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Diagram of the Smart Wound Management Microneedle Patch. Smart microneedle patches combine treatment and monitoring for real-time diagnosis.

In recent years, chemodynamic therapy (CDT) has received extensive attention as a novel means of cancer treatment. The CDT agents can exert Fenton and Fenton-like reactions in the acidic tumor microenvironment (TME), converting hydrogen peroxide (H

Magnetoelectric (ME) sandwich structure is a common form in device applications. Poling directions of component materials are essential for the improvement of ME device properties. In this paper, the effects of the electric and magnetic poling directions on the interface fracture of a ME sandwich structure are investigated by integral transform and singular integral equation techniques. The expressions of the normalized stress intensity factors (NSIFs) are derived, and some numerical examples are presented. It is found that the poling direction of active layer can greatly affect the interface cracking mode. And the crack propagation can be promoted or impeded by adjusting the applied field. The structure with a larger volume fraction of active material will be more likely to crack.

Hypoxia is a major stressor and a prominent feature of pathological conditions, such as bacterial infections, inflammation, wounds, and cardiovascular defects. In this study, we investigated whether reoxygenation has a protective effect against hypoxia-induced acute injury and burn using the C57BL/6 mouse model. C57BL/6 mice were exposed to hypoxia and treated with both acute and burn injuries and were in hypoxia until wound healing. Next, C57BL/6 mice were exposed to hypoxia for three days and then transferred to normoxic conditions for reoxygenation until wound healing. Finally, skin wound tissue was collected to analyze healing-related markers, such as inflammation, vascularization, and collagen. Hypoxia significantly increased inflammatory cell infiltration and decreased vascular and collagen production, and reoxygenation notably attenuated hypoxia-induced infiltration of inflammatory cells, upregulation of pro-inflammatory cytokine levels (IL-6 and TNF-α) in the wound, and remission of inflammation in the wound. Immunofluorescence analysis showed that reoxygenation increased the expression of the angiogenic factor α-SMA and decreased ROS expression in burn tissues compared to hypoxia-treated animals. Moreover, further analysis by qPCR showed that reoxygenation could alleviate the expression of hypoxic-induced inflammatory markers (IL-6 and TNF), increase angiogenesis (SMA) and collagen synthesis (Col I), and thus promote wound healing. It is suggested that oxygen can be further evaluated in combination with oxygen-releasing materials as a supplementary therapy for patients with chronic hypoxic wounds.

Tubulointerstitial fibrosis (TIF) is an important pathological change that occurs during the development of diabetic kidney disease. The epithelial‑mesenchymal transition (EMT) of renal tubular epithelial cells is a manifestation of TIF. STAT1, a member of the STAT family of transcription factors, can be modified by the small ubiquitin‑related modifier (SUMO), thus affecting the activity of STAT1. The present study investigated the role of STAT1 SUMOylation in high glucose‑induced tubular EMT by western blotting, immunocytochemistry, immunofluorescence, co‑immunoprecipitation and dual luciferase reporter analysis. The results indicated that in the process of high glucose‑induced EMT, STAT1 activation protected the cells from EMT. However, high glucose also increased the SUMOylation of STAT1, which prevented STAT1 from exerting an effective protective role by inhibiting its activity.

Hypoxic nonhealing wounds are a common complication in chronic patients, and chronic hypoxia is the main reason for delayed wound healing, so local wound oxygenation may be an effective way to address this problem. Here, we proposed a system consisting of oxygen-releasing microsphere (GC) and self-healing hydrogel (QGO). QGO/GC hydrogel could promote survival, migration and tube formation of human umbilical vein endothelial cells under hypoxic conditions. Moreover, QGO/GC hydrogels exhibited biocompatibility in vitro and in vivo. The hypoxic mouse burn model further confirmed that QGO/GC hydrogel could promote tissue repair by reducing inflammation (TNF-α and IL-1β), increasing angiogenesis (CD31, VEGF and α-SMA) and collagen deposition. This study provided an effective oxygen-releasing hydrogel that could offer a simple and effective method for the clinical treatment of chronic hypoxic wounds. STATEMENT OF SIGNIFICANCE: Burn injury is caused by various exogenous factors such as friction, cold, radiations, electricity, chemicals, hot surfaces or liquids. Severe burn can damage the entire skin layer, and the healing process is delayed due to an unbalanced inflammatory response, excessive reactive oxygen species, lack of angiogenesis (insufficient nutrient and oxygen availability), and susceptibility to infection. In the present study, we proposed an oxygen-releasing hydrogel (QGO/GC). QGO/GC hydrogel could promote survival, migration, and tube formation of human umbilical vein endothelial cells under hypoxic conditions. And QGO/GC hydrogels could promote tissue repair by reducing inflammation, increasing angiogenesis and collagen deposition. This work provided an effective oxygen-releasing hydrogel for the clinical management of chronic hypoxic wounds.

