Sleep status of centenarians and its association with death in the China Hainan Centenarian Cohort Study.

OBJECTIVE: This study investigated the associations of sleep status (duration and quality) with all-cause death among centenarians, using data from the China Hainan Centenarians Cohort Study. METHOD: The epidemiological distribution of sleep duration and sleep quality (estimated using the Pittsburgh Sleep Quality Index) was described based on the data from the China Hainan Centenarians Cohort Study. Cox regression was used to analyze the association between sleep status and all-cause mortality. RESULTS: A total of 994 centenarians, with an average age of 102.77 ± 2.75years, were included. The median (Q1, Q3) daytime sleep duration was 1.00 (0.50, 1.50) hour, while nighttime sleep duration and total sleep duration were 8.00 (7.00, 9.00) hours and 9.00 (8.00, 10.50) hours, respectively. By the end of the follow-up period, 517 centenarians had died, with a median follow-up time of 4.2 (1.3-5.0) years. A noteworthy finding emerged: male centenarians with a daytime sleep duration of at least 2 hours had a 97% greater risk of all-cause mortality (HR=1.97, 95%CI: 1.07-3.62, P = .039) than those who got less daytime sleep, after adjusting for potential confounders. CONCLUSION: The sleep duration patterns of centenarians in Hainan were comparable to those in other provinces of China. Centenarians who sleep longer had a higher risk of all-cause mortality. This risk plateaued after more than 9 hours of sleep, with no gender differences observed. Furthermore, the duration of daytime sleep was significantly associated with all-cause mortality among male centenarians.

Catalyst-free regeneration of plasma-activated water via ultrasonic cavitation: Removing aggregation concealment of antibiotic-resistant bacteria with enhanced wastewater sustainability.

Aggregation is a crucial factor in bacterial biofilm formation, and comprehending its properties is vital for managing waterborne antibiotic-resistant bacteria. In this study, we examined Methicillin-resistant Staphylococcus aureus (MRSA) cell aggregation under varying conditions and assessed the inactivation efficiency of a novel disinfection method, micro-nano bubbles plasma-activated water via ultrasonic stirring cavitation (MPAW-US), on aggregated MRSA cells. Aggregation efficiency increased over time and at low salt concentrations but diminished at higher concentrations. Elevated MRSA cell aggregation in actual water samples represented significant real-life biohazard risks. Unlike conventional disinfection, MPAW-US treatment exhibited minimal change in the inactivation rate constant despite protective outer layers. Enhanced inactivation efficiency results from the synergistic effects of increased intracellular oxidative stress damage and extracellular substance disruption, triggered by ultrasound-activated micro-nano bubbles that improve PAW reactivity and applicability. This approach neither induced MRSA cross-resistance to unfavorable conditions nor increased toxicity or regrowth potential of aggregative MRSA, utilizing ATP levels as potential regrowth capability indicators. Ultimately, this energy-efficient disinfection technology functions effectively across diverse temperature ranges, showcasing exceptional sterilization and nutritional bean sprout production after cyclic filtering, thereby promoting wastewater sustainability amidst carbon emission concerns.

A Prediction Model for Detecting Dysthyroid Optic Neuropathy Based on Clinical Factors and Imaging Markers of the Optic Nerve and Cerebrospinal Fluid in the Optic Nerve Sheath.

OBJECTIVE: This study aimed to develop and test a model for predicting dysthyroid optic neuropathy (DON) based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid (CSF) in the optic nerve sheath. METHODS: This retrospective study included patients with thyroid-associated ophthalmopathy (TAO) without DON and patients with TAO accompanied by DON at our hospital. The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and, together with clinical factors, were screened by Least absolute shrinkage and selection operator. Subsequently, we constructed a prediction model using multivariate logistic regression. The accuracy of the model was verified using receiver operating characteristic curve analysis. RESULTS: In total, 80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study. Two variables (optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath) were found to be independent predictive factors and were included in the prediction model. In the development cohort, the mean area under the curve (AUC) was 0.994, with a sensitivity of 0.944, specificity of 0.967, and accuracy of 0.901. Moreover, in the validation cohort, the AUC was 0.960, the sensitivity was 0.889, the specificity was 0.893, and the accuracy was 0.890. CONCLUSIONS: A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath, serving as a noninvasive potential tool to predict DON.

