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1.
Angew Chem Int Ed Engl ; : e202409556, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38988065

ABSTRACT

Platinum-based supported intermetallic alloys (IMAs) demonstrate exceptional performance in catalytic propane dehydrogenation (PDH) primarily because of their remarkable resistance to coke formation. However, these IMAs still encounter a significant hurdle in the form of catalyst deactivation. Understanding the complex deactivation mechanism of supported IMAs, which goes beyond conventional coke deposition, requires meticulous microscopic structural elucidation. In this study, we unravel a nonclassical deactivation mechanism over a PtZn/γ-Al2O3 PDH catalyst, dictated by the PtZn to Pt3Zn nanophase transformation accompanied with dezincification. The physical origin lies in the metal support interaction (MSI) that enables strong chemical bonding between hydroxyl groups on the support and Zn sites on the PtZn phase to selectively remove Zn species followed by the reconstruction towards Pt3Zn phase. Building on these insights, we have devised a solution to circumvent the deactivation by passivating the MSI through surface modification of γ-Al2O3 support. By exchanging protons of hydroxyl groups with potassium ions (K) on the γ-Al2O3 support, such a strategy significantly minimizes the dezincification of PtZn IMA via diminished metal-support bonding, which dramatically reduces the deactivation rate from 0.2044 to 0.0587 h-1.

2.
Heliyon ; 10(11): e31996, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38882334

ABSTRACT

Sustainable smart ecotourism, utilizing smart technologies like smartphones, artificial intelligence (AI), and the Internet of Things (IoT), aims to minimize harm to natural and cultural ecosystems, promoting education and environmental conservation. This review aims to examine the concept of sustainable smart ecotourism, analyzing existing literature to gain insights into the significance, components, challenges, and contributions to sustainable development on a global scale. A systematic review was conducted to evaluate sustainable smart ecotourism using PRISMA guidelines. The review focused on scholarly, peer-reviewed studies from developing countries, using databases like ScienceDirect, Jstor, Taylor & Francis, and IEEE. The study used Joanna Briggs Institute and Cochrane Risk of Bias tools to assess study quality. Thematic analysis techniques were used to extract and synthesize data, identifying patterns and trends relevant to smart ecotourism sustainability. Dual analyst verification ensured data integrity and reliability. After conducting a thorough quality evaluation using the Joanna Briggs Institute Checklist and Cochrane Risk of Bias Tool, we identified 29 studies of exceptional quality from an original pool of 9583 records. The use of thematic analysis sheds light on the diverse and important role of the IoT in promoting sustainable ecotourism. This study uncovered both the obstacles and possibilities associated with this technology. The findings provide important insights into the worldwide implementation of smart ecotourism techniques and highlight the significant impact of technology in promoting sustainable tourism models. Smart ecotourism involves multiple stakeholders to enhance environmental impact. Key characteristics include dynamic interactions, co-creation of value, sustainable development, resource sharing, and innovation services. Technology like IoT is crucial for sustainable tourism management. Collaboration with governments, local stakeholders, and organizations is recommended for sustainable policies. As a result of this study, sustainable ecotourism policies result from a collaborative effort between local communities, government agencies, and practitioners in the industry. Smart technologies, including AR/VR and AI, have the potential to enhance operational efficiency while reducing environmental concerns. Ecotourism, partnerships, and education are key to successful implementation and capacity building.

3.
Molecules ; 29(12)2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38930891

ABSTRACT

The current study involved the preparation of a number of MnOx/Sep catalysts using the impregnation (MnOx/Sep-I), hydrothermal (MnOx/Sep-H), and precipitation (MnOx/Sep-P) methods. The MnOx/Sep catalysts that were produced were examined for their ability to catalytically oxidize formaldehyde (HCHO). Through the use of several technologies, including N2 adsorption-desorption, XRD, FTIR, TEM, H2-TPR, O2-TPD, CO2-TPD, and XPS, the function of MnOx in HCHO elimination was examined. The MnOx/Sep-H combination was shown to have superior catalytic activities, outstanding cycle stability, and long-term activity. It was also able to perform complete HCHO conversion at 85 °C with a high GHSV of 6000 mL/(g·h) and 50% humidity. Large specific surface area and pore size, a widely dispersed active component, a high percentage of Mn3+ species, and lattice oxygen concentration all suggested a potential reaction route for HCHO oxidation. This research produced a low-cost, highly effective catalyst for HCHO purification in indoor or industrial air environments.

