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Myosteatosis, by increasing skeletal and systemic insulin resistance, induces endothelial dysfunction and increases the risk of hypertension.Myosteatosis, by increasing skeletal and systemic insulin resistance, induces endothelial dysfunction and increases the risk of hypertension.

Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor’s glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects. SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.

Since its discovery, the Clustered Regularly Interspaced Short Palindromic Repeat (the CRISPR) system has been increasingly applied to therapeutic genome editing. Employment of several viral and non-viral vectors has enabled efficient delivery of the CRISPR system to target cells or tissues. In addition, the CRISPR system is able to modulate the target gene’s expression in various ways, such as mutagenesis, gene integration, epigenome regulation, chromosomal rearrangement, base editing and mRNA editing. However, there are still limitations hindering an ideal application of the system: inefficient delivery, dysregulation of the delivered gene, the immune response against the CRISPR system, the off-target effects or the unintended on-target mutations. In addition, there are recent discoveries that have not been yet applied to CRISPR-mediated therapeutic genome editing. Here, we review the overall principles related to the therapeutic application of the CRISPR system, along with new strategies for the further application and prospects to overcome the limitations.

We introduce a novel benchmark dataset, CRxK Dataset, featuring surveillance images based on meticulously re-enacted crime events with curated annotations. CRxK dataset includes a collection of crime re-enacted videos and images categorized into 13 different categories, encompassing a set of offenses such as assault, intoxication, swoon, and more. In addition, we cover a separate normal dataset extracted from scenes occurring five seconds before the crime event and spanning a 10-second duration. Among 13 categories, we employ six core categories, which are the most frequent occurrences in the collected dataset. These categories are assault, robbery, swooning, kidnapping, burglary, and normal scenarios. We conducted experiments using a total of 2,054,013 frames randomly selected and shuffled from the videos. Our training and validation involved four convolutional neural network (CNN) models and a single transformer model. We utilized a smaller sub-dataset, CRxK-6 dataset, containing 8,500 frames randomly sampled from each category video, resulting in 51,000 frames. Despite employing a train-test split ratio of 1:40 and applying face masking using RetinaFace, the dataset exhibited excellent performance with common CNN models, achieving an accuracy exceeding 0.940 for each model. However, it presented some challenges for the Transformer model.

As digital health services advance, digital health equity has become a significant concern. However, people with disability and older adults still face health management limitations, particularly in the COVID-19 pandemic. An essential area of investigation is proposing a patient-centered design strategy that uses patient-generated health data (PGHD) to facilitate optimal communication with caregivers and health care service providers. This study aims to conceptualize, develop, and validate a digitally integrated health care service platform for people with disability, caregivers, and health care professionals, using Internet of Things devices and PGHD to contribute to improving digital health equity. The methodology consists of 5 stages. First, a collaborative review of the previous app, Daily Healthcare 1.0, was conducted with individuals with disabilities, caregivers, and health care professionals. Secondly, user needs were identified via personas, scenarios, and user interface sketches to shape a user-centered service design. The third stage created an enhanced app that integrated these specifications. In the fourth stage, heuristic evaluations by clinical and app experts paved the way for Daily Healthcare 2.0, now featuring Internet of Things device integration. Conclusively, in the fifth stage, an extensive 2-month usability evaluation was executed with user groups comprising individuals with disabilities using the app and their caregivers. Among the participants, \"disability welfare information and related institutional linkage\" was the highest priority. Three of the 14 user interface sketches the participants created were related to \"providing educational content.\" The 11 heuristic evaluation experts identified \"focusing on a single task\" as a crucial issue and advocated redesigning the home menu to simplify it and integrate detailed menus. Subsequently, the app Daily Healthcare 2.0 was developed, incorporating wearable devices for collecting PGHD and connecting individuals with disabilities, caregivers, and health care professionals. After the 2-month usability evaluation with 27 participants, all participants showed an increase in eHealth literacy, particularly those who used the caregiver app. Relatively older users demonstrated improved scores in health IT usability and smartphone self-efficacy. All users' satisfaction and willingness to recommend increased, although their willingness to pay decreased. In this study, we underscore the significance of incorporating the distinct needs of individuals with disabilities, caregivers, and health care professionals from the design phase of a digital health care service, highlighting its potential to advance digital health equity. Our findings also elucidate the potential benefits of fostering partnerships between health consumers and providers, thereby attenuating the vulnerability of marginalized groups, even amid crises such as the COVID-19 pandemic. Emphasizing this imperative, we advocate for sustained endeavors to bolster the digital literacy of individuals with disabilities and champion collaborative cocreation, aiming to uphold the collective ethos of health and digital health equity.

