Circulating B Cell-Derived Small RNA Delivered by Extracellular Vesicles: A Dialogue Mechanism for Long-Range Targeted Renal Mitochondrial Injury in Obesity.

The intricate processes that govern the interactions between peripatetic immune cells and distal renal injury in obesity are not fully understood. Employing transcriptomic analysis of circulating extracellular vesicles (EVs), a marked amplification of small RNA (miR-3960) is discerned within CD3-CD19+ B cells. This RNA is found to be preferentially augmented in kidney tissues, contrasting with its subdued expression in other organs. By synthesizing dual-luciferase reporter assay with co-immunoprecipitation analysis, it is pinpointed that miR-3960 specifically targets the nuclear gene TRMT5, a pivotal actor in the methylation of mitochondrial tRNA. This liaison instigates aberrations in the post-transcriptional modifications of mitochondrial tRNA, engendering deficiencies within the electron respiratory chain, primarily attributable to the diminution of the mitochondrial bioenergetic compound (NDUFA7) complex I. Such perturbations lead to a compromised mitochondrial respiratory capacity in renal tubular cells, thereby exacerbating tubular injury. In contrast, EV blockade or miR-3960 depletion markedly alleviates renal tubular injury in obesity. This investigation unveils a hitherto unexplored pathway by which obesity-induced circulating immune cells remotely manipulate mitochondrial metabolism in target organs. The strategic targeting of obese EVs or infiltrative immune cells and their specifically secreted RNAs emerges as a promising therapeutic avenue to forestall obesity-related renal afflictions.

Tunable composite lattice structure for low-frequency and ultra-broadband underwater sound absorption.

The underwater sound absorption technique in low-frequency and broadband has far-reaching prospects since it is essential for noise reduction of deep-sea operation requirements and evading advanced underwater target detection. Here, we propose an underwater sound-absorbing composite lattice with low-frequency and ultra-broadband characteristics. The composite lattice is constructed by regular spatially stacking cells with different sizes of metallic core spheres. All the core spheres are coated with silicon rubbers, and cells are embedded in the rubber matrix. In the composite lattice stereostructure, the lattice cells convert incident longitudinal waves into transverse waves through multiple local resonance coupling and multiple scattering. The energy is localized and dissipated in the composite lattice. We analyze the relationship among the corresponding absorption spectrums, the displacement clouds, and the resonance modes of lattice cells. Then, we construct a composite lattice and realize low-frequency broadband absorption from 693 to 1106 Hz with absorptance above 0.8. Further, our investigation demonstrates that the absorption bandwidth can be extended to ultra-broadband from 1077 to 10 000 Hz, where the thickness of the composite lattice is λ/17.05. The proposed composite lattice provides a practical approach to designing ultrathin low-frequency and ultra-broadband acoustic absorption coating for underwater noise suppression.

Calycosin-loaded nanoliposomes as potential nanoplatforms for treatment of diabetic nephropathy through regulation of mitochondrial respiratory function.

BACKGROUNDS: One of the most common complications in diabetic nephropathy is generation of high levels of ROS which can be regulated by herbal antioxidants. However, polyphenols like calycosin, the bioactive compound of Radix astragali suffer from low solubility and poor bioavailability. METHODS: Therefore, in the present study, calycosin-loaded nanoliposomes were fabricated and characterized by TEM, DLS and FTIR techniques. Afterwards, the drug loading (DL) and entrapment efficiency (EE), drug release, solubility, stability, and pharmacodynamic assays were performed. Finally, the antinephropathic effects of calycosin-loaded-nanoliposomes on mitochondria of kidney cells were explored by MTT, ROS, MDA, mitochondrial respiratory function assays. RESULTS: The result showed that the size, hydrodynamic radius, zeta potential, EE, and DL were, 80 nm, 133.99 ± 21.44 nm, - 20.53 ± 3.57, 88.37 ± 2.28%, and 7.48 ± 1.19%, respectively. The outcomes of in vitro release assay showed that calycosin-loaded nanoliposomes were significantly slow-release in dialysis media with pH 1.2, pH 6.9 and pH 7.4, at about 30 min, the dissolution of calycosin from nanoliposome became almost complete, and after 2 months, the calycosin-loaded nanoliposomes were still stable. Pharmacokinetic assay revealed that the AUC0-t of calycosin in calycosin-loaded nanoliposome group was 927.39 ± 124.91 µg/L*h, which was 2.26 times than that of the free calycosin group (**P < 0.01). Additionally, the MRT0-t and t1/2 of calycosin in the calycosin-loaded nanoliposome group were prolonged by 1.54 times and 1.33 times than that of free calycosin group, respectively (*P < 0.05). Finally, it was shown that calycosin-loaded nanoliposomes regulated the viability, ROS production, lipid peroxidation and function of mitochondria in kidney cells of diabetic rats as a model of diabetic nephropathy. CONCLUSION: In conclusion it may be suggested that new therapies based on nano-formulated calycosin can restore mitochondrial function which can improve diabetic nephropathy.

