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1.
Article de Anglais | MEDLINE | ID: mdl-38988275

RÉSUMÉ

Antireflective coatings with superhydrophobicity have many outdoor applications, such as solar photovoltaic panels and windshields. In this study, we fabricated an omnidirectional antireflective and superhydrophobic coating with good mechanical robustness and environmental durability via the spin coating technique. The coating consisted of a layer of phytic acid (PA)/polyacrylamide (PAM)/calcium ions (Ca2+) (referred to as Binder), an antireflective layer composed of chitin nanofibers (ChNFs), and a hydrophobic layer composed of methylsilanized silica (referred to as Mosil). The transmittance of a glass slide with the Binder/ChNFs/Mosil coating had a 5.2% gain at a wavelength of 550 nm, and the antireflective coating showed a water contact angle as high as 160° and a water sliding angle of 8°. The mechanical robustness and environmental durability of the coating, including resistance to peeling, dynamic impact, chemical erosion, ultraviolet (UV) irradiation, and high temperature, were evaluated. The coating retained excellent antireflective capacity and self-cleaning performance in the harsh conditions. The increase in voltage per unit area of a solar panel with a Binder/ChNFs/Mosil coating reached 0.4 mV/cm2 compared to the solar panel exposed to sunlight with an intensity of 54.3 × 103 lx. This work not only demonstrates that ChNFs can be used as raw materials to fabricate antireflective superhydrophobic coatings for outdoor applications but also provides a feasible and efficient approach to do so.

2.
Pediatr Neurol ; 158: 86-93, 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-39002355

RÉSUMÉ

BACKGROUND: To improve diagnostic precision in pediatric vertigo, particularly in Vestibular Migraine of Childhood (VMC), probable VMC (pVMC), Recurrent Vertigo of Childhood (RVC), and unspecified categories, by delineating clinical characteristics and prevalence to refine diagnostics and treatments. METHODS: Retrospective analysis of 102 pediatric patients (five to 18 years; 46 females, 56 males) at the Dizziness Center of the Otolaryngology Department in a tertiary-level hospital from January 2019 to December 2023. Patients were classified into VMC, pVMC, RVC, and indeterminate groups. Evaluations included audiometry and vestibular tests (video head impulse test [vHIT] or caloric testing), conducted in the audiology unit and vestibular testing laboratory. Data were analyzed using IBM SPSS 20.0. RESULTS: Diagnoses were 8.8% VMC, 31.4% pVMC, 51.0% RVC, and 8.8% indeterminate. Nausea and vomiting were common in VMC and pVMC; cochlear symptoms like tinnitus and hearing loss predominated in VMC. Although vestibular testing showed no significant group differences, VMC had more vHIT abnormalities and RVC had more caloric test anomalies. CONCLUSIONS: This study highlights the need for comprehensive diagnostics in pediatric vestibular disorders, revealing unique and overlapping traits across VMC, pVMC, and RVC. Insights call for further research to refine diagnostic criteria and improve treatment methods.

3.
Int J Mol Sci ; 25(13)2024 Jun 30.
Article de Anglais | MEDLINE | ID: mdl-39000356

RÉSUMÉ

The glucose-lowering drug metformin alters the composition of the gut microbiome in patients with type 2 diabetes mellitus (T2DM) and other diseases. Nevertheless, most studies on the effects of this drug have relied on fecal samples, which provide limited insights into its local effects on different regions of the gut. Using a high-fat diet (HFD)-induced mouse model of T2DM, we characterize the spatial variability of the gut microbiome and associated metabolome in response to metformin treatment. Four parts of the gut as well as the feces were analyzed using full-length sequencing of 16S rRNA genes and targeted metabolomic analyses, thus providing insights into the composition of the microbiome and associated metabolome. We found significant differences in the gut microbiome and metabolome in each gut region, with the most pronounced effects on the microbiomes of the cecum, colon, and feces, with a significant increase in a variety of species belonging to Akkermansiaceae, Lactobacillaceae, Tannerellaceae, and Erysipelotrichaceae. Metabolomics analysis showed that metformin had the most pronounced effect on microbiome-derived metabolites in the cecum and colon, with several metabolites, such as carbohydrates, fatty acids, and benzenoids, having elevated levels in the colon; however, most of the metabolites were reduced in the cecum. Thus, a wide range of beneficial metabolites derived from the microbiome after metformin treatment were produced mainly in the colon. Our study highlights the importance of considering gut regions when understanding the effects of metformin on the gut microbiome and metabolome.