Ice crystals at low temperatures exhibit structural polymorphs including hexagonal ice, cubic ice, or a hetero-crystalline mixture of the two phases. Despite the significant implications of structure-dependent roles of ice, mechanisms behind the growths of each polymorph have been difficult to access quantitatively. Using in-situ cryo-electron microscopy and computational ice-dynamics simulations, we directly observe crystalline ice growth in an amorphous ice film of nanoscale thickness, which exhibits three-dimensional ice nucleation and subsequent two-dimensional ice growth. We reveal that nanoscale ice crystals exhibit polymorph-dependent growth kinetics, while hetero-crystalline ice exhibits anisotropic growth, with accelerated growth occurring at the prismatic planes. Fast-growing facets are associated with low-density interfaces that possess higher surface energy, driving tetrahedral ordering of interfacial H 2 O molecules and accelerating ice growth. These findings, based on nanoscale observations, improve our understanding on early stages of ice formation and mechanistic roles of the ice interface. In-situ cryo-electron microscopy in thin amorphous ice films and ice-dynamics simulations reveal polymorph-dependent growth kinetics of nanoscale ice crystals. Hetero-crystalline ice exhibits anisotropic growth: fast-growing facets are associated with low-density interfaces, driving tetrahedral ordering of interfacial H 2 O molecules and accelerating ice growth.

Background The effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD). Methods A randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change. Results Combination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; p = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; p < 0.001 and 15.0 to 12.4%; p = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, p > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; p = 0.018), but not in the monotherapy group (323 to 311 dB/m; p = 0.104). Conclusions Ezetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population. Trial registration The trial was registered at ClinicalTrials.gov (registration number: NCT03434613 ).

Four distinct pore-filling anion exchange membranes (PFAEMs) were prepared, and their mechanical properties, ion conductivity, and performance in anion exchange membrane water electrolysis (AEMWE) were evaluated. The fabricated PFAEMs demonstrated exceptional tensile strength, which was approximately 14 times higher than that of the commercial membrane, despite being nearly half as thin. Ion conductivity measurements revealed that acrylamide-based membranes outperformed benzyl-based ones, exhibiting 25% and 41% higher conductivity when using crosslinkers with two and three crosslinking sites, respectively. The AEMWE performance directly correlated with the hydrophilicity and ion exchange capacity (IEC) of the membranes. Specifically, AE_3C achieved the highest performance, supported by its superior IEC and ionic conductivity. Durability tests showed that AE_3C outlasted the commercial membrane, with a delayed voltage increase corresponding to its higher IEC, confirming the importance of increased ion-exchange functional groups in ensuring longevity. These results highlight the critical role of hydrophilic monomers and crosslinker structure in optimizing PFAEMs for enhanced performance and durability in AEMWE applications.

The circadian clock synchronizes biological processes to daily cycles of light and temperature. Clock components, including CIRCADIAN CLOCK-ASSOCIATED1 (CCA1), are also associated with cold acclimation. However, it is unknown how CCA1 activity is modulated in coordinating circadian rhythms and cold acclimation. Here, we report that self-regulation of Arabidopsis thaliana CCA1 activity by a splice variant, CCA1β, links the clock to cold acclimation. CCA1β interferes with the formation of CCA1α-CCA1α and LATE ELONGATED HYPOCOTYL (LHY)-LHY homodimers, as well as CCA1α-LHY heterodimers, by forming nonfunctional heterodimers with reduced DNA binding affinity. Accordingly, the periods of circadian rhythms were shortened in CCA1β-overexpressing transgenic plants (35S:CCA1β), as observed in the cca1 lhy double mutant. In addition, the elongated hypocotyl and leaf petiole phenotypes of CCA1α-overexpressing transgenic plants (35S:CCA1α) were repressed by CCA1β coexpression. Notably, low temperatures suppressed CCA1 alternative splicing and thus reduced CCA1β production. Consequently, whereas the 35S:CCA1α transgenic plants exhibited enhanced freezing tolerance, the 35S:CCA1β transgenic plants were sensitive to freezing, indicating that cold regulation of CCA1 alternative splicing contributes to freezing tolerance. On the basis of these findings, we propose that dynamic self-regulation of CCA1 underlies the clock regulation of temperature responses in Arabidopsis.

Chronic wounds in diabetic patients are challenging because their prolonged inflammation makes healing difficult, thus burdening patients, society, and health care systems. Customized dressing materials are needed to effectively treat such wounds that vary in shape and depth. The continuous development of 3D‐printing technology along with artificial intelligence has increased the precision, versatility, and compatibility of various materials, thus providing the considerable potential to meet the abovementioned needs. Herein, functional 3D‐printing inks comprising DNA from salmon sperm and DNA‐induced biosilica inspired by marine sponges, are developed for the machine learning‐based 3D‐printing of wound dressings. The DNA and biomineralized silica are incorporated into hydrogel inks in a fast, facile manner. The 3D‐printed wound dressing thus generates provided appropriate porosity, characterized by effective exudate and blood absorption at wound sites, and mechanical tunability indicated by good shape fidelity and printability during optimized 3D printing. Moreover, the DNA and biomineralized silica act as nanotherapeutics, enhancing the biological activity of the dressings in terms of reactive oxygen species scavenging, angiogenesis, and anti‐inflammation activity, thereby accelerating acute and diabetic wound healing. These bioinspired 3D‐printed hydrogels produce using a DNA‐induced biomineralization strategy are an excellent functional platform for clinical applications in acute and chronic wound repair. The healing of chronic wounds in diabetic patients is challenging due to prolonged inflammation. In this study, bioinspired 3D printing inks comprising of functionalized sodium alginate (FSA), biomineralized silica, and DNA are developed. Bioinspired hydrogel dressings fabricated with DNA‐bSi@FSA inks and the 3D printing process are optimized using machine learning. The potential of using biomineralization‐based nanotherapeutics for chronic wound repair is evaluated.