SP1 regulates BMSC osteogenic differentiation through the miR-133a-3p/MAPK3 axis : SP1 regulates osteogenic differentiation of BMSCs.

BACKGROUND: The progression of osteoporosis (OP) can dramatically increase the risk of fractures, which seriously disturb the life of elderly individuals. Specific protein 1 (SP1) is involved in OP progression. However, the mechanism by which SP1 regulates OP progression remains unclear. OBJECTIVE: This study investigated the mechanism underlying the function of SP1 in OP. METHODS: SAMP6 mice were used to establish an in vivo model of age-dependent OP, and BALB/c mice were used as controls. BMSCs were extracted from two subtypes of mice. Hematoxylin and eosin staining were performed to mark the intramedullary trabecular bone structure to evaluate histological changes. ChIP assay was used to assess the targeted regulation between SP1 and miR-133a-3p. The binding sites between MAPK3 and miR-133a-3p were verified using a dual-luciferase reporter assay. The mRNA levels of miR-133a-3p and MAPK3 were detected using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The protein expression of SP1, MAPK3, Colla1, OCN, and Runx2 was examined using Western blotting. Alkaline phosphatase (ALP) kit and Alizarin Red S staining were used to investigate ALP activity and mineralized nodules, respectively. RESULTS: The levels of SP1 and miR-133a-3p were upregulated, whereas the expression of MAPK3 was downregulated in BMSCs from SAMP6 mice, and miR-133a-3p inhibitor accelerated osteogenic differentiation in BMSCs. SP1 directly targeted miR-133a-3p, and MAPK3 was the downstream mRNA of miR-133a-3p. Mechanically, SP1 accelerated osteogenic differentiation in BMSCs via transcriptional mediation of the miR-133a-3p/MAPK3 axis. CONCLUSION: SP1 regulates osteogenic differentiation by mediating the miR-133a-3p/MAPK3 axis, which would shed new light on strategies for treating senile OP.

Treadmill running on neuropathic pain: via modulation of neuroinflammation.

Neuropathic pain is a type of chronic pain caused by an injury or somatosensory nervous system disease. Drugs and exercise could effectively relieve neuropathic pain, but no treatment can completely stop neuropathic pain. The integration of exercise into neuropathic pain management has attracted considerable interest in recent years, and treadmill training is the most used among exercise therapies. Neuropathic pain can be effectively treated if its mechanism is clarified. In recent years, the association between neuroinflammation and neuropathic pain has been explored. Neuroinflammation can trigger proinflammatory cytokines, activate microglia, inhibit descending pain modulatory systems, and promote the overexpression of brain-derived neurotrophic factor, which lead to the generation of neuropathic pain and hypersensitivity. Treadmill exercise can alleviate neuropathic pain mainly by regulating neuroinflammation, including inhibiting the activity of pro-inflammatory factors and over activation of microglia in the dorsal horn, regulating the expression of mu opioid receptor expression in the rostral ventromedial medulla and levels of γ-aminobutyric acid to activate the descending pain modulatory system and the overexpression of brain-derived neurotrophic factor. This article reviews and summarizes research on the effect of treadmill exercise on neuropathic pain and its role in the regulation of neuroinflammation to explore its benefits for neuropathic pain treatment.

Prevalence, Genotype Diversity, and Distinct Pathogenicity of 205 Gammacoronavirus Infectious Bronchitis Virus Isolates in China during 2019-2023.

Gammacoronavirus infectious bronchitis virus (IBV) causes a highly contagious disease in chickens and seriously endangers the poultry industry. The emergence and co-circulation of diverse IBV serotypes and genotypes with distinct pathogenicity worldwide pose a serious challenge to the development of effective intervention measures. In this study, we report the epidemic trends of IBV in China from 2019 to 2023 and a comparative analysis on the antigenic characteristics and pathogenicity of isolates among major prevalent lineages. Phylogenetic and recombination analyses based on the nucleotide sequences of the spike (S) 1 gene clustered a total of 205 isolates into twelve distinct lineages, with GI-19 as a predominant lineage (61.77 ± 4.56%) exhibiting an overall increasing trend over the past five years, and demonstrated that a majority of the variants were derived from gene recombination events. Further characterization of the growth and pathogenic properties of six representative isolates from different lineages classified four out of the six isolates as nephropathogenic types with mortality rates in one-day-old SPF chickens varying from 20-60%, one as a respiratory type with weak virulence, and one as a naturally occurring avirulent strain. Taken together, our findings illuminate the epidemic trends, prevalence, recombination, and pathogenicity of current IBV strains in China, providing key information for further strengthening the surveillance and pathogenicity studies of IBV.

