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With the development of high-temperature packaging technology, silicon carbide (SiC) metal-oxide-semiconductor field-effect transistors (mosfets) can operate under high-temperature conditions with junction temperatures exceeding 175 °C, providing a solution for pulsed power applications facing instantaneous high currents and significant temperature fluctuations. However, the electro-thermal coupling behaviors and safe operating area (SOA) of SiC mosfets in a wide temperature range are unclear, and there is a lack of guiding principles for SiC module packaging and heat dissipation design in pulsed power applications. In this article, an electro-thermal coupling model of SiC mosfet modules is established. The electrical model over a wide temperature range (25 °C–375 °C) is built in Simulink, and the thermal finite element model is established in COMSOL, while MATLAB script is used to implement interaction between the two models. Then, detailed analyses are conducted on the electro-thermal coupling behaviors of SiC mosfet modules. Besides, the impact of packaging on the SOA of SiC mosfet modules is researched. In addition, a transient junction temperature measurement method of SiC mosfets is proposed by using the on-state resistance Rds(on) as the temperature-sensitive electrical parameter. Finally, the discharge experiments of the capacitor bank through resistive loads are carried out under short pulse and long pulse, respectively, and the experimental results are consistent with the model.

Eye tracking has shown great promise in many scientific fields and daily applications, ranging from the early detection of mental health disorders to foveated rendering in virtual reality (VR). These applications all call for a robust system for high-frequency near-eye movement sensing and analysis in high precision, which cannot be guaranteed by the existing eye tracking solutions with CCD/CMOS cameras. To bridge the gap, in this paper, we propose Swift-Eye, an offline precise and robust pupil estimation and tracking framework to support high-frequency near-eye movement analysis, especially when the pupil region is partially occluded. Swift-Eye is built upon the emerging event cameras to capture the high-speed movement of eyes in high temporal resolution. Then, a series of bespoke components are designed to generate high-quality near-eye movement video at a high frame rate over kilohertz and deal with the occlusion over the pupil caused by involuntary eye blinks. According to our extensive evaluations on EV-Eye, a large-scale public dataset for eye tracking using event cameras, Swift-Eye shows high robustness against significant occlusion. It can improve the IoU and F1-score of the pupil estimation by 20% and 12.5% respectively, compared with the second-best competing approach, when over 80% of the pupil region is occluded by the eyelid. Lastly, it provides continuous and smooth traces of pupils in extremely high temporal resolution and can support high-frequency eye movement analysis and a number of potential applications, such as mental health diagnosis, behaviour-brain association, etc. The implementation details and source codes can be found at https://github.com/ztysdu/Swift-Eye.

Reperfusion injury presents a significant obstacle to neuronal survival following successful recanalization in ischemic stroke, which is characterized by intricate pathophysiological processes comprising numerous interconnected pathways. Oxidative stress-induced neuronal ferroptosis and the overactivation of glial cells play important roles in this phenomenon. In this study, we developed a targeted cross-linked micelle loaded with idebenone to rescue the ischemic penumbra by inhibiting neuronal ferroptosis and glial overactivation. In rat models, the CREKA peptide-modified micelles accumulate in the damaged brain via binding to microthrombi in the ipsilateral microvessels. Upon reactive oxygen species (ROS) stimulation, diselenide bonds within the micelles are transformed to hydrophilic seleninic acids, enabling synchronized ROS consumption and responsive drug release. The released idebenone scavenges ROS, prevents oxidative stress-induced neuronal ferroptosis, attenuates glial overactivation, and suppresses pro-inflammatory factors secretion, thereby modulating the inflammatory microenvironment. Finally, this micelle significantly reinforces neuronal survival, reduces infarct volume, and improves behavioral function compared to the control groups. This pleiotropic therapeutic micelle provides a proof-of-concept of remodeling the lesion microenvironment by inhibiting neuronal ferroptosis and glial overactivation to treat cerebral ischemia-reperfusion injury.

