Dynamic Reversible Oxidation-Reduction of Iodide Ions for Operationally Stable Perovskite Solar Cells under ISOS-L-3 Protocol.

Despite rapid advancements in the photovoltaic efficiencies of perovskite solar cells (PSCs), their operational stability remains a significant challenge for commercialization. This instability mainly arises from light-induced halide ion migration and subsequent oxidation into iodine (I2). The situation is exacerbated when considering the heat effects at elevated temperatures, leading to the volatilization of I2 and resulting in irreversible device degradation. Mercaptoethylammonium iodide (ESAI) is thus incorporated into perovskite as an additive to inhibit the oxidation of iodide anion (I-) and  the light-induced degradation pathway of FAPbI3→FAI+PbI2. Additionally, the formation of a thiol-disulfide/I--I2 redox pair within the perovskite film provides a dynamic mechanism for the continuous reduction of I2 under light and thermal stresses, facilitating the healing of iodine-induced degradations. This approach significantly enhances the operational stability of PSCs. Under the ISOS-L-3 testing protocol (maximum power point (MPP) tracking in an environment with relative humidity of ≈50% at ≈65 °C), the treated PSCs maintain 97% of their original power conversion efficieney (PCE) after 300 h of aging. In contrast, control devices exhibit almost complete degradation, primarily due to rapid thermal-induced I2 volatilization. These results demonstrate a promising strategy to overcome critical stability challenges in PSCs, particularly in scenarios involving thermal effects.

Application of Multimodal Transformer Model in Intelligent Agricultural Disease Detection and Question-Answering Systems.

In this study, an innovative approach based on multimodal data and the transformer model was proposed to address challenges in agricultural disease detection and question-answering systems. This method effectively integrates image, text, and sensor data, utilizing deep learning technologies to profoundly analyze and process complex agriculture-related issues. The study achieved technical breakthroughs and provides new perspectives and tools for the development of intelligent agriculture. In the task of agricultural disease detection, the proposed method demonstrated outstanding performance, achieving a precision, recall, and accuracy of 0.95, 0.92, and 0.94, respectively, significantly outperforming the other conventional deep learning models. These results indicate the method's effectiveness in identifying and accurately classifying various agricultural diseases, particularly excelling in handling subtle features and complex data. In the task of generating descriptive text from agricultural images, the method also exhibited impressive performance, with a precision, recall, and accuracy of 0.92, 0.88, and 0.91, respectively. This demonstrates that the method can not only deeply understand the content of agricultural images but also generate accurate and rich descriptive texts. The object detection experiment further validated the effectiveness of our approach, where the method achieved a precision, recall, and accuracy of 0.96, 0.91, and 0.94. This achievement highlights the method's capability for accurately locating and identifying agricultural targets, especially in complex environments. Overall, the approach in this study not only demonstrated exceptional performance in multiple tasks such as agricultural disease detection, image captioning, and object detection but also showcased the immense potential of multimodal data and deep learning technologies in the application of intelligent agriculture.

Rapid and non-invasive detection of cystic echinococcosis in sheep based on serum fluorescence spectrum combined with machine learning algorithms.

Cystic echinococcosis (CE) is a grievous zoonotic parasitic disease. Currently, the traditional technology of screening CE is laborious and expensive, developing an innovative technology is urgent. In this study, we combined serum fluorescence spectroscopy with machine learning algorithms to develop an innovative screening technique to diagnose CE in sheep. Serum fluorescence spectra of Echinococcus granulosus sensu stricto-infected group (n = 63) and uninfected E. granulosus s.s. group (n = 60) under excitation at 405 nm were recorded. The linear support vector machine (Linear SVM), Quadratic SVM, medium radial basis function (RBF) SVM, K-nearest neighbor (KNN), and principal component analysis-linear discriminant analysis (PCA-LDA) were used to analyze the spectra data. The results showed that Quadratic SVM had the great classification capacity, its sensitivity, specificity, and accuracy were 85.0%, 93.8%, and 88.9%, respectively. In short, serum fluorescence spectroscopy combined with Quadratic SVM algorithm has great potential in the innovative diagnosis of CE in sheep.