Ensuring food safety by artificial intelligence-enhanced nanosensor arrays.

Current analytical methods utilized for food safety inspection requires improvement in terms of their cost-efficiency, speed of detection, and ease of use. Sensor array technology has emerged as a food safety assessment method that applies multiple cross-reactive sensors to identify specific targets via pattern recognition. When the sensor arrays are fabricated with nanomaterials, the binding affinity of analytes to the sensors and the response of sensor arrays can be remarkably enhanced, thereby making the detection process more rapid, sensitive, and accurate. Data analysis is vital in converting the signals from sensor arrays into meaningful information regarding the analytes. As the sensor arrays can generate complex, high-dimensional data in response to analytes, they require the use of machine learning algorithms to reduce the dimensionality of the data to gain more reliable outcomes. Moreover, the advances in handheld smart devices have made it easier to read and analyze the sensor array signals, with the advantages of convenience, portability, and efficiency. While facing some challenges, the integration of artificial intelligence with nanosensor arrays holds promise for enhancing food safety monitoring.

Temporomandibular joint disc responses to installation and removal of the experimental malocclusion.

BACKGROUND: Aberrant occlusion and aging are two main risks for temporomandibular joint (TMJ) degeneration. OBJECTIVE: To assess the combined impact of occlusion and age on TMJ disc. METHODS: To avoid the confounding impact of gender, presently, 126 female C57BL/6J mice, 63 youngsters, 6-week old and 63 adults, 28-week old, were used. An experimental bilateral anterior crossbite (BAC) relation was created by installing metal tubes onto the mandibular incisors. Mice were sacrificed at 3, 7 and 11 weeks (n = 9). Additionally, the installed tubes were removed at 7 weeks in removal groups and the TMJs were sampled after another 4 weeks (n = 9). Disc changes were detected by histomorphology, immunohistochemistry, and western blot assays. RESULTS: Disc deformation was obvious in BAC groups. The typical change was hyperplasia at the posterior region of the disc where there was significant infiltration of inflammatory cells. Expressions of the inflammatory markers, including tumour necrosis factor-α and interleukin-1ß, and the catabolic markers, including fibronectin (FN), FN N-terminal fragments, and vascular endothelial growth factor-A, were all increased. The changes were more obvious in adults than in youngsters. Removal of BAC attenuated inflammatory and catabolic changes in the youngsters, but the inflammatory markers recovered little in the adults. CONCLUSION: TMJ disc responds to BAC by degeneration and inflammation, and respond to BAC removal by rehabilitation. Adult discs show severer degeneration responses to BAC and a lower level of anti-inflammatory capability to BAC removal than the youngster's discs. Animals cannot be equated with humans. The human disc response to occlusion changes worth further exploration.

Fat-suppression T2 relaxation time and water fraction predict response to intravenous glucocorticoid therapy for thyroid-associated ophthalmopathy.