Due to the outstanding material properties, silicon carbide (SiC) power device is the most promising alternative to silicon devices and can work at higher junction temperature. However, existing packaging technologies obstruct the use of SiC devices at high temperature and impede the continued exploration of SiC devices in high-temperature applications. This article proposes a novel hermetic metal packaging method called compact-interleaved package. The compact-interleaved power module handles the mentioned problems from three key considerations: packaging parasitic parameters, direct electrode measurement structure, and packaging materials. Based on the elaborate high-temperature double pulse test platform, dynamic characteristics of 1.2-kV/13-mΩ 4H-SiC power mosfet are studied under the condition of extremely high junction temperature (up to 550 °C) and extremely high switching speed (about 3 kA/μs). The dynamic characteristics of SiC mosfet are theoretically analyzed and verified by experimental measurements. Compared with other SiC bipolar devices, SiC mosfet maintains outstanding dynamic characteristics at extremely high temperatures and has an optimal operating high-temperature range. Finally, this article demonstrates an extreme-high-temperature power electronic converter to verify the superiority of the packaging method, and also proves the extreme-high-temperature power converting capability of SiC mosfet.

Characterizing package parasitic inductance is significant for package design, dynamic characteristic evaluation, thermal management, and insulation breakdown protection. As package parasitic inductances become smaller and the switching speed of the power semiconductor becomes higher, traditional and widely-used double pulse tests based on the “$L = V/({di/dt})$” and “$L = {\rm{ }}1/({4{\pi }^2{f}^2C})$” present more critical drawbacks in accuracy and adaptability. This letter proposes a novel method called objective-based low-frequency-range parasitic inductance characterization to accurately obtain the parasitic inductance of semiconductor packages. The proposed method directly extracts the package inductances instead of the current commutation loop and can be carried out under low bus voltage and low frequency. Thus, the proposed method features higher robustness, adaptability, and accuracy. Experimental results in the commercial silicon carbide power device/module validate the feasibility and superiority of the proposed method.

This paper proposes a highly integrated multichip silicon carbide (SiC) MOSFET power module packaging with optimized electrical and thermal performances. The structure of the module is to stack the two power switches up and down with the cooling system and the decoupling circuit integrated inside the module. The structural characteristics of the module realize the co-optimization of the switching performance, thermal management, and electromagnetic interference (EMI) issue of the multichip SiC module, which effectively solve the contradiction in the optimization of the electrical and thermal performance. In addition, by optimizing the process flow and designing a variety of soldering fixtures, the feasibility of the process and the engineering margin is increased. Experiments and simulations show that the proposed SiC power module has good electrical and thermal performance. The loop parasitic inductance is reduced to 2.02 nH and the common-mode (CM) current is eliminated. The drain–source voltage overshoot during the turn-off transient is reduced by 76.5%, and the voltage oscillation is significantly improved due to the integration of the decoupling circuit. At the same time, the integrated liquid-cooling heatsink greatly improves the cooling efficiency of the module on the premise of ensuring the insulation performance of the module.

Metabolic interactions between different cell types in the tumor microenvironment (TME) often result in reprogramming of the metabolism to be totally different from their normal physiological processes in order to support tumor growth. Many studies have attempted to inhibit tumor growth and activate tumor immunity by regulating the metabolism of tumors and other cells in TME. However, metabolic inhibitors often suffer from the heterogeneity of tumors, since the favorable metabolic regulation of malignant cells and other cells in TME is often inconsistent with each other. Therefore, we reported the design of a pH-sensitive drug delivery system that targets different cells in TME successively. Outer membrane vesicles (OMVs) derived from Gram-negative bacteria were applied to coload paclitaxel (PTX) and regulated in development and DNA damage response 1 (Redd1)-siRNA and regulate tumor metabolism microenvironment and suppress tumor growth. Our siRNA@M-/PTX-CA-OMVs could first release PTX triggered by the tumor pH (pH 6.8). Then the rest of it would be taken in by M2 macrophages to increase their level of glycolysis. Great potential was observed in TAM repolarization, tumor suppression, tumor immune activation, and TME remolding in the triple-negative breast cancer model. The application of the OMV provided an insight for establishing a codelivery platform for chemical drugs and genetic medicines.

