Progress in diagnosis and treatment of hypertension combined with left ventricular hypertrophy.

BACKGROUND: Hypertension, a worldwide cardiovascular issue, is known to result in significant damage to the left ventricle. Left ventricular hypertrophy refers to an increase in ventricular mass, which is not only the primary independent risk factor for cardiovascular disease onset but also independently related to the risk of death. OBJECTIVES: We sought to synthesize the existing literature on the occurrence and correlation between hypertension and left ventricular hypertrophy and the progress. METHODS: A scoping review was performed based on the methodological framework developed by Arksey & O'Malley. Search in the Pubmed database with no language restrictions, as of September 1, 2024. RESULTS: Of the 8110 articles retrieved, 110 were finally included. The selected articles were published between 1987 and 2024, with 55.5% (61/110) of the studies in the last five years and 14.5% (16/110) of 2024. The studies covered diagnosis, epidemiology, pathophysiology, prognosis, and treatment of hypertension with left ventricular hypertrophy. CONCLUSION: The literature reviewed suggests that studies on hypertension combined with left ventricular hypertrophy covered a variety of clinical progress, especially the clinical trial results of some new drugs that may bring great hope for treatment.

Continuous development of 3D echocardiographic technology may provide more accurate measurements; however, studies with the aim of establishing standard reference values remain in exploratory stages.The field of metabolomics offers a promising approach for studying biomarkers by detecting changes in metabolites associated with physiological or pathological processes induced by diseases. This avenue of research holds potential for the early diagnosis and assessment of LVH.Sodium-glucose co-transporter 2 (SGLT2) inhibitors and metformin are initially indicated for conditions other than left ventricular hypertrophy (LVH); however, emerging evidence suggests that these medications may possess potential clinical value in reversing LVH.

Shikonin, a natural naphthoquinone phytochemical, exerts anti-leukemia effects in human CBF-AML cell lines and zebrafish xenograft models.

Core binding factor acute myeloid leukemia (CBF-AML) stands out as the most common type of adult AML, characterized by specific chromosomal rearrangements involving CBF genes, particularly t(8;21). Shikonin (SHK), a naphthoquinone phytochemical widely employed as a food colorant and traditional Chinese herbal medicine, exhibits antioxidant, anti-inflammatory, and anti-cancer activities. In this study, we aim to investigate the antileukemic effects of SHK and its underlying mechanisms in human CBF-AML cells and zebrafish xenograft models. Our study revealed that SHK reduced the viability of CBF-AML cells. SHK induced cell cycle arrest, promoted cell apoptosis, and induced differentiation in Kasumi-1 cells. Additionally, SHK downregulated the gene expression of AML1-ETO and c-KIT in Kasumi-1 cells. In animal studies, SHK showed no toxic effects in zebrafish and markedly inhibited the growth of leukemia cells in zebrafish xenografts. Transcriptomic analysis showed that differentially expressed genes (DEGs) altered by SHK are linked to key biological processes like DNA repair, replication, cell cycle regulation, apoptosis, and division. Furthermore, KEGG pathways associated with cell growth, such as the cell cycle and p53 signaling pathway, were significantly enriched by DEGs. Analysis of AML-associated genes in response to SHK treatment using DisGeNET and the STRING database indicated that SHK downregulates the expression of cell division regulators regarding AML progression. Finally, we found that SHK combined with cytarabine synergistically reduced the viability of Kasumi-1 cells. In conclusion, our findings provide novel insights into the mechanisms of SHK in suppressing leukemia cell growth, suggesting its potential as a chemotherapeutic agent for human CBF-AML.

Effects of chronic social defeat stress on social behavior and cognitive flexibility for early and late adolescent.