OBJECTIVE: To investigate the value of fat-suppression (FS) T2 relaxation time (T2RT) derived from FS T2 mapping and water fraction (WF) derived from T2 IDEAL to predict the treatment response to intravenous glucocorticoids (IVGC) in patients with thyroid-associated ophthalmopathy (TAO) based on texture analysis. MATERIALS AND METHODS: In this study, 89 patients clinically diagnosed with active and moderate-to-severe TAO were enroled (responsive group, 48 patients; unresponsive group, 41 patients). The baseline clinical characteristics and texture features were compared between the two groups. Multivariate analysis was performed to identify the independent predictors of treatment response to IVGC. ROC analysis and the DeLong test were used to assess and compare the predictive performance of different models. RESULTS: The responsive group exhibited significantly shorter disease duration and higher 90th percentile of FS T2RT and kurtosis of WF in the extraocular muscle (EOM) and 95th percentile of WF in the orbital fat (OF) than the unresponsive group. Model 2 (disease duration + WF; AUC, 0.816) and model 3 (disease duration + FS T2RT + WF; AUC, 0.823) demonstrated superior predictive efficacy compared to model 1 (disease duration + FS T2RT; AUC, 0.756), while there was no significant difference between models 2 and 3. CONCLUSIONS: The orbital tissues of responders exhibited more oedema and heterogeneity. Furthermore, OF is as valuable as EOM for assessing the therapeutic efficacy of IVGC. Finally, WF derived from T2 IDEAL processed by texture analysis can provide valuable information for predicting the treatment response to IVGC in patients with active and moderate-to-severe TAO. CLINICAL RELEVANCE STATEMENT: The texture features of FS T2RT and WF are different between responders and non-responders, which can be the predictive tool for treatment response to IVGC. KEY POINTS: Texture analysis can be used for predicting response to IVGC in TAO patients. TAO patients responsive to IVGC show more oedema and heterogeneity in the orbital tissues. WF from T2 IDEAL is a tool to predict the therapeutic response of TAO.

Identification of BAF60b as a Chromatin-Remodeling Checkpoint of Diet-Induced Fatty Liver Disease.

Overnutrition has gradually become the primary causative factor in nonalcoholic fatty liver disease (NAFLD). However, how nutritional signals are integrated to orchestrate the transcriptional programs important for NAFLD progression remains poorly understood. We identified hepatic BAF60b as a lipid-sensitive subunit of the switch/sucrose nonfermentable chromatin-remodeling complex that is negatively associated with liver steatosis in mice and humans. Hepatic BAF60b deficiency promotes high-fat diet (HFD)-induced liver steatosis in mice, whereas transgenic expression of BAF60b in the liver attenuates HFD-induced obesity and NAFLD, both accompanied by a marked regulation of peroxisome proliferator-activated receptor γ (PPARγ) expression. Mechanistically, through motif analysis of liver assay for transposase-accessible chromatin sequencing and multiple validation experiments, we identified C/EBPß as the transcription factor that interacts with BAF60b to suppress Pparγ gene expression, thereby controlling hepatic lipid accumulation and NAFLD progression. This work identifies hepatic BAF60b as a negative regulator of liver steatosis through C/EBPß-dependent chromatin remodeling.

Prenatal diagnosis and family analysis of 17q12 microdeletion syndrome with fetal renal abnormalities.

Purpose: To analyze the prenatal diagnosis, parental verification, and pregnancy outcomes of three fetuses with 17ql2 microdeletion syndrome. Methods: We retrospectively reviewed 46 singleton pregnancies with anomalies in the urinary system who underwent amniocentesis from Feb 2022 to October 2023 in the Prenatal Diagnosis Center of Lianyungang Maternal and Child Health Hospital. These fetuses were subjected to chromosomal microarray analysis (CMA) and/or trio whole-exome sequencing (Trio-WES). We specifically evaluated these cases' prenatal renal ultrasound findings and clinical characteristics of the affected parents. Results: Three fetuses were diagnosed as 17q12 microdeletions, and the detection rate was 6.5% in fetuses with anomalies in the urinary system (3/46). The heterogeneous deletions range from 1.494 to 1.66 Mb encompassing the complete hepatocyte nuclear factor 1 homeobox B (HNF1B) gene. Fetuses with 17q12 deletion exhibited varied renal phenotypes. Moreover, the clinical phenotypes of the affected parents differed greatly in the two cases (case 2 and case 3) in which the deletion was inherited. For case 3, the mother manifested classic symptoms of 17q12 deletion syndrome as well as unreported characteristics, such as very high myopia. Conclusion: Our findings demonstrate the necessity and significance of offering prenatal genetic testing when various renal anomalies are detected. In addition, our study broadens the phenotypic spectrum of 17q12 deletions. Most importantly, our findings may allow timely supportive genetic counseling and guidance for pregnancy in affected families, e.g., with the help of preimplantation genetic testing (PGT).