Low-frequency multi-order acoustic absorber based on spiral metasurface.

In this work, we propose a spiral metasurface for multi-order sound absorption in the low-frequency range (<1000 Hz). By dividing the long channel of the spiral metasurface into a series of tunable sub-cavities and employing recessed necks, the metasurface can quasi-perfectly (>0.95 in experiments) absorb airborne sound at multiple low-frequency orders without being limited by the number of equivalent cavities. Owing to the superior impedance manipulation provided by the spiral metasurface, each absorption order can be tuned flexibly with a constant external shape. By suitably modulating the sub-cavities and the recessed necks, we obtained multi-order high-absorption metasurfaces with dual-chamber, tri-chamber, and four-chamber designs. The ratio of the lowest resonant wavelength to the thickness is as high as 78. The samples, which are fabricated by three-dimensional printing technology, were measured to verify the theoretical results. We also investigate the relationship between the geometric parameters of the recessed necks and the sound absorption performance, which facilitates the more feasibly designed multi-order metasurfaces. The concept can be further applied to broadband absorption with ultra-thin thickness and has potential applications for noise reduction.

Acoustic perfect absorbers via Helmholtz resonators with embedded apertures.

Acoustic perfect absorption via a structure with deep subwavelength thickness is of great and continuing interest in research and engineering. This study analytically and experimentally investigates acoustic systems based on Helmholtz resonators which have embedded-apertures. The strategy of embedding apertures greatly improves the ability to manipulate the impedance of the systems. Based on the inverted configuration, perfect absorption has been realized (reaching 0.999 in experiments) via a design whose thickness is only ∼1/50th of the operating wavelength. Moreover, a tunable resonant frequency (137-300 Hz) and tunable absorption frequency bandwidth (22%-46%) can be achieved while preserving the perfect absorption performance and constant external shape. In tuning the perfect absorbers having a constant thickness, a conservation factor is revealed experimentally and then verified analytically, which could guide absorbers' design and facilitate the tuning. In addition, the distinct features of the proposed design were evaluated and validated and were compared with those of a related structure, a metasurface with a coiled backing cavity. The results have the potential to help with the design of highly efficient, thin, and tunable acoustic absorbers.

Inflammation-related nomogram for predicting survival of patients with unresectable hepatocellular carcinoma received conversion therapy.

BACKGROUND: The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC) is a common clinical concern. AIM: To analyse the prognostic factors of overall survival (OS) in patients with unresectable HCC who received conversion therapy. METHODS: One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort (n = 120) and a validation cohort (n = 30). Using the independent risk factors in the training cohort, a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection. The nomogram was internally validated with the bootstrapping method. The predictive performance of nomogram was assessed by Harrell's concordance index (C-index), calibration plot and time-dependent receiver operating characteristic curves and compared with six other conventional HCC staging systems. RESULTS: Multivariate Cox analysis identified that albumin, blood urea nitrogen, gamma-glutamyl transpeptidase to platelet ratio, platelet to lymphocyte ratio, macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model. The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS, which were higher than those of the six conventional HCC staging systems (0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort). The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS. Decision curve analyses indicated satisfactory clinical utility. With a total nomogram score of 196, patients were accurately classified into low-risk and high-risk groups. Furthermore, we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/. CONCLUSION: The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy, which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.

Broadband impedance modulation via non-local acoustic metamaterials.