Sujet(s)
Diabète de type 2 , Alimentation riche en graisse , Modèles animaux de maladie humaine , Microbiome gastro-intestinal , Métabolome , Metformine , Metformine/pharmacologie , Animaux , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Alimentation riche en graisse/effets indésirables , Diabète de type 2/métabolisme , Diabète de type 2/microbiologie , Diabète de type 2/traitement médicamenteux , Souris , Métabolome/effets des médicaments et des substances chimiques , Mâle , Fèces/microbiologie , ARN ribosomique 16S/génétique , Hypoglycémiants/pharmacologie , Souris de lignée C57BL , Caecum/microbiologie , Caecum/métabolisme , Caecum/effets des médicaments et des substances chimiques , Côlon/métabolisme , Côlon/effets des médicaments et des substances chimiques , Côlon/microbiologie , Métabolomique/méthodes
4.
Cancer Sci ; 2024 Jul 14.
Article de Anglais | MEDLINE | ID: mdl-39004911

RÉSUMÉ

Forkhead box M1 (FOXM1) is a key regulator of mitosis and is identified as an oncogene involved in several kinds of human malignancies. However, how it induces carcinogenesis and related therapeutic approaches remains not fully understood. In this study, we aimed to identify a regulatory axis involving FOXM1 and its target gene DEP domain containing 1 (DEPDC1) and investigate their biological functions. FOXM1 bound to the promoter and transcriptionally induced DEPDC1 expression, in turn, DEPDC1 physically interacted with FOXM1, promoted its nuclear translocation, and reinforced its transcriptional activities. The FOXM1/DEPDC1 axis was indispensable for cancer cells, as evidenced by the fact that DEPDC1 rescued cell growth inhibition caused by FOXM1 knockdown, and silencing DEPDC1 efficiently attenuated tumor growth in a murine hepatocellular carcinoma model. Furthermore, strong positive associations between FOXM1/DEPDC1 axis and poor clinical outcome were observed in human hepatocellular carcinoma samples, further indicating their significance for hepatocarcinogenesis. Finally, we attempted to exploit immunotherapy approaches to target the FOXM1/DEPDC1 axis. Several HLA-A24:02-restricted T-cell epitopes targeting FOXM1 or DEPDC1 were identified through bioinformatic analysis. Then, T cell receptor (TCR)-engineered T cells targeting FOXM1262-270 or DEPDC1294-302 were successfully established and proved to efficiently eradicate tumor cells. Our findings highlight the significance of the FOXM1/DEPDC1 axis in the process of oncogenesis and indicate their potential as immunotherapy targets.

5.
Bioinformatics ; 40(7)2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38954836

RÉSUMÉ

MOTIVATION: Accurately detecting pathogenic microorganisms requires effective primers and probe designs. Literature-derived primers are a valuable resource as they have been tested and proven effective in previous research. However, manually mining primers from published texts is time-consuming and limited in species scop. RESULTS: To address these challenges, we have developed MiPRIME, a real-time Microbial Primer Mining platform for primer/probe sequences extraction of pathogenic microorganisms with three highlights: (i) comprehensive integration. Covering >40 million articles and 548 942 organisms, the platform enables high-frequency microbial gene discovery from a global perspective, facilitating user-defined primer design and advancing microbial research. (ii) Using a BioBERT-based text mining model with 98.02% accuracy, greatly reducing information processing time. (iii) Using a primer ranking score, PRscore, for intelligent recommendation of species-specific primers. Overall, MiPRIME is a practical tool for primer mining in the pan-microbial field, saving time and cost of trial-and-error experiments. AVAILABILITY AND IMPLEMENTATION: The web is available at {{https://www.ai-bt.com}}.