4.
Proc Natl Acad Sci U S A ; 121(25): e2321614121, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38857401

ABSTRACT

The medial prefrontal cortex (mPFC) is a key brain structure for higher cognitive functions such as decision-making and goal-directed behavior, many of which require awareness of spatial variables including one's current position within the surrounding environment. Although previous studies have reported spatially tuned activities in mPFC during memory-related trajectory, the spatial tuning of mPFC network during freely foraging behavior remains elusive. Here, we reveal geometric border or border-proximal representations from the neural activity of mPFC ensembles during naturally exploring behavior, with both allocentric and egocentric boundary responses. Unlike most of classical border cells in the medial entorhinal cortex (MEC) discharging along a single wall, a large majority of border cells in mPFC fire particularly along four walls. mPFC border cells generate new firing fields to external insert, and remain stable under darkness, across distinct shapes, and in novel environments. In contrast to hippocampal theta entrainment during spatial working memory tasks, mPFC border cells rarely exhibited theta rhythmicity during spontaneous locomotion behavior. These findings reveal spatially modulated activity in mPFC, supporting local computation for cognitive functions involving spatial context and contributing to a broad spatial tuning property of cortical circuits.


Subject(s)
Prefrontal Cortex , Theta Rhythm , Prefrontal Cortex/physiology , Prefrontal Cortex/cytology , Animals , Theta Rhythm/physiology , Male , Mice , Entorhinal Cortex/physiology , Neurons/physiology , Hippocampus/physiology , Spatial Memory/physiology , Mice, Inbred C57BL , Memory, Short-Term/physiology
5.
Front Public Health ; 12: 1335553, 2024.
Article in English | MEDLINE | ID: mdl-38832224

ABSTRACT

Introduction: This study aims to evaluate the qualifications and identify skill enhancement areas for epidemiological investigators in Centers for Disease Control and Prevention (CDCs) in Guizhou's, informing future training and policy initiatives to strengthen public health responses. Methods: A cross-sectional survey was conducted in August 2022, and an online, self-designed questionnaire on the Epidemiological Dynamic Data Collection platform was administered to evaluate the professional staff in CDCs. The responses were scored and presented using descriptive statistical methods, and the factors influencing the total score were analyzed by one-way ANOVA and linear regression. Results and discussion: A total of 1321 questionnaires were collected, yielding an average score of 14.86±3.49 and a qualification rate of 29.9%. The scoring rate of ability of individual protection and coordination in epidemic control was high (87.25%). Meanwhile, improvements in further training were needed in areas such as data analysis ability (23.67%), knowledge of site disinfection (40.40%), and epidemiological investigation skills (42.50%). No significant difference was observed between the scores of city and county CDCs, (t = 1.071, p =0.284). The effects of gender and age could be disregarded, and the experience in epidemiological work and training (including investigation on COVID-19 cases and contacts), educational background, and professional title partially explained the survey outcome (R Square of the linear regression model was 0.351). The survey indicated the need for additional well-trained epidemiologic investigators in Guizhou. Specified training was effective in improving epidemiologic investigation, and enhancement in data analysis ability and knowledge of field disinfection are recommended in professional staff cultivation.


Subject(s)
Professional Competence , Humans , Cross-Sectional Studies , China/epidemiology , Female , Male , Surveys and Questionnaires , Adult , Middle Aged , Professional Competence/statistics & numerical data , COVID-19/prevention & control , COVID-19/epidemiology
6.
Biomed Opt Express ; 15(5): 3366-3381, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38855705

ABSTRACT

A surface-enhanced Raman scattering (SERS) detection platform was constructed based on Au nano-dodecahedrons (AuNDs) functionalized with nucleic acid aptamer-specific binding and self-assembly techniques. SERS labels were prepared by modifying Raman signaling molecules and complementary aptamer chains and were bound on the aptamer-functionalized AuNDs array. Using this protocol, the limits of detection (LODs) of miR-21 and miR-18a in the serum were 6.8 pM and 7.6 pM, respectively, and the detection time was 5 min. Additionally, miR-21 and miR-18a were detected in the serum of a mouse model of colorectal cancer. The results of this protocol were consistent with quantitative real-time polymerase chain reaction (qRT-PCR). This method provides an efficient and rapid method for the simultaneous testing of miRNAs, which has great potential clinical value for the early detection of colorectal cancer (CRC).

