.
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BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs), a type of cystic pancreatic cancer (PC) precursors, are increasingly identified on cross-sectional imaging and present a significant diagnostic challenge. While surgical resection of IPMN-related advanced neoplasia, i.e., IPMN-related high-grade dysplasia or PC, is an essential early PC detection strategy, resection is not recommended for IPMN-low-grade dysplasia (LGD) due to minimal risk of carcinogenesis, and significant procedural risks. Based on their promising results in prior validation studies targeting early detection of classical PC, DNA hypermethylation-based markers may serve as a biomarker for malignant risk stratification of IPMNs. This study investigates our DNA methylation-based PC biomarker panel (ADAMTS1, BNC1, and CACNA1G genes) in differentiating IPMN-advanced neoplasia from IPMN-LGDs. METHODS: Our previously described genome-wide pharmaco-epigenetic method identified multiple genes as potential targets for PC detection. The combination was further optimized and validated for early detection of classical PC in previous case-control studies. These promising genes were evaluated among micro-dissected IPMN tissue (IPMN-LGD: 35, IPMN-advanced neoplasia: 35) through Methylation-Specific PCR. The discriminant capacity of individual and combination of genes were delineated through Receiver Operating Characteristics curve analysis. RESULTS: As compared to IPMN-LGDs, IPMN-advanced neoplasia had higher hypermethylation frequency of candidate genes: ADAMTS1 (60% vs. 14%), BNC1 (66% vs. 3%), and CACGNA1G (25% vs. 0%). We observed Area Under Curve (AUC) values of 0.73 for ADAMTS1, 0.81 for BNC1, and 0.63 for CACNA1G genes. The combination of the BNC1/ CACNA1G genes resulted in an AUC of 0.84, sensitivity of 71%, and specificity of 97%. Combining the methylation status of the BNC1/CACNA1G genes, blood-based CA19-9, and IPMN lesion size enhanced the AUC to 0.92. CONCLUSION: DNA-methylation based biomarkers have shown a high diagnostic specificity and moderate sensitivity for differentiating IPMN-advanced neoplasia from LGDs. Addition of specific methylation targets can improve the accuracy of the methylation biomarker panel and enable the development of noninvasive IPMN stratification biomarkers.
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Tumeurs kystiques, mucineuses et séreuses , Tumeurs intracanalaires pancréatiques , Tumeurs du pancréas , Humains , Méthylation de l'ADN , Tumeurs intracanalaires pancréatiques/génétique , Tumeurs du pancréas/diagnostic , Tumeurs du pancréas/génétique , Tumeurs du pancréas/anatomopathologie , Marqueurs biologiques tumoraux/génétique , Tumeurs kystiques, mucineuses et séreuses/génétique , ADN , Appréciation des risques , Tumeurs du pancréasRÉSUMÉ
Background: Thyroid cancer (TC) accounts for more than 90% of endocrine tumours and is a typical head and neck tumour in adults. The aim of this study was to develop a predictive tool to predict cancer-specific survival (CSS) in middle-aged patients with papillary thyroid carcinoma (PTC). Methods: The patients from 2004 to 2015 were randomly divided into a training cohort (n = 25,342) and a internal validation cohort (n = 10,725). The patients from 2016 to 2018 were treated as an external validation cohort (n = 11353). COX proportional hazard model was used to screen meaningful independent risk factors. These factors were constructed into a nomogram to predict CSS in middle-aged patients with PTC. The performance and accuracy of the nomogram were then evaluated using the concordance index (C-index), calibration curve and the area under the curve (AUC). The clinical value of nomogram was evaluated by decision curve analysis (DCA). Results: Age, gender, marriage, tumour grade, T stage, N stage, M stage, surgery, chemotherapy, and tumour size were independent prognostic factors. The C-indexes of the training, internal validation, and external validation cohorts were 0.906, 0.887, and 0.962, respectively. The AUC and calibration curves show good accuracy. DCA shows that the clinical value of the nomogram is higher than that of Tumour, Node and Metastasis (TNM) staging. Conclusion: We developed a new prediction tool to predict CSS in middle-aged patients with PTC. The model has good performance after internal and external validation, which can be friendly to help doctors and patients predict CSS.
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Bone malignant tumors are metastatic and aggressive, with poor treatment outcomes and prognosis. Rapid and accurate diagnosis is crucial for limb salvage and increasing the survival rate. There is a lack of research on deep learning to segment bone malignant tumor lesions in medical images with complex backgrounds and blurred boundaries. Therefore, we propose a new intelligent auxiliary framework for the medical image segmentation of bone malignant tumor lesions, which consists of a supervised edge-attention guidance segmentation network (SEAGNET). We design a boundary key points selection module to supervise the learning of edge attention in the model to retain fine-grained edge feature information. We precisely locate malignant tumors by instance segmentation networks while extracting feature maps of tumor lesions in medical images. The rich contextual-dependent information in the feature map is captured by mixed attention to better understand the uncertainty and ambiguity of the boundary, and edge attention learning is used to guide the segmentation network to focus on the fuzzy boundary of the tumor region. We implement extensive experiments on real-world medical data to validate our model. It validates the superiority of our method over the latest segmentation methods, achieving the best performance in terms of the Dice similarity coefficient (0.967), precision (0.968), and accuracy (0.996). The results prove the important contribution of the framework in assisting doctors to improve the accuracy of diagnosis and clinical efficiency.