Dietary supplementation of Sida rhombifolia enhances the plasma antioxidation and modulates gut microbiota in Anyi tile-like grey chickens.

Sida rhombifolia (S. rhombifolia) is a widely used herbal plant for humans because of its antioxidant and antibacterial effects, but its potential use as a feed additive for livestock has not been investigated. Twenty 350 days-old Anyi tile-like grey chickens were randomly divided into a control group (fed basal diet) and a treatment group (fed basal diet + 3% of S. rhombifolia), and these chickens were feed for 31 days. Dietary S. rhombifolia remarkably enhanced plasma antioxidants, including the significantly increased total antioxidant capability (p < 0.01), catalase (p = 0.04), and superoxide dismutase (p < 0.01) in the treatment group. Furthermore, dietary S. rhombifolia also modulated chicken cecal microbiota, including an increased microbial diversity (Shannon, p = 0.03; Chao1, p = 0.03) in the treatment group. Regarding taxonomic analysis, 34 microbial taxa showed significant differences between the two groups. Meanwhile, the dominant phylum Actinobacteriota (p = 0.04), and dominant genera Desulfovibrio (p = 0.04) and Olsenella (p = 0.02) were significantly increased after treatment, whereas the pathogenic genus Escherichia-Shigella (p = 0.04) was significantly decreased after feeding S. rhombifolia. The results indicating that S. rhombifolia has potential for use as a natural plant feed additive for chickens.

Identification and Evaluation of Reversible Covalent Binders to Cys55 of Bfl-1 from a DNA-Encoded Chemical Library Screen.

Bfl-1 is overexpressed in both hematological and solid tumors; therefore, inhibitors of Bfl-1 are highly desirable. A DNA-encoded chemical library (DEL) screen against Bfl-1 identified the first known reversible covalent small-molecule ligand for Bfl-1. The binding was validated through biophysical and biochemical techniques, which confirmed the reversible covalent mechanism of action and pointed to binding through Cys55. This represented the first identification of a cyano-acrylamide reversible covalent compound from a DEL screen and highlights further opportunities for covalent drug discovery through DEL screening. A 10-fold improvement in potency was achieved through a systematic SAR exploration of the hit. The more potent analogue compound 13 was successfully cocrystallized in Bfl-1, revealing the binding mode and providing further evidence of a covalent interaction with Cys55.

The mental health and traumatic experiences of mothers of children with 22q11DS.

Background: 22q11 Deletion Syndrome (22q11DS) is the most common microdeletion syndrome with broad phenotypic variability, leading to significant morbidity and some mortality. The varied health problems associated with 22q11DS and the evolving phenotype (both medical and developmental/behavioural) across the lifespan can strongly impact the mental health of patients as well as their caregivers. Like caregivers of children with other chronic diseases, caregivers of children with 22q11DS may experience an increased risk of traumatisation and mental health symptoms.Objective: The study's primary objective was to assess the frequency of traumatic experiences and mental health symptoms among mothers of children with 22q11DS. The secondary objective was to compare their traumatic experiences to those of mothers of children with other neurodevelopmental disorders (NDDs).Method: A total of 71 mothers of children diagnosed with 22q11DS completed an online survey about their mental health symptoms and traumatic experiences. Descriptive statistics were used to summarise the prevalence of their mental health symptoms and traumatic experiences. Logistic regression models were run to compare the traumatic experiences of mothers of children with 22q11DS to those of 335 mothers of children with other neurodevelopmental disorders (NDDs).Results: Many mothers of children with 22q11DS experienced clinically significant mental health symptoms, including depression (39%), anxiety (25%), and post-traumatic stress disorder (PTSD) symptoms (30%). The types of traumatic events experienced by mothers of children with 22q11DS differed from those of mothers of children with other NDDs as they were more likely to observe their child undergoing a medical procedure, a life-threatening surgery, or have been with their child in the intensive care unit.Conclusion: 22q11DS caregivers are likely to require mental health support and trauma-informed care, tailored to the specific needs of this population as they experience different kinds of traumatic events compared to caregivers of children with other NDDS.