7.
Article in English | MEDLINE | ID: mdl-38829755

ABSTRACT

Deep-brain Magnetic Stimulation (DMS) can improve the symptoms caused by Alzheimer's disease by inducing rhythmic electric field in the deep brain, and the induced electric field is rhythm-dependent. However, calculating the induced electric field requires building a voxel model of the brain for the stimulated object, which usually takes several hours. In order to obtain the rhythm-dependent electric field induced by DMS in real time, we adopt a CNN-Transformer model to predict it. A data set with a sample size of 7350 is established for the training and testing of the model. 10-fold cross validation is used to determine the optimal hyperparameters for training CNN-Transformer. The combination of 5-layer CNN and 6-layer Transformer is verified as the optimal combination of CNN-Transformer model. The experimental results show that the CNN-Transformer model can complete the prediction in 0.731s (CPU) or 0.042s (GPU), and the overall performance metrics of prediction can reach: MAE =0.0269, RMSE =0.0420, MAPE =4.61% and R2=0.9627. The prediction performance of the CNN-Transformer model for the hippocampal electric field is better than that of the brain grey matter electric field, and the stimulation rhythm has less influence on the model performance than the coil configuration. Taking the same dataset to train and test the separate CNN model and Transformer model, it is found that CNN-Transformer has better prediction performance than the separate CNN model and Transformer model in the task of predicting electric field induced by DMS.


Subject(s)
Deep Brain Stimulation , Neural Networks, Computer , Humans , Brain/physiology , Algorithms , Alzheimer Disease
8.
J Biomed Opt ; 29(6): 066001, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38737790

ABSTRACT

Significance: Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes. Aim: We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT. Approach: Twenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers. Results: Normalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles (p=0.042). In addition, the change in normalized tumor StO2 upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle (p=0.038). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI. Conclusions: These findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens.


Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Tomography, Optical , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Female , Neoadjuvant Therapy/methods , Middle Aged , Tomography, Optical/methods , Adult , Hemodynamics , Treatment Outcome , Mammography/methods , Breast/diagnostic imaging , Breast/pathology , Hemoglobins/analysis , Aged , Biomarkers, Tumor/analysis , ROC Curve
9.
Medicine (Baltimore) ; 103(15): e37643, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38608104

ABSTRACT

To investigate the status of the drug-resistant tuberculosis (DR-TB) among children in Sichuan, and to find out the risk factors and high-risk population related to drug resistance among children. The clinical data of tuberculosis patients ≤14 years old with culture-confirmed tuberculosis hospitalized in Chengdu Public Health Clinical Center from January 2013 through December 2022 were collected. Clinical data such as gender, age, ethnicity, history of anti-TB treatment, history of exposure to tuberculosis, nutritional status, and specific drug resistance of the children were collected and recorded. The drug resistance of children in different age groups (0-4 years old, 5-9 years old, 10-14 years old) and different periods (2013-2017 and 2018-2022) were grouped and compared. Logistic regression analysis was to analyze analysis of risk factors of drug resistance in children. A total of 438 children with culture-confirmed tuberculosis were screened. Among them, 26.19% (11/42) were 0 to 4 years old, 33.33% (22/66) were 5 to 9 years old, and 36.67% (121/330) were 10 to 14 years old among the resistant children. There was no statistically significant difference in the resistance rate among the 3 groups (P = .385). The proportions of DR-TB, monoresistant tuberculosis, polydrug-resistant tuberculosis were decreased during 2019 to 2022 compared with 2013 to 2017 (P < .0001). The resistance rates of drug resistant, monoresistant, polydrug-resistant, isoniazid-resistant, and rifampicin resistant during 2018 to 2022 were decreased compared with those from 2013 to 2017 (P < .05), but the multi-drug resistance rate was not decreased (P = .131, without statistical difference). The results of logistic regression analysis showed that male gender OR = 1.566 (95% CI 1.035-2.369), a history of antituberculosis therapy OR = 4.049 (95% CI 1.442-11.367), and pulmonary and extrapulmonary tuberculosis OR = 7.335 (95% CI 1.401-38.392) were risk factors for the development of drug resistance; but fever OR = 0.581 (95% CI 0.355-0.950) was Protective factor. The total drug resistance rate of children in Sichuan showed a downward trend, but the rate of multi-drug-resistant tuberculosis was still at a high level, and the form of drug resistance was still severe. Absence of fever, male, retreatment, and pulmonary concurrent with extrapulmonary tuberculosis are risk factors for DR-TB in children.