Causality of linear time-invariant systems inherently defines the wave-matter interaction process in wave physics. This principle imposes strict constraints on the interfacial response of materials on various physical platforms. A typical consequence is that a delicate balance has to be struck between the conflicting bandwidth and geometric thickness when constructing a medium with desired impedance, which makes it challenging to realize broadband impedance modulation with compact structures. In pursuit of improvement, the over-damped recipe and the reduced excessive response recipe are creatively presented in this work. As a proof-of-concept demonstration, we construct a metamaterial with intensive mode density that supports strong non-locality over a frequency band from 320 Hz to 6400 Hz. Under the guidelines of the over-damped recipe and the reduced excessive response recipe, the metamaterial realizes impedance matching to air and exhibits broadband near-perfect absorption without evident impedance oscillation and absorption dips in the working frequency band. We further present a dual-functional design capable of frequency-selective absorption and reflection by concentrating the resonance modes in three frequency bands. Our research reveals the significance of over-damped recipe and the strong non-local effect in broadband impedance modulation, which may open up avenues for constructing efficient artificial impedance boundaries for energy absorption and other wave manipulation.

Conceptual Framework for Smart Health: A Multi-Dimensional Model Using IPO Logic to Link Drivers and Outcomes.

Smart health is considered to be a new phase in the application of information and communication technologies (ICT) in healthcare that can improve its efficiency and sustainability. However, based on our literature review on the concept of smart health, there is a lack of a comprehensive perspective on the concept of smart health and a framework for how to link the drivers and outcomes of smart health. This paper aims to interweave the drivers and outcomes in a multi-dimensional framework under the input-process-output (IPO) logic of the "system view" so as to promote a deeper understanding of the model of smart health. In addition to the collection of studies, we used the modified Delphi method (MDM) to invite 10 experts from different fields, and the views of the panelists were analyzed and integrated through a three-round iterative process to reach a consensus on the elements included in the conceptual framework. The study revealed that smart health contains five drivers (community, technology, policy, service, and management) and eight outcomes (efficient, smart, sustainable, planned, trustworthy, safe, equitable, health-beneficial, and economic). They all represent a unique aspect of smart health. This paper expands the research horizon of smart health, shifting from a single technology to multiple perspectives, such as community and management, to guide the development of policies and plans in order to promote smart health.

Topological Supercavity Resonances in the Finite System.

Acoustic resonant cavities play a vital role in modern acoustical systems. The ultrahigh quality-factor resonances are highly desired for some applications such as high-resolution acoustic sensors and acoustic lasers. Here, a class of supercavity resonances is theoretically proposed and experimentally demonstrated in a coupled acoustic resonator system, arising from the merged bound states in the continuum (BICs) in geometry space. Their topological origin is demonstrated by explicitly calculating their topological charges before and after BIC merging, accompanied by charges annihilation. Compared with other types of BICs, they are robust to the perturbation brought by fabrication imperfection. Moreover, it is found that such supercavity modes can be linked with the Friedrich-Wintgen BICs supported by an entire rectangular (cuboid) resonator sandwiched between two rectangular (or circular) waveguides and thus more supercavity modes are constructed. Then, these coupled resonators are fabricated and such a unique phenomenon-moving, merging, and vanishing of BICs-is experimentally confirmed by measuring their reflection spectra, which show good agreement with the numerical simulation and theoretical prediction of mode evolution. The results may find exciting applications in acoustic and photonics, such as enhanced acoustic emission, filtering, and sensing.

Sound trapping in an open resonator.

The ability of sound energy confinement with high-quality factor resonance is of vital importance for acoustic devices requiring high intensity and hypersensitivity in biological ultrasonics, enhanced collimated sound emission (i.e. sound laser) and high-resolution sensing. However, structures reported so far have been experimentally demonstrated with a limited quality factor of acoustic resonances, up to several tens in an open resonator. The emergence of bound states in the continuum makes it possible to realize high quality factor acoustic modes. Here, we report the theoretical design and experimental demonstration of acoustic bound states in the continuum supported by a single open resonator. We predicted that such an open acoustic resonator could simultaneously support three types of bound states in the continuum, including symmetry protected bound states in the continuum, Friedrich-Wintgen bound states in the continuum induced by mode interference, as well as a new type-mirror symmetry induced bound states in the continuum. We also experimentally demonstrated their existence with quality factor up to one order of magnitude greater than the highest quality factor reported in an open resonator.

miR-6869-5p Transported by Plasma Extracellular Vesicles Mediates Renal Tubule Injury and Renin-Angiotensin System Activation in Obesity.

