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Recombinant adeno-associated viruses (rAAVs) have been extensively studied for decades as carriers for delivering therapeutic genes. However, designing rAAV vectors with selective tropism for specific cell types and tissues has remained challenging. Here, we introduce a strategy for redirecting rAAV by attaching nanobodies with desired tropism at specific sites, effectively replacing the original tropism. To demonstrate this concept, we initially modified the genetic code of rAAV2 to introduce an azido-containing unnatural amino acid at a precise site within the capsid protein. Following a screening process, we identified a critical site (N587+1) where the introduction of unnatural amino acid eliminated the natural tropism of rAAV2. Subsequently, we successfully redirected rAAV2 by conjugating various nanobodies at the N587+1 site, using click and SpyTag-Spycatcher chemistries to form nanobody-AAV conjugates (NACs). By investigating the relationship between NACs quantity and effect and optimizing the linker between rAAV2 and the nanobody using a cathepsin B-susceptible valine-citrulline (VC) dipeptide, we significantly improved gene delivery efficiency both in vitro and in vivo. This enhancement can be attributed to the facilitated endosomal escape of rAAV2. Our method offers an exciting avenue for the rational modification of rAAV2 as a retargeting vehicle, providing a convenient platform for precisely engineering various rAAV2 vectors for both basic research and therapeutic applications. STATEMENT OF SIGNIFICANCE: AAVs hold great promise in the treatment of genetic diseases, but their clinical use has been limited by off-target transduction and efficiency. Here, we report a strategy to construct NACs by conjugating a nanobody or scFv to an rAAV capsid site, specifically via biorthogonal click chemistry and a spy-spycatcher reaction. We explored the structure-effect and quantity-effect relationships of NACs and then optimized the transduction efficiency by introducing a valine-citrulline peptide linker. This approach provides a biocompatible method for rational modification of rAAV as a retargeting platform without structural disruption of the virus or alteration of the binding capacity of the nanobody, with potential utility across a broad spectrum of applications in targeted imaging and gene delivery.
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BACKGROUND: This study aimed to quantify the global stroke burden attributable to low physical activity and high body mass index in adults aged ≥55 years using data from the Global Burden of Disease 2019 study. METHODS: We extracted data on stroke mortality, disability-adjusted life years, and risk factor exposure from the Global Burden of Disease 2019 study for people aged ≥55 years. We calculated the population-attributable fraction and absolute number of stroke cases and disability-adjusted life years attributable to low physical activity and high body mass index by location, age group, sex, and year. RESULTS: Globally, body mass index and physical inactivity-attributable stroke burden have declined modestly since 1990, but with diverging escalatory regional trajectories. Population growth and aging drive this rising burden. CONCLUSIONS: Multidimensional, context-specific strategies focused on modifiable lifestyle risks are imperative to address the modest declines and escalatory regional trajectories in body mass index and physical inactivity-attributable stroke burden.
Subject(s)
Body Mass Index , Exercise , Stroke , Humans , Male , Aged , Female , Stroke/epidemiology , Middle Aged , Aged, 80 and over , Global Burden of Disease , Risk Factors , Disability-Adjusted Life Years , Sedentary BehaviorABSTRACT
Lung cancer stands as the most prevalent form of cancer globally, posing a significant threat to human well-being. Due to the lack of effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still a potential means of eradicating lung cancer, patients with advanced lung cancer usually miss the best chance for surgical treatment, and even after surgical resection patients may still experience tumor recurrence. Additionally, chemotherapy, the mainstay of treatment for patients with advanced lung cancer, has the potential to be chemo-resistant, resulting in poor clinical outcomes. The emergence of liquid biopsies has garnered considerable attention owing to their noninvasive nature and the ability for continuous sampling. Technological advancements have propelled circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), tumor metabolites, tumor-educated platelets (TEPs), and tumor-associated antigens (TAA) to the forefront as key liquid biopsy biomarkers, demonstrating intriguing and encouraging results for early diagnosis and prognostic evaluation of lung cancer. This review provides an overview of molecular biomarkers and assays utilized in liquid biopsies for lung cancer, encompassing CTCs, ctDNA, non-coding RNA (ncRNA), EVs, tumor metabolites, TAAs and TEPs. Furthermore, we expound on the practical applications of liquid biopsies, including early diagnosis, treatment response monitoring, prognostic evaluation, and recurrence monitoring in the context of lung cancer.