Sujet(s)
Amorces ADN , Fouille de données , Fouille de données/méthodes , Logiciel , Bactéries/génétique , Bactéries/classification
6.
Front Microbiol ; 15: 1368293, 2024.
Article de Anglais | MEDLINE | ID: mdl-38946897

RÉSUMÉ

Introduction: The drawbacks of using antibiotics as feed additives for blue foxes have gradually become apparent; moreover, thymol has wide-spectrum antimicrobial activity and has the potential to replace antibiotics in various animals. However, there are few reports on the effects of thymol on blue foxes. Methods: This study aimed to investigate the effects of different concentrations of thymol on the growth performance, apparent nutrient digestibility, serum biochemical indicators, intestinal morphology, and gut microbiota of blue foxes. Twenty-four male blue foxes (120 ± 5 d) of similar weight (6.05 ± 0.16 kg) were randomly divided into 4 groups. 0, 100, 200, and 300 mg/kg thymol were added to the basal diets of groups C, L, M, and H, respectively. Results: Compared with those in the C group, the addition of 100 mg/kg thymol to the diet significantly increased organic matter (OM) digestibility, crude protein (CP) digestibility, immunoglobulin (Ig) A, IgM, the VH of the duodenum, the CD of the jejunum, the VH of the ileum, and the VH/CD of the ileum (P < 0.05) and strongly significantly increased IgG (P < 0.01). The addition of 200 mg/kg thymol to the diet increased the VH/CD of the duodenum (P < 0.05). The addition of 300 mg/kg thymol to the diet significantly increased the VH and CD of the jejunum (P < 0.05). The addition of 200 mg/kg and 300 mg/kg thymol to the diets increased the final weight (FW) (P < 0.05). Adding 100 mg/kg thymol significantly increased the levels of interleukin-4 (IL-4) and catalase (CAT) compared with those in the other groups (P < 0.05). 16S rRNA gene detection revealed that thymol can change the abundances of Bifidobacterium, Fusobacterium, Allobaculum, Streptococcus, Megasphaera, and Lactobacillus in the gut. Conclusion: The addition of thymol to diets can increase the abundance of Bifidobacterium, Fusobacterium, and Allobaculum, which may contribute to improving the growth performance of blue foxes.

7.
Pest Manag Sci ; 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38979967

RÉSUMÉ

BACKGROUND: Monochamus saltuarius is a destructive trunk-borer of pine forest and an effective dispersal vector for pinewood nematode (PWN), a causative agent of pine wilt disease (PWD), which leads to major ecological disasters. Cold winter temperatures determine insect survival and distribution. However, little is known about the cold tolerance and potential physiological mechanisms of M. saltuarius. RESULTS: We demonstrated that dead Pinus koraiensis trunks do not provide larvae with insulation. The M. saltuarius larvae are freeze-tolerant species. Unlike most other freeze-tolerant insects, they can actively freeze extracellular fluid at higher subzero temperatures by increasing their supercooling points. The main energy sources for larvae overwintering are glycogen and the mid-late switch to lipid. The water balance showed a decrease in free and an increase in bound water of small magnitude. Cold stress promoted lipid peroxidation, thus activating the antioxidant system to prevent cold-induced oxidative damage. We found eight main pathways linked to cold stress and 39 important metabolites, ten of which are cryoprotectants, including maltose, UDP-glucose, d-fructose 6P, galactinol, dulcitol, inositol, sorbitol, l-methionine, sarcosine, and d-proline. The M. saltuarius larvae engage in a dual respiration process involving both anaerobic and aerobic pathways when their bodily fluids freeze. Cysteine and methionine metabolism, as well as alanine, aspartate, and glutamate metabolism, are the most important pathways linked to antioxidation and energy production. CONCLUSIONS: The implications of our findings may help strengthen and supplement the management strategies for monitoring, quarantine, and control of this pest, thereby contributing to controlling the further spread of PWD. © 2024 Society of Chemical Industry.