Background Although stent-assisted coiling embolization (SAC) has been associated with a higher risk of ischemic and hemorrhagic complications, the use of SAC continues to rise for treating ruptured intracranial aneurysms (RIAs). This study aims to assess the safety and effectiveness of dual antiplatelet therapy (DAPT) in the context of RIAs.Methods We conducted a retrospective analysis at a single center, involving patients with aneurysmal subarachnoid hemorrhage (aSAH) between May 1, 2017 and December 31, 2021. Patients were categorized into two groups: the SAC group and the non-SAC (NSC) group. Patients in the SAC group received DAPT. We compared modified Rankin Scale (mRS) score, along with hemorrhagic and ischemic complications, between the two groups to evaluate the safety and efficacy of DAPT for SAC.Results The study included a total of 541 patients, of whom 38 (7.0%) experienced hemorrhagic complications and 48 (8.9%) developed ischemic complications. Additionally, 99 (18.3%) and 84 (15.5%) had poor clinical outcomes at discharge and 6 months, respectively. However, no statistically significant differences were observed between the two groups. Our analysis revealed that aneurysm location in the posterior circulation was a significant risk factor for an unfavorable prognosis when antiplatelet drugs were used following SAC (p= 0.025).Conclusions Administering antiplatelet drugs after SAC for RIAs has demonstrated both safety and effectiveness. However, caution should be exercised when considering this treatment strategy for RIAs located in the posterior circulation due to the potentially elevated risk.

In mammals, the neonatal heart can regenerate upon injury within a short time after birth, while adults lose this ability. Metabolic reprogramming has been demonstrated to be critical for cardiomyocyte proliferation in the neonatal heart. Herein, we reveal that cardiac metabolic reprogramming could be regulated by altering global protein lactylation. Through performing 4D label-free proteomics and lysine lactylation (Kla) omics analyses in postnatal day 1, 5, and 7 mouse hearts, 2297 Kla sites from 980 proteins are identified, among which 1262 Kla sites from 409 proteins are quantified. Functional clustering analysis reveals that the proteins with altered Kla sites are mainly involved in metabolic processes. The expression and Kla levels of proteins in glycolysis show a positive correlation, while a negative correlation in fatty acid oxidation. Furthermore, we verify the Kla levels of several differentially modified proteins, including ACAT1, ACADL, ACADVL, PFKM, PKM, and NPM1. Overall, our study reports a comprehensive Kla map in the neonatal mouse heart, which will aid in understanding the regulatory network of metabolic reprogramming and cardiac regeneration.

Zika virus (ZIKV) infection can lead to neurological complications and fetal defects, and it has attracted global public health concerns. Effective treatment for ZIKV infection remains elusive, and a preventative vaccine is not yet available. Therapeutics for fetuses need to overcome placenta barriers to reach the fetuses and require higher safety standards. In the present study, we engineered mammalian extracellular vesicles (EVs) to deliver a host restriction factor, interferon-induced transmembrane protein 3 (IFITM3), for the treatment of ZIKV infection. Our results demonstrated that the IFITM3-containing EVs (IFITM3-Exos) suppressed ZIKV viremia by a 2-log reduction in pregnant mice. Moreover, the engineered EVs effectively delivered IFITM3 protein across the placental barrier and suppressed ZIKV in the fetuses with significant reduction of viremia in key fetal organs as measured by quantitative real-time PCR. Mechanistic study showed that IFITM3 was delivered to late endosomes/lysosomes where it inhibited viral entry into the host cells. Our study demonstrated that EVs could act as a cross-placenta drug delivery vehicle to the fetus, and IFITM3, an endogenous restriction factor, is a potential treatment for ZIKV infection during pregnancy.