Machine learning-assisted serum SERS strategy for rapid and non-invasive screening of early cystic echinococcosis.

Early and accurate diagnosis of cystic echinococcosis (CE) with existing technologies is still challenging. Herein, we proposed a novel strategy based on the combination of label-free serum surface-enhanced Raman scattering (SERS) spectroscopy and machine learning for rapid and non-invasive diagnosis of early-stage CE. Specifically, by establishing early- and middle-stage mouse models, the corresponding CE-infected and normal control serum samples were collected, and silver nanoparticles (AgNPs) were utilized as the substrate to obtain SERS spectra. The early- and middle-stage discriminant models were developed using a support vector machine, with diagnostic accuracies of 91.7% and 95.7%, respectively. Furthermore, by analyzing the serum SERS spectra, some biomarkers that may be related to early CE were found, including purine metabolites and protein-related amide bands, which was consistent with other biochemical studies. Thus, our findings indicate that label-free serum SERS analysis is a potential early-stage CE detection method that is promising for clinical translation.

Zero-Strain Na3 V2 (PO4 )2 F3 @Rgo/CNT Composite as a Wide-Temperature-Tolerance Cathode for Na-Ion Batteries with Ultrahigh-Rate Performance.

Sodium-ion batteries (SIBs) are widely considered a hopeful alternative to lithium-ion battery technology. However, they still face challenges, such as low rate capability, unsatisfactory cycling stability, and inferior variable-temperature performance. In this study, a hierarchical Na3 V2 (PO4 )2 F3 (NVPF) @reduced graphene oxide (rGO)/carbon nanotube (CNT) composite (NVPF@rGO/CNT) is successfully constructed. This composite features 0D Na3 V2 (PO4 )2 F3 nanoparticles are coated by a cross-linked 3D conductive network composed of 2D rGO and 1D CNT. Furthermore, the intrinsic Na+ storage mechanism of NVPF@rGO/CNT through comprehensive characterizations is unveiled. The synthesized NVPF@rGO/CNT exhibits fast ionic/electronic transport and excellent structural stability within wide working temperatures (-40-50 °C), owing to the zero-strain NVPF and the coated rGO/CNT conductive network that reduces diffusion distance for ions and electrons. Moreover, the stable integration between NVPF and rGO/CNT enables outstanding structural stability to alleviate strain and stress induced during the cycle. Additionally, a practice full cell is assembled employing a hard carbon anode paired with an NVPF@rGO/CNT cathode, which provides a decent capacity of 105.2 mAh g-1 at 0.2 C, thereby attaining an ideal energy density of 242.7 Wh kg-1 . This work provides valuable insights into developing high-energy and power-density cathode materials for SIBs.

Bile acids-mediated intracellular cholesterol transport promotes intestinal cholesterol absorption and NPC1L1 recycling.

Niemann-Pick C1-like 1 (NPC1L1) is essential for intestinal cholesterol absorption. Together with the cholesterol-rich and Flotillin-positive membrane microdomain, NPC1L1 is internalized via clathrin-mediated endocytosis and transported to endocytic recycling compartment (ERC). When ERC cholesterol level decreases, NPC1L1 interacts with LIMA1 and moves back to plasma membrane. However, how cholesterol leaves ERC is unknown. Here, we find that, in male mice, intracellular bile acids facilitate cholesterol transport to other organelles, such as endoplasmic reticulum, in a non-micellar fashion. When cholesterol level in ERC is decreased by bile acids, the NPC1L1 carboxyl terminus that previously interacts with the cholesterol-rich membranes via the A1272LAL residues dissociates from membrane, exposing the Q1277KR motif for LIMA1 recruitment. Then NPC1L1 moves back to plasma membrane. This study demonstrates an intracellular cholesterol transport function of bile acids and explains how the substantial amount of cholesterol in NPC1L1-positive compartments is unloaded in enterocytes during cholesterol absorption.

2D-Layer-Structure Bi to Quasi-1D-Structure NiBi3 : Structural Dimensionality Reduction to Superior Sodium and Potassium Ion Storage.

