Mid1 promotes synovitis in rheumatoid arthritis via ubiquitin-dependent post-translational modification.

INTRODUCTION: Current anti-rheumatic drugs are primarily modulating immune cell activation, yet their effectiveness remained suboptimal. Therefore, novel therapeutics targeting alternative mechanisms, such as synovial activation, is urgently needed. OBJECTIVES: To explore the role of Midline-1 (Mid1) in synovial activation. METHODS: NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were used to establish a subcutaneous xenograft model. Wild-type C57BL/6, Mid1-/-, Dpp4-/-, and Mid1-/-Dpp4-/- mice were used to establish a collagen-induced arthritis model. Cell viability, cell cycle, qPCR and western blotting analysis were used to detect MH7A proliferation, dipeptidyl peptidase-4 (DPP4) and Mid1 levels. Co-immunoprecipitation and proteomic analysis identified the candidate protein of Mid1 substrates. Ubiquitination assays were used to determine DPP4 ubiquitination status. RESULTS: An increase in Mid1, an E3 ubiquitin ligase, was observed in human RA synovial tissue by GEO dataset analysis, and this elevation was confirmed in a collagen-induced mouse arthritis model. Notably, deletion of Mid1 in a collagen-induced arthritis model completely protected mice from developing arthritis. Subsequent overexpression and knockdown experiments on MH7A, a human synoviocyte cell line, unveiled a previously unrecognized role of Mid1 in synoviocyte proliferation and migration, the key aspects of synovial activation. Co-immunoprecipitation and proteomic analysis identified DPP4 as the most significant candidate of Mid1 substrates. Mechanistically, Mid1 promoted synoviocyte proliferation and migration by inducing ubiquitin-mediated proteasomal degradation of DPP4. DPP4 deficiency led to increased proliferation, migration, and inflammatory cytokine production in MH7A, while reconstitution of DPP4 significantly abolished Mid1-induced augmentation of cell proliferation and activation. Additionally, double knockout model showed that DPP4 deficiency abolished the protective effect of Mid1 defect on arthritis. CONCLUSION: Overall, our findings suggest that the ubiquitination of DPP4 by Mid1 promotes synovial cell proliferation and invasion, exacerbating synovitis in RA. These results reveal a novel mechanism that controls synovial activation, positioning Mid1 as a promising target for therapeutic intervention in RA.

Dental pulp regeneration strategies: A review of status quo and recent advances.

Microorganisms, physical factors such as temperature or mechanical injury, and chemical factors such as free monomers from composite resin are the main causes of dental pulp diseases. Current clinical treatment methods for pulp diseases include the root canal therapy, vital pulp therapy and regenerative endodontic therapy. Regenerative endodontic therapy serves the purpose of inducing the regeneration of new functional pulp tissues through autologous revascularization or pulp tissue engineering. This article first discusses the current clinical methods and reviews strategies as well as the research outcomes regarding the pulp regeneration. Then the in vivo models, the prospects and challenges for regenerative endodontic therapy were further discussed.

Impact of Single Acyclic Phosphonate Nucleotide (ZNA) Modifications on DNA Duplex Stability.

An acyclic phosphonate-linked nucleic acid backbone (ZNA) demonstrated the capability to support duplex formation and propagate genetic information in vivo, unveiling its potential for evolution into a synthetic genetic system (XNA). To determine the structural impact of such modification, modified Dickerson Drew DNA dodecamers (DDDs) were prepared by solid phase synthesis, each containing either an (R) or (S) isomeric form of a cytosine ZNA nucleotide. While the DDD is known to adopt a stable duplex, both duplex and hairpin forms were simultaneously observed for both modified oligonucleotides by NMR spectroscopy over a broad temperature range (5-65 °C). Diffusion-ordered spectroscopy (DOSY) experiments allowed to separate duplex and hairpin signals based on the different diffusion constants of both conformational states. For the oligomer containing (R)-ZNA, only the duplex form occurred at 5 °C, while it was not possible to determine by NMR a single hairpin conformation at higher temperatures. In the case of the (S)-ZNA nucleoside modified oligomer, both hairpin and duplex forms were observable at 0 °C, while a single hairpin conformation was detected at 37 °C, suggesting a higher destabilizing effect on dsDNA.