Health literacy and falls among community-dwelling older people in China: is there a sex difference?

BACKGROUND: Health literacy is one of the important determinants of healthy aging, yet few studies have focused on the association between health literacy and falls. AIMS: This study aims to explore the relationship between health literacy and falls, with a focus on sex differences among older people in China. METHODS: This cross-sectional study enrolled 2,144 older people aged ≥ 60 years from Shandong Province, China in 2021. We used general health literacy screening scale to assess health literacy, and collected the incidence of falls in the past year. Logistic regression models were employed to analyze the relationship between health literacy and falls. We investigated the sex differences by subgroup analyses. RESULTS: The prevalence of adequate health literacy and falls was 21.7% (95% CI: 20.0-23.5%) and 25.4% (95% CI: 23.6-27.3%), respectively. In a fully-adjusted model, adequate health literacy was associated with a lower prevalence of falls in older adults (OR = 0.71, 95%CI: 0.52-0.96). Subgroup analysis revealed sex differences in this relationship (Pfor interaction <0.05). Specifically, the female group showed no significant relationship between health literacy and falls (OR = 0.92, 95% CI: 0.59-1.44); however, the male group demonstrated a robust and significant relationship (OR = 0.58, 95% CI: 0.37-0.90). CONCLUSIONS: Older people with adequate health literacy have lower prevalence of falls, which appears to differ by sex. This relationship was significant among men but not among women. These findings emphasize the need for policymakers and healthcare providers to consider sex differences when designing and implementing programs aimed at improving health literacy and preventing falls in the older population. Improving health literacy among older women could be a strategic component in bridging sex inequality in falls.

Immune cell related signature predicts prognosis in esophageal squamous cell carcinoma based on single-cell and bulk-RNA sequencing.

Background: It has been reported that tumor immune microenvironment performs a vital role in tumor progress. However, acting mechanism of immune cell related genes (IRGs) in esophageal squamous cell carcinoma (ESCC) is uncertain. Methods: TCGA-ESCC, GSE23400, GSE26886, GSE75241, and GSE196756 datasets were gained via public databases. First, differentially expressed genes (DEGs) between ESCC and control samples from GSE23400, GSE26886, and GSE75241 were screened out by differential expression analysis, and overlapping DEGs were identified. Single-cell transcriptome data of GSE196756 were applied to explore immune cells that might be involved in regulation of ESCC. Then, weighted gene co-expression network analysis was applied to screen IRGs. Next, differentially expressed IRGs (DE-IRGs) were identified by overlapping IRGs and DEGs, and were incorporated into univariate Cox, least absolute shrinkage and selection operator, and multivariate Cox to acquire prognosis-related genes, and ESCC samples were grouped into high-/low-risk groups on the basis of median risk score. Finally, the role of prognosis model in immunotherapy was analyzed. Results: Totally 248 DEGs were yielded by overlapping 3,915 DEGs in GSE26886, 459 DEGs in GSE23400, and 1,641 DEGs in GSE75241. Single-cell analysis found that B cells, dendritic cells, monocytes, neutrophils, natural killer cells, and T cells were involved in ESCC development. Besides, MEred, MEblack, MEpink, MEblue and MEbrown modules were considered as key modules because of their highest correlations with immune cell subtypes. A total of 154 DE-IRGs were yielded by taking intersection of DEGs and genes in key modules. Moreover, CTSC, ALOX12, and RMND5B were identified as prognosis-related genes in ESCC. Obviously, Exclusion and TIDE scores were notably lower in high-risk group than in the other one, indicating that high-risk group was more responsive to immunotherapy. Conclusions: Through bioinformatic analysis, we identified a prognosis model consisting of IRGs (CTSC, ALOX12, and RMND5B) in ESCC, providing new ideas for studies related to treatment and prognosis of ESCC.

Unique features of conventional and nonconventional introns in Euglena gracilis.