Mothers of children with 22q11DS experience clinically significant levels of depression, anxiety, and PTSD.Mothers of children with 22q11DS experience many and diverse trauma particularly related to medical interventions of their child.The types of traumatic events experienced by mothers of children with 22q11DS are different from those of the mothers of children with other neurodevelopmental disorders.

Anlotinib induces neuronal-like differentiation of neuroblastoma by downregulating CRMP5.

The therapeutic effect of anlotinib on neuroblastoma is still not fully understood. This study aims to explore the differentiation therapeutic effects of anlotinib on neuroblastoma and its potential association with the neural development regulatory protein collapsin response mediator protein 5 (CRMP5), both in vivo and in vitro. A patient-derived xenograft (PDX) model was established to observe the therapeutic effect of anlotinib. Neuroblastoma cell lines SK-N-SH and SK-N-AS were cultured to observe the morphological impact of anlotinib. Transwell assay was used to evaluate the cell invasion, and Western blot analysis and immunohistochemistry were employed to detect the expressions of neuronal differentiation-related proteins. Results indicate that anlotinib effectively inhibited tumor growth in the PDX model, modulated the expressions of neuronal differentiation markers. In vitro, anlotinib treatment induced neurite outgrowth in neuroblastoma cells and inhibited their invasive ability, reflecting a change in neuronal marker expression patterns consistent with the PDX model. Similarly, in the SK-N-AS mouse xenograft model, anlotinib demonstrated comparable tumor-suppressing effects and promoted neuronal-like differentiation. Additionally, anlotinib significantly downregulated CRMP5 expression in neuroblastoma both in vivo and in vitro. Overexpression of CRMP5 significantly reversed the differentiation therapy effect of anlotinib, exacerbating the aggressiveness and reducing the differentiation level of neuroblastoma. These findings highlight the potential of anlotinib as an anti-neuroblastoma agent. It may suppress tumor proliferation and invasion by promoting the differentiation of tumor cells towards a neuronal-like state, and this differentiation therapy effect involves the inhibition of CRMP5 signaling.

The Inverted U-Shaped Association between Serum Vitamin D and Serum Uric Acid Status in Children and Adolescents: A Large Cross-Sectional and Longitudinal Analysis.

BACKGROUND: Serum vitamin D is associated with hyperuricemia. However, previous studies have been controversial, with limited focus on children and adolescents. OBJECTIVE: This study aimed to examine the cross-sectional and longitudinal associations between serum vitamin D and serum uric acid (SUA) levels in children and adolescents. METHODS: The cross-sectional survey comprised 4777 participants aged 6 to 18 years, while the longitudinal survey involved 1641 participants aged 6 to 12 years, all derived from an ongoing cohort study in Shenzhen, China. Restricted cubic splines were used to visualize the dose-response relationship between vitamin D and SUA and the risk of higher SUA status. Two-segment generalized linear models (GLM) and logistic models were used to assess the association between vitamin D and SUA and higher SUA status, respectively. The longitudinal analysis used GLM. RESULTS: We observed an inverted U-shaped relationship between vitamin D and SUA (p-overall < 0.0001, p-nonlinear = 0.0002), as well as the risk of higher SUA status (p-overall = 0.0054, p-nonlinear = 0.0015), with the vitamin D inflection point at 24.31 and 21.29 ng/mL, respectively. A 10 ng/mL increment in 25(OH)D3 levels, when below 20.92 ng/mL, was associated with a 68% rise in the risk of higher SUA status (OR: 1.68, 95%CI: 1.07-2.66). Conversely, when 25(OH)D3 levels were above or equal to 20.92 ng/mL, a 10 ng/mL increment was associated with a 45% reduction risk of higher SUA status (OR: 0.55, 95%CI: 0.36-0.84). Longitudinal analysis indicated that the annual change of SUA was from -4.80 (ß, 95%CI: -10.74, 1.13) to -9.00 (ß, 95%CI: -15.03, -2.99) and then to -6.77 (ß, 95%CI: -12.83, -0.71, p for trend = 0.0212) µmol/L when increasing the quartile of vitamin D3. CONCLUSIONS: An inverse U-shaped relationship was observed between vitamin D and SUA as well as the risk of higher SUA status. Sufficient vitamin D levels appear to play a preventative role against the age-related increase in SUA. Ensuring adequate vitamin D levels may be beneficial in improving uric acid metabolism.