Subject(s)
Tuberculosis, Extrapulmonary , Tuberculosis, Multidrug-Resistant , Child , Humans , Male , Infant, Newborn , Infant , Child, Preschool , Adolescent , Retrospective Studies , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Risk Factors , China/epidemiology , Fever
10.
Article in English | MEDLINE | ID: mdl-38615695

ABSTRACT

BACKGROUND: Predicting the long-term survival in adenoid cystic carcinoma (ACC) patients remains challenging. Inflammatory cell-based indices are emerging as prognostic indicators of oncology. PURPOSE: This study aimed to determine the associations between the preoperative systemic inflammatory response index (SIRI) and the systemic immunoinflammatory index (SII) and the 10-year survival rates in patients with ACC of the head and neck (ACCHN). STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study comprised ACCHN patients treated at the Chinese People's Liberation Army General Hospital between November 2003 and December 2020. PREDICTOR VARIABLE: The inflammatory response, assessed using the SIRI and SII, was the predictor variable. The optimal cutoff values were based on the maximum Youden index values (sensitivity + specificity-1). The patients were divided into two groups each, based on the SIRI (low, ≤ 0.15) and (high, > 0.15), and SII (low, ≤ 562.8 and high, > 562.8) values. MAIN OUTCOME VARIABLE(S): Overall survival (OS), or the number of days, weeks, or months between treatment initiation and death (or the last follow-up date), was the primary outcome variable. COVARIATES: The covariates were classified as demographic (age, gender, body mass index), medical (hypertension, diabetes), inflammatory (neutrophils, lymphocytes, monocytes, platelets, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, neutrophil-lymphocyte ratio), and perioperative (tumor stage, lymph node metastasis, tumor size, treatment type). ANALYSES: Descriptive, univariate, and multivariate Cox proportional risk regression analyses were performed to determine whether the SIRI and SII were independent prognostic factors for OS. Kaplan-Meier survival curves and log-rank tests were used to determine their associations with the OS. RESULTS: The study sample comprised 162 patients (mean age, 52 ± 14; males, 39.5%). The median follow-up time was 6.81 ± 0.23, and the 10-year OS rate was 7.68 ± 0.25. The low and high SIRI groups comprised 109 and 53 patients, while the low and high SII groups comprised 116 and 46 patients, respectively. SIRI was identified as a prognostic factor (P < .01; hazard ratio, 2.45; 95% confidence interval, 1.35-4.45). CONCLUSION AND RELEVANCE: The SIRI has the advantages of reproducibility, convenience, noninvasiveness, and affordability, making it a promising prognostic inflammatory index for patients with ACCHN.

11.
Psychol Med ; : 1-11, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563283

ABSTRACT

BACKGROUND: The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders. RESULTS: SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07­1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06­1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04­1.18, p = 1.84 × 10−3). CONCLUSIONS: We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.

12.
Front Immunol ; 15: 1369311, 2024.
Article in English | MEDLINE | ID: mdl-38601162

ABSTRACT

Background: Coronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living with HIV, characterized by compromised immune systems, face an elevated risk of severe outcomes and increased mortality when affected by COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, and HIV remain unclear. Our research endeavors to elucidate the shared pathways and molecular markers in individuals with HIV concurrently infected with COVID-19 and influenza. Furthermore, we aim to identify potential medications that may prove beneficial in managing these three interconnected illnesses. Methods: Sequencing data for COVID-19 (GSE157103), influenza (GSE185576), and HIV (GSE195434) were retrieved from the GEO database. Commonly expressed differentially expressed genes (DEGs) were identified across the three datasets, followed by immune infiltration analysis and diagnostic ROC analysis on the DEGs. Functional enrichment analysis was performed using GO/KEGG and Gene Set Enrichment Analysis (GSEA). Hub genes were screened through a Protein-Protein Interaction networks (PPIs) analysis among DEGs. Analysis of miRNAs, transcription factors, drug chemicals, diseases, and RNA-binding proteins was conducted based on the identified hub genes. Finally, quantitative PCR (qPCR) expression verification was undertaken for selected hub genes. Results: The analysis of the three datasets revealed a total of 22 shared DEGs, with the majority exhibiting an area under the curve value exceeding 0.7. Functional enrichment analysis with GO/KEGG and GSEA primarily highlighted signaling pathways associated with ribosomes and tumors. The ten identified hub genes included IFI44L, IFI44, RSAD2, ISG15, IFIT3, OAS1, EIF2AK2, IFI27, OASL, and EPSTI1. Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, and hsa-miR-6069), five essential transcription factors (CREB1, CEBPB, EGR1, EP300, and IRF1), and the top ten significant drug chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) were identified. Conclusion: This research provides valuable insights into shared molecular targets, signaling pathways, drug chemicals, and potential biomarkers for individuals facing the complex intersection of COVID-19, influenza, and HIV. These findings hold promise for enhancing the precision of diagnosis and treatment for individuals with HIV co-infected with COVID-19 and influenza.


