Ultra-thin gate insulator of atomic-layer-deposited AlOxand HfOxfor amorphous InGaZnO thin-film transistors.

To strengthen the downscaling potential of top-gate amorphous oxide semiconductor (AOS) thin-film transistors (TFTs), the ultra-thin gate insulator (GI) was comparatively implemented using the atomic-layer-deposited (ALD) AlOxand HfOx. Both kinds of high-kGIs exhibit good insulating properties even with the physical thickness thinning to 4 nm. Compared to the amorphous indium-gallium-zinc oxide (a-IGZO) TFTs with 4 nm AlOxGI, the 4 nm HfOxenables a larger GI capacitance, while the HfOx-gated TFT suffers higher gate leakage current and poorer subthreshold slope, respectively originating from the inherently small band offset and the highly defective interface between a-IGZO and HfOx. Such imperfect a-IGZO/HfOxinterface further causes noticeable positive bias stress instability. Both ALD AlOxand HfOxwere found to react with the underneath a-IGZO channel to generate the interface defects, such as metal interstitials and oxygen vacancies, while the ALD process of HfOxgives rise to a more severe reduction of a-IGZO. Moreover, when such a defective interface is covered by the top gate, it cannot be readily restored using the conventional oxidizing post-treatments and thus desires the reduction-resistant pre-treatments of AOSs.

Surface Engineering of Laser-Induced Graphene Enables Long-Term Monitoring of On-Body Uric Acid and pH Simultaneously.

Laser-induced graphene (LIG) suffers from serious decay in long-term biosensing, which greatly restricts its practical applications. Herein, we report a new strategy to engineer the LIG surface with Au clusters and chitosan sequentially to form a C-Au-LIG electrode with a superhydrophilic and highly conductive 3D graphene surface, which demonstrates superior performance and negligible decay in both long-term storage and practical usage in vitro and in vivo environments. Moreover, the C-Au-LIG electrode can be used for detecting uric acid (UA) and pH simultaneously from a single differential pulse voltammetry curve with low-detection limitation, high accuracy, and negligible interference with other sweat biomarkers. The integrated C-Au-LIG wearable biosensor was employed to continuously monitor the UA content in human sweat, which can well reflect the daily intake of purines for at least 10 days. Therefore, the C-Au-LIG electrode demonstrates significant application potential and provides inspiration for surface engineering of other biosensor materials and electrodes.

Oridonin ameliorates acetaminophen-induced acute liver injury through ATF4/PGC-1α pathway.

Acetaminophen (APAP) overdose-induced acute liver injury (ALI) causes hepatocyte cell death, oxidative stress, and inflammation. Oridonin (Ori), a covalent NLRP3-inflammasome inhibitor, ameliorates APAP-induced ALI through an unclear molecular mechanism. This study found that Ori decreased hepatic cytochrome P450 2E1 level and increased glutathione content to prevent APAP metabolism, and then reduced the necrotic area, improved liver function, and inhibited APAP-induced proinflammatory cytokines and oxidative stress. Ori also decreased activating transcription factor 4 (ATF4) protein levels and increased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) to reduce APAP-induced endoplasmic reticulum stress activation and mitochondrial dysfunction. Furthermore, western blot and luciferase assay found that ATF4 inhibited transcription in the PGC-1α promoter -507 to -495 region to reduce PGC-1α levels, while ATF4 knockdown neutralized the hepatoprotective effect of Ori. Molecular docking showed that Ori bound to ATF4's amino acid residue glutamate 302 through 6, 7, and 18 hydroxyl bands. Our findings demonstrated that Ori prevented metabolic activation of APAP and further inhibited the ATF4/PGC-1α pathway to alleviate APAP overdose-induced hepatic toxicity, which illuminated its potential therapeutic effects on ALI.

Differential proteomics of placentas reveals metabolic disturbance and oxidative damage participate yak spontaneous miscarriage during late pregnancy.