8.
Infect Med (Beijing) ; 3(2): 100106, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38827562

RÉSUMÉ

China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.

9.
Int J Biol Macromol ; 274(Pt 1): 133337, 2024 Jun 20.
Article de Anglais | MEDLINE | ID: mdl-38908624

RÉSUMÉ

Chitin nanofibers are widely used in many fields because of their biocompatibility, renewability and excellent mechanical properties. Herein, zwitterionically charged chitin nanofibers (ZC-ChNFs) were prepared from chitin via one step chemical modification (oxalic acid pretreatment) and subsequent ultrasound treatment. Effects of pretreatment time on size of the ZC-ChNFs and pH of ZC-ChNF suspensions on the thickness, porosity, refractive index and antireflective capacity of ZC-ChNF coatings were investigated. It was found that, by adjusting pH of the ZC-ChNF suspension, porosity and refractive index of the ZC-ChNF coatings could be controlled. The ZC-ChNF coatings fabricated with smaller ZC-ChNFs had higher antireflective performance and the transmittance gain of a glass with a ZC-ChNF coating was about 3.5 % at a wavelength of 550 nm compared to the bare glass. The results of this work provide a promising pathway to fabricate antireflective coating with ZC-ChNFs just by controlling the pH of ZC-ChNF suspensions.

10.
Respir Res ; 25(1): 223, 2024 May 29.
Article de Anglais | MEDLINE | ID: mdl-38811936

RÉSUMÉ

BACKGROUND: Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. METHODS: We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. RESULTS: The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. CONCLUSION: Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.


Sujet(s)
Infections communautaires , Microbiote , Indice de gravité de la maladie , Expectoration , Humains , Infections communautaires/microbiologie , Infections communautaires/diagnostic , Infections communautaires/épidémiologie , Mâle , Femelle , Expectoration/microbiologie , Adulte d'âge moyen , Sujet âgé , Études rétrospectives , Études longitudinales , Études de cohortes , Dysbiose/microbiologie , Dysbiose/diagnostic , Pneumopathie infectieuse/microbiologie , Pneumopathie infectieuse/diagnostic , Pneumopathie bactérienne/microbiologie , Pneumopathie bactérienne/diagnostic , Pneumopathie bactérienne/épidémiologie , Sujet âgé de 80 ans ou plus , Adulte
11.
Int J Mol Sci ; 25(9)2024 Apr 30.
Article de Anglais | MEDLINE | ID: mdl-38732123

RÉSUMÉ

The pine wood nematode (PWN) uses several Monochamus species as vehicles, through a temporary hitchhiking process known as phoresy, enabling it to access new host plant resources. Monochamus saltuarius acts as a new and major vector of the PWN in Northeastern China, showing lower PWN carrying capacity and a shorter transmission cycle compared to established vectors. The apparently altered symbiotic relationship offers an interesting area for researching the costs and adaptions involved in nematode-beetle, a specialized phoresy. We analyzed the response and fitness costs of M. saltuarius through physiological measurements and transcriptomics. The PWN exerted adverse repercussions on the growth and development of M. saltuarius. The PWN accelerated larval development into pupae, while beetle adults carrying the PWN exhibited an elevated abnormality rate and mortality, and reduced starvation resistance. During the pupal stage, the expression of growth-related genes, including ecdysone-inducible genes (E74EA), cuticle proteins, and chitin genes (CHTs), markedly increased. Meanwhile, the induced immune response, mainly by the IMD and Toll signaling pathways, could be a contributing factor to adult abnormality and mortality. Adult gonads and trachea exhibited enrichment in pathways related to fatty acid elongation, biosynthesis, and metabolism. FASN, ELOVL, and SCD possibly contributed to resistance against PWN. Our research indicated that phoretic interactions between vector beetles and PWN vary throughout the vector's lifespan, particularly before and after entry into the trachea. This study highlighted the fitness costs of immunity and metabolism on the vector beetle, indicating the adaptation mechanisms and evolutionary trade-offs to PWN.