Subject(s)
COVID-19 , HIV Infections , Influenza, Human , MicroRNAs , Humans , Influenza, Human/genetics , COVID-19/genetics , SARS-CoV-2 , Computational Biology , MicroRNAs/genetics , Transcription Factors , Gene Expression Regulation , HIV Infections/drug therapy , HIV Infections/genetics
13.
Purinergic Signal ; 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38642324

ABSTRACT

In clinical practice, depression and anxiety frequently coexist, and they are both comorbid with somatic diseases. The P2X7R is an adenosine 5'-triphosphate (ATP)-gated non-selective cation channel that is widely expressed in immune-related cells. Under conditions of stress, chronic pain, and comorbid chronic physical illness, P2X7R activation in glial cells leads to neuroinflammation. This could contribute to the development of anxiety and depression-related emotional disturbances. Previous studies have shown that the P2X7 receptor (P2X7R) plays an important role in the pathogenesis of both anxiety and depression. Thus, the P2X7R may play a role in the comorbidity of anxiety and depression. Positron emission tomography can be used to assess the degree and location of neuroinflammation by monitoring functional and expression-related changes in P2X7R, which can facilitate clinical diagnoses and guide the treatment of patients with anxiety and depression. Moreover, single nucleotide polymorphisms (SNPs) in the P2X7R gene are associated with susceptibility to different types of psychiatric disorders. Thus, evaluating the SNPs of the P2X7R gene could enable personalized mood disorder diagnoses and treatments. If the P2X7R were set as a therapeutic target, selective P2X7R antagonists may modulate P2X7R function, thereby altering the balance of intra- and extra-cellular ATP. This could have therapeutic implications for treating anxiety and depression, as well as for pain management. According to in vitro and in vivo studies, the P2X7R plays an important role in anxiety and depression. In this review, we consider the potential of the P2X7R as a therapeutic target for comorbid anxiety and depression, and discuss the potential diagnostic and therapeutic value of this receptor.

14.
Clin Drug Investig ; 44(5): 343-355, 2024 May.
Article in English | MEDLINE | ID: mdl-38615091

ABSTRACT

BACKGROUND: Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects. METHODS: An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period. RESULTS: The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. CONCLUSION: The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CLINICAL TRIALS REGISTRATION: CTR20230643.


Subject(s)
Amoxicillin , Benzene Derivatives , Bismuth , Clarithromycin , Drug Interactions , Adult , Female , Humans , Male , Young Adult , Amoxicillin/adverse effects , Amoxicillin/pharmacokinetics , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacokinetics , Area Under Curve , Bismuth/adverse effects , Bismuth/pharmacokinetics , China , Clarithromycin/adverse effects , Clarithromycin/pharmacokinetics , East Asian People , Healthy Volunteers , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/pharmacokinetics , Imidazoles/adverse effects , Imidazoles/pharmacokinetics , Benzene Derivatives/adverse effects , Benzene Derivatives/pharmacokinetics
16.
Pest Manag Sci ; 80(8): 4013-4023, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38554028