Subject(s)
Lung Neoplasms , Neoplastic Cells, Circulating , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Biomarkers, Tumor/analysis , Neoplasm Recurrence, Local , Liquid Biopsy/methods , Prognosis , Neoplastic Cells, Circulating/metabolismABSTRACT
OBJECTIVE: This modelling study aimed to estimate the burden for allergic diseases in children during a period of 30 years. DESIGN: Population-based observational study. MAIN OUTCOMES AND MEASURES: The data on the incidence, mortality and disability-adjusted life years (DALYs) for childhood allergic diseases, such as atopic dermatitis (AD) and asthma, were retrieved from the Global Burden of Disease study 2019 online database. This data set spans various groups, including different regions, ages, genders and Socio-Demographic Indices (SDI), covering the period from 1990 to 2019. RESULTS: In 2019, there were approximately 81 million children with asthma and 5.6 million children with AD worldwide. The global incidence of asthma in children was 20 million. Age-standardised incidence rates showed a decrease of 4.17% for asthma, from 1075.14 (95% uncertainty intervals (UI), 724.63 to 1504.93) per 100 000 population in 1990 to 1030.33 (95% UI, 683.66 to 1449.53) in 2019. Similarly, the rates for AD decreased by 5.46%, from 594.05 (95% UI, 547.98 to 642.88) per 100 000 population in 1990 to 561.61 (95% UI, 519.03 to 608.29) in 2019. The incidence of both asthma and AD was highest in children under 5 years of age, gradually decreasing with age. Interestingly, an increase in SDI was associated with a rise in the incidence of both conditions. However, the mortality rate and DALYs for asthma showed a contrasting trend. CONCLUSIONS: Over the past three decades, there has been a worldwide increase in new asthma and AD cases, even though mortality rates have significantly declined. However, the prevalence of these allergic diseases among children varies considerably across regions, countries and age groups. This variation highlights the need for precise prevalence assessments. These assessments are vital in formulating effective strategies for prevention and treatment.
Subject(s)
Asthma , Dermatitis, Atopic , Child , Humans , Male , Female , Child, Preschool , Global Burden of Disease , Quality-Adjusted Life Years , Prevalence , Incidence , Asthma/epidemiology , Dermatitis, Atopic/epidemiology , Global Health , Risk FactorsABSTRACT
To investigate the difference between rumen-protected niacin (RPN) and rumen-protected nicotinamide (RPM) in the transcriptome of genes relating to the lipid metabolism of the liver of periparturient dairy cows, 10 healthy Chinese Holstein cows were randomly divided into two groups and fed diets supplemented with 18.4 g/d RPN or 18.7 g/d RPM, respectively. The experiment lasted from 14 days before to 21 days after parturition. Liver biopsies were taken 21 days postpartum for transcriptomic sequencing. In addition, human LO2 cells were cultured in a medium containing 1.6 mmol/L of non-esterified fatty acids and 1 mmol/L niacin (NA) or 2 mmol/L nicotinamide (NAM) to verify the expression of the 10 genes selected from the transcriptomic analysis of the liver biopsies. The expression of a total of 9837 genes was detected in the liver biopsies, among which 1210 differentially expressed genes (DEGs) were identified, with 579 upregulated and 631 downregulated genes. These DEGs were associated mainly with lipid metabolism, oxidative stress, and some inflammatory pathways. Gene ontology (GO) enrichment analysis showed that 355 DEGs were enriched in 38 GO terms. The differences in the expression of these DEGs between RPN and RPM were predominantly related to the processes of steroid catabolism, steroid hydroxylase, monooxygenase activity, oxidoreductase activity, hemoglobin binding, and ferric iron binding, which are involved mainly in lipid anabolism and redox processes. The expressions of FADS2, SLC27A6, ARHGAP24, and THRSP in LO2 cells were significantly higher (p < 0.05) while the expressions of BCO2, MARS1, GARS1, S100A12, AGMO, and OSBPL11 were significantly lower (p < 0.05) on the NA treatment compared to the NAM treatment, indicating that NA played a role in liver metabolism by directly regulating fatty acid anabolism and transport, inflammatory factor expression, and oxidative stress; and NAM functioned more as a precursor of nicotinamide adenine dinucleotide (NAD, coenzyme I) and nicotinamide adenine dinucleotide phosphate (NADP, coenzyme II) to participate indirectly in biological processes such as ether lipid metabolism, cholesterol metabolism, energy metabolism, and other processes.