Assessing recent recurrence after hepatectomy for hepatitis B-related hepatocellular carcinoma by a predictive model based on sarcopenia.

BACKGROUND: Sarcopenia may be associated with hepatocellular carcinoma (HCC) following hepatectomy. But traditional single clinical variables are still insufficient to predict recurrence. We still lack effective prediction models for recent recurrence (time to recurrence < 2 years) after hepatectomy for HCC. AIM: To establish an interventable prediction model to estimate recurrence-free survival (RFS) after hepatectomy for HCC based on sarcopenia. METHODS: We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time, and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography. 94 of these patients were enrolled for external validation. Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort. A nomogram model was developed to predict the RFS of HCC patients, and its predictive performance was validated. The predictive efficacy of this model was evaluated using the receiver operating characteristic curve. RESULTS: Multivariate analysis showed that sarcopenia [Hazard ratio(HR) = 1.767, 95%CI: 1.166-2.678, P < 0.05], alpha-fetoprotein ≥ 40 ng/mL (HR = 1.984, 95%CI: 1.307-3.011, P < 0.05), the maximum diameter of tumor > 5 cm (HR = 2.222, 95%CI: 1.285-3.842, P < 0.05), and hepatitis B virus DNA level ≥ 2000 IU/mL (HR = 2.1, 95%CI: 1.407-3.135, P < 0.05) were independent risk factors associated with postoperative recurrence of HCC. Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease (SAMD) was established combined with other the above risk factors. The area under the curve of the SAMD model was 0.782 (95%CI: 0.705-0.858) in the training cohort (sensitivity 81%, specificity 63%) and 0.773 (95%CI: 0.707-0.838) in the validation cohort. Besides, a SAMD score ≥ 110 was better to distinguish the high-risk group of postoperative recurrence of HCC. CONCLUSION: Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC. A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC, which is superior to other models and contributes to prognosis prediction.

Identification of a novel ANK1 gene variant c.1504-9G>A and its mechanism of intron retention in hereditary spherocytosis.

Objective: The objective of this study was to pinpoint pathogenic genes and assess the mutagenic pathogenicity in two pediatric patients with hereditary spherocytosis. Methods: We utilized whole-exome sequencing (WES) for individual analysis (case 1) and family-based trio analysis (case 2). The significance of the intronic mutation was validated through a Minigene splicing assay and supported by subsequent in vitro experiments. Results: Both probands received a diagnosis of hereditary spherocytosis. WES identified a novel ANK1 c.1504-9G>A mutation in both patients, causing the retention of seven nucleotides at the 5' end of intron 13, as substantiated by the Minigene assay. This variant results in a premature stop codon and the production of a truncated protein. In vitro studies indicated a reduced expression of the ANK1 gene. Conclusion: The novel ANK1 c.1504-9G>A variant is established as the causative factor for hereditary spherocytosis, with the c.1504-9G site functioning as a splicing receptor.

A highly sensitive Lock-Cas12a biosensor for detection and imaging of miRNA-21 in breast cancer cells.

The expression levels of microRNA (miRNA) vary significantly in correlation with the occurrence and progression of cancer, making them valuable biomarkers for cancer diagnosis. However, their quantitative detection faces challenges due to the high sequence homology, low abundance and small size. In this work, we established a strand displacement amplification (SDA) approach based on miRNA-triggered structural "Lock" nucleic acid ("Lock" DNA), coupled with the CRISPR/Cas12a system, for detecting miRNA-21 in breast cancer cells. The "Lock" DNA freed the CRISPR-derived RNA (crRNA) from the dependence on the target sequence and greatly facilitated the extended detection of different miRNAs. Moreover, the CRISPR/Cas12a system provided excellent amplification ability and specificity. The designed biosensor achieved high sensitivity detection of miRNA-21 with a limit of detection (LOD) of 28.8 aM. In particular, the biosensor could distinguish breast cancer cells from other cancer cells through intracellular imaging. With its straightforward sequence design and ease of use, the Lock-Cas12a biosensor offers significant advantages for cell imaging and early clinical diagnosis.

Effect of Dietary Protein Intake from Different Sources on Maternal and Umbilical Cord Plasma Amino Acid Levels.