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A total of 12 OBPs were identified in the antennae of ladybird Hippodamia variegata. HvarOBP1/2/5/6/10/11 were highly expressed in adults, whereas HvarOBP3/4/7/8/9/12 had higher expression levels in larvae. In adults, HvarOBP1/2/4/5/6/7/8/11/12 were highly expressed in antennae. Among these, recombinant HvarOBP5 strong bound with (E)-ß-farnesene (EßF), (R)-(+)-limonene, (E,E)-4,8,12-trimethyltrideca-l,3,7,11-tetraene (TMTT), (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), hexyl hexanoate, and geranyl acetate. Molecular docking indicated that Leu42, Lys43, and His64 were the key binding sites of HvarOBP5. All six ligands evoked electroantennography (EAG) responses in ladybirds. Moreover, (R)-(+)-limonene and hexyl hexanoate were attractive to both sexes. After RNA interference for 72 h, the EAGs of dsRNA-injected ladybirds to DMNT and hexyl hexanoate were significantly decreased by 73.8 and 78.6%, respectively. Both dsRNA-injected males and females showed significantly lower behavioral preferences for DMNT and hexyl hexanoate. These findings suggest that HvarOBP5 in H. variegata plays an important role in the perception of semiochemical cues from preys and habitat plants.
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Phéromones , Récepteurs olfactifs , Femelle , Mâle , Animaux , Phéromones/métabolisme , Caproates , Limonène , Simulation de docking moléculaire , Récepteurs olfactifs/métabolisme , Perception , Protéines d'insecte/génétique , Antennes des arthropodes/métabolismeRÉSUMÉ
Preventing initial colonization of bacteria on biomaterial surfaces is crucial to address the medical device-associated infection issues. Antimicrobial peptide (AMP) or cationic polymer modified surfaces have shown promising potentials to inhibit the initial colonization of bacteria by contact killing. However, their development has been impeded because of bacterial adhesion and high cytotoxicity. Herein, we report a series of brush polypeptide coatings with anionic backbones and cationic AMP mimetic side-chains that displayed superior bactericidal activity, antibacterial adhesion property, and biocompatibility. The cationic side-chain density played an important role in the bioactivities of the brush polypeptide modified surfaces. Brush polypeptide coating with low side-chain density exhibited improved bactericidal activity and antibacterial adhesion property, ascribing to the cooperative effects of adjacent side-chains and backbones/side-chains, respectively. It also showed negligible hemolysis/cytotoxicity in vitro and potent anti-infection property (≥99.9% bactericidal efficacy) in vivo. Brush polymers with anionic backbones and cationic side-chains can be used as a promising design motif to potentiate both antibacterial property and biocompatibility of coatings for combating device-associated infections. STATEMENT OF SIGNIFICANCE: Device-associated infections (DAIs) have led to increased medical cost, pain, and even mortality of patients. Antimicrobial peptide and cationic polymer coatings provide an important strategy to combat DAIs by preventing initial colonization of bacteria on biomaterial surfaces. Nevertheless, they have suffered bacterial adhesion and cytotoxicity issues. Herein, we developed a brush polypeptide coating with anionic backbones and cationic side-chains. The brush polypeptide coating showed superior bactericidal and antibacterial adhesion properties outperforming conventional antibacterial coatings based on antimicrobial peptide (i.e., melittin), lysozyme (i.e., lysostaphin), cationic polymer, anionic polymer, and the blends of cationic/anionic polymers. It also showed good biocompatibility and potent anti-infection property, making it a promising candidate to combat the DAIs.
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Anti-infectieux , Matériaux revêtus, biocompatibles , Humains , Matériaux revêtus, biocompatibles/pharmacologie , Matériaux revêtus, biocompatibles/composition chimique , Antibactériens/pharmacologie , Antibactériens/composition chimique , Peptides antimicrobiens cationiques/pharmacologie , Peptides antimicrobiens cationiques/composition chimique , Polymères/composition chimique , BactériesRÉSUMÉ
The Aphis gossypii is a major threat of cotton worldwide due to its short life cycle and rapid reproduction. Chemical control is the primary method used to manage the cotton aphid, which has significant environmental impacts. Therefore, prioritizing eco-friendly alternatives is essential for managing the cotton aphid. The ladybird, Hippodamia variegata, is a predominant predator of the cotton aphid. Its performance in cotton plantation is directly linked to chemical communication, where volatile compounds emitted from aphid-infested plants play important roles in successful predation. Here, we comprehensively studied the chemical interaction between the pest, natural enemy and host plants by analyzing the volatile profiles of aphid-infested cotton plants using gas chromatography-mass spectrometry (GC-MS). We then utilized the identified volatile compounds in electrophysiological recording (EAG) and behavioral assays. Through behavioral tests, we initially demonstrated the clear preference of both larvae and adults of H. variegata for aphid-infested plants. Subsequently, 13 compounds, namely α-pinene, cis-3-hexenyl acetate, 4-ethyl-1-octyn-3-ol, ß-ocimene, dodecane, E-ß-farnesene, decanal, methyl salicylate, ß-caryophyllene, α-humulene, farnesol, DMNT, and TMTT were identified from aphid-infested plants. All these compounds were electrophysiologically active and induced detectable EAG responses in larvae and adults. Y-tube olfactometer assays indicated that, with few exceptions for larvae, all identified chemicals were attractive to H. variegata, particularly at the highest tested concentration (100 mg/ml). The outcomes of this study establish a practical foundation for developing attractants for H. variegata and open avenues for potential advancements in aphid management strategies by understanding the details of chemical communication at a tritrophic level.
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Inspired by the charge composition and distribution of proteins and peptides, we designed and prepared a series of brush polypeptides with positive and negative charges separately distributed in the side chains and the backbones. The brush polypeptides can self- or co-deposit on various substrates forming ultrathin and stable coatings. They showed potent bactericidal activity and antibiofilm property, outperforming conventional linear polypeptide coatings with randomly distributed positive and negative charges. Keeping the balance of positive/negative charges and increasing the numbers of positive/negative charges can further improve the antibacterial property of brush polypeptide coatings without sacrificing their biocompatibility.