Cancer seriously endangers human life and health. Recently, the development of AIEgens with aggregation-induced emission (AIE) effect as a new generation of photosensitizers (PSs) to circumvent aggregation-induced fluorescence quenching and reduction of ROS generation has received extensive attention in photodynamic therapy (PDT), a non-invasive anticancer therapy. Rational molecular design can enhance the photosensitization of AIE PSs to achieve effective PDT and can realize the construction of functionalized AIE PSs and synergistic therapy based on AIE PSs. To improve the efficacy of AIE PSs for cancer treatment, many groups have conducted molecular design studies and produced exciting results. This review summarizes the molecular design strategies of three types of AIE PSs for effective photodynamic therapy, focusing on the design strategies of pure organic small molecule type AIE PSs, and reviews the existing design strategies of metal complexes and conjugated polymers. Subsequently, the design strategy to achieve synergistic treatment of AIE PSs from molecular modifications is summarized. The challenges and prospects of the AIE PSs research field are further discussed.

Tripartite motif-containing 27 (TRIM27) belongs to the triple motif (TRIM) protein family, which plays a role in a variety of biological activities. Our previous study showed that the TRIM27 protein was highly expressed in the glomerular endothelial cells of patients suffering from lupus nephritis (LN). However, whether TRIM27 is involved in the injury of glomerular endothelial cells in lupus nephritis remains to be clarified. Here, we detected the expression of the TRIM27 protein in glomerular endothelial cells in vivo and in vitro. In addition, the influence of TRIM27 knockdown on endothelial cell damage in MRL/lpr mice and cultured human renal glomerular endothelial cells (HRGECs) was explored. The results revealed that the expression of TRIM27 in endothelial cells was significantly enhanced in vivo and in vitro. Downregulating the expression of TRIM27 inhibited the breakdown of the glycocalyx and the injury of endothelial cells via the FoxO1 pathway. Moreover, HRGECs transfected with the WT-FoxO1 plasmid showed a reduction in impairment caused by LN plasma. Furthermore, suppression of the protein kinase B (Akt) pathway could attenuate damage by mediating the expression of TRIM27. Thus, the present study showed that TRIM27 participated in the injury of glomerular endothelial cells and served as a potential therapeutic target for the treatment of lupus nephritis.

The propagation of shear-horizontal (SH) waves in the periodic layered nanocomposite is investigated by using both the nonlocal integral model and the nonlocal differential model with the interface effect. Based on the transfer matrix method and the Bloch theory, the band structures for SH waves with both vertical and oblique incidences to the structure are obtained. It is found that by choosing appropriate interface parameters, the dispersion curves predicted by the nonlocal differential model with the interface effect can be tuned to be the same as those based on the nonlocal integral model. Thus, by propagating the SH waves vertically and obliquely to the periodic layered nanostructure, we could invert, respectively, the interface mass density and the interface shear modulus, by matching the dispersion curves. Examples are further shown on how to determine the interface mass density and the interface shear modulus in theory.

Love-type wave propagation has been studied in a layered structure consisting of a thin layer of PMN-PT single crystal deposited on an elastic half-space. The weakly periodic undulations of the upper surface of the layered system and the common interface between the PMN-PT layer and the elastic substrate are considered. The PMN-PT single crystal is poled along the [011]_c direction so that the macroscopic symmetry is orthonormal mm2. The dispersion relations for electrically open and shorted circuits are obtained. The effects of various parameters including corrugation, undulatory, position and electrical boundary conditions on dispersion properties of Love-type waves are discussed. The results show that corrugations of the surface and the interface play a dominant role in the propagation of a Love-type wave, especially, the interfacial corrugation can produce an anomalous dispersion in the case of an electrically shorted condition. The surface corrugation enhances the phase velocity of a Love-type wave while the interface corrugation reduces the phase velocity in the range of relatively smaller wavenumber, and these variations gradually tend to vanish with increase in wavenumber. The undulatory parameter and the position parameter present a secondary impact on the dispersion behaviors of a Love-type wave compared with the corrugation parameters, both of them slightly enhance the phase velocity. The obtained results can offer some fundamentals for improving the efficiency and sensitivity of the interface response in the design and application of piezoelectric SAW devices.

In this paper, the nonlinear vibration control of sandwich shallow doubly-curved nanoshells with functionally graded piezoelectric (FGP) nanocomposite sensors and actuators is investigated based on...