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Acute pancreatitis (AP) have been documented to have severe impact on pancreatic function. Frequent incidence of AP can result in chronic pancreatitis and thereby it can increase the probability of pancreatic cancers. This study intended to examine the effect of selenium nanoparticles (Se-NPs) synthesized from Coleus forskohlii leaf extract on pancreatic function and AP in rat. Primarily, Se-NPs was fabricated using the C. forskohlii leaf extract. The synthesized nanomaterial was characterized through UV-visible, XRD, and FTIR spectroscopies. Notably, the zeta potential of Se-NPs was found to be -32.8 mV with a polydispersity index (PDI) of 0.18. Morphological analysis on SEM unveiled the spherical shape of Se-NP with an average particle size of 12.69 nm. Strikingly, cytotoxicity analysis on pancreatic cancer and normal cells unveiled the concentration-dependent toxicity profile. However, IC 50 value is lower in normal pancreatic cell lines in comparison to pancreatic cancer cells lines. Assessment of Se-NPs on AP rats revealed the positive impact of Se-NPs. It effectively decreased the amount of lipase, amylase, IL-1ß, MDA, NO, and Bcl-2 while increased the glucose, insulin, HOMA-ß and antioxidant potential in AP rats. In addition, an evaluation of Se-NPs in the pancreatic functions revealed the non-harmful effect of Se-NPs.
Subject(s)
Nanoparticles , Pancreatic Neoplasms , Pancreatitis , Plectranthus , Selenium , Animals , Rats , Pancreatitis/chemically induced , Pancreatitis/drug therapy , Acute Disease , Plant ExtractsABSTRACT
The development of cancer neoantigen vaccines that prime the anti-tumor immune responses has been hindered in part by challenges in delivery of neoantigens to the tumor. Here, using the model antigen ovalbumin (OVA) in a melanoma model, we demonstrate a chimeric antigenic peptide influenza virus (CAP-Flu) system for delivery of antigenic peptides bound to influenza A virus (IAV) to the lung. We conjugated attenuated IAVs with the innate immunostimulatory agent CpG and, after intranasal administration to the mouse lung, observed increased immune cell infiltration to the tumor. OVA was then covalently displayed on IAV-CPG using click chemistry. Vaccination with this construct yielded robust antigen uptake by dendritic cells, a specific immune cell response and a significant increase in tumor-infiltrating lymphocytes compared to peptides alone. Lastly, we engineered the IAV to express anti-PD1-L1 nanobodies that further enhanced regression of lung metastases and prolonged mouse survival after rechallenge. Engineered IAVs can be equipped with any tumor neoantigen of interest to generate lung cancer vaccines.
Subject(s)
Cancer Vaccines , Influenza A virus , Lung Neoplasms , Animals , Mice , Lung Neoplasms/prevention & control , Cancer Vaccines/genetics , Antigens , Lung , Peptides , Vaccination , Antigens, Neoplasm/geneticsABSTRACT
Epilepsy is a profound disorder, accounting for roughly 1% of the global disease burden. It can result in premature death and significant disability. To comprehensively understand the current dynamics and trends of idiopathic epilepsy, a deep insight into its epidemiological attributes is vital. We evaluated the incidence, prevalence, mortality, and disability-adjusted life years associated with idiopathic epilepsy from 1990 to 2019 using data and methodologies from the Global Burden of Disease Study. In 2019, there were approximately 2,898,222 individuals diagnosed with idiopathic epilepsy. Intriguingly, from 1990 to 2019, the age-standardized incidence rate of idiopathic epilepsy was consistently lower in women compared to men. Over these three decades, global mortality connected to idiopathic epilepsy increased by 13.95%. However, within the same period, age-standardized death rates for idiopathic epilepsy decreased from 1.94 per 100,000 population to 1.46 per 100,000 population. Predictions indicate an increase in the incidence of idiopathic epilepsy across all age brackets through 2035, especially among the elderly aged 80 and above. Mortality rates are projected to climb for those aged 80 and above while remaining relatively unchanged in other age demographics. Idiopathic epilepsy continues to be a significant contributor to both disability and death. The findings of our study underscore the critical importance of incorporating idiopathic epilepsy management into modern healthcare frameworks. Such strategic inclusion can enhance public awareness of relevant risk factors and the range of available therapeutic interventions.