BACKGROUND: High spontaneous miscarriage rate in yak, especially during late pregnancy, have caused a great economic loss to herdsmen living in the Qinghai-Tibet plateau. However, the mechanism underlying spontaneous miscarriage is still poorly understood. In the present study, placenta protein markers were identified to elucidate the pathological reasons for yak spontaneous miscarriage through isobaric tags for relative and absolute quantification (iTRAQ) proteomic technology and bioinformatic approaches. RESULTS: Subsequently, a total of 415 differentially expressed proteins (DEPs) were identified between aborted and normal placentas. The up-regulated DEPs in the aborted placentas were significantly associated with "spinocerebellar ataxia", "sphingolipid signalling", "relaxin signalling", "protein export", "protein digestion and absorption" and "aldosterone synthesis and secretion" pathway. While the down-regulated DEPs in the aborted placentas mainly participated in "valine, leucine and isoleucine degradation", "PPAR signalling", "peroxisome", "oxidative phosphorylation", "galactose metabolism", "fatty acid degradation", "cysteine and methionine metabolism" and "citrate cycle" pathway. CONCLUSIONS: The results implied that the identified DEPs could be considered as placental protein markers for yak miscarriage during late pregnancy, and biomacromolecule metabolic abnormality and oxidative damage might be responsible for the high spontaneous miscarriage rate in yak. These findings provide an important theoretical basis for deciphering the pathologic mechanism of late spontaneous miscarriage in yak.

Differential proteomic analysis demonstrates follicle fluid participate immune reaction and protein translation in yak.

BACKGROUND: Ovarian follicle fluid (FF) as a microenvironment surrounding oocyte plays critical roles in physio-biochemical processes of follicle development and oocyte maturation. It is hypothesized that proteins in yak FF participate in the physio-biochemical pathways. The primary aims of this study were to find differentially expressed proteins (DEPs) between mature and immature FF, and to elucidating functions of the mature and immature FF in yak. RESULTS: The mature and immature FF samples were obtained from three healthy yaks that were nonpregnant, aged from four to five years, and free from any anatomical reproductive disorders. The FF samples were subjected to mass spectrometry with the isobaric tags for relative and absolute quantification (iTRAQ). The FF samples went through correlation analysis, principle component analysis, and expression pattern analysis based on quantification of the identified proteins. Four hundred sixty-three DEPs between mature and immature FF were identified. The DEPs between the mature and immature FF samples underwent gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) analysis. The DEPs highly expressed in the mature FF mainly took parts in the complement and coagulation cascades, defense response, acute-phase response, response to other organism pathways to avoid invasion of exogenous microorganisms. The complement activation pathway contains eight DEPs, namely C2, C5, C6, C7, C9, C4BPA, CFH, and MBL2. The three DEPs, CATHL4, CHGA, and PGLYRP1, take parts in defense response pathway to prevent invasion of exogenetic microorganism. The coagulation cascades pathway involves many coagulation factors, such as F7, F13A1, FGA, FGB, FGG, KLKB1, KNG1, MASP1, SERPINA1, and SERPIND1. While the DEPs highly expressed in the immature FF participated in protein translation, peptide biosynthetic process, DNA conformation change, and DNA geometric change pathways to facilitate follicle development. The translation pathway contains many ribosomal proteins, such as RPL3, RPL5, RPS3, RPS6, and other translation factors, such as EIF3J, EIF4G2, ETF1, MOV10, and NARS. The DNA conformation change and DNA geometric change involve nine DEPs, DDX1, G3BP1, HMGB1, HMGB2, HMGB3, MCM3, MCM5, MCM6, and RUVBL2. Furthermore, the expressed levels of the main DEPs, C2 and SERPIND1, were confirmed by western blot. CONCLUSIONS: The differential proteomics revealed the up-regulated DEPs in mature FF take parts in immunoreaction to prevent invasion of microorganisms and the up-regulated DEPs in immature FF participate in protein synthesis, which may improve our knowledge of the follicular microenvironment and its biological roles for reproductive processes in yak. The DEPs, C2 and SERPIND1, can be considered as protein markers for mature yak follicle.

