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Background: Obesity is major cause of heart failure (HF), but it is related with a better prognosis among the elderly. Therefore, we aimed to examine whether metabolically healthy obesity (MHO) in late life increases HF risk and is reflected in impaired left ventricular (LV) function. Methods: The participants were grouped into four metabolic phenotypes based on obesity and metabolic status: metabolically healthy non-obesity (MHN), MHO, metabolically unhealthy non-obesity (MUN), metabolically unhealthy obesity (MUO). Association of metabolic phenotypes with LV function was evaluated using multiple linear regression models. And association between metabolic phenotypes and risk of HF was assessed using multivariable logistic regression models. In addition, we validated the association of metabolic phenotypes and HF risk in a separate longitudinal cohort. Results: In the primary cohort of 6335 participant, there were 434 participants diagnosed with HF. Compared to MHN participants, the risk of HF was higher among older individuals with MUN (OR = 1.51 [95% CI: 1.14–1.99]) and MUO (OR = 2.01 [95% CI: 1.39–2.91]), but not older individuals with MHO (OR = 0.86 [95% CI: 0.30–2.43). Regarding to LV function, worse LV diastolic function was noted among MUN and MUO individuals rather than MHO individuals. Older adults with MHO were also not associated with risk of HF in the validation cohort. Conclusion: Among older individuals, the metabolic health status might modify the association of obesity with risk of HF and LV diastolic dysfunction. Worse LV diastolic function and higher risk of HF were just noted in individuals with MUO, but not in those with MHO.

Patients with overweight/obesity and type 2 diabetes are encouraged to lose weight, but not all losing weight gain better cardiovascular health, especially old adults. The change in skeletal muscle mass (SMM) could be the key that explains the heterogenous cardiovascular effects of weight loss. This study aims to assess whether the cardiovascular effects of weight loss vary for those gaining skeletal muscle along with weight loss. The old adults with overweight/obesity and type 2 diabetes in the Look AHEAD study having muscle measurement from dual‐energy X‐ray absorptiometry were included. Based on the weight change (WC) and SMM change (SMMC) between baseline and the 4‐year follow‐up, participants were allocated into three groups—weight gain (WG) group, weight loss with muscle loss (WL‐ML) group and weight loss with muscle gain (WL‐MG) group. Cox proportional hazards regression was performed to evaluate the cardiovascular risk of those gaining or losing SMM with weight loss compared with those gaining weight. Among the participants with weight loss, the ratio of SMMC/WC was calculated, and the association of SMMC/WC with primary cardiovascular outcome was assessed. A total of 491 participants were included in the study with an average age of 64.56 ± 3.81 years old. A total of 47.0% were male and 49.9% were from the intensive lifestyle intervention arm. Based on their WC and SMMC, 43 were assigned to the WG group, 373 to the WL‐ML group and 75 to the WL‐MG group. Over a follow‐up of almost 10 years, 97 participants encountered the primary endpoint. The WG group had the highest incidence of 25.59%, the WL‐MG group had the lowest incidence of 9.33% and the WL‐ML group had 21.18% (P= 0.040). In the fourth adjusted Cox model, the WL‐MG group achieved significantly decreased odds of the primary endpoint compared with the WG group (hazard ratio [HR] 0.33, 95% confidence interval [CI] [0.12, 0.87], P= 0.026), whilst the WL‐ML group did not (HR 0.91, 95% CI [0.47, 1.78], P= 0.670). Among the participants with weight loss, when SMMC/WC reached around 50%, this HR soared to approximately two‐fold. The participants gaining SMM along with weight loss achieved the lowest odds of adverse cardiovascular events, whilst those who lost SMM along with weight loss had comparable cardiovascular risk with those gaining weight. The more muscle lost during weight loss, the greater the harm. The cardiovascular effects of weight loss were modulated by whether the participants gained SMM meanwhile losing weight.

Regenerative medicine mainly relies on heterologous transplantation, often hindered by sample availability and ethical issues. Furthermore, patients are required to take immunosuppressive medications to prevent adverse side effects. Stem cell-derived 3D-organoid culture has provided new alternatives for transplantation and regenerative medicine. Scholars have combined organoids with tissue engineering technology to improve reproducibility, the accuracy of constitution and throughput, and genetic correction to achieve a more personalized therapy. Here, we review the available applications of organoids in regenerative medicine and the current challenges concerning this field.Graphical Abstract