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Xiaoqinglong decoction (XQLD) is widely used clinically in the treatment of childhood cough variant asthma (CVA). However, its potential mechanism is still unknown. In the present study, the authors investigate the biological network and signalling pathway of XQLD in treatment of childhood CVA using network pharmacology-based analysis and experimental validation. By using the Bioinformatics Analysis Tool Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, the authors confirmed the correlation between XQLD and asthma, and the authors screened 1338 potential target genes of Mahuang and Guizhi, the most active herbs in XQLD. By overlapping "Childhood asthma-related genes" of DisGeNET database, the authors identified 58 intersecting genes of Childhood asthma and 1338 target genes of Mahuang and Guizhi. The intersecting genes were used to construct the protein-to-protein interaction and performed Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Gene Ontology enrichment analysis demonstrated 359 Biological Process terms, 16 Cellular Component terms, and 26 Molecular Function terms. Meantime, 75 terms of Kyoto Encyclopedia of Genes and Genomes signalling pathway were involved in enrichment analysis. These candidates showed a significant correlation with inflammatory response and positive regulation of tyrosine phosphorylation of STAT protein. In addition, XQLD treatment significantly upregulated serum interferon-γ expression, and downregulated serum interlukin-6 expression of CVA mice. XQLD treatment significantly inhibited phosphorylation of STAT3 in bronchial-lung tissues. Our data suggest that XQLD effectively alleviated bronchial-lung tissue damage in CVA mice and inhibited the body inflammatory response by regulating interlukin-6/STAT3 signalling pathway.
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In this work, we demonstrated a new type of biomimetic multispectral curved compound eye camera (BM3C) inspired by insect compound eyes for aerial multispectral imaging in a large field of view. The proposed system exhibits a maximum field of view (FOV) of 120 degrees and seven-waveband multispectral images ranging from visible to near-infrared wavelengths. Pinhole imaging theory and the image registration method from feature detection are used to reconstruct the multispectral 3D data cube. An airborne imaging experiment is performed by assembling the BM3C on an unmanned aerial vehicle (UAV). As a result, radiation intensity curves of several objects are successfully obtained, and a land type classification is performed using the K-means method based on the aerial image as well. The developed BM3C is proven to have the capability for large FOV aerial multispectral imaging and shows great potential applications for distant detecting based on aerial imaging.
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BACKGROUND: Percutaneous balloon compression (PBC) has become one of the most common and effective minimally invasive treatments for trigeminal neuralgia (TN). However, the initial and long-term pain outcomes, as well as the complication rates of PBC for patients with TN with concomitant continuous pain (CCP) have yet to be specifically documented. OBJECTIVE: In this clinical study, we aimed to evaluate and compare the results of PBC in treating TN with and without CCP. STUDY DESIGN: Retrospective study. METHODS: This research retrospectively analyzed the pain outcomes and complications of 57 patients with TN with CCP and 118 patients with TN without CCP who had undergone PBC at our institution from January 2019 through June 2022. Procedures were performed by one senior neurosurgeon in a single center. The postdischarge follow-up and the collection of clinical data, including immediate and long-term pain relief, time to recurrence, and complications, were completed through phone contact by an independent neurosurgeon blind to the patients' information. Then, the results of the 2 groups were compared; demographic and clinical data were evaluated for possible predictive factors for poor pain outcomes. RESULTS: In this study, PBC immediately resulted in complete pain relief in 70.2% of patients with CCP and significant pain relief in 84.2% of patients with CCP. For patients without CCP, the rates were 73.7% for complete pain relief and 85.6% for significant pain relief. After a minimum 6-month follow-up period, the rates decreased to 52.6% for complete pain relief and 73.7% for significant pain relief in patients with CCP, compared to 54.2% and 75.4% in those without CCP. The initial and long-term pain control rates in patients without CCP were slightly higher than those with CCP, but the differences were not statistically significant (P = 0.878, P = 0.968, respectively). The incidences of postoperative complications were similar between patients with and without CCP (21.1% vs 22.0%, P = 0.883), whereas the remission rate of complications in patients with CCP was significantly lower than that in patients without CCP (25.0% vs 69.2%, P = 0.011). A longer symptoms duration and having a history of neurodestructive procedures were predictive factors for poor outcomes following PBC. LIMITATIONS: The study was performed in a single-center. The nature of this research is retrospective instead of prospective and randomized, with the inability to control completely for variables. Additionally, the follow-up duration was not long enough to observe recurrence in some patients. CONCLUSIONS: This is the first specifically reported experience treating TN with CCP with PBC. PBC can result in significant relief of both episodic and constant pain from TN with CCP. Patients with a longer duration of pain and prior neurodestructive procedures have a higher risk of poor outcomes. The presence of CCP is not associated with pain outcomes and should not be considered a contraindication to PBC.