•We develop a spin-coating and in-situ photoelectrochemical reduction method to prepare dispersed Cu on a photocathode.•We find that thiourea in the precursor plays an important role in obtaining dispersed Cu particles on the Si surface.•The performance of Cu/Si prepared with thiourea in the precursor solution is higher than a sample without thiourea.

Association between alcohol intake and Coronavirus disease 2019 (COVID-19) risk has been explored in several observational studies, but the results are still controversial. These associations may be biased by reverse causation or confounded by other environmental exposures. To avoid potential biases, we used Mendelian randomization (MR) method to evaluate whether alcohol intake is the causal risk factor for COVID-19. Two-sample MR analyses were performed utilizing summary data from the UK Biobank with 38,984 COVID-19 patients and 1,644,784 control participants. Both inverse-variance weighted (IVW) and genetic risk score (GRS) methods were applied to estimate the relationship including COVID-19 vs. general population, hospitalized COVID-19 vs. not hospitalized COVID-19, hospitalized COVID-19 vs. general population, and severe COVID-19 vs. general population. Additionally, we conducted various sensitivity analyses to evaluate the impact of assumptions on the findings and ensure the robustness of the results. Using 80 single nucleotide polymorphisms as instrumental variables, we found that alcohol intake was not significantly associated with the occurrence of COVID-19 in both IVW and GRS methods (IVW: beta = 0.0372; 95% CI − 0.1817 to 0.2561; P= 0.74; GRS: beta = 0.0372, 95% CI − 0.1737 to 0.2481, P= 0.73). Furthermore, similar results were also observed in comparison hospitalized COVID-19 with not hospitalized COVID-19 (IVW: beta = − 0.3625; 95% CI − 1.4151 to 0.6900; P= 0.50; GRS: beta = − 0.3625, 95% CI − 1.3633 to 0.6383, P= 0.48), hospitalized COVID-19 with general population (IVW: beta = − 0.1203; 95% CI − 0.5997 to 0.3591; P= 0.62; GRS: beta = − 0.1203, 95% CI − 0.5352 to 0.2946, P= 0.57), and severe COVID-19 with general population (IVW: beta = 0.2963; 95% CI − 0.3682 to 0.9607; P= 0.38; GRS: beta = 0.2963, 95% CI − 0.3240 to 0.9166, P= 0.35). Besides, the heterogeneity and sensitivity tests suggested absence of bias due to pleiotropy. Our results highlight no evidence to support the causal role of alcohol consumption in COVID-19 risk. Further large-scale prospective studies are warranted to replicate our findings.

High dropping moisture (DM) in poultry production has deleterious effects on the environment, feeding cost, and public health of people and animals. To explore the contributing genetic components, we classified DM of 67-wk-old Rhode Island Red (RIR) hens at 4 different levels and evaluated the underlying genetic heritability. We found the heritability of DM to be 0.219, indicating a moderately heritable trait. We then selected chickens with the highest and lowest DM levels. Using transcriptome, we only detected 12 differentially expressed genes (DEGs) between these 2 groups from the spleen, and 1,507 DEGs from intestinal tissues (jejunum and cecum). The low number of DEGs observed in the spleen suggests that differing moisture levels are not attributed to pathogenic infection. Fourteen of the intestinal high expressed genes are associated with water-salt metabolism (WSM). We also investigated the gut microbial composition by 16S rRNA gene amplicon sequencing. Six different microbial operational taxonomic units (OTUs) (Cetobacterium, Sterolibacterium, Elusimicrobium, Roseburia, Faecalicoccus, and Megamonas) between the 2 groups from jejunum and cecum are potentially biomarkers related to DM levels. Our results identify a genetic component to chicken DM, and can guide breeding strategies.