This study investigated the risk to social behavior and cognitive flexibility induced by chronic social defeat stress (CSDS) during early and late adolescence (EA and LA). Utilizing the "resident-intruder" stress paradigm, adolescent male Sprague-Dawley rats were exposed to CSDS during either EA (postnatal days 29-38) or LA (postnatal days 39-48) to explore how social defeat at different stages of adolescence affects behavioral and cognitive symptoms commonly associated with psychiatric disorders. After stress exposure, the rats were assessed for anxiety-like behavior in the elevated plus maze, social interaction, and cognitive flexibility through set-shifting and reversal-learning tasks under immediate and delayed reward conditions. The results showed that CSDS during EA, but not LA, led to impaired cognitive flexibility in adulthood, as evidenced by increased perseverative and regressive errors in the set-shifting and reversal-learning tasks, particularly under the delayed reward condition. This suggests that the timing of stress exposure during development has a significant impact on the long-term consequences for behavioral and cognitive function. The findings highlight the vulnerability of the prefrontal cortex, which undergoes critical maturation during early adolescence, to the effects of social stress. Overall, this study demonstrates that the timing of social stressors during adolescence can differentially shape the developmental trajectory of cognitive flexibility, with important implications for understanding the link between childhood/adolescent adversity and the emergence of psychiatric disorders.

Detecting early-stage breast cancer with GATA3-positive circulating tumor cells.

OBJECTIVE: This case demonstrated the possibility of using GATA3-positive circulating tumor cells (CTCs) to detect early-stage breast cancer (BrC). CASE REPORT: The 86 years old female patient received a mammographic examination with no evidence of malignancy (Breast Imaging Reporting and Data System, (BI-RADS category 2). However, CTC testing on the same day revealed four GATA3-positive CTCs in 4 ml of peripheral blood. Core needle biopsy was performed in the suspicious area even with no evidence of malignant image on breast ultrasound. Pathologic examination showed invasive carcinoma of no special type of the breast. The patient then received an oncoplastic partial mastectomy of right breast and sentinel lymph node biopsy. The surgical staging was cT1N0M0. Post-operation follow-up examination showed absence of GATA3-positive CTCs and the presence of HER2/ER positive CTCs. CONCLUSION: The role of GATA3-positive CTCs as a potential biomarker for early-stage BrC should be explored.

Flexible and robust polyaniline/cross-linked collagen sponge with fibrils network structure as a piezoresistive sensing material.

The polyaniline/cross-linked collagen sponge (PANI/CCS) was synthesized by polymerizing PANI onto the collagen skeleton using mesoscopic collagen fibrils (CFs) as building blocks, serving as a piezoresistive sensing material. The structure and morphology of PANI/CCS were characterized using scanning electron microscopy (SEM), Fourier infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermal analysis (TA). The mechanical properties of PANI/CCS could be controlled by adjusting the CFs content and polymerization conditions. PANI/CCS treated with pure water exhibited exceptional compressive elasticity under 1000 compression cycles, demonstrating a wide strain range (0-85 %), rapid response time (200 ms), recovery time (90 ms), and high sensitivity (6.72 at 40-50 % strain). The treatment of the ionic liquid further improved the elasticity and the strain sensing range (0-95 %). The presence of PANI nanoparticles and mesoscopic collagen fibrils imparted antibacterial properties, stability in solvents, and biodegradability to PANI/CCS. Utilizing PANI/CCS as a piezoresistive sensing material enabled monitoring human movement behavior through the assembled sensor, showing significant potential for flexible wearable devices.

Femtogram-Sensitive Cantilever Platform for Dynamic Graphene Oxide Nanosheet Monitoring.

This study introduces a new approach to optimizing graphene oxide (GO) properties using liquid-phase plasma treatment in a microenvironment. Our innovation exploits atomic force microscopy (AFM) cantilever frequency tracking to monitor mass variations in GO, which are indicative of surface oxidation-reduction processes or substituent doping (boron/nitrogen). Complementary in situ Raman spectroscopy has observed D/G band shifts, and X-ray photoelectron spectroscopy (XPS) determined the C/O ratio and B/N doping levels pre- and post-treatment, confirming chemical tuning to GO. We can achieve femtogram-level precision in detecting nanomaterial mass changes by correlating elemental ratios with AFM cantilever frequency measurements. This multifaceted approach not only enhances our understanding of the chemical properties of GO but also establishes a new, versatile method for monitoring, modifying, and optimizing the properties of nanomaterials.

High-yield, plant-based production of an antimicrobial peptide with potent activity in a mouse model.