Sujet(s)
Coléoptères , Transcriptome , Animaux , Coléoptères/physiologie , Coléoptères/génétique , Tylenchida/physiologie , Tylenchida/génétique , Tylenchida/pathogénicité , Analyse de profil d'expression de gènes/méthodes , Larve , Interactions hôte-parasite/génétique , Aptitude génétique
12.
Research (Wash D C) ; 7: 0389, 2024.
Article de Anglais | MEDLINE | ID: mdl-38779486

RÉSUMÉ

The gut microbiota undergoes substantial changes in COVID-19 patients; yet, the utility of these alterations as prognostic biomarkers at the time of hospital admission, and its correlation with immunological and hematological parameters, remains unclear. The objective of this study is to investigate the gut microbiota's dynamic change in critically ill patients with COVID-19 and evaluate its predictive capability for clinical outcomes alongside immunological and hematological parameters. In this study, anal swabs were consecutively collected from 192 COVID-19 patients (583 samples) upon hospital admission for metagenome sequencing. Simultaneously, blood samples were obtained to measure the concentrations of 27 cytokines and chemokines, along with hematological and biochemical indicators. Our findings indicate a significant correlation between the composition and dynamics of gut microbiota with disease severity and mortality in COVID-19 patients. Recovered patients exhibited a higher abundance of Veillonella and denser interactions among gut commensal bacteria compared to deceased patients. Furthermore, the abundance of gut commensal bacteria exhibited a negative correlation with the concentration of proinflammatory cytokines and organ damage markers. The gut microbiota upon admission showed moderate prognostic prediction ability with an AUC of 0.78, which was less effective compared to predictions based on immunological and hematological parameters (AUC 0.80 and 0.88, respectively). Noteworthy, the integration of these three datasets yielded a higher predictive accuracy (AUC 0.93). Our findings suggest the gut microbiota as an informative biomarker for COVID-19 prognosis, augmenting existing immune and hematological indicators.

13.
Epidemiol Infect ; 152: e80, 2024 May 09.
Article de Anglais | MEDLINE | ID: mdl-38721832

RÉSUMÉ

Environmental exposures are known to be associated with pathogen transmission and immune impairment, but the association of exposures with aetiology and severity of community-acquired pneumonia (CAP) are unclear. A retrospective observational study was conducted at nine hospitals in eight provinces in China from 2014 to 2019. CAP patients were recruited according to inclusion criteria, and respiratory samples were screened for 33 respiratory pathogens using molecular test methods. Sociodemographic, environmental and clinical factors were used to analyze the association with pathogen detection and disease severity by logistic regression models combined with distributed lag nonlinear models. A total of 3323 CAP patients were included, with 709 (21.3%) having severe illness. 2064 (62.1%) patients were positive for at least one pathogen. More severe patients were found in positive group. After adjusting for confounders, particulate matter (PM) 2.5 and 8-h ozone (O3-8h) were significant association at specific lag periods with detection of influenza viruses and Klebsiella pneumoniae respectively. PM10 and carbon monoxide (CO) showed cumulative effect with severe CAP. Pollutants exposures, especially PM, O3-8h, and CO should be considered in pathogen detection and severity of CAP to improve the clinical aetiological and disease severity diagnosis.


Sujet(s)
Infections communautaires , Exposition environnementale , Indice de gravité de la maladie , Humains , Infections communautaires/épidémiologie , Infections communautaires/diagnostic , Infections communautaires/microbiologie , Chine/épidémiologie , Mâle , Femelle , Adulte d'âge moyen , Études rétrospectives , Sujet âgé , Exposition environnementale/effets indésirables , Matière particulaire/analyse , Adulte , Pneumopathie infectieuse/diagnostic , Pneumopathie infectieuse/épidémiologie , Pneumopathie infectieuse/microbiologie , Pneumopathie infectieuse/étiologie , Hôpitaux , Sujet âgé de 80 ans ou plus
14.
Int Immunopharmacol ; 134: 112169, 2024 Jun 15.
Article de Anglais | MEDLINE | ID: mdl-38728879