ABSTRACT

BACKGROUND: Citrus huanglongbing (HLB) is a devastating disease caused by Candidatus Liberibacter asiaticus (CLas) that affects the citrus industry. In nature, CLas relies primarily on Diaphorina citri Kuwayama as its vector for dissemination. After D. citri ingests CLas-infected citrus, the pathogen infiltrates the insect's body, where it thrives, reproduces, and exerts regulatory control over the growth and metabolism of D. citri. Previous studies have shown that CLas alters the composition of proteins in the saliva of D. citri, but the functions of these proteins remain largely unknown. RESULTS: In this study, we detected two proteins (DcitSGP1 and DcitSGP3) with high expression levels in CLas-infected D. citri. Quantitative PCR and Western blotting analysis showed that the two proteins were highly expressed in the salivary glands and delivered into the host plant during feeding. Silencing the two genes significantly decreased the survival rate for D. citri, reduced phloem nutrition sucking and promoted jasmonic acid (JA) defenses in citrus. By contrast, after overexpressing the two genes in citrus, the expression levels of JA pathway-associated genes decreased. CONCLUSION: Our results suggest that CLas can indirectly suppress the defenses of citrus and support feeding by D. citri via increasing the levels of effectors in the insect's saliva. This discovery facilitates further research into the interaction between insect vectors and pathogens. © 2024 Society of Chemical Industry.


Subject(s)
Citrus , Cyclopentanes , Hemiptera , Oxylipins , Rhizobiaceae , Hemiptera/microbiology , Hemiptera/physiology , Hemiptera/metabolism , Cyclopentanes/metabolism , Oxylipins/metabolism , Animals , Citrus/microbiology , Rhizobiaceae/physiology , Plant Diseases/microbiology , Liberibacter/metabolism , Insect Vectors/microbiology , Insect Vectors/physiology
17.
Orthop Surg ; 16(4): 851-863, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38384172

ABSTRACT

OBJECTIVE: The connection between alterations in the disc structure following percutaneous endoscopic lumbar discectomy (PELD) and symptoms in patients postsurgery has not been reported yet. The purpose of the present study was to discuss the potential correlation between the changes in the morphological characteristics of various reference surfaces of the intervertebral disc after percutaneous endoscopic lumbar discectomy (PELD) and clinical outcomes, to identify the morphological parameters that affect efficacy and provide an evidence-based foundation for assessing postoperative efficacy. METHODS: From October 2019 to October 2021, after percutaneous endoscopic lumbar discectomy (PELD), 98 individuals were enrolled. MRI DICOM data of the lumbar spine were obtained before and after surgery, specifically around 3 months. The morphological parameters of the operated and adjacent segments of the discs were measured using T2-weighted images from three reference planes. Outcomes were assessed using the Oswestry disability index (ODI), visual analogue pain scores for the back and leg (VAS-back/VAS-leg), Japanese Orthopaedic Association (JOA) scores, and recovery rates. Postoperative changes in disc parameters and outcomes were compared between patients with different severity and types of LDH based on the MSU staging. Patients completed the questionnaire during outpatient follow-up appointments 3, 6, and 12 months after the surgery. The follow-up period was 14.69 ± 4.21 months, ranging from 12 to 24 months. RESULTS: Parameters such as area and circumference of intervertebral discs in the cross-section were not associated with the change in the efficacy index. Postoperatively, a negative correlation between the variation of the disc height, disc height index, and protrusion distance and the difference in VAS scores for low back pain at 3 and 6 months was observed among the two sagittal change parameters. Differences between changes in disc imaging parameters and postoperative efficacy were not statistically significant between various types of lumbar disc herniation. CONCLUSION: For the patients after percutaneous endoscopic lumbar discectomy, the changes in parameters such as disc area and circumference in the cross-sectional plane are not associated with efficacy, and the changes in disc height and herniation distance in the sagittal plane provide a morphologic basis for the assessment of short-term postoperative efficacy. In addition, the changes in disc morphologic parameters and postoperative efficacy do not differ between various types of lumbar disc herniation.


Subject(s)
Diskectomy, Percutaneous , Intervertebral Disc Displacement , Humans , Follow-Up Studies , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/surgery , Intervertebral Disc Displacement/etiology , Diskectomy, Percutaneous/methods , Cross-Sectional Studies , Endoscopy/methods , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Treatment Outcome , Retrospective Studies , Diskectomy/methods
18.
Front Immunol ; 15: 1323307, 2024.
Article in English | MEDLINE | ID: mdl-38404571