Plants offer a promising chassis for the large-scale, cost-effective production of diverse therapeutics, including antimicrobial peptides (AMPs). However, key advances will reduce production costs, including simplifying the downstream processing and purification steps. Here, using Nicotiana benthamiana plants, we present an improved modular design that enables AMPs to be secreted via the endomembrane system and sequestered in an extracellular compartment, the apoplast. Additionally, we translationally fused an AMP to a mutated small ubiquitin-like modifier sequence, thereby enhancing peptide yield and solubilizing the peptide with minimal aggregation and reduced occurrence of necrotic lesions in the plant. This strategy resulted in substantial peptide accumulation, reaching around 2.9 mg AMP per 20 g fresh weight of leaf tissue. Furthermore, the purified AMP demonstrated low collateral toxicity in primary human skin cells, killed pathogenic bacteria by permeabilizing the membrane and exhibited anti-infective efficacy in a preclinical mouse (Mus musculus) model system, reducing bacterial loads by up to three orders of magnitude. A base-case techno-economic analysis demonstrated the economic advantages and scalability of our plant-based platform. We envision that our work can establish plants as efficient bioreactors for producing preclinical-grade AMPs at a commercial scale, with the potential for clinical applications.

Rhodiola and Salidroside Attenuate Oxidative Stress-Triggered H9c2 Cardiomyoblast Apoptosis Through IGF1R-Induced ERK1/2 Activation.

Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H2O2-induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H2O2 for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H2O2 (100 µM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 µg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H2O2-induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated phosphorylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H2O2-induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health.

Utilizing radiomics and dosiomics with AI for precision prediction of radiation dermatitis in breast cancer patients.

PURPOSE: This study explores integrating clinical features with radiomic and dosiomic characteristics into AI models to enhance the prediction accuracy of radiation dermatitis (RD) in breast cancer patients undergoing volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS: This study involved a retrospective analysis of 120 breast cancer patients treated with VMAT at Kaohsiung Veterans General Hospital from 2018 to 2023. Patient data included CT images, radiation doses, Dose-Volume Histogram (DVH) data, and clinical information. Using a Treatment Planning System (TPS), we segmented CT images into Regions of Interest (ROIs) to extract radiomic and dosiomic features, focusing on intensity, shape, texture, and dose distribution characteristics. Features significantly associated with the development of RD were identified using ANOVA and LASSO regression (p-value < 0.05). These features were then employed to train and evaluate Logistic Regression (LR) and Random Forest (RF) models, using tenfold cross-validation to ensure robust assessment of model efficacy. RESULTS: In this study, 102 out of 120 VMAT-treated breast cancer patients were included in the detailed analysis. Thirty-two percent of these patients developed Grade 2+ RD. Age and BMI were identified as significant clinical predictors. Through feature selection, we narrowed down the vast pool of radiomic and dosiomic data to 689 features, distributed across 10 feature subsets for model construction. In the LR model, the J subset, comprising DVH, Radiomics, and Dosiomics features, demonstrated the highest predictive performance with an AUC of 0.82. The RF model showed that subset I, which includes clinical, radiomic, and dosiomic features, achieved the best predictive accuracy with an AUC of 0.83. These results emphasize that integrating radiomic and dosiomic features significantly enhances the prediction of Grade 2+ RD. CONCLUSION: Integrating clinical, radiomic, and dosiomic characteristics into AI models significantly improves the prediction of Grade 2+ RD risk in breast cancer patients post-VMAT. The RF model analysis demonstrates that a comprehensive feature set maximizes predictive efficacy, marking a promising step towards utilizing AI in radiation therapy risk assessment and enhancing patient care outcomes.

Clinical Features and Outcomes of Pediatric and Adult Patients Hospitalized for Coronavirus Disease 2019: A Comparison Across Age Strata.