SCOPE: To assess the associations of dietary protein intake from different sources during pregnancy with maternal and umbilical cord plasma amino acid levels. METHODS AND RESULTS: The study includes 216 pregnant women and 39 newborns from the Tongji Birth Cohort in Wuhan, China. The study examines the levels of 21 amino acids in maternal and cord plasma samples using ultra-performance liquid chromatography with tandem mass spectrometry. A significant positive relationship is observed between dietary protein intake from refined grains and maternal plasma cysteine levels. Dietary protein intake from dairy products is positively associated with maternal plasma levels of sulfur amino acid (mainly cystine), but negatively associated with maternal plasma levels of glutamic acid. In addition, the study observes that pre-pregnancy body mass index and parity may be potential determinants of maternal plasma amino acid levels, whereas a history of passive smoking during pregnancy is an important factor influencing cord plasma amino acid levels. CONCLUSIONS: These findings suggest that dietary protein intakes from specific sources during pregnancy may affect maternal plasma levels of amino acids.

Association of serum 25-hydroxyvitamin D with bone health measured by calcaneal quantitative ultrasound: a large cross-sectional analysis in children and adolescents.

Background: Vitamin D plays a crucial role in bone health; however, findings in children and adolescents remain inconsistent, and few studies have examined its impact on bone health measured by quantitative ultrasound (QUS). This study aims at assessing the relationship between serum vitamin D levels and bone health, as evaluated by QUS, across varying pubertal stages and genders. Methods: A baseline cross-sectional survey of an ongoing cohort study included 4682 children and adolescents aged 6 to 18 years from Shenzhen, China. Serum levels of 25-hydroxyvitamin D (25(OH)D), which is the sum of 25(OH)D2 and 25(OH)D3, were quantified using liquid chromatography-mass spectrometry. Bone health was measured through calcaneal QUS, utilizing the speed of sound (SOS) in the heel as a principal measure-a higher SOS indicating a denser bone structure. Generalized linear models were used to evaluate the association of serum 25(OH)D, 25(OH)D2, and 25(OH)D3 levels with the SOS. Results: Forty-one point-one percent of this population was vitamin D deficient (serum 25(OH)D < 20 ng ml-1), with only 11.1% being sufficient. In the fully adjusted model, we observed a significant positive association between increased serum 25(OH)D quartiles and SOS. Compared with the participants in the lowest quartiles of serum 25(OH)D, those in successive quartiles of 25(OH)D were 3.54 (95% CI: 0.81, 6.28) m s-1, 5.74 (95% CI: 2.87, 8.61) m s-1, and 8.83 (95% CI: 5.83, 11.84) m s-1, respectively (P for trend < 0.0001). The correlations observed for serum 25(OH)D2 and 25(OH)D3 with SOS were similar to those of serum 25(OH)D. Importantly, this association was primarily observed in post-pubertal children and adolescents but was absent in pre- and mid-pubertal participants (P for interaction = 0.0004). Conclusion: Elevated serum 25(OH)D levels were associated with better bone health, as measured through calcaneal QUS, in children and adolescents, particularly among those who had reached the post-pubertal stage. These findings highlight the crucial importance of maintaining sufficient vitamin D levels to support optimal bone health in this demographic.

User-Centered Design and Usability of a Culturally Adapted Virtual Survivorship Care App for Chinese Canadian Prostate Cancer Survivors: Qualitative Descriptive Study.

BACKGROUND: Cultural adaptations of digital health innovations are a growing field. However, digital health innovations can increase health inequities. While completing exploratory work for the cultural adaptation of the Ned Clinic virtual survivorship app, we identified structural considerations that provided a space to design digitally connected and collective care. OBJECTIVE: This study used a community-based participatory research and user-centered design process to develop a cultural adaptation of the Ned Clinic app while designing to intervene in structural inequities. METHODS: The design process included primary data collection and qualitative analysis to explore and distill design principles, an iterative design phase with a multidisciplinary team, and a final evaluation phase with participants throughout the design process as a form of member checking and validation. RESULTS: Participants indicated that they found the final adapted prototype to be acceptable, appropriate, and feasible for their use. The changes made to adapt the prototype were not specifically culturally Chinese. Instead, we identified ways to strengthen connections between the survivor and their providers; improve accessibility to resources; and honor participants' desires for relationality, accountability, and care. CONCLUSIONS: We grounded the use of user-centered design to develop a prototype design that supports the acts of caring through digital technology by identifying and designing to resist structures that create health inequities in the lives of this community of survivors. By designing for collective justice, we can provide accessible, feasible, and relational care with digital health through the application of Indigenous and Black feminist ways of being and knowing.