ABSTRACT

Introduction: In 2021, the World Health Organization published a new classification system for central nervous system tumors. This study reclassified the adult diffuse glioma (ADG) into astrocytoma, oligodendroglioma, and glioblastoma (GBM) according to the new tumor classification. Methods: The association of TERT promoter (pTERT) mutation, MGMT methylation, and CD47/TIGIT expression with patient prognosis was investigated. Results: Immunohistochemical analysis showed that the expression levels of CD47 and TIGIT in tumor tissues were significantly higher than those in normal brain tissues. CD47 levels were higher in GBM and grade 4 astrocytoma tissues. TIGIT expression was also higher in patients with GBM. The high expressions of CD47, TIGIT, and CD47/TIGIT were positively correlated with MGMT unmethylation but not pTERT mutation. Moreover, MGMT unmethylation was associated with poor overall survival in astrocytoma. High CD47, TIGIT, and CD47/TIGIT levels were associated with significantly reduced survival in ADG and GBM. GBM, MGMT unmethylation, and high CD47 expression were independent prognostic factors for overall survival in ADG. Discussion: Collectively, these results showed that the MGMT unmethylation and high levels of CD47 and TIGIT are associated with a poor prognosis in ADG. Patients with high CD47 and TIGIT expression may benefit from anti-CD47 and TIGIT immunotherapy.


Subject(s)
Astrocytoma , Brain Neoplasms , Glioblastoma , Glioma , Adult , Humans , Brain Neoplasms/pathology , CD47 Antigen/genetics , Glioma/pathology , Glioblastoma/genetics , Prognosis , DNA Modification Methylases/genetics , Tumor Suppressor Proteins/genetics , DNA Repair Enzymes/genetics , Receptors, Immunologic/genetics
19.
Diabetes Metab Syndr Obes ; 17: 575-584, 2024.
Article in English | MEDLINE | ID: mdl-38343582

ABSTRACT

Background: Type 2 diabetes (T2DM) combined nonalcoholic fatty liver disease (NAFLD) are characterized by metabolic disruptions. Liraglutide has been proved to be effective in T2DM. If LRG could regulate NAFLD combined T2DM has not been reported. Methods: Intraperitoneal injection of 1% streptozotocin (STZ) plus high-sugar and high-fat diet was used to induce NAFLD combined T2DM animal model. Palmitic acid (200 µmol/L) and glucose (25 mmol/L) incubation were used to induce cell model. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and Western blotting, respectively. Results: Liraglutide significantly improved the liver injury of NAFLD combined T2DM rats, but Com-C reversed the effect of liraglutide. The decreased AMPK/mTOR signaling pathway in the NAFLD combined T2DM animals was greatly activated by liraglutide. Com-C reversed the protection effects of liraglutide on palmitic acid+glucose induced cell damage. Conclusion: Liraglutide could greatly alleviate the damage caused by NAFLD+T2DM and palmitic acid+glucose. The protection effects of liraglutide were greatly inhibited by suppressing AMPK/mTOR signaling pathway. This research might provide a novel therapeutic strategy for the prevention and treatment of NAFLD combined T2DM disease.

20.
Front Neurol ; 15: 1322228, 2024.
Article in English | MEDLINE | ID: mdl-38322584

ABSTRACT

Background: Inflammation plays a pivotal role in the pathogenesis of Parkinson's disease (PD). However, the correlation between peripheral inflammatory markers and the severity of PD remains unclear. Methods: The following items in plasma were collected for assessment among patients with PD (n = 303) and healthy controls (HCs; n = 303) were assessed for the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-high-density-lipoprotein ratio (NHR) in plasma, and neuropsychological assessments were performed for all patients with PD. Spearman rank or Pearson correlation was used to evaluate the correlation between the NLR, the LMR and the NHR and the severity of PD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the NLR, LMR and NHR for PD. Results: The plasma NLR and NHR were substantially higher in patients with PD than in HCs, while the plasma LMR was substantially lower. The plasma NLR was positively correlated with Hoehn and Yahr staging scale (H&Y), Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS-I, UPDRS-II, and UPDRS-III scores. Conversely, it exhibited a negative relationship with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Furthermore, the plasma NHR was positively correlated with H&Y, UPDRS, UPDRS-I, UPDRS-II and UPDRS-III scores. Moreover, negative associations were established between the plasma LMR and H&Y, UPDRS, UPDRS-I, UPDRS-II, and UPDRS-III scores. Finally, based on the ROC curve analysis, the NLR, LMR and NHR exhibited respectable PD discriminating power. Conclusion: Our research indicates that a higher NLR and NHR and a lower LMR may be relevant for assessing the severity of PD and appear to be promising disease-state biomarker candidates.

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