RÉSUMÉ

GUANKE is a Lactobacillus plantarum isolated from the feces of healthy volunteer. We have previously shown that GUANKE enhances the efficacy of the SARS-CoV-2 vaccine and prolongs the duration of vaccine protection by upregulating the IFN pathway and T and B lymphocyte functions of the host. The purpose of this study was to evaluate the protective effects and mechanism of oral administration of Lactobacillus plantarum GUANKE in the influenza (A virus A/Puerto Rico/8/34) infection mouse model. In our experiment, oral administration of GUANKE significantly decreased viral load and increased tight junction proteins expression in lung tissues of influenza-infected mice. After GUANKE was co-cultured with mBMDCs in vitro, mBMDCs' maturity and antiviral ability were enhanced, and matured mBMDCs induced polarization of naïve CD4+ T cells into T helper (Th) 1 cells. Adoptive transfer of GUANKE-treated mBMDCs could protect mice from influenza infections. This study suggests that oral administration of Lactobacillus plantarum GUANKE could provide protection against influenza infection in mice, and this protective effect may be mediated, at least in part, by dendritic cells.


Sujet(s)
Cellules dendritiques , Lactobacillus plantarum , Infections à Orthomyxoviridae , Animaux , Lactobacillus plantarum/immunologie , Cellules dendritiques/immunologie , Infections à Orthomyxoviridae/immunologie , Souris , Probiotiques/administration et posologie , Femelle , Souris de lignée C57BL , Humains , COVID-19/immunologie , COVID-19/prévention et contrôle , Administration par voie orale , Charge virale , Poumon/immunologie , Poumon/virologie , Poumon/microbiologie , Modèles animaux de maladie humaine , Souris de lignée BALB C , SARS-CoV-2/immunologie , Virus de la grippe A/immunologie
15.
Nat Commun ; 15(1): 3860, 2024 May 08.
Article de Anglais | MEDLINE | ID: mdl-38719824

RÉSUMÉ

Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT.


Sujet(s)
Cholestérol , Protéome , Humains , Cholestérol/sang , Cholestérol/métabolisme , Protéome/métabolisme , Femelle , Mâle , Adulte d'âge moyen , Antigène CTLA-4/antagonistes et inhibiteurs , Antigène CTLA-4/métabolisme , Antigène CTLA-4/sang , Récepteur-1 de mort cellulaire programmée/antagonistes et inhibiteurs , Récepteur-1 de mort cellulaire programmée/métabolisme , Récepteur-1 de mort cellulaire programmée/sang , Marqueurs biologiques/sang , Sujet âgé , Tri-iodothyronine/sang , Apprentissage machine , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Inhibiteurs de points de contrôle immunitaires/pharmacologie , Tumeurs/traitement médicamenteux , Tumeurs/sang , Tumeurs/métabolisme , Protéomique/méthodes
16.
Open Forum Infect Dis ; 11(4): ofae137, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38577029

RÉSUMÉ

The immune mechanisms of long coronavirus disease 2019 (COVID) are not yet fully understood. We aimed to investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory immune responses in discharged COVID-19 patients with and without long COVID symptoms. In this cross-sectional study, we included 1041 hospitalized COVID-19 patients with the original virus strain in Wuhan (China) 12 months after initial infection. We simultaneously conducted a questionnaire survey and collected peripheral blood samples from the participants. Based on the presence or absence of long COVID symptoms during the follow-up period, we divided the patients into 2 groups: a long COVID group comprising 480 individuals and a convalescent group comprising 561 individuals. Both groups underwent virus-specific immunological analyses, including enzyme-linked immunosorbent assay, interferon-γ-enzyme-linked immune absorbent spot, and intracellular cytokine staining. At 12 months after infection, 98.5% (1026/1041) of the patients were found to be seropositive and 93.3% (70/75) had detectable SARS-CoV-2-specific memory T cells. The long COVID group had significantly higher levels of receptor binding domain (RBD)-immunoglobulin G (IgG) levels, presented as OD450 values, than the convalescent controls (0.40 ± 0.22 vs 0.37 ± 0.20; P = .022). The magnitude of SARS-CoV-2-specific T-cell responses did not differ significantly between groups, nor did the secretion function of the memory T cells. We did not observe a significant correlation between SARS-CoV-2-IgG and magnitude of memory T cells. This study revealed that long COVID patients had significantly higher levels of RBD-IgG antibodies when compared with convalescent controls. Nevertheless, we did not observe coordinated SARS-CoV-2-specific cellular immunity. As there may be multiple potential causes of long COVID, it is imperative to avoid adopting a "one-size-fits-all" approach to future treatment modalities.