Different expression of LHR, PRLR, GH and IGF1 during testicular development of yak.

Luteinizing hormone receptor (LHR), prolactin receptor (PRLR), growth hormone (GH) and insulin-like growth factor 1 (IGF1) have been shown to be key regulators of germ cell development. However, the role of LHR, PRLR, GH and IGF1 in the development of yak testis remains unclear. In this study, we aimed to describe and compare gene expression and protein localization of LHR, PRLR, GH and IGF1 in the development of yak testes. Testes were collected from 6, 24, 36 and 72 months yak, and the kidney, liver, testicular, lung, skeletal muscle, heart and spleen tissues were collected from 36 months yak. The quantitative real-time PCR (qRT-PCR) results showed that the expression of these four genes was widely expressed in kidney, liver, testicular, lung, skeletal muscle, heart and spleen, while the LHR and PRLR were highly expressed in the kidney, skeletal muscle and testis, and higher levels of GH and IGF were expressed in spleen and testis. Moreover, the mRNA expression of these genes in adults was higher than in pre-pubertal yak. In the testis, the LHR-, PRLR-, GH- and IGF1-positive signals were detected in the Leydig cells of the 6 months, while the intense positive signals were discovered in Leydig cells, spermatogonia and spermatocytes of the 36 and 72 months. Thus, LHR, PRLR, GH and IGF1 may be involved in the development of spermatids and spermatocytes, and in the regulation of spermatogonia proliferation and Leydig cell function.

Size-dependent optical extinction of MoS2 nanosheets and their aptamer-induced dispersion behavior for the label-free detection of Escherichia coli O157:H7.

For aptamer-modified nanomaterial biosensors label-free detection methods are desirable due to them being simple and low in cost. Among these methods, nanomaterial aggregation for signal conversion is common, using materials such as gold nanoparticles. However, for MoS2 nanosheets (MoS2-NSs), signal conversion of its aggregation is difficult, resulting in the limited development of its label-free sensing applications. Herein, for the first time, the extinction spectrum has been employed to quickly transform the signal of MoS2-NS aggregation and reveal the size-dependent extinction response of MoS2-NS aggregation. Moreover, the size-dependent optical extinction behavior of MoS2-NSs, using aptamers to induce the dispersion of the MoS2-NSs and greatly improve their ability to identify targets, is studied. Importantly, this method has been employed to achieve the label-free detection of Escherichia coli O157:H7. The present investigation shows the promising use of MoS2-NSs for the development of label-free detection.

Microporous Carbon Nanofibers Derived from Poly(acrylonitrile-co-acrylic acid) for High-Performance Supercapacitors.

Carbon nanofiber (CNF)-based supercapacitors have promising applications in the field of energy storage. It is desirable, but remains challenging, to develop CNF electrode materials with large specific surface area (SSA), high specific capacitance (SC), and high power density, as well as excellent cycling stability and high reliability. Herein, acrylonitrile-acrylic acid copolymer P(AN-co-AA) was synthesized for the preparation of nitrogen-doped microporous CNFs. Thermal degradation of the AA segment leads to the formation of micropores that are distributed not only on the CNF surface, but also inside the material. The microporous structure and nitrogen content can be manipulated at the molecular level by adjusting the weight ratio between AN and AA, and the SSA and SC could reach as high as 1099 m2 g-1 and 156 F g-1 , respectively. After KOH activation, the activated CNFs have an extremely high SSA of 2117 m2 g-1 and SC of 320 F g-1 , which are among the highest values ever reported for electric double-layer supercapacitors with an alkaline electrolyte. Furthermore, the capacitance retention, which can be maintained at 99 % even after 16 000 cyclic tests, reveals outstanding durability and repeatability.