A full-coupling model on the current-voltage (J-V) characteristics of PN junctions is put forward in the paper by taking into account both the whole junction and the two electrode regions consisting of metal/semiconductor (M/S) contacts. The depletion layer assumption proposed by the Shockley model is discarded. Gauss’ law on the electric potential and the electric field is applied in the whole junction region such that the majority-carrier currents inside and outside the P/N barrier region are able to be exactly defined and clearly calculated. Then, the stable continuity equations of the electron and hole currents are established to show the current conversion between minority- and majority-carriers inside the whole PN junction region. By analyzing all the conversion procedure, the J-V characteristics of a PN junction are obtained with good agreement to the experimental results, which are closely dependent on the minority-carrier lifetime and doping concentrations. Obviously, the study on this topic possesses referential significance to mechanically tuning the performance of piezoelectric PN junctions and piezotronics devices.

Due to the incompatibility of the interlaminar deformations, the interface debonding or cracking usually happens in a layered magnetoelectric (ME) structure under an applied load. In this paper, the transient responses of the anti-plane interface cracks in piezoelectric (PE)-piezomagnetic (PM) sandwich structures are studied by the standard methods of the integral transform and singular integral equation. Discussion on the numerical examples indicates that the PE-PM-PE structure under electric impact is more likely to fracture than the PM-PE-PM structure under a magnetic impact. The dynamic stress intensity factors (DSIFs) are more sensitive to the variation of the active layer thickness. The effects of the material constants on the DSIFs are dependent on the roles played by PE and PM media during the deformation process.

Circular RNAs (circRNAs) are regulators of gene expression that can regulate cell proliferation and programmed cell death and serve as biomarkers in renal diseases. However, the specific traits and underlying mechanisms of circRNAs in the progression of lupus nephritis (LN) have not been elucidated. In the present study, we clarified that hsa_circ_0054595 (circRTN4) was upregulated in human renal mesangial cells (HRMCs). In cultured HRMCs, circRTN4 could enhance FN expression by directly interacting with miR-513a-5p. High circRTN4 expression in monocytes disseminated into HRMCs in an exosomal manner, thereby accelerating cell proliferation and extracellular matrix deposition. In addition, knockdown of circRTN4 in the kidney or peripheral blood alleviated renal damage in MRL/lpr and BALB/c mice. Clinically, high levels of circRTN4 were found in peripheral blood mononuclear cells and kidney tissues of LN patients, hence serving as an effective biomarker for LN detection and a novel therapeutic target. Our findings indicated that circRTN4 exacerbates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis.

IntroductionAlthough various lipid and non-lipid analytes measured by nuclear magnetic resonance (NMR) spectroscopy have been associated with type 2 diabetes, a structured comparison of the ability of NMR-derived biomarkers and standard lipids to predict individual diabetes risk has not been undertaken in larger studies nor among individuals at high risk of diabetes.Research design and methodsCumulative discriminative utilities of various groups of biomarkers including NMR lipoproteins, related non-lipid biomarkers, standard lipids, and demographic and glycemic traits were compared for short-term (3.2 years) and long-term (15 years) diabetes development in the Diabetes Prevention Program, a multiethnic, placebo-controlled, randomized controlled trial of individuals with pre-diabetes in the USA (N=2590). Logistic regression, Cox proportional hazards model and six different hyperparameter-tuned machine learning algorithms were compared. The Matthews Correlation Coefficient (MCC) was used as the primary measure of discriminative utility.ResultsModels with baseline NMR analytes and their changes did not improve the discriminative utility of simpler models including standard lipids or demographic and glycemic traits. Across all algorithms, models with baseline 2-hour glucose performed the best (max MCC=0.36). Sophisticated machine learning algorithms performed similarly to logistic regression in this study.ConclusionsNMR lipoproteins and related non-lipid biomarkers were associated but did not augment discrimination of diabetes risk beyond traditional diabetes risk factors except for 2-hour glucose. Machine learning algorithms provided no meaningful improvement for discrimination compared with logistic regression, which suggests a lack of influential latent interactions among the analytes assessed in this study.Trial registration numberDiabetes Prevention Program: NCT00004992; Diabetes Prevention Program Outcomes Study: NCT00038727.

Based on the surface/interface theory, the effective magnetoelectric (ME) properties of piezoelectric (PE)–piezomagnetic (PM) composites with elliptical nanofibers are investigated analytically. Using the complex function theory, conformal mapping and the Mori–Tanaka mean-field method, the solutions of magneto-electro-elastic (MEE) fields are obtained, which satisfy both the interface and the single-valued conditions. The closed-form expression of the ME coefficient of the composites shows that the effect of ME coefficient is related to the interface parameters, elliptical aspect ratio, material properties of both fiber and matrix and the fiber volume fraction. Numerical calculation shows that by properly selecting some of these parameters, the effective ME coefficient could be substantially enhanced.