Layer-structured bismuth (Bi) is an attractive anode for Na-ion and K-ion batteries due to its large volumetric capacity and suitable redox potentials. However, the cycling stability and rate capability of the Bi anode are restricted by the large volume expansion and sluggish Na/K-storage kinetics. Herein, a structural dimensionality reduction strategy is proposed and developed by converting 2D-layer-structured Bi into a quasi-1D structured NiBi3 with enhanced reaction kinetics and reversibility to realize high-rate and stable cycling performance for Na/K-ion storage. As a proof of concept, the quasi-1D intermetallic NiBi3 with low formation energy, metallic conductivity, and 3D Na/K-ion diffusion pathways delivers outstanding capacity retention of 94.1% (332 mAh g-1 ) after 15 000 cycles for Na-ion storage, and high initial coulombic efficiency of 93.4% with improved capacity retention for K-ion storage. Moreover, investigations on the highly reversible Na/K-storage reaction mechanisms and cycling-driven morphology reconstruction further reveal the origins of the high reversibility and the accommodation to volume expansion. The finding of this work provides a new strategy for high-performance anode design by structural dimensionality manipulation and cycling-driven morphology reconstruction.

High-Performance Aqueous Zinc-Ion Batteries Based on Multidimensional V2 O3 Nanosheets@Single-Walled Carbon Nanohorns@Reduced Graphene Oxide Composite and Optimized Electrolyte.

The drawbacks of poor electronic conductivity and structural instability during the cycling process limit the electrochemical property of vanadium-based cathode materials for aqueous zinc-ion batteries. In addition, continuous growth and accumulation of zinc dendrites can puncture the separator and cause an internal short circuit in the battery. In this work, a unique multidimensional nanocomposite is designed by a facile freeze-drying method with subsequent calcination, consisting of V2 O3 nanosheets and single-walled carbon nanohorns (SWCNHs) crosslinked together and wrapped by reduced graphene oxide (rGO). The multidimensional structure can largely enhance the structural stability and electronic conductivity of the electrode material. Besides, additive Na2 SO4 in the ZnSO4 aqueous electrolyte not only prevents the dissolution of cathode materials but also suppresses the Zn dendrite growth. After considering the influence of additive concentration on ionic conductivity and electrostatic force for electrolyte, V2 O3 @SWCNHs@rGO electrode delivers a high initial discharge capacity of 422 mAh g-1 at 0.2 A g-1 and a high discharge capacity of 283 mAh g-1 after 1000 cycles at 5 A g-1 in 2 m ZnSO4 + 2 m Na2 SO4 electrolyte. Experimental techniques reveal that the electrochemical reaction mechanism can be expressed as the reversible phase transformation between V2 O5 and V2 O3 with Zn3 (VO4 )2 .

A facile synthesis of highly efficient In2S3 photocatalysts for the removal of cationic dyes with size-dependent photocatalysis.

In this study, a 3D thornball-like hierarchical ß-In2S3, displaying extremely rapid photodegradation of cationic dyes, was synthesized by a facile method. The formation of a uniform thornball-like structure depended on the microwave reaction method and citric acid as the pH regulator. The size of In2S3 was easily adjusted by changing the microwave irradiation time from 5 min to 15 min. The morphology, structure, composition, energy level, charge separation, and surface properties of different-sized In2S3 were characterized. The results showed that In2S3 synthesized in 10 min (In2S3-10) displayed optimal interface property for the electron-hole separation, maximum hydrophilia with most surface negative charges for the surface adsorption, contributing to the complete photodegradation of rhodamine B (RhB) in just 25 minutes of visible light illumination. The photodegradation path of RhB was speculated with four possible paths, including the processes of de-ethylation, open-ring of xanthene, and rupture of carbon-carbon bonds up to the decomposition into small molecules. Finally, the reusability of In2S3-10 was tested, obtaining nearly 96% photodegradation efficiency after sequential 5 cycles.

Rapid and accurate screening of cystic echinococcosis in sheep based on serum Fourier-transform infrared spectroscopy combined with machine learning algorithms.