Hydrocephalus due to aqueductal stenosis presenting with acute bilateral ptosis: case report.

Hydrocephalus may cause Parinaud's syndrome which consists of vertical gaze palsy, convergence palsy, lid retraction and pupil light-near dissociation. We are aware of only two prior reports of hydrocephalus presenting with bilateral ptosis. Both were cured by ventriculoperitoneal shunts. We report a 28-month-old girl who presented acute bilateral ptosis but full eye movements both sides. Neuroimages revealed chronic hydrocephalus and aqueductal stenosis. The bilateral ptosis resolved quickly after endoscopic third ventriculostomy (ETV).

An immune-related lncRNA signature for patients with anaplastic gliomas.

We investigated immune-related long non-coding RNAs (lncRNAs) that may be exploited as potential therapeutic targets in anaplastic gliomas. We obtained 572 lncRNAs and 317 immune genes from the Chinese Glioma Genome Atlas microarray and constructed immune-related lncRNAs co-expression networks to identify immune-related lncRNAs. Two additional datasets (GSE16011, REMBRANDT) were used for validation. Gene set enrichment analysis and principal component analysis were used for functional annotation. Immune-lncRNAs co-expression networks were constructed. Nine immune-related lncRNAs (SNHG8, PGM5-AS1, ST20-AS1, LINC00937, AGAP2-AS1, MIR155HG, TUG1, MAPKAPK5-AS1, and HCG18) signature was identified in patients with anaplastic gliomas. Patients in the low-risk group showed longer overall survival (OS) and progression-free survival than those in the high-risk group (P < 0.0001; P < 0.0001). Additionally, patients in the high-risk group displayed no-deletion of chromosomal arms 1p and/or 19q, isocitrate dehydrogenase wild-type, classical and mesenchymal TCGA subtype, G3 CGGA subtype, and lower Karnofsky performance score (KPS). Moreover, the signature was an independent factor and was significantly associated with the OS (P = 0.000, hazard ratio (HR) = 1.434). These findings were further validated in two additional datasets (GSE16011, REMBRANDT). Low-risk and high-risk groups displayed different immune status based on principal components analysis. Our results showed that the nine immune-related lncRNAs signature has prognostic value for anaplastic gliomas.

Repair of Concomitant Incisional and Parastomal Hernias Using a Hybrid Technique: A Series of 32 Patients.

BACKGROUND: Concomitant incisional and parastomal hernias is a challenging condition. We used a hybrid technique of sublay and onlay to treat patients with this condition. MATERIAL AND METHODS: The clinical data of 32 consecutive patients treated from February 2008 to April 2014 for concomitant incisional and parastomal hernias were retrospectively reviewed. The mean diameter was 9 (range 4-13) cm of the incisional hernias, and 6 (range 4.5-8) cm of the parastomal hernias. RESULTS: The mean operative time was 247 (range 220-290) min. The mean hospital stay was 20 (range 14-27) days. All surgical wounds healed by primary intention. Seven patients had postoperative seroma and were well managed with puncture and compression. All 32 patients were followed up for a mean of 48 (range 5-68) months. Four patients recurred with parastomal hernias and were treated with secondary surgery. No further recurrence occurred until the last follow-up. CONCLUSIONS: This hybrid technique of sublay and onlay is only suitable for the repair of complex incisional and parastomal hernias.

Enhanced CO2 Electroreduction to Multi-Carbon Products on Copper via Plasma Fluorination.