BACKGROUND: Nuclear introns in Euglenida have been understudied. This study aimed to investigate nuclear introns in Euglenida by identifying a large number of introns in Euglena gracilis (E. gracilis), including cis-spliced conventional and nonconventional introns, as well as trans-spliced outrons. We also examined the sequence characteristics of these introns. RESULTS: A total of 28,337 introns and 11,921 outrons were identified. Conventional and nonconventional introns have distinct splice site features; the former harbour canonical GT/C-AG splice sites, whereas the latter are capable of forming structured motifs with their terminal sequences. We observed that short introns had a preference for canonical GT-AG introns. Notably, conventional introns and outrons in E. gracilis exhibited a distinct cytidine-rich polypyrimidine tract, in contrast to the thymidine-rich tracts observed in other organisms. Furthermore, the SL-RNAs in E. gracilis, as well as in other trans-splicing species, can form a recently discovered motif called the extended U6/5' ss duplex with the respective U6s. We also describe a novel type of alternative splicing pattern in E. gracilis. The tandem repeat sequences of introns in this protist were determined, and their contents were comparable to those in humans. CONCLUSIONS: Our findings highlight the unique features of E. gracilis introns and provide insights into the splicing mechanism of these introns, as well as the genomics and evolution of Euglenida.

Transgenic mice applications in the study of endometriosis pathogenesis.

Endometriosis (EM), characterized by ectopic growth of endometrial tissues and recurrent pelvic pain, is a common disease with severe negative impacts on the life quality of patients. Conventional uterine tissue transplantation-based models have been broadly used to investigate the pathogenic mechanism(s) of EM. Transgenic mice with whole body or uterine/pelvic tissue-specific labelling by the expression of GFP, ß-gal or other light-emitting or chromogenic markers enable investigators to analyze the contribution to endometriotic lesions by the donor or recipient side after uterine tissue transplantation. Moreover, when coupled to uterine tissue transplantation, transgenic mice with a specific EM-related gene knocked out or overexpressed make it possible to determine the gene's in vivo role(s) for EM pathogenesis. Furthermore, observations on the rise of de novo endometriotic lesions as well as structural/functional changes in the eutopic endometrium or pelvic tissues after gene manipulation will directly relate the cognate gene to the onset of EM. A major advantage of transgenic EM models is their efficiency for analyzing gene interactions with hormonal, dietetic and/or environmental factors. This review summarizes the features/sources/backgrounds of transgenic mice and their applications to EM studies concerning hormonal regulation, angiogenesis and inflammation. Findings from these studies, the advantages/disadvantages of transgenic EM models, and future expectations are also discussed.

One stone, two birds: An eco-friendly aerogel based on waste pomelo peel cellulose for the efficient adsorption of dyes and heavy metal ions.

To achieve the objective of "waste control by waste", in this study, a green aerogel adsorbent comprised of pomelo-peel cellulose and sodium alginate (PCC/SA) was prepared through dual-network crosslinking. The resulting 3D hierarchical porous structured PCC/SA aerogel exhibited good structural stability, and kept the morphological integrity during 10 days in a wide pH range (2-10), suggesting its potential for recycling in diverse complex environments. Besides, the superior adsorption capacities for methylene blue (MB) and Cu(II) were observed, with the qm values and adsorption equilibrium times were recorded to be 1299.59 mg/g (300 min) and 287.55 mg/g (120 min), correspondingly. Furthermore, the favorable reusability of the PCC/SA aerogel was also demonstrated, with the removal efficiency for MB remaining almost unchanged (about 94 %) after 10 adsorption-desorption cycles, while there was a slight reduction for Cu(II) from 85.28 % to 72.47 %. XPS and FTIR analysis revealed that electrostatic attraction, hydrogen bonding, cation exchange and coordination were the major adsorption mechanisms. Importantly, the PCC/SA aerogel can be naturally degraded in soil within 10 weeks. Therefore, the as-prepared aerogel bead derived from pomelo peel shows great promise as an adsorbent for wastewater treatment containing dye and heavy metal ions.

Association of anemia with all-cause mortality in Chinese centenarians: a prospective cohort study.