Cystic echinococcosis (CE) in sheep is a serious zoonotic parasitic disease caused by Echinococcus granulosus sensu stricto (s.s.). Presently, the screening technology for CE in sheep is time-consuming and inaccurate, and novel screening technology is urgently needed. In this work, we combined machine-learning algorithms with Fourier transform infrared (FT-IR) spectroscopy of serum to establish a quick and accurate screening approach for CE in sheep. Serum samples from 77 E. granulosus s.s.-infected sheep to 121 healthy control sheep were measured by FT-IR spectrometer. To optimize the classification accuracy of the serum FI-TR method for the E. granulosus s.s.-infected sheep and healthy control sheep, principal component analysis (PCA), linear discriminant analysis, and support vector machine (SVM) algorithms were used to analyze the data. Among all the bands, 1500-1700 cm-1 band has the best classification effect; its diagnostic sensitivity, specificity, and accuracy of PCA-SVM were 100%, 95.74%, and 96.66%, respectively. The study showed that serum FT-IR spectroscopy combined with machine learning algorithms has great potential for rapid and accurate screening methods for the CE in sheep.

Bayesian group testing with dilution effects.

A Bayesian framework for group testing under dilution effects has been developed, using lattice-based models. This work has particular relevance given the pressing public health need to enhance testing capacity for coronavirus disease 2019 and future pandemics, and the need for wide-scale and repeated testing for surveillance under constantly varying conditions. The proposed Bayesian approach allows for dilution effects in group testing and for general test response distributions beyond just binary outcomes. It is shown that even under strong dilution effects, an intuitive group testing selection rule that relies on the model order structure, referred to as the Bayesian halving algorithm, has attractive optimal convergence properties. Analogous look-ahead rules that can reduce the number of stages in classification by selecting several pooled tests at a time are proposed and evaluated as well. Group testing is demonstrated to provide great savings over individual testing in the number of tests needed, even for moderately high prevalence levels. However, there is a trade-off with higher number of testing stages, and increased variability. A web-based calculator is introduced to assist in weighing these factors and to guide decisions on when and how to pool under various conditions. High-performance distributed computing methods have also been implemented for considering larger pool sizes, when savings from group testing can be even more dramatic.

Inhibition of ASGR1 decreases lipid levels by promoting cholesterol excretion.

High cholesterol is a major risk factor for cardiovascular disease1. Currently, no drug lowers cholesterol through directly promoting cholesterol excretion. Human genetic studies have identified that the loss-of-function Asialoglycoprotein receptor 1 (ASGR1) variants associate with low cholesterol and a reduced risk of cardiovascular disease2. ASGR1 is exclusively expressed in liver and mediates internalization and lysosomal degradation of blood asialoglycoproteins3. The mechanism by which ASGR1 affects cholesterol metabolism is unknown. Here, we find that Asgr1 deficiency decreases lipid levels in serum and liver by stabilizing LXRα. LXRα upregulates ABCA1 and ABCG5/G8, which promotes cholesterol transport to high-density lipoprotein and excretion to bile and faeces4, respectively. ASGR1 deficiency blocks endocytosis and lysosomal degradation of glycoproteins, reduces amino-acid levels in lysosomes, and thereby inhibits mTORC1 and activates AMPK. On one hand, AMPK increases LXRα by decreasing its ubiquitin ligases BRCA1/BARD1. On the other hand, AMPK suppresses SREBP1 that controls lipogenesis. Anti-ASGR1 neutralizing antibody lowers lipid levels by increasing cholesterol excretion, and shows synergistic beneficial effects with atorvastatin or ezetimibe, two widely used hypocholesterolaemic drugs. In summary, this study demonstrates that targeting ASGR1 upregulates LXRα, ABCA1 and ABCG5/G8, inhibits SREBP1 and lipogenesis, and therefore promotes cholesterol excretion and decreases lipid levels.

Fully Active Bimetallic Phosphide Zn0.5Ge0.5P: A Novel High-Performance Anode for Na-Ion Batteries Coupled with Diglyme-Based Electrolyte.