The electroreduction of carbon dioxide (CO2) to multi-carbon (C2+) compounds offers a viable approach for the up-conversion of greenhouse gases into valuable fuels and feedstocks. Nevertheless, current industrial applications face limitations due to unsatisfactory conversion efficiency and high overpotential. Herein, a facile and scalable plasma fluorination method is reported. Concurrently, self-evolution during CO2 electroreduction is employed to control the active sites of Cu catalysts. The copper catalyst modified with fluorine exhibits an impressive C2+ Faradaic efficiency (FE) of 81.8% at a low potential of -0.56 V (vs a reversible hydrogen electrode) in an alkaline flow cell. The presence of modified fluorine leads to the exposure and stabilization of high-activity Cu+ species, enhancing the adsorption of *CO intermediates and the generation of *CHO, facilitating the subsequent dimerization. This results in a notably improved conversion efficiency of 13.1% and a significant reduction in the overpotential (≈100 mV) for the C2+ products. Furthermore, a superior C2+ FE of 81.6% at 250 mA cm-2, coupled with an energy efficiency of 31.0%, can be achieved in a two-electrode membrane electrode assembly electrolyzer utilizing the fluorine-modified copper catalyst. The strategy provides novel insights into the controllable electronic modification and surface reconstruction of electrocatalysts with practical potential.

6-Gingerol attenuates hepatic ischemia/reperfusion injury through regulating MKP5-mediated P38/JNK pathway.

6-Gingerol, the main bioactive compound of ginger, has antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. However, it is unclear whether 6-Gingerol has protective effects against hepatic ischemia/reperfusion (I/R) injury. In this study, the mouse liver I/R injury model and the mouse AML12 cell hypoxia/reoxygenation (H/R) model were established by pretreatment with 6-Gingerol at different concentrations to explore the potential effects of 6-Gingerol. Serum transaminase levels, liver necrotic area, cell viability, inflammatory response, and cell apoptosis were used to assess the effect of 6-Gingerol on hepatic I/R or cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to detect the mRNA and protein expression. The results show that 6-Gingerol decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, liver necrosis, inflammatory cytokines IL-1ß, IL-6, MCP-1, TNF-α expression, Ly6g+ inflammatory cell infiltration, protein phosphorylation of NF-κB signaling pathway, Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positive cells, cell apoptosis rate, the protein expression of pro-apoptotic protein BAX and C-Caspase3, increased cell viability, and expression of anti-apoptotic protein BCL-2. Moreover, 6-Gingerol could increase the mRNA and protein expression of mitogen activated protein kinase phosphatase 5 (MKP5) and inhibit the activation of P38/JNK signaling pathway. In MKP5 knockout (KO) mice, the protective effect of 6-gingerol and the inhibition of P38/JNK pathway were significantly weakened. Therefore, our results suggest that 6-Gingerol exerts anti-inflammatory and anti-apoptotic effects to attenuate hepatic I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.

Plasmonic Bound States in the Continuum Metasurface-Semiconductor-Metal Architecture Enables Efficient Hot-Electron-Based Photodetector.

Plasmonic hot-electron-based photodetectors (HEB-PDs) have received widespread attention for their ability to realize effective carrier collection under sub-bandgap illumination. However, due to the low hot electron emission probability, most of the existing HEB-PDs exhibit poor responsivity, which significantly restricts their practical applications. Here, by employing the binary-pore anodic alumina oxide template technique, we proposed a compact plasmonic bound state in continuum metasurface-semiconductor-metal-based (BIC M-S-M) HEB-PD. The symmetry-protected BIC can manipulate a strong gap surface plasmon in the stacked M-S-M structure, which effectively enhances light-matter interactions and improves the photoresponse of the integrated device. Notably, the optimal M-S-M HEB-PD with near-unit absorption (∼90%) around 800 nm delivers a responsivity of 5.18 A/W and an IPCE of 824.23% under 780 nm normal incidence (1 V external bias). Moreover, the ultrathin feature of BIC M-S-M (∼150 nm) on the flexible substrate demonstrates excellent stability under a wide range of illumination angles from -40° to 40° and at the curvature surface from 0.05 to 0.13 mm-1. The proposed plasmonic BIC strategy is very promising for many other hot-electron-related fields, such as photocatalysis, biosensing, imaging, and so on.

Alternative Oxidase: From Molecule and Function to Future Inhibitors.