Tunable schiff-based networks with different bonding sites for enhanced photocatalytic activity under visible-light irradiation: The effects of steric hindrance.

Organic polymers hold great potential in photocatalysis considering their low cost, structural tailorability, and well-controlled degree of conjugation for efficient electron transfer. Among the polymers, Schiff base networks (SNWs) with high nitrogen content have been noticed. Herein, a series of SNWs is synthesized based on the melamine units and dialdehydes with different bonding sites. The chemical and structural variation caused by steric hindrance as well as the related photoelectric properties of the SNW samples are investigated, along with the application exploration on photocatalytic degradation and energy production. The results demonstrate that only SNW-o based on o-phthalaldehyde responds to visible light, which extends to over 550 nm. SNW-o shows the highest tetracycline degradation rate of 0.02516 min-1, under 60-min visible light irradiation. Moreover, the H2O2 production of SNW-o is 2.14 times higher than that of g-C3N4. The enhanced photocatalytic activity could be ascribed to the enlarged visible light adsorption and intramolecular electron transfer. This study indicates the possibility to regulate the optical and electrical properties of organic photocatalysts on a molecular level, providing an effective strategy for rational supramolecular engineering to the applications of organic materials in photocatalysis.

Knee arthroscopy has limited effects on relieving local symptoms of knee osteoarthritis: an analysis of data from the Osteoarthritis Initiative.

BACKGROUND: Knee arthroscopy's efficacy in symptom improvement for knee osteoarthritis remains debated. In this study, we analyzed a multicenter database to investigate local symptom improvement. METHODS: We extracted and analyzed the data of 163 patients from the Osteoarthritis Initiative cohort who underwent unilateral knee arthroscopy (UKA) and were followed up for at least 24 months. UKA patients were matched to non-UKA patients (n = 163) according to sex, age, abdominal circumference, and Kellgren-Lawrence grade. The verified KOOS questionnaires (knee catching, locking, grinding, or clicking) and common local symptoms (frequent knee pain, aching, or stiffness) were set as outcomes. Furthermore, we built a binary logistic regression model to examine the relationship between UKA and local symptom improvement and new-onset symptoms, adjusting for conservative therapeutic covariables (injection of steroids or transparent acid into the knee joint, oral chondroitin sulfate, amino glucose, or analgesics). RESULT: Analysis showed that the UKA and non-UKA groups showed no obvious difference in the three knee symptoms, but the probability of new-onset grinding or clicking, and frequent knee pain, aching, or stiffness symptoms in the UKA group were respectively 5.82 and 5.65-fold higher than that in the non-UKA group. After analyzing conservative treatment data using a multiple imputation method, the results were consistent with previous regression analyses. CONCLUSION: Compared to the non-UKA group, the UKA group showed no noticeable differences in the improvement of the three knee symptoms and showed an increased the probability of new-onset grinding or clicking and frequent knee pain, aching, or stiffness symptoms. Key Points • Knee arthroscopy may increase the probability of new-onset grinding or clicking and frequent knee pain, aching, or stiffness symptoms. • We found no difference in the improvement of local knee symptoms (knee catching, locking, grinding, clicking or frequent pain, aching, or stiffness) improvement between the two groups with or without knee arthroscopy.

Preparation, structural and functional characterization of corn peptide-chelated calcium microcapsules using synchronous dual frequency ultrasound.