Metal phosphides are promising candidates for sodium-ion battery (SIB) anode owing to their large capacities with suitable redox potential, while the reversibility and rate performances are limited due to some electrochemically inactive transition-metal components and sluggish reaction kinetics. Here, we report a fully active bimetallic phosphide Zn0.5Ge0.5P anode and its composite (Zn0.5Ge0.5P-C) with excellent performance attributed to the Zn, Ge, and P components exerting their respective Na-storage merit in a cation-disordered structure. During Na insertion, Zn0.5Ge0.5P undergoes an alloying-type reaction, along with the generation of NaP, Na3P, NaGe, and NaZn13 phases, and the uniform distribution of these phases ensures the electrochemical reversibility during desodiation. Based on this reaction mechanism, excellent electrochemical properties such as a high reversible capacity of 595 mAh g-1 and an ultrafast charge-discharge capability of 377.8 mAh g-1 at 50C for 500 stable cycles were achieved within the Zn0.5Ge0.5P-C composite in a diglyme-based electrolyte. This work reveals the Na-storage reaction mechanism within Zn0.5Ge0.5P and offers a new perspective on designing high-performance anodes.

RIP3 knockdown inhibits necroptosis of human intestinal epithelial cells via TLR4/MyD88/NF-κB signaling and ameliorates murine colitis.

BACKGROUND: Ulcerative colitis (UC) is a common inflammatory bowel disease, during which cell necroptosis plays key roles in driving inflammation initiation and aggravation. Previous studies reported Receptor Interacting Protein Kinase 3 (RIP3)-mediated necroptosis in multiple diseases, and RIP3 protein in Paneth cells significantly enriched in the intestines of both humans and mice. Therefore, we hypothesized targeting RIP3 to inhibit necroptosis may depress UC. METHODS: We classified clinical UC samples according to the modified Truelove & Witts criterion. The expression of RIP3 was measured by western blot and immunohistochemistry. Cell proliferation and apoptosis were analyzed by MTT assay and flow cytometry. ROS production and the secretion of inflammatory cytokines were measured by DCFH-DA probe and ELISA assay. TLR4/MyD88/NF-κB signaling pathway was analyzed by western blot. We established experimental colitis model in RIP3 knockout and wild-type mice and disease activity index (DAI) score was calculated. The expression and distribution of tight junction protein were analyzed by immunofluorescence. The ratio of CD4+Foxp3+ T cells in the spleen was detected by flow cytometry. Oxidative damage of mouse colon was assessed by detecting the levels of SOD, MDA and MPO. Data were analyzed by one-way ANOVA or student's t test. RESULTS: The expression of RIP3 in human colon is positively associated with the severity of UC. RIP3 inhibitor GSK872 or RIP3 knockdown reverses the inhibitory effect of TNF-α on proliferation and the promoting effect of TNF-α on apoptosis and necrosis in human intestinal epithelial cells. In addition, RIP3 deficiency inhibits the secretion of inflammatory cytokines (IL-16, IL-17 and IFN-γ) and ROS production induced by TNF-α. In vivo, RIP3 inhibitor Nec-1 effectively improves DSS-induced colitis in mice. In mechanism, RIP3 depression could upregulate the proportion of CD4+Foxp3+ immunosuppressive Treg cells in the spleen while suppressed TLR4/MyD88/NF-κB signaling pathway and ROS generation, and all these anti-inflammation factors together suppress the secretion of inflammatory cytokines and necroptosis of intestinal epithelial cells. CONCLUSIONS: This study preliminarily explored the regulating mechanism of RIP3 on UC, and Nec-1 may be a promising drug to alleviate the inflammation and necroptosis of the colon in UC patients.

Ablation of Plasma Prekallikrein Decreases Low-Density Lipoprotein Cholesterol by Stabilizing Low-Density Lipoprotein Receptor and Protects Against Atherosclerosis.