Subject(s)
Trigeminal Neuralgia , Humans , Trigeminal Neuralgia/therapy , Retrospective Studies , Aftercare , Patient Discharge , Pain/surgery , Treatment OutcomeABSTRACT
Enterotypes, which are defined as bacterial clusters in the gut microbiome, have been found to have a close relationship to host metabolism and health. However, this concept has never been used in the rumen, and little is known about the complex biological relationships between ruminants and their rumen bacterial clusters. In this study, we used young goats (n = 99) as a model, fed them the same diet, and analyzed their rumen microbiome and corresponding bacterial clusters. The relationships between the bacterial clusters and rumen fermentation and growth performance in the goats were further investigated. Two bacterial clusters were identified in all goats: the P-cluster (dominated by genus Prevotella, n = 38) and R-cluster (dominated by Ruminococcus, n = 61). Compared with P-cluster goats, R-cluster goats had greater growth rates, concentrations of propionate, butyrate, and 18 free amino acids¸ and proportion of unsaturated fatty acids, but lower acetate molar percentage, acetate to propionate ratio, and several odd and branched chain and saturated fatty acids in rumen fluid (P < 0.05). Several members of Firmicutes, including Ruminococcus, Oscillospiraceae NK4A214 group, and Christensenellaceae R-7 group were significantly higher in the R-cluster, whereas Prevotellaceae members, such as Prevotella and Prevotellaceae UCG-003, were significantly higher in P-cluster (P < 0.01). Co-occurrence networks showed that R-cluster enriched bacteria had significant negative correlations with P-cluster enriched bacteria (P < 0.05). Moreover, we found the concentrations of propionate, butyrate and free amino acids, and the proportions of unsaturated fatty acids were positively correlated with R-cluster enriched bacteria (P < 0.05). The concentrations of acetate, acetate to propionate ratio, and the proportion of odd and branched chain and saturated fatty acids were positively correlated with P-cluster enriched bacteria (P < 0.05). Overall, our results indicated that rumen bacterial clusters can influence rumen fermentation and growth performance of young goats, which may shed light on modulating the rumen microbiome in early life to improve the growth performance of ruminant animals.
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Background: Oral microbiota is closely related to the homeostasis of the oral cavity and lungs. To provide potential information for the prediction, screening, and treatment strategies of individuals, this study compared and investigated the bacterial signatures in periodontitis and chronic obstructive pulmonary disease (COPD). Materials and methods: We collected subgingival plaque and gingival crevicular fluid samples from 112 individuals (31 healthy controls, 24 patients with periodontitis, 28 patients with COPD, and 29 patients with both periodontitis and COPD). The oral microbiota was analyzed using 16S rRNA gene sequencing and diversity and functional prediction analysis were performed. Results: We observed higher bacterial richness in individuals with periodontitis in both types of oral samples. Using LEfSe and DESeq2 analyses, we found differentially abundant genera that may be potential biomarkers for each group. Mogibacterium is the predominant genus in COPD. Ten genera, including Desulfovibrio, Filifactor, Fretibacterium, Moraxella, Odoribacter, Pseudoramibacter Pyramidobacter, Scardovia, Shuttleworthia and Treponema were predominant in periodontitis. Bergeyella, Lautropia, Rothia, Propionibacterium and Cardiobacterium were the signature of the healthy controls. The significantly different pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) between healthy controls and other groups were concentrated in genetic information processing, translation, replication and repair, and metabolism of cofactors and vitamins. Conclusions: We found the significant differences in the bacterial community and functional characterization of oral microbiota in periodontitis, COPD and comorbid diseases. Compared to gingival crevicular fluid, subgingival plaque may be more appropriate for reflecting the difference of subgingival microbiota in periodontitis patients with COPD. These results may provide potentials for predicting, screening, and treatment strategies for individuals with periodontitis and COPD.