The utilization of peptide-chelated calcium is low due to the influence of factors such as solubility, heat and digestive environmental conditions; therefore, it is crucial to protect, prolong and stabilize this nutrient in order to enhance its efficacy. This study was conducted to prepare corn peptide-chelated calcium microcapsules using ß-cyclodextrin (ß-CD) as the wall material through an improved ultrasonic-assisted method. The structure, solubility, thermal stability, and in vitro gastrointestinal digestion of these microcapsules were thoroughly investigated and analyzed. The microcapsules were prepared using the following recommended conditions: a chelate concentration of 5 mg/mL, a mass ratio of chelate to ß-CD of 1:8 g/g, and a synchronous dual-frequency ultrasound (20/28 kHz) at a power of 75 W, a duty ratio of 20/5 s/s, and a time of 20 min. These specific parameters were carefully selected to ensure the optimal fabrication of the microcapsules. The results showed that the utilization of dual-frequency ultrasound resulted in a significant increase in both the encapsulation rate and yield, which were enhanced by 15.84 % and 15.68 %, respectively, reaching impressive values of 79.17 % and 90.60 %. Moreover, the results of the structure index analysis provided further confirmation that ultrasonic treatment had a significant impact on the structure of the microcapsules, leading to a noticeable reduction in particle size and transformation into nanoparticles. Furthermore, the microcapsules demonstrated excellent solubility within a wide pH range of 2 to 10, with solubility ranging from 93.54 % to 88.68 %. Additionally, these microcapsules exhibited remarkable thermal stability, retaining a minimum of 84.8 % of their stability when exposed to temperatures ranging from 40 to 80 °C. Moreover, during gastric and intestinal digestion, these microcapsules exhibited a high slow-release rate of 44.66 % and 51.6 %, indicating their ability to gradually release calcium contents. The inclusion of dual-frequency ultrasound in the preparation of high calcium microcapsules yielded promising outcomes. Overall, our work presents a novel method for synthesizing corn peptide-chelated calcium microcapsules with desirable properties such as good solubility, excellent thermal stability, and a significant slow-release effect. These microcapsules have the potential to serve as fortified high calcium supplements.

Design of a Dyadic Digital Health Module for Chronic Disease Shared Care: Development Study.

BACKGROUND: The COVID-19 pandemic forced the spread of digital health tools to address limited clinical resources for chronic health management. It also illuminated a population of older patients requiring an informal caregiver (IC) to access this care due to accessibility, technological literacy, or English proficiency concerns. For patients with heart failure (HF), this rapid transition exacerbated the demand on ICs and pushed Canadians toward a dyadic care model where patients and ICs comanage care. Our previous work identified an opportunity to improve this dyadic HF experience through a shared model of dyadic digital health. We call this alternative model of care "Caretown for Medly," which empowers ICs to concurrently expand patients' self-care abilities while acknowledging ICs' eagerness to provide greater support. OBJECTIVE: We present the systematic design and development of the Caretown for Medly dyadic management module. While HF is the outlined use case, we outline our design methodology and report on 6 core disease-invariant features applied to dyadic shared care for HF management. This work lays the foundation for future usability assessments of Caretown for Medly. METHODS: We conducted a qualitative, human-centered design study based on 25 semistructured interviews with self-identified ICs of loved ones living with HF. Interviews underwent thematic content analysis by 2 coders independently for themes derived deductively (eg, based on the interview guide) and inductively refined. To build the Caretown for Medly model, we (1) leveraged the Knowledge to Action (KTA) framework to translate knowledge into action and (2) borrowed Google Sprint's ability to quickly "solve big problems and test new ideas," which has been effective in the medical and digital health spaces. Specifically, we blended these 2 concepts into a new framework called the "KTA Sprint." RESULTS: We identified 6 core disease-invariant features to support ICs in care dyads to provide more effective care while capitalizing on dyadic care's synergistic benefits. Features were designed for customizability to suit the patient's condition, informed by stakeholder analysis, corroborated with literature, and vetted through user needs assessments. These features include (1) live reports to enhance data sharing and facilitate appropriate IC support, (2) care cards to enhance guidance on the caregiving role, (3) direct messaging to dissolve the disconnect across the circle of care, (4) medication wallet to improve guidance on managing complex medication regimens, (5) medical events timeline to improve and consolidate management and organization, and (6) caregiver resources to provide disease-specific education and support their self-care. CONCLUSIONS: These disease-invariant features were designed to address ICs' needs in supporting their care partner. We anticipate that the implementation of these features will empower a shared model of care for chronic disease management through digital health and will improve outcomes for care dyads.

Honoring the Care Experiences of Chinese Canadian Survivors of Prostate Cancer to Cultivate Cultural Safety and Relationality in Digital Health: Exploratory-Descriptive Qualitative Study.

BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed nonskin cancer for Canadian men and has one of the highest 5-year survival rates, straining systems to provide care. Virtual care can be one way to relieve this strain, but survivors' care needs and technology use are influenced by intersecting social and cultural structures. Cultural adaptation has been posited as an effective method to tailor existing interventions to better serve racialized communities, including Chinese men. However, cultural adaptations may inadvertently draw attention away from addressing structural inequities. OBJECTIVE: This study used qualitative methods to (1) explore the perceptions and experiences of Chinese Canadian PCa survivors with follow-up and virtual care, and (2) identify implications for the cultural adaptation of a PCa follow-up care app, the Ned (no evidence of disease) Clinic. METHODS: An axiology of relational accountability and a relational paradigm underpinned our phenomenologically informed exploratory-descriptive qualitative study design. A community-based participatory approach was used, informed by cultural safety and user-centered design principles, to invite Chinese Canadian PCa survivors and their caregivers to share their stories. Data were inductively analyzed to explore their unmet needs, common experiences, and levels of digital literacy. RESULTS: Unmet needs and technology preferences were similar to broader trends within the wider community of PCa survivors. However, participants indicated that they felt uncomfortable, unable to, or ignored when expressing their needs. Responses spoke to a sense of isolation and reflected a reliance on culturally informed coping mechanisms, such as "eating bitterness," and familial assistance to overcome systemic barriers and gaps in care. Moreover, virtual care was viewed as "better than nothing;" it did not change a perceived lack of focus on improving quality of life or care continuity in survivorship care. Systemic changes were identified as likely to be more effective in improving care delivery and well-being rather than the cultural adaptation of Ned for Chinese Canadians. Participants' desires for care reflected accessibility issues that were not culturally specific to Chinese Canadians. CONCLUSIONS: Chinese Canadian survivors are seeking to strengthen their connections in a health care system that provides privacy and accessibility, protects relationality, and promotes transparency, accountability, and responsibility. Designing "trickle-up" adaptations that address structural inequities and emphasize accessibility, relationality, and privacy may be more effective and efficient at improving care than creating cultural adaptations of interventions.

Estradiol-mediated small GTP-binding protein GDP dissociation stimulator induction contributes to sex differences in resilience to ferroptosis in takotsubo syndrome.

BACKGROUND: Declining beneficial cardiovascular actions of estradiol (E2) have been associated with disproportionate susceptibility to takotsubo syndrome (TTS) in postmenopausal women. However, the underlying mechanisms between E2 and this marked disproportion remain unclear. SmgGDS (small GTP-binding protein GDP dissociation stimulator), as a key modulator of cardiovascular disease, plays protective roles in reducing oxidative stress and exerts pleiotropic effects of statins. Whether SmgGDS levels are influenced by E2 status and the effect of SmgGDS on sex differences in TTS are poorly understood. METHODS: Clinical data were reviewed from TTS inpatients. Echocardiography, immunofluorescence, and immunohistochemistry were performed together with expression analysis to uncover phenotypic and mechanism changes in sex differences in TTS-like wild-type (WT) and SmgGDS± mice. HL-1 cardiomyocytes were used to further examine and validate molecular mechanisms. RESULTS: In 14 TTS inpatients, TTS had a higher incidence in postmenopausal women as compared to premenopausal women and men. In murine TTS, female WT mice exhibited higher cardiac SmgGDS levels than male WT mice. Ovariectomy reduced SmgGDS expression in female WT mice similar to that observed in male mice, whereas E2 replacement in these ovariectomized (OVX) female mice reversed this effect. The physiological importance of this sex-specific E2-mediated SmgGDS response is underscored by the disparity in cardiac adaptation to isoproterenol (ISO) stimulation between both sexes of WT mice. E2-mediated SmgGDS induction conferred female protection against TTS-like acute cardiac injury involving ferritinophagy-mediated ferroptosis. No such cardioprotection was observed in male WT mice and OVX female. A causal role for SmgGDS in this sex-specific cardioprotective adaptation was indicated, inasmuch as SmgGDS deficiency abolished E2-modulated cardioprotection against ferritinophagy and aggravates TTS progression in both sexes. Consistently, knockdown of SmgGDS in HL-1 cardiomyocytes exacerbated ferroptosis in a ferritinophagy-dependent manner and abrogated the protective role of E2 against ferritinophagy. Mechanistically, our findings revealed that SmgGDS regulated E2-dependent cardioprotective effects via AMPK/mTOR signaling pathway. SmgGDS deficiency abolished E2-conferred protection against ferritinophagy through activating AMPK/mTOR pathway, while treatment with recombinant SmgGDS in HL-1 cells significantly mitigated this pathway-associated ferritinophagy activity. CONCLUSIONS: These results demonstrate that SmgGDS is a central mediator of E2-conferred female cardioprotection against ferritinophagy-mediated ferroptosis in TTS.