17.
Pest Manag Sci ; 2024 Apr 17.
Article de Anglais | MEDLINE | ID: mdl-38629795

RÉSUMÉ

BACKGROUND: Hylurgus ligniperda, an invasive species originating from Eurasia, is now a major forestry quarantine pest worldwide. In recent years, it has caused significant damage in China. While traps have been effective in monitoring and controlling pests, manual inspections are labor-intensive and require expertise in insect classification. To address this, we applied a two-stage cascade convolutional neural network, YOLOX-MobileNetV2 (YOLOX-Mnet), for identifying H. ligniperda and other pests captured in traps. This method streamlines target and non-target insect detection from trap images, offering a more efficient alternative to manual inspections. RESULTS: Two cascade convolutional neural network models were employed in two stages to detect both target and non-target insects from images captured in the same forest. Initially, You Only Look Once X (YOLOX) served as the target detection model, identifying insects and non-insects from the collected images, with non-insect targets subsequently filtered out. In the second stage, MobileNetV2, a classification network, classified the captured insects. This approach effectively reduced false positives from non-insect objects, enabled the inclusion of additional classification terms for multi-class insect classification models, and utilized sample control strategies to enhance classification performance. CONCLUSION: Application of the cascade convolutional neural network model accurately identified H. ligniperda, and Mean F1-score of all kinds of insects in the trap was 0.98. Compared to traditional insect classification, this method offers great improvement in the identification and early warning of forest pests, as well as provide technical support for the early prevention and control of forest pests. © 2024 Society of Chemical Industry.

19.
Front Pharmacol ; 15: 1347047, 2024.
Article de Anglais | MEDLINE | ID: mdl-38617792

RÉSUMÉ

Metformin is the initial medication recommended for the treatment of type 2 diabetes mellitus (T2DM). In addition to diabetes treatment, the function of metformin also can be anti-aging, antiviral, and anti-inflammatory. Nevertheless, further exploration is required to fully understand its mode of operation. Historically, the liver has been acknowledged as the main location where metformin reduces glucose levels, however, there is increasing evidence suggesting that the gastrointestinal tract also plays a significant role in its action. In the gastrointestinal tract, metformin effects glucose uptake and absorption, increases glucagon-like peptide-1 (GLP-1) secretion, alters the composition and structure of the gut microbiota, and modulates the immune response. However, the side effects of it cannot be ignored such as gastrointestinal distress in patients. This review outlines the impact of metformin on the digestive system and explores potential explanations for variations in metformin effectiveness and adverse effects like gastrointestinal discomfort.

20.
Nat Biotechnol ; 2024 Apr 23.
Article de Anglais | MEDLINE | ID: mdl-38653798

RÉSUMÉ

T cell receptor (TCR) gene therapy is a potent form of cellular immunotherapy in which patient T cells are genetically engineered to express TCRs with defined tumor reactivity. However, the isolation of therapeutic TCRs is complicated by both the general scarcity of tumor-specific T cells among patient T cell repertoires and the patient-specific nature of T cell epitopes expressed on tumors. Here we describe a high-throughput, personalized TCR discovery pipeline that enables the assembly of complex synthetic TCR libraries in a one-pot reaction, followed by pooled expression in reporter T cells and functional genetic screening against patient-derived tumor or antigen-presenting cells. We applied the method to screen thousands of tumor-infiltrating lymphocyte (TIL)-derived TCRs from multiple patients and identified dozens of CD4+ and CD8+ T-cell-derived TCRs with potent tumor reactivity, including TCRs that recognized patient-specific neoantigens.

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