BACKGROUND: High blood cholesterol accelerates the progression of atherosclerosis, which is an asymptomatic process lasting for decades. Rupture of atherosclerotic plaques induces thrombosis, which results in myocardial infarction or stroke. Lowering cholesterol levels is beneficial for preventing atherosclerotic cardiovascular disease. METHODS: Low-density lipoprotein (LDL) receptor (LDLR) was used as bait to identify its binding proteins in the plasma, and the coagulation factor prekallikrein (PK; encoded by the KLKB1 gene) was revealed. The correlation between serum PK protein content and lipid levels in young Chinese Han people was then analyzed. To investigate the effects of PK ablation on LDLR and lipid levels in vivo, we genetically deleted Klkb1 in hamsters and heterozygous Ldlr knockout mice and knocked down Klkb1 using adeno-associated virus-mediated shRNA in rats. The additive effect of PK and proprotein convertase subtilisin/kexin 9 inhibition also was evaluated. In addition, we applied the anti-PK neutralizing antibody that blocked the PK and LDLR interaction in mice. Mice lacking both PK and apolipoprotein e (Klkb1-/-Apoe-/-) were generated to assess the role of PK in atherosclerosis. RESULTS: PK directly bound LDLR and induced its lysosomal degradation. The serum PK concentrations positively correlated with LDL cholesterol levels in 198 young Chinese Han adults. Genetic depletion of Klkb1 increased hepatic LDLR and decreased circulating cholesterol in multiple rodent models. Inhibition of proprotein convertase subtilisin/kexin 9 with evolocumab further decreased plasma LDL cholesterol levels in Klkb1-deficient hamsters. The anti-PK neutralizing antibody could similarly lower plasma lipids through upregulating hepatic LDLR. Ablation of Klkb1 slowed the progression of atherosclerosis in mice on Apoe-deficient background. CONCLUSIONS: PK regulates circulating cholesterol levels through binding to LDLR and inducing its lysosomal degradation. Ablation of PK stabilizes LDLR, decreases LDL cholesterol, and prevents atherosclerotic plaque development. This study suggests that PK is a promising therapeutic target to treat atherosclerotic cardiovascular disease.

Fabrication of hierarchical MoO3@NixCo2x(OH)6x core-shell arrays on carbon cloth as enhanced-performance electrodes for asymmetric supercapacitors.

Advanced integrated electrode materials with designedcore-shell nanostructureplay a crucial role for the application in alternative energy storage system. Herein, hierarchical MoO3@NixCo2x(OH)6x core-shell arrays were equably grown on face of carbon cloth after a series of hydrothermal growth and electrochemical deposition processes. This core-shell arrays structure can not only provide large electroactive surface areas and high speed ion transport paths, but also keep the material structure stable during the process of redox reactions. Thus MoO3@NixCo2x(OH)6x displays excellent electrochemical performance (4.7 F cm-2 at 10 mA cm-2). Moreover, the asymmetric supercapacitor is assembled with MoO3@NixCo2x(OH)6x and carbon nanotubes, which delivers a maximal energy density of 0.50 mWh cm-2 at 4.25 mW cm-2, high specific capacitance and superior cycling stability (94.5% capacitance retention after 5000 cycles). We believe that MoO3@NixCo2x(OH)6x arrays could be a great prospective candidate energy storage materials.

BAYESIAN GROUP TESTING WITH DILUTION EFFECTS.

A Bayesian framework for group testing under dilution effects has been developed, using lattice-based models. This work has particular relevance given the pressing public health need to enhance testing capacity for COVID-19 and future pandemics, and the need for wide-scale and repeated testing for surveillance under constantly varying conditions. The proposed Bayesian approach allows for dilution effects in group testing and for general test response distributions beyond just binary outcomes. It is shown that even under strong dilution effects, an intuitive group testing selection rule that relies on the model order structure, referred to as the Bayesian halving algorithm, has attractive optimal convergence properties. Analogous look-ahead rules that can reduce the number of stages in classification by selecting several pooled tests at a time are proposed and evaluated as well. Group testing is demonstrated to provide great savings over individual testing in the number of tests needed, even for moderately high prevalence levels. However, there is a trade-off with higher number of testing stages, and increased variability. A web-based calculator is introduced to assist in weighing these factors and to guide decisions on when and how to pool under various conditions. High performance distributed computing methods have also been implemented for considering larger pool sizes, when savings from group testing can be even more dramatic.