OBJECTIVES: This study aimed to examine the relationship between anemia and all-cause mortality in Chinese centenarians. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: We included 1002 Chinese centenarians from the China Hainan Centenarian Cohort Study (CHCCS) MEASUREMENTS: Standard procedures were followed to perform blood analysis, home interviews, and physical examinations. Anemia was defined as a hemoglobin level of less than 130 g/L for men and less than 120 g/L for women. RESULTS: During the 9-year follow-up period, a total of 929 (92.7%) deaths were identified. Cox proportional hazards regression models revealed that anemia (hazard ratio [HR] 1.289, 95% confidence interval [CI]: 1.117-1.489) was significantly associated with all-cause mortality. There was an apparent dose-response relationship between anemia and all-cause mortality. Centenarians with severe anemia had approximately 1.6 times higher likelihood of all-cause mortality than those without anemia (HR 1.662; 95% CI: 1.154-2.394). CONCLUSION: Anemia is associated with an increased risk of all-cause mortality in Chinese centenarians. Further research will be needed to collect more comprehensive data on the etiology of anemia and causes of death in centenarians.

Soil moisture decline in China's monsoon loess critical zone: More a result of land-use conversion than climate change.

Soil moisture (SM) is essential for sustaining services from Earth's critical zone, a thin-living skin spanning from the canopy to groundwater. In the Anthropocene epoch, intensive afforestation has remarkably contributed to global greening and certain service improvements, often at the cost of reduced SM. However, attributing the response of SM in deep soil to such human activities is a great challenge because of the scarcity of long-term observations. Here, we present a 37 y (1985 to 2021) analysis of SM dynamics at two scales across China's monsoon loess critical zone. Site-scale data indicate that land-use conversion from arable cropland to forest/grassland caused an 18% increase in SM deficit over 0 to 18 m depth (P < 0.01). Importantly, this SM deficit intensified over time, despite limited climate change influence. Across the Loess Plateau, SM storage in 0 to 10 m layer exhibited a significant decreasing trend from 1985 to 2021, with a turning point in 1999 when starting afforestation. Compared with SM storage before 1999, the relative contributions of climate change and afforestation to SM decline after 1999 were -8% and 108%, respectively. This emphasizes the pronounced impacts of intensifying land-use conversions as the principal catalyst of SM decline. Such a decline shifts 18% of total area into an at-risk status, mainly in the semiarid region, thereby threatening SM security. To mitigate this risk, future land management policies should acknowledge the crucial role of intensifying land-use conversions and their interplay with climate change. This is imperative to ensure SM security and sustain critical zone services.

Exploring the Mechanism of Salvianolic Acid B against Myocardial Ischemia-Reperfusion Injury Based on Network Pharmacology.

This study aimed to explore the mechanisms through which salvianolic acid B (Sal-B) exerts its effects during myocardial ischemia-reperfusion injury (MI/RI), aiming to demonstrate the potential pharmacological characteristics of Sal-B in the management of coronary heart disease. First, Sal-B-related targets and MI/RI-related genes were compiled from public databases. Subsequent functional enrichment analyses using the protein-protein interaction (PPI) network, gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) predicted the core targets and approaches by which Sal-B counters MI/RI. Second, a Sal-B-treated MI/RI mouse model and oxygen-glucose deprivation/reoxygenation (OGD/R) H9C2 cell model were selected to verify the main targets of the network pharmacological prediction. An intersectional analysis between Sal-B and MI/RI targets identified 69 common targets, with a PPI network analysis highlighting caspase-3, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) as central targets. GO and KEGG enrichment analyses indicated remarkable enrichment of the apoptosis pathway among these targets, suggesting their utility in experimental studies in vivo. Experimental results demonstrated that Sal-B treatment not only mitigated myocardial infarction size following MI/RI injury in mice but also modulated the expression of key apoptotic regulators, including Bcl-2-Associated X (Bax), caspase-3, JNK, and p38, alongside enhancing the B-cell lymphoma-2 (Bcl-2) expression, thereby inhibiting myocardial tissue apoptosis. This study leveraged an integrative network pharmacology approach to predict Sal-B's potential targets in MI/RI treatment and verified the involvement of key target proteins within the predicted signaling pathways through both in vivo and in vitro experiments, offering a comprehensive insight into Sal-B's pharmacological mechanism in MI/RI management.