The rapid postoperative recurrence and short survival time of glioblastoma (GBM) patients necessitate immediate and effective postoperative treatment. Herein, an immediate and mild postoperative local treatment strategy is developed that regulates the postoperative microenvironment and delays GBM recurrence. Briefly, an injectable hydrogel system (imGEL) loaded with Zn(II)2‐AMD3100 (AMD‐Zn) and CpG oligonucleotide nanoparticles (CpG NPs) is injected into the operation cavity, with long‐term function to block the recruitment of microglia/ macrophages and activate cytotoxic T cells. The finding indicated that the imGEL can regulate the immune microenvironment, inhibit GBM recurrence, and gain valuable time for subsequent adjuvant clinical chemotherapy. Based on the current clinical dilemma of glioblastoma, this study describes a simple and mild postoperative local treatment strategy with clinical transformation prospects. Specifically, it is an injectable hydrogel system with the function of regulating the immune post‐operative micro‐environment to kill the residual tumor cells in the empty window period, which has gained valuable time for subsequent adjuvant treatment.

Small heterodimer partner (SHP) is a crucial regulator of bile acid (BA) transport and synthesis; however, its intestine-specific role is not fully understood. Here, we report that male intestine-specific Shpknockout (IShpKO) mice exhibit higher intestinal BA but not hepatic or serum BA levels compared with the f/f Shpanimals when challenged with an acute (5-day) 1% cholic acid (CA) diet. We also found that BA synthetic genes Cyp7a1and Cyp8b1are not repressed to the same extent in IShpKOcompared with control mice post-CA challenge. Loss of intestinal SHP did not alter Fxrαmessenger RNA (mRNA) but increased Asbt(BA ileal uptake transporter) and Ostα(BA ileal efflux transporter) expression even under chow-fed conditions. Surprisingly, the acute CA diet in IShpKOdid not elicit the expected induction of Fgf15but was able to maintain the suppression of Asbt, and Ostα/βmRNA levels. At the protein level, apical sodium-dependent bile acid transporter (ASBT) was downregulated, while organic solute transporter-α/β (OSTα/β) expression was induced and maintained regardless of diet. Examination of ileal histology in IShpKOmice challenged with acute CA diet revealed reduced villi length and goblet cell numbers. However, no difference in villi length, and the expression of BA regulator and transporter genes, was seen between f/f Shpand IShpKOanimals after a chronic (14-day) CA diet, suggesting a potential adaptive response. We found the upregulation of the Pparα-Ugtaxis after 14 days of CA diet may reduce the BA burden and compensate for the ileal SHP function. Thus, our study reveals that ileal SHP expression contributes to both overall intestinal structure and BA homeostasis.

Vascular development is essential for the establishment of the circulatory system during embryonic development and requires the proliferation of endothelial cells. However, the underpinning regulatory mechanisms are not well understood. Here, we report that geranylgeranyl pyrophosphate (GGPP), a metabolite involved in protein geranylgeranylation, plays an indispensable role in embryonic vascular development. GGPP is synthesized by geranylgeranyl pyrophosphate synthase (GGPPS) in the mevalonate pathway. The selective knockout of Ggppsin endothelial cells led to aberrant vascular development and embryonic lethality, resulting from the decreased proliferation and enhanced apoptosis of endothelial cells during vasculogenesis. The defect in protein geranylgeranylation induced by GGPP depletion inhibited the membrane localization of RhoA and enhanced yes-associated protein (YAP) phosphorylation, thereby prohibiting the entry of YAP into the nucleus and the expression of YAP target genes related to cell proliferation and the antiapoptosis process. Moreover, inhibition of the mevalonate pathway by simvastatin induced endothelial cell proliferation defects and apoptosis, which were ameliorated by GGPP. Geranylgeraniol (GGOH), a precursor of GGPP, ameliorated the harmful effects of simvastatin on vascular development of developing fetuses in pregnant mice. These results indicate that GGPP-mediated protein geranylgeranylation is essential for endothelial cell proliferation and the antiapoptosis process during embryonic vascular development.