Background: Coronavirus disease 2019 (COVID-19) continues to cause hospitalizations and severe disease in children and adults. Methods: This study compared the risk factors, symptoms, and outcomes of children and adults hospitalized for COVID-19 from March 2020 to May 2023 across age strata at 5 US sites participating in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence consortium. Eligible patients had an upper respiratory swab that tested positive for severe acute respiratory syndrome coronavirus 2 by nucleic acid amplification. Adjusted odds ratios (aOR) of clinical outcomes were determined for children versus adults, for pediatric age strata compared to adolescents (12-17 years), and for adult age strata compared to young adults (22-49 years). Results: Of 9101 patients in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence cohort, 1560 were hospitalized for COVID-19 as the primary reason. Compared to adults (22-105 years, n = 675), children (0-21 years, n = 885) were less commonly vaccinated (14.3% vs 34.5%), more commonly infected with the Omicron variant (49.5% vs 26.1%) and had fewer comorbidities (P < .001 for most comparisons), except for lung disease (P = .24). After adjusting for confounding variables, children had significantly lower odds of receiving supplemental oxygen (aOR, 0.57; 95% confidence interval, .35-.92) and death (aOR, 0.011; 95% confidence interval, <.01-.58) compa--red to adults. Among pediatric age strata, adolescents 12-17 years had the highest odds of receiving supplemental oxygen, high-flow oxygen, and ICU admission. Among adults, those 50-64 years had the highest odds of mechanical ventilation and ICU admission. Conclusions: Clinical outcomes of COVID-19 differed across pediatric and adult age strata. Adolescents experienced the most severe disease among children, whereas adults 50-64 years experienced the most severe disease among adults.

Vitamin D and Cognitive Performance in Older Adults: A Cross-Sectional and Mendelian Randomization Study.

Background: Cognitive decline is a prevalent health problem in older adults, and effective treatments remain to be produced. Serum vitamin D, a commonly used biochemical marker, is widely recognized as an indicator of various diseases. Existing research has not fully elucidated the relationship between vitamin D and cognitive function. The aim of this study is to investigate the real relationship between vitamin D and cognitive function and to identify indicators that have a strong predictive effect on cognitive decline. Methods: At first, we used the dataset of the genome-wide association studies studying vitamin D and cognitive performance to conduct Mendelian randomization analysis. Subsequently, we employed linear regression and smooth curve fitting methods to assess the relationship using the National Health and Nutrition Examination Survey data. Finally, we investigated other predictive features of cognitive performance utilizing a machine learning model. Results: We found that a 1-unit increase in vitamin D is associated with a 6.51% reduction (P < .001) in the risk of cognitive decline. The correlation between vitamin D and cognitive performance is nonlinear, with the inflection point at 79.9 nmol/L (left: ß = 0.043, P < .001; right: ß = -0.007, P = .420). In machine learning, the top 5 predictors are vitamin D, weight, height, age, and body mass index. Conclusion: There is a causal relationship between vitamin D and cognitive performance. 79.9 nmol/L could be the optimal dose for vitamin D supplementation in the elderly. Further consideration of other factors in vitamin D interventions is necessary.

Long-term effects of fecal microbiota transplantation on gut microbiota after Helicobacter pylori eradication with bismuth quadruple therapy: A randomized controlled trial.

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.

A solar-driven atmospheric water extractor for off-grid freshwater generation and irrigation.

Solar-driven atmospheric water extraction (SAWE) is a sustainable technology for decentralized freshwater supply. However, most SAWE systems produce water intermittently due to the cyclic nature, with adoption hindered by complex design requirements or periodic manual operations. Herein, a fully passive SAWE system that can continuously produce freshwater under sunlight is presented. By optimizing the three-dimensional architecture to facilitate spontaneous mass transport and efficient energy utilization, this system can consistently produce 0.65 L m-2 h-1 of freshwater under 1-sun illumination at 90% relative humidity (RH) and functions in arid environments with an RH as low as 40%. We test the practical performance of a scaled-up system in Thuwal, Saudi Arabia over 35 days across two seasons. The system produces 2.0-3.0 L m-2 per day of freshwater during the summer and 1.0-2.8 L m-2 per day of freshwater during the fall, without requiring additional maintenance. Intriguingly, we demonstrate the system's potential for off-grid irrigation by successfully growing cabbage plants using atmospheric water. This passive SAWE system, harnessing solar energy to continuously extract moisture from air for drinking and irrigation, offers a promising solution to address the intertwined challenges of energy, water, and food supply, particularly for remote and water-scarce regions.

The Distribution and Host-Association of the Vector Chigger Species Leptotrombidium imphalum in Southwest China.