Introduction:The inhibition of Nrf2 pathway is regarded as the dominant process that correlates with the pathogenesis of diabetic cardiomyopathy (DCM). Recently, accumulating evidence reveals that lncRNAs play key roles in regulating Nrf2 pathway. However, the underlying mechanisms remain unclear. Here, we found that adipocyte lncRNA SBF2-AS1 (SBF2-AS1) enhanced the SUMOylation of hnRNPA1, which subsequently facilitated the package of SBF2-AS1 into exosomes under high glucose conditions.Hypothesis:We hypothesized that AdEXO-SBF2-AS1 promotes diabetic myocardial fibrosis through regulating the hnRNPA1/Nrf2 pathway via SUMOylation.Methods:We examined the effect of exosomes from diabetic (db/db) mice-derived adipocytes on ANG-II-induced cardiac fibrosis and function in non-diabetic mice. In the invitrostudy, HG (33mmol/L)-induced AdEXO were cultured with adult human cardiac fibroblasts (aHCFs). Differentially expressed lncRNAs in AdEXO were screened using lncRNA sequencing.Results:Intramyocardial injection of diabetic AdEXO in the non-diabetic heart exacerbated myocardial fibrosis. Whereas administration of an exosomes biogenesis inhibitor attenuated cardiac fibrosis in diabetic mice. We identified SBF2-AS1 is a common molecule significantly increased in diabetic AdEXO and HG-stimulated non-diabetic AdEXO. After four weeks of ANG II infusion, EXO-db/dbWT-injected mice displayed significant fibrosis in the heart. However, interestingly, mice receiving SBF2-AS1-deficient db/db-EXO showed a decrease in cardiac fibrosis. Similarly, AdEXO-SBF2-AS1 promoted aHCFs proliferation and transformation capabilities in vitro. Mechanistically, SBF2-AS1 induced UBC9 overexpression to catalyze the SUMOylation of hnRNPA1, which facilitated its packaging into exosomes. Subsequently, exosomal SBF2-AS1 was specifically transmitted into aHCFs and epigenetically downregulated Nrf2 expression by decreasing H3K9 acetylation level in the Nrf2 promoter.Conclusions:Our findings highlight a novel mechanism whereby the AdEXO-mediated SBF2-AS1/hnRNPA1/Nrf2 regulatory axis promotes diabetic myocardial fibrosis in a SUMOylation-dependent manner and implicate SBF2-AS1 as an attractive therapeutic target for DCM.

Purely concentration-gradient driven liquid-liquid interface laser beam deflection detection was studied theoretically and used experimentally to monitor the kinetics of diffusion between water and sugar as a simple model system. The combination of data from both sides of the interface was used to determine the initial position of the interface plane. The developed one-dimensional model of the dependence of the laser beam deflection on the diffusion parameters was found to be in good agreement with the experimental data, especially at early interdiffusion times. The model was thus able to yield the values for the diffusion coefficient Dsof sugar in water, and for the refractive index gradient ∂n/∂Cs.

Since the commercialization of surface acoustic wave (SAW) devices, the technology is steadily increasing the device performances without compromising their power handling, size and price. Herein, one‐port SAW resonators are fabricated on scandium aluminum nitride (Sc0.26Al0.74N)/polycrystalline diamond heterostructures. SAW propagation properties are studied using three different piezoelectric thin‐film thicknesses within the heterostructure. The Rayleigh and Sezawa resonance frequencies are above 1.5 and 2.5 GHz, respectively, achieving Sezawa mode reflection coefficients below −50 dB. The polycrystalline diamond substrate is synthesized by microwave plasma chemical vapor deposition (MPCVD) on top of a 500 μm‐thick Si (001) substrate. The Sc0.26Al0.74N thin films are synthesized by reactive sputtering at nominally room temperature. The thin film's composition is analyzed by Rutherford backscattering spectrometry (RBS). The full width at half maximum (FWHM) of the X‐ray diffraction (XRD) ωscans below 3° indicates that the synthesized Sc0.26Al0.74N thin films are highly c‐axis oriented. The electromechanical coupling coefficient, quality factor, and dielectric loss parameters are computed by curve fitting the device electrical measurements to the simulation results of a modified Butterworth Van Dyke (mBVD) model implemented in the advance design system (ADS) tool. Herein, the characteristics of a novel piezoelectric compound in devices are studied within the scope of their use in the 5G telecommunications industry.

The ferroelectric domain layer wave (FDLW) in the ABA type 180° domain sandwich has been discussed. The polarized direction of A material is opposite to that of B material. The results show that there exist two types of ferroelectric domain layer waves in the structure. One is the FDLW of symmetric vibration [X. Li, J. Appl. Phys. 56, 88 (1984)], another is the FDLW of asymmetric vibration. The asymmetric vibration FDLW is a new FDLW, it has a cutoff frequency. From the dispersion relation of the two modes, it is shown that the frequency of the asymmetry mode is higher than the frequency of the symmetry mode. The amplitudes of displacement fields and potential fields of the asymmetry mode are smaller than that of the symmetry mode in the B layer. The system that is composed of the different A, B materials have been analyzed and the general dispersion relation is given; it has a very simple formation, and the relations between the parameter of A, B material and dispersion relation have been discussed.