We show systematically that when an interface between two materials is treated as a thin layer modelled by the first-order plate theory, the conventional mechanically, electrically and magnetically imperfect interface conditions can be derived from the plate theory. Specifically, the continuity of those components of the stress tensor, electric displacement vector and magnetic induction vector related to the normal of the interface are continuous at the interface as a consequence of the zero-order plate equations, but the displacement vector, electric potential and magnetic potential may have discontinuities across the interface as a consequence of the first-order plate equations. This procedure also shows the conditions or limitations of the conventional imperfect interface conditions.

The rapid development of computer technology has enabled thousands of stock tradings to happen within a fraction of a second. In this fast-moving market, it is crucial to automate trading with the help of machine learning and deep learning algorithms to free operators from repetitive work and to maximize profit. Buying low and selling high sounds easy but can be difficult to achieve in a highly volatile market. This paper proposes a method that ensembles ResNet, Multi-layer Perceptron and XGBoost to make profitable short-term trading decisions in real-time. The ensemble model outperforms each of the individual model, achieving a reward of 9052 on the Jane Street Market Prediction dataset.

BackgroundIn the evaluation of performance of HIV assays, extreme sample proportions often occur, with test sensitivity and/or specificity of 100%, which making it challenging to assess the assays accuracies. To overcome these challenges, we propose using median estimate as an evaluation indicator for such testing.MethodsBased on the principles of binomial distribution and confidence interval, median estimate was defined as \(p={0.5}^{\frac{1}{n}}\), which means that, when the sample size n is equal to the event number x, namely the sample proportion (e.g., test sensitivity) is 100%, the 50th percentile (median) of p (the estimate of population proportion) is \({0.5}^{\frac{1}{n}}\). After demonstrating the mathematical proof of the median estimate, the key programming commands of commercial software SAS and free software R were given. Subsequently, we developed an Excel-based calculation tool that allows users to fill in data in an Excel sheet without writing any program. Six cases of HIV screening and diagnostic tests and HIV infections incidence data were selected from related articles and World Health Organization reports published between 2009 and 2020.ResultsThe median estimates, which were proved in the range from \(\frac{n-1}{n}\) to 1 and within the confidence interval range, showed statistical plausibility. Six HIV testing cases were presented to illustrate its application and elaborate on the relationship between the median estimate and the conventional simple estimate. These cases demonstrate that, when extreme proportions occurred (i.e., false positive and/or false negative in testing were zero), the conventional simple estimates of sensitivity, specificity, positive predictive value, and negative predictive value were 100% regardless of the sample size and prevalence. In contrast, the corresponding median estimates varied depending on the sample size and prevalence.ConclusionsAs evaluation indicators of HIV assays with extreme proportions, median estimates were more effective than conventional simple estimates. However, simple estimates objectively expressed the results of HIV testing. Because the correlation between median estimates and simple estimates was seamless, the two types of indicators were complementary in the evaluation of testing with extreme proportions. Hence, using both types of estimates could help evaluate HIV assays with extreme proportions more comprehensively.

Tripartite motif-containing 27 (TRIM27) belongs to the triple motif (TRIM) protein family, which plays a role in a variety of biological activities. Our previous study showed that the TRIM27 protein was highly expressed in the glomerular endothelial cells of patients suffering from lupus nephritis (LN). However, whether TRIM27 is involved in the injury of glomerular endothelial cells in lupus nephritis remains to be clarified. Here, we detected the expression of the TRIM27 protein in glomerular endothelial cells in vivo and in vitro. In addition, the influence of TRIM27 knockdown on endothelial cell damage in MRL/lpr mice and cultured human renal glomerular endothelial cells (HRGECs) was explored. The results revealed that the expression of TRIM27 in endothelial cells was significantly enhanced in vivo and in vitro. Downregulating the expression of TRIM27 inhibited the breakdown of the glycocalyx and the injury of endothelial cells via the FoxO1 pathway. Moreover, HRGECs transfected with the WT-FoxO1 plasmid showed a reduction in impairment caused by LN plasma. Furthermore, suppression of the protein kinase B (Akt) pathway could attenuate damage by mediating the expression of TRIM27. Thus, the present study showed that TRIM27 participated in the injury of glomerular endothelial cells and served as a potential therapeutic target for the treatment of lupus nephritis.