Leptotrombidium imphalum is a species of chigger mites, and it can serve as a transmitting vector of scrub typhus. Southwest China is an important focus of scrub typhus. Based on the field investigation in southwest China from 2001 to 2022, this article presents the first report on the distribution and infestation of L. imphalum on rodents and other sympatric small mammals in the region. A total of 2161 L. imphalum were identified from 218 small mammal hosts in 21 of 114 survey sites. The 17 host species of L. imphalum crossed 13 genera and 5 families in 3 orders (Rodentia, Eulipotyphla, and Scandentia), indicating the low host specificity of the mite. The Asian house rat (Rattus tanezumi) was the dominant host species in the 21 sites where L. imphalum were collected, and 49.38% of mites were found on R. tanezumi. Different small mammals had different susceptibility to the infestation of L. imphalum. The prevalence (PM = 27.66%), infestation mean abundance (MA = 6 mites/per examined host), and mean intensity (MI = 21.69 mites/per infested host) for L. imphalum on the shrew gymnure (Neotetracus sinensis) were much higher than those on other host species (p < 0.05), indicating N. sinensis had a high susceptibility to the infestation of L. imphalum. The infestation indices for L. imphalum on small mammal hosts varied along different altitude and latitude gradients (p < 0.05), indicating the environmental heterogeneity of the mite infestation. Leptotrombidium imphalum exhibited an aggregated distribution among different individuals of its hosts. Besides the low host specificity of L. imphalum, the prevalence of the mite was positively correlated with the occurrence of scrub typhus, indicating the potential risk of the mite.

Cancer Antibody Engineering: Comparison of Mammalian, Yeast, Bacterial, Plants, Cell-free and Hybridoma Expression Systems.

BACKGROUND: Cancer is a significant issue worldwide. Generally, commercially available treatments, such as surgery, radiotherapy, and chemotherapy, are associated with undesirable complications. Hence, immunotherapy serves as a crucial alternative to those treatment options. OBJECTIVE: This modality is aimed to boost the immune system through the application of engineered antibodies, which can be produced using recombinant DNA technology. RESULTS: The discussion of the technologies leads to an introduction of the single-chain variable fragment (scFv). Thereafter, the advantages, disadvantages, and challenges associated with different expression systems, such as mammalian cells, yeast cells, bacterial cells, plant cells, and phage display were discussed comprehensively. CONCLUSION: Furthermore, conventional approaches such as hybridoma and modern approaches such as cell-free protein synthesis (CFPS) and simple colony assays are included. In short, this article has compiled evidence relating to each display system and may serve as a reference for those who aim to explore antibody engineering using one of the methods listed in this article.

Age-related differences in retinal function and structure in C57BL/6J and Thy1-YFPh mice.

Age-related neuronal adaptations are known to help maintain function. This study aims to examine gross age-related in vivo retinal functional adaptations (using electroretinography) in young and middle aged C57BL/6J and Thy1-YFPh mice and to relate this to in vivo retinal structure (using optical coherence tomography). Electroretinography responses were generally larger in Thy1-YFPh mice than in C57BL/6J mice, with similar in vivo retinal layer thicknesses except for longer inner/outer photoreceptor segment in Thy1-YFPh mice. Relative to 3-month-old mice, 12-month-old mice showed reduced photoreceptor (C57BL/6J 84.0±2.5 %; Thy1-YFPh 80.2±5.2 %) and bipolar cell (C57BL/6J 75.6±2.3 %; Thy1-YFPh 68.1±5.5 %) function. There was relative preservation of ganglion cell function (C57BL/6J 79.7±3.7 %; Thy1-YFPh 91.7±5.0 %) with age, which was associated with increased b-wave (bipolar cell) sensitivities to light. Ganglion cell function was correlated with both b-wave amplitude and sensitivity. This study shows that there are normal age-related adaptations to preserve functional output. Different mouse strains may have varied age-related adaptation capacity and should be taken into consideration when examining age-related susceptibility to injury.

Toxicokinetics and bioavailability of indoxacarb enantiomers and their new metabolites in rats.