Subject(s)
Chronic Periodontitis , Periodontitis , Pulmonary Disease, Chronic Obstructive , Humans , Dysbiosis/microbiology , RNA, Ribosomal, 16S/genetics , Periodontitis/complications , Periodontitis/microbiology , Bacteria/genetics , Pulmonary Disease, Chronic Obstructive/complications , Chronic Periodontitis/microbiologyABSTRACT
Interleukin-2 (IL-2) is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells (Tregs) and effector cells, leading to paradoxical consequences. Here, we report a strategy that exploited genetic code expansion-guided incorporation of the latent bioreactive artificial amino acid fluorosulfate-L-tyrosine (FSY) into IL-2 for proximity-enabled covalent binding to IL-2Rα to selectively promote Treg activation. We found that FSY-bearing IL-2 variants, such as L72-FSY, covalently bound to IL-2Rα via sulfur-fluoride exchange when in proximity, resulting in persistent recycling of IL-2 and selectively promoting the expansion of Tregs but not effector cells. Further assessment of L72-FSY-expanded Tregs demonstrated that L72-FSY maintained Tregs in a central memory phenotype without driving terminal differentiation, as demonstrated by simultaneously attenuated expression of lymphocyte activation gene-3 (LAG-3) and enhanced expression of programmed cell death protein-1 (PD-1). Subcutaneous administration of L72-FSY in murine models of pristane-induced lupus and graft-versus-host disease (GvHD) resulted in enhanced and sustained therapeutic efficacy compared with wild-type IL-2 treatment. The efficacy of L72-FSY was further improved by N-terminal PEGylation, which increased its circulatory retention for preferential and sustained effects. This proximity-enabled covalent binding strategy may accelerate the development of pleiotropic cytokines as a new class of immunomodulatory therapies.
Subject(s)
Interleukin-2 , T-Lymphocytes, Regulatory , Mice , Animals , Interleukin-2 Receptor alpha Subunit , AutoimmunityABSTRACT
Domain adaption has become an effective solution to train neural networks with insufficient training data. In this paper, we investigate the vulnerability of domain adaption that potentially breaches sensitive information about the training dataset. We propose a new membership inference attack against domain adaption models, to infer the membership information of samples from the target domain. By leveraging the background knowledge about an additional source-domain in domain adaptation tasks, our attack can exploit the similar distributions between the target and source domain data to determine if a specific data sample belongs in the training set with high efficiency and accuracy. In particular, the proposed attack can be deployed in a practical scenario where the attacker cannot obtain any details of the model. We conduct extensive evaluations for object and digit recognition tasks. Experimental results show that our method can achieve the attack against domain adaptation models with a high success rate.
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INTRODUCTION: Cardiopulmonary bypass (CPB) -induced lung ischemia-reperfusion (I/R) injury remains a large challenge in cardiac surgery; up to date, no effective treatment has been found. Annexin A1 (AnxA1) has an anti-inflammatory effect, and it has been proven to have a protective effect on CPB-induced lung injury. However, the specific mechanism of AnxA1 in CPB-induced lung injury is not well studied. Therefore, we established a CPB-induced lung injury model to explore the relevant mechanism of AnxA1 and try to find an effective treatment for lung protection. METHODS: Male rats were randomized into five groups (n = 6, each): sham (S group), I/R exposure (I/R group), I/R + dimethyl sulfoxide (D group), I/R + Ac2-26 (AnxA1 peptide) (A group), and I/R + LY294002 (a PI3K specific inhibitor) (AL group). Arterial blood gas analysis and calculation of the oxygenation index, and respiratory index were performed. The morphological changes in lung tissues were observed under light and electron microscopes. TNF-α and IL-6 and total protein in lung bronchoalveolar lavage fluid were detected via enzyme-linked immunosorbent assay. The expressions of PI3K, Akt, and NF-κB (p65) as well as p-PI3K, p-Akt, p-NF-κB (p65), and AnxA1 were detected via western blotting. RESULTS: Compared with the I/R group, the A group showed the following: lower lung pathological damage score; decreased expression of IL-6 and total protein in the bronchoalveolar lavage fluid, and TNF-α in the lung; increased lung oxygenation index; and improved lung function. These imply the protective role of Ac2-26, and show that LY294002 inhibited the ameliorative preconditioning effect of Ac2-26. CONCLUSION: This finding suggested that the AnxA1 peptide Ac2-26 decreased the inflammation reaction and CPB-induced lung injury in rats, the lung protective effects of AnxA1may be correlated with the activation of PI3K/Akt signaling pathway.