Label-free detection of echinococcosis and liver cirrhosis based on serum Raman spectroscopy combined with multivariate analysis.

In this paper, we investigated the feasibility of using serum Raman spectroscopy and multivariate analysis method to discriminate echinococcosis and liver cirrhosis from healthy volunteers. Raman spectra of serum samples from echinococcosis, liver cirrhosis, and healthy volunteers were recorded under 532 nm excitation. The normalized mean Raman spectra revealed specific biomolecular differences associated with the disease, mainly manifested as the contents of ß carotene in the serum of patients with echinococcosis and liver cirrhosis were lower than those of healthy people. Furthermore, principal components analysis (PCA), combined with linear discriminant analysis (LDA), was adopted to distinguish patients with echinococcosis, liver cirrhosis, and healthy volunteers. The overall diagnostic accuracy based on the PCA-LDA algorithm was 87.7 %. The diagnostic sensitivities to healthy volunteers, patients with echinococcosis, and liver cirrhosis were 92.5 %, 81.5 %, and 89.1 %, and the specificities were 93.2 %, 96.1 %, and 92.4 %, respectively. This exploratory work demonstrated that serum Raman spectroscopy technology combined with PCA-LDA diagnostic algorithm has great potential for the non-invasive identification of echinococcosis and liver cirrhosis.

Feeding induces cholesterol biosynthesis via the mTORC1-USP20-HMGCR axis.

Cholesterol is an essential lipid and its synthesis is nutritionally and energetically costly1,2. In mammals, cholesterol biosynthesis increases after feeding and is inhibited under fasting conditions3. However, the regulatory mechanisms of cholesterol biosynthesis at the fasting-feeding transition remain poorly understood. Here we show that the deubiquitylase ubiquitin-specific peptidase 20 (USP20) stabilizes HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the cholesterol biosynthetic pathway, in the feeding state. The post-prandial increase in insulin and glucose concentration stimulates mTORC1 to phosphorylate USP20 at S132 and S134; USP20 is recruited to the HMGCR complex and antagonizes its degradation. The feeding-induced stabilization of HMGCR is abolished in mice with liver-specific Usp20 deletion and in USP20(S132A/S134A) knock-in mice. Genetic deletion or pharmacological inhibition of USP20 markedly decreases diet-induced body weight gain, reduces lipid levels in the serum and liver, improves insulin sensitivity and increases energy expenditure. These metabolic changes are reversed by expression of the constitutively stable HMGCR(K248R). This study reveals an unexpected regulatory axis from mTORC1 to HMGCR via USP20 phosphorylation and suggests that inhibitors of USP20 could be used to lower cholesterol levels to treat metabolic diseases including hyperlipidaemia, liver steatosis, obesity and diabetes.

The role of Hrd1 in ultraviolet (UV) radiation induced photoaging.

The purpose of the present study was to evaluate the role of Hrd1 in the ultraviolet (UV) radiation induced photoaging and explore its potential mechanism. The nude mice were exposed to the UVA/UVB irradiation for 10 weeks. The animals were subcutaneously injected with AAV5-NC, Hrd1-shRNA-AAV5, or Hrd1-overexpression-AAV5. The HSF cells were also transfected with Ad-NC, Ad-shRNA-Hrd1, or Ad-Hrd1, and irradiated by UVA/UVB stimulation. The clinical skin samples were harvested for detecting Hrd1 and IGF-1R expressions. As a result, the knockdown of Hrd1 attenuated the histopathological alteration and collagen degradation in UV-induced nude mice. The inhibition of Hrd1 by Hrd1-shRNA-AAV5 and Ad-shRNA-Hrd1 inhibited the Hrd1 expression and promoted IGF-1R, Type I collagen and type III collagen in mice and HSF cells. The overexpression of Hrd1 exerted the reverse effect. The Co-IP assay also indicated the interaction between Hrd1 and IGF-1R. Hrd1-mediated IGF-1R downregulation and collagen degradation were also observed in clinical skin samples. In conclusion, the present results demonstrated that Hrd1 degraded IGF-1R and collagen formation in UV-induced photoaging.