Indoxacarb is a chiral insecticide that consists of two enantiomers, S-(+)-indoxacarb and R-(-)-indoxacarb, of which only S-(+)-indoxacarb has insecticidal activity. Previous enantioselective toxicology studies of indoxacarb focused mostly on simple environmental model organisms. The lack of a toxicology evaluation of indoxacarb conducted in a mammalian system could mean that the extent of the potential health risk posed by the insecticide to humans is not adequately known. In this study, we reported on a new pair of enantiomers, S-IN-RM294 and R-IN-RM294, derived from the metabolic breakdown of S-(+)-indoxacarb and R-(-)-indoxacarb, respectively, in rats. The toxicokinetics of S-(+)-indoxacarb, R-(-)-indoxacarb, S-IN-RM294, and R-IN-RM294 in rats were evaluated to provide a more comprehensive risk assessment of these molecules. The bioavailability and excretion rates of both S-(+)-indoxacarb and R-(-)-indoxacarb were relatively low, which may be due to their faster metabolism and accumulation in the tissues. In addition, there were significant differences in the metabolism and distribution between the two indoxacarb enantiomers and their metabolites in vivo. S-(+)-Indoxacarb was found to be more easily metabolized in the blood compared with R-(-)-indoxacarb, as shown by the differences in pharmacokinetic parameters between oral and intravenous administration. Analysis of their tissue distribution showed that S-(+)-indoxacarb was less likely to accumulate in most tissues. The results obtained for the two metabolites were consistent with those of the two parent compounds. S-IN-RM294 was more readily cleared from the blood and less likely to accumulate in the tissues compared with R-IN-RM294. Therefore, whether from the perspective of insecticidal activity or from the perspective of mammalian and environmental friendliness, the application of optically pure S-(+)-indoxacarb in agriculture may be a more efficient and safer strategy.

Retinal hyperspectral imaging in mouse models of Parkinson's disease and healthy aging.

Retinal hyperspectral imaging (HSI) is a non-invasive in vivo approach that has shown promise in Alzheimer's disease. Parkinson's disease is another neurodegenerative disease where brain pathobiology such as alpha-synuclein and iron overaccumulation have been implicated in the retina. However, it remains unknown whether HSI is altered in in vivo models of Parkinson's disease, whether it differs from healthy aging, and the mechanisms which drive these changes. To address this, we conducted HSI in two mouse models of Parkinson's disease across different ages; an alpha-synuclein overaccumulation model (hA53T transgenic line M83, A53T) and an iron deposition model (Tau knock out, TauKO). In comparison to wild-type littermates the A53T and TauKO mice both demonstrated increased reflectivity at short wavelengths ~ 450 to 600 nm. In contrast, healthy aging in three background strains exhibited the opposite effect, a decreased reflectance in the short wavelength spectrum. We also demonstrate that the Parkinson's hyperspectral signature is similar to that from an Alzheimer's disease model, 5xFAD mice. Multivariate analyses of HSI were significant when plotted against age. Moreover, when alpha-synuclein, iron or retinal nerve fibre layer thickness were added as a cofactor this improved the R2 values of the correlations in certain groups. This study demonstrates an in vivo hyperspectral signature in Parkinson's disease that is consistent in two mouse models and is distinct from healthy aging. There is also a suggestion that factors including retinal deposition of alpha-synuclein and iron may play a role in driving the Parkinson's disease hyperspectral profile and retinal nerve fibre layer thickness in advanced aging. These findings suggest that HSI may be a promising translation tool in Parkinson's disease.

Sustained-release, antibacterial, adhesive gelatin composite hydrogel with AgNPs double-capped with curdlan derivatives.

In this work, carboxymethylated curdlan (CMCD) was utilized as a capping and stabilizing agent for the green synthesis of silver nanoparticles. Subsequently, quaternized curdlan (QCD) was introduced as the second capping layer through electrostatic attraction, leading to the preparation of double-capped silver nanoparticles (AgNPs@CQ). The successful synthesis of silver nanoparticles was characterized using UV-vis, FTIR, XRD, TEM, and DLS. AgNPs@CQ were incorporated into gelatin and a AgNPs@CQ/Gel composite hydrogel was obtained. The incorporation of AgNPs@CQ imparts excellent antibacterial properties to the composite hydrogel, thereby enhancing its antimicrobial efficacy. The presence of double-capping layers significantly retards the release rate of silver, contributing to prolonged antimicrobial activity. The MTT and live/dead fluorescence staining results demonstrate that the gelatin hydrogel incorporating double-capped AgNPs exhibits enhanced cell viability compared to the one incorporating single-capped AgNPs. Additionally, the composite hydrogel exhibits remarkable mechanical strength and adhesive performance. The AgNPs@CQ/Gel composite hydrogel demonstrates a cost-effective and facile preparation, showing significant potential in the field of dressings.