Subject(s)
Annexin A1 , Lung Injury , Reperfusion Injury , Rats , Male , Animals , Lung Injury/etiology , Lung Injury/prevention & control , Cardiopulmonary Bypass/adverse effects , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Annexin A1/metabolism , Annexin A1/pharmacology , NF-kappa B/metabolism , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6 , Signal Transduction , Peptides/metabolism , Peptides/pharmacology , Reperfusion Injury/etiology , Reperfusion Injury/prevention & control , Reperfusion Injury/metabolismABSTRACT
Background: Headache disorders have become a significant global public health issue, with a notably high prevalence observed in developing countries. However, few studies have assessed headache disorders trends in Brazil, Russia, India, China and South Africa (BRICS). This study aimed to assess the prevalence of headache disorders in individuals across the BRICS, spanning the years 1990 to 2019. Methods: We obtained headache disorders data from the Global Burden of Disease 2019 study (GBD2019). This evaluation examined incidence rates, prevalence, and disability-adjusted life-years (DALYs) for migraine and tension-type headache (TTH) across demographic factors like age, gender, year, and country. Migraine and TTH were diagnosed based on the International Classification of Headache Disorders (ICHD-3) criteria. We used disease codes from the International Classification of Diseases, 10th revision to identify migraine and TTH cases. Statistical analyzes included calculating age-standardized rates and estimated annual percentage changes. Future disease burden was projected using a log-linear age-period-cohort model. Results: In 2019, India had the highest prevalence of migraine (213890207.93 cases) and TTH (374,453,700 cases). Brazil had the highest migraine age-standardized prevalence rate (18,331 per 100,000) and incidence rate (1,489 per 100,000). For TTH, India had the highest prevalence (26,160 per 100,000) while Russia had the highest incidence (11,512 per 100,000). From 1990 to 2019, China showed the greatest increase in migraine and TTH prevalence. India had the highest migraine (7,687,692) and TTH (741,392) DALYs in 2019. Conclusion: Migraine and TTH remain highly prevalent in BRICS nations, inflicting considerable disability burden. While India and China face mounting disease prevalence, Brazil contends with high incidence rates. Tailored interventions based on country-specific epidemiological profiles are warranted to mitigate the public health impact.
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The bionic curved compound-eye camera is a bionic-inspired multi-aperture camera, which can be designed to have an overlap on the field of view (FOV) in between adjacent ommatidia so that 3D measurement is possible. In this work, we demonstrate the 3D measurement with a working distance of up to 3.2 m by a curved compound-eye camera. In that there are hundreds of ommatidia in the compound-eye camera, traditional calibration boards with a fixed-pitch pattern arrays are not applicable. A batch calibration method based on the CALTag calibration board for the compound-eye camera was designed. Next, the 3D measurement principle was described and a 3D measurement algorithm for the compound-eye camera was developed. Finally, the 3D measurement experiment on objects placed at different distances and directions from the compound-eye camera was performed. The experimental results show that the working range for 3D measurement can cover the whole FOV of 98° and the working distance can be as long as 3.2 m. Moreover, a complete depth map was reconstructed from a raw image captured by the compound-eye camera and demonstrated as well. The 3D measurement capability of the compound-eye camera at long working distance in a large FOV demonstrated in this work has great potential applications in areas such as unmanned aerial vehicle (UAV) obstacle avoidance and robot navigation.
Subject(s)
Algorithms , CalibrationABSTRACT
Chitinases, the chitin-degrading enzymes, have been shown to play important role in defense against the chitin-containing fungal pathogens. In this study, we identified 48 chitinase-coding genes from the woody model plant Populus trichocarpa. Based on phylogenetic analysis, the Populus chitinases were classified into seven groups. Different gene structures and protein domain architectures were found among the seven Populus chitinase groups. Selection pressure analysis indicated that all the seven groups are under purifying selection. Phylogenetic analysis combined with chromosome location analysis showed that Populus chitinase gene family mainly expanded through tandem duplication. The Populus chitinase gene family underwent marked expression divergence and is inducibly expressed in response to treatments, such as chitosan, chitin, salicylic acid and methyl jasmonate. Protein enzymatic activity analysis showed that Populus chitinases had activity towards both chitin and chitosan. By integrating sequence characteristic, phylogenetic, selection pressure, gene expression and protein activity analysis, this study shed light on the evolution and function of chitinase family in poplar.