In the respiratory chain of the majority of aerobic organisms, the enzyme alternative oxidase (AOX) functions as the terminal oxidase and has important roles in maintaining metabolic and signaling homeostasis in mitochondria. AOX endows the respiratory system with flexibility in the coupling among the carbon metabolism pathway, electron transport chain (ETC) activity, and ATP turnover. AOX allows electrons to bypass the main cytochrome pathway to restrict the generation of reactive oxygen species (ROS). The inhibition of AOX leads to oxidative damage and contributes to the loss of adaptability and viability in some pathogenic organisms. Although AOXs have recently been identified in several organisms, crystal structures and major functions still need to be explored. Recent work on the trypanosome alternative oxidase has provided a crystal structure of an AOX protein, which contributes to the structure-activity relationship of the inhibitors of AOX. Here, we review the current knowledge on the development, structure, and properties of AOXs, as well as their roles and mechanisms in plants, animals, algae, protists, fungi, and bacteria, with a special emphasis on the development of AOX inhibitors, which will improve the understanding of respiratory regulation in many organisms and provide references for subsequent studies of AOX-targeted inhibitors.

[Effect of elemene on reversing chemoresistance to adriamycin in human stomach cancer cell line].

OBJECTIVE: To investigate the effect of elemene on reversing chemoresistance to adriamycin (ADM) in human stomach cancer cell, and explore its possible mechanism. METHODS: SGC7901/ADM were divided imto two groups: control group and elemene treatment group. The cytotoxicity of ADM on SGC7901/ADM was determined by MTT assay. The activity of nuclear factor-kappa B (NF-kappaB) was measured by immunohistochemical staining. The apoptosis rate of stomach cancer cell line was determined by flow cyotometric analysis. RESULTS: The immunohistochemical staining result showed that the activity of NF-kappaB in SGC7901/ADM was increased after treated with ADM for 9 - 12 h, while that of the elemene treatment group decreased with the increasing of the elemene concentration and the lowest level was 8 - 12%. The apoptosis rate of SGC7901/ADM stomach cancer cell line was increased with the increasing of elemene concentration. At the same elemene concentration, the apoptosis rate increased with ADM treatment time prolonged. MTT result showed that the non-cytotoxic dose of elemene had synergistic effect on rilling SGC7901/ADM stomach cancer cell line and was in a dose-dependant manner. CONCLUSION: The inhibitory effect of elemene on reversing chemoresistance to ADM in human stomach cancer cell line maybe related to inhibiting NF-kappaB activity.

Natural Flavonoids and Ferroptosis: Potential Therapeutic Opportunities for Human Diseases.

Flavonoids are a class of bioactive phytochemicals containing a core 2-phenylchromone skeleton and are widely found in fruits, vegetables, and herbs. Such natural compounds have gained significant attention due to their various health benefits. Ferroptosis is a recently discovered unique iron-dependent mode of cell death. Unlike traditional regulated cell death (RCD), ferroptosis is associated with excessive lipid peroxidation on cellular membranes. Accumulating evidence suggests that this form of RCD is involved in a variety of physiological and pathological processes. Notably, multiple flavonoids have been shown to be effective in preventing and treating diverse human diseases by regulating ferroptosis. In this review, we introduce the key molecular mechanisms of ferroptosis, including iron metabolism, lipid metabolism, and several major antioxidant systems. Additionally, we summarize the promising flavonoids targeting ferroptosis, which provides novel ideas for the management of diseases such as cancer, acute liver injury, neurodegenerative diseases, and ischemia/reperfusion (I/R) injury.

Endoscopy-assisted purely total outer wall excision for pediatric Sylvian arachnoid cysts.