Obesity increases the risk of other diseases, including kidney disease. Local renal tubular renin-angiotensin system (RAS) activation may play a role in obesity-associated kidney disease. Extracellular vehicles (EVs) transmit necessary information in obesity and cause remote organ damage, but the mechanism is unclear. The aim of the study was to investigate whether the plasma EVs cargo miR-6869-5p causes RAS activation and renal tubular damage. We isolated plasma EVs from obese and lean subjects and analyzed differentially-expressed miRNAs using RNA-seq. Then, EVs were co-cultured with human proximal renal tubular epithelial cells (PTECs) in vitro. Immunohistochemical pathology was used to assess the degree of RAS activation and tubule injury in vivo. The tubule damage-associated protein and RAS activation components were detected by Western blot. Obesity led to renal tubule injury and RAS activation in humans and mice. Obese-EVs induce RAS activation and renal tubular injury in PTECs. Importantly, miR-6869-5p-treated PTECs caused RAS activation and renal tubular injury, similar to Obese-EVs. Inhibiting miR-6869-5p decreased RAS activation and renal tubular damage. Our findings indicate that plasma Obese-EVs induce renal tubule injury and RAS activation via miR-6869-5p transport. Thus, miR-6869-5p in plasma Obese-EVs could be a therapeutic target for local RAS activation in obesity-associated kidney disease.

Compact broadband acoustic sink with coherently coupled weak resonances.

Broadband sound sink/absorber via a structure with deep sub-wavelength thickness is of great and continuing interest in physics and engineering communities. An intuitive technique extensively used is to combine components (resonators) with quasi-perfect absorption to piece together a broad absorbing band, but the requirement of quasi-perfect absorption substantially places a very strict restriction on the impedance and thickness of the components. Here, we theoretically and experimentally demonstrate that a compact broadband acoustic sink that quasi-perfectly absorbs broadband arriving sound waves can be achieved with coherently coupled "weak resonances" (resonant sound absorbing systems with low absorption peaks). Although each component exhibits rather low absorption peak alone, via manipulating the coherent coupling effect among the components, they collectively provide a remarkably improved performance over a wide frequency range with a significantly compressed thickness. To illustrate the design principle, a hybrid metasurface utilizing the coaction of parallel and cascade couplings is presented, which possesses an average absorption coefficient of 0.957 in the quasi-perfect band (α>0.9) from 870 to 3224 Hz with a thickness of only 3.9 cm. Our results open new avenues for the development of novel and highly efficient acoustic absorbers against low frequency noise, and more essentially, suggest an efficient approach towards on-demand acoustic impedance engineering in broadband.

Activation of G protein coupled estrogen receptor (GPER) promotes the migration of renal cell carcinoma via the PI3K/AKT/MMP-9 signals.

Renal cell carcinoma (RCC) is the third most frequent malignancy within urological oncology. However, the mechanisms responsible for RCC metastasis are still needed further illustration. Our present study revealed that a seven-transmembrane receptor G-protein coupled estrogen receptor (GPER) was highly detected in various RCC cell lines such as ACHN, OS-RC-2 and SW839. The activation of GPER by its specific agonist G-1 significantly promoted the in vitro migration and invasion of ACHN and OS-RC-2 cells. G-1 also up regulated the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. The inhibitor of MMP-9 (Cat-444278), but not MMP-2 (Sc-204092), abolished G-1 induced cell migration, which suggested that MMP-9 is the key molecule mediating G-1 induced RCC progression. Further, G-1 treatment resulted in phosphorylation of AKT and ERK in RCC cells. PI3K/AKT inhibitor (LY294002), while not ERK inhibitor (PD98059), significantly abolished G-1 induced up regulation of MMP-9 in both AHCN and OS-RC-2 cells. Generally, our data revealed that activation of GPER by its specific agonist G-1 promoted the metastasis of RCC cells through PI3K/AKT/MMP-9 signals, which might be a promising new target for drug discovery of RCC patients.