Chlorogenic acid attenuates cardiac hypertrophy via up-regulating Sphingosine-1-phosphate receptor1 to inhibit endoplasmic reticulum stress.

AIMS: Cardiac hypertrophy, an adaptive response of the heart to stress overload, is closely associated with heart failure and sudden cardiac death. This study aimed to investigate the therapeutic effects of chlorogenic acid (CGA) on cardiac hypertrophy and elucidate the underlying mechanisms. METHODS AND RESULTS: To simulate cardiac hypertrophy, myocardial cells were exposed to isoproterenol (ISO, 10 µM). A rat model of ISO-induced cardiac hypertrophy was also established. The expression levels of cardiac hypertrophy markers, endoplasmic reticulum stress (ERS) markers, and apoptosis markers were measured using quantitative reverse transcription PCR and western blotting. The apoptosis level, size of myocardial cells, and heart tissue pathological changes were determined by terminal deoxynucleotidyl transferase dUTP nick-end labelling staining, immunofluorescence staining, haematoxylin and eosin staining, and Masson's staining. We found that CGA treatment decreased the size of ISO-treated H9c2 cells. Moreover, CGA inhibited ISO-induced up-regulation of cardiac hypertrophy markers (atrial natriuretic peptide, brain natriuretic peptide, and ß-myosin heavy chain), ERS markers (C/EBP homologous protein, glucose regulatory protein 78, and protein kinase R-like endoplasmic reticulum kinase), and apoptosis markers (bax and cleaved caspase-12/9/3) but increased the expression of anti-apoptosis marker bcl-2 in a dose-dependent way (0, 10, 50, and 100 µM). Knockdown of sphingosine-1-phosphate receptor 1 (S1pr1) reversed the protective effect of CGA on cardiac hypertrophy, ERS, and apoptosis in vitro (P < 0.05). CGA also restored ISO-induced inhibition on the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signalling in H9c2 cells, while S1pr1 knockdown abolished these CGA-induced effects (P < 0.05). CGA (90 mg/kg/day, for six consecutive days) protected rats against cardiac hypertrophy in vivo (P < 0.05). CONCLUSIONS: CGA treatment attenuated ISO-induced ERS and cardiac hypertrophy by activating the AMPK/SIRT1 pathway via modulation of S1pr1.

Multi-DNA-Modified Double-Network Hydrogel with Customized Microstructure: A Novel System for Living Circulating Tumor Cells Capture and Real-Time Detection.

The precise and effective isolation of living circulating tumor cells (CTCs) from peripheral blood, followed by their real-time monitoring, is crucial for diagnosing cancer patients. In this study, a cell-imprinted double-network (DN) hydrogel modified with circular multi-DNA (CMD), coined the CMD-imprinted hydrogel with fixed cells as templates (CMD-CIDH), was developed. The hydrogel featured a customized surface for proficient capture of viable CTCs and in situ real-time fluorescent detection without subsequent release. The customized surface, constructed using polyacrylamide/chitosan DN hydrogel as the matrix on the cell template, had a dense network structure, thereby ensuring excellent stability and a low degradation rate. Optimal capture efficiencies, recorded at 93 ± 3% for MCF-7 cells and 90 ± 2% for Hela cells, were achieved by grafting the CMD and adjusting the nodule size on the customized surface. The capture efficiency remained significantly high at 67 ± 11% in simulated breast cancer patient experiments even at a minimal concentration of 5 cells mL-1. Furthermore, CMD grafted onto the surface produced a potent fluorescence signature, enabling in situ real-time fluorescent detection of the target cell's growth state even in complex environments. The customized surface is highly efficient for screening CTCs in peripheral blood and has promising potential for setting up the CTCs culture.