BACKGROUND: To present a novel endoscopy-assisted surgical strategy of Sylvian arachnoid cysts (ACs). CASE PRESENTATION: Endoscopy-assisted surgery was performed on 9 children (May 2019-December 2021). All patients were evaluated with CT and/or MRI and had regular follow-up examinations. The procedure consisted of performing a small temporal craniotomy (2 cm) behind the hairline. After dural opening, the surgery was performed with the assistance of a rigid 30-degree transcranial endoscope, self-irrigating bipolar forceps, and other standard endoscopic instruments. Steps included total excision of the AC outer wall and dissection of arachnoid adhesion around the cystic edge to communicate the residual cyst cavity with subdural space. Compared with the microscopical procedure, a 30-degree transcranial endoscope provides a wider view, especially for the lateral part exposure of the outer wall. The average age of the patients was 27.7 months (range 13-44 months). The Sylvian AC was in the right hemisphere in three patients and six in the left, respectively. 1 patient suffered transient postoperative epilepsy. There was no mortality or additional postoperative neurological deficit in this series. All of the patients achieved significant clinical improvement after surgery. Radiological examination after the operation showed a significant reduction in all cases (100%, 9/9) and disappearance in one case (11.1%, 1/9). Postoperative subdural fluid collection occurred in six cases and completely resolved spontaneously in 9 months. CONCLUSION: The study demonstrated the minimally invasive, safety, and effectivity of the endoscopy-assisted purely total outer wall excision.

Customizing 2.5D Out-of-Plane Architectures for Robust Plasmonic Bound-States-in-the-Continuum Metasurfaces.

Bound states in the continuum (BICs) have a superior ability to confine electromagnetic waves and enhance light-matter interactions. However, the quality-factor of quasi-BIC is extremely sensitive to structural perturbations, thus the BIC metasurfaces usually require a very-high precision nanofabrication technique that greatly restricts their practical applications. Here, distinctive 2.5D out-of-plane architectures based plasmonic symmetry protected (SP)-BIC metasurfaces are proposed, which could deliver robust quality factors even with large structural perturbations. The high-throughput fabrication of such SP-BIC metasurfaces is realized by using the binary-pore anodic aluminum oxide template technique. Moreover, the deep neural network (DNN) is adapted to conduct multiparameter fittings, where the 2.5D hetero-out-of-plane architectures with robust high quality-factors and figures of merit are rapidly predicted and fabricated. Finally, owning to its large second-order surface sensitivity, the desired 2.5D hetero-out-of-plane architecture demonstrates a detection limit of endotoxin as low as 0.01 EU mL-1 , showing a good perspective of biosensors and others.

Mitogen activated protein kinase phosphatase 5 alleviates liver ischemia-reperfusion injury by inhibiting TAK1/JNK/p38 pathway.

Mitogen activated protein kinase phosphatase 5 (MKP5) is a member of the MKP family and has been implicated in diverse biological and pathological conditions. However, it is unknown what role MKP5 plays in liver ischemia/reperfusion (I/R) injury. In the present study, we used MKP5 global knockout (KO) and MKP5 overexpressing mice to establish a liver I/R injury model in vivo, and MKP5 knockdown or MKP5 overexpressing HepG2 cells to establish a hypoxia-reoxygenation (H/R) model in vitro. In this study we demonstrated that protein expression of MKP5 was significantly downregulated in liver tissue of mice after I/R injury, and HepG2 cells subjected to H/R injury. MKP5 KO or knockdown significantly increased liver injury, as demonstrated by elevated serum transaminases, hepatocyte necrosis, infiltrating inflammatory cells, secretion of pro-inflammatory cytokines, apoptosis, oxidative stress. Conversely, MKP5 overexpression significantly attenuated liver and cell injury. Furthermore, we showed that MKP5 exerted its protective effect by inhibiting c-Jun N-terminal kinase (JNK)/p38 activity, and its action was dependent on Transforming growth factor-ß-activated kinase 1 (TAK1) activity. According to our results, MKP5 inhibited the TAK1/JNK/p38 pathway to protect liver from I/R injury. Our study identifies a novel target for the diagnosis and treatment of liver I/R injury.