Novel Zn0.079V2O5·0.53H2O/Graphene aerogel as high-rate and long-life cathode materials of aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (ZIBs) have attracted more and more attention due to their advantages of low cost, high safety and environmental protection. Unfortunately, the unsatisfactory capacity at high current density and long-term cycling performance of cathode materials hinder the development of ZIBs. Here, a novel Zn0.079V2O5·0.53H2O/graphene (ZVOH@rGO) hybrid aerogel composed of ultrathin Zn0.079V2O5·0.53H2O (ZVOH) nanoribbons and 3D continuous graphene conductive network was successfully prepared and used as cathode of ZIBs. Taking advantage of the synergistic effects associated with ion doping, morphology control and unique aerogel structure, the ZVOH@rGO electrode demonstrated ultrafast charge/discharge capability and remarkable cycling stability: A high reversible capacity of 286.7 mAh g-1 was achieved at a current density as large as 30 A g-1, and an impressive capacity retention ratio of 75.6 % was realized over 9800 ultra-long cycles at 12 A g-1. This work is of great significance for the synthesis modification of vanadium oxides and the development of high performance ultrafast charge-discharge ZIBs.

Upstream nitrogen availability determines the Microcystis salt tolerance and influences microcystins release in brackish water.

The occurrence of large Microcystis biomass in brackish waters is primarily caused by its downward transportation from the upstream freshwater lakes and reservoirs through rivers rather than due to in situ bloom formation. Factors that determine the survival of freshwater cyanobacteria in brackish waters have not been well investigated. Here, we studied the spatiotemporal variability of inorganic nitrogen in an upstream lake and conducted laboratory and in-situ experiments to assess the role of nitrogen availability on the salt tolerance of Microcystis and the release of microcystins. A series of field experiments were carried out during bloom seasons to evaluate the salt tolerance of natural Microcystis colonies. The salt tolerance threshold varied from 7 to 17 and showed a positive relationship with intracellular carbohydrate content and a negative relationship with nitrogen availability in water. In August when upstream nitrogen availability was lower, the Microcystis colonies could maintain their biomass even after a sudden increase in salinity from 4 to 10. Laboratory-cultivated Microcystis that accumulated higher carbohydrate content at lower nitrogen availability showed better cell survival at higher salinity. The sharp release of microcystins into the surrounding water occurred when salinity exceeded the salt tolerance threshold of the Microcystis. Thus, Microcystis with higher salt tolerance can accumulate more toxins in cells. The obtained results suggest that the cell survival and toxin concentration in brackish waters depend on the physiological properties of Microcystis formed in the upstream waters. Thus, the life history of Microcystis in upstream waters could have a significant impact on its salt tolerance in downstream brackish waters, where the ecological risk of the salt-tolerant Microcystis requires special and careful management in summer at low nitrogen availability.

Midline-1 regulates effector T cell motility in experimental autoimmune encephalomyelitis via mTOR/microtubule pathway.

Background: Effector T cell activation, migration, and proinflammatory cytokine production are crucial steps in autoimmune disorders such as multiple sclerosis (MS). While several therapeutic approaches targeting T cell activation and proinflammatory cytokines have been developed for the treatment of autoimmune diseases, there are no therapeutic agents targeting the migration of effector T cells, largely due to our limited understanding of regulatory mechanisms of T cell migration in autoimmune disease. Here we reported that midline-1 (Mid1) is a key regulator of effector T cell migration in experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS. Methods: Mid1-/- mice were generated by Crispr-Cas9 technology. T cell-specific Mid1 knockout chimeric mice were generated by adoptive transfer of Mid1-/- T cells into lymphocyte deficient Rag2-/- mice. Mice were either immunized with MOG35-55 (active EAE) or received adoptive transfer of pathogenic T cells (passive EAE) to induce EAE. In vitro Transwell® assay or in vivo footpad injection were used to assess the migration of T cells. Results: Mid1 was significantly increased in the spinal cord of wild-type (Wt) EAE mice and disruption of Mid1 in T cells markedly suppressed the development of both active and passive EAE. Transcriptomic and flow cytometric analyses revealed a marked reduction in effector T cell number in the central nervous system of Mid1-/- mice after EAE induction. Conversely, an increase in the number of T cells was observed in the draining lymph nodes of Mid1-/- mice. Mice that were adoptively transferred with pathogenic Mid1-/- T cells also exhibited milder symptoms of EAE, along with a lower T cell count in the spinal cord. Additionally, disruption of Mid1 significantly inhibited T-cell migration both in vivo and in vitro. RNA sequencing suggests a suppression in multiple inflammatory pathways in Mid1-/- mice, including mTOR signaling that plays a critical role in cell migration. Subsequent experiments confirmed the interaction between Mid1 and mTOR. Suppression of mTOR with rapamycin or microtubule spindle formation with colcemid blunted the regulatory effect of Mid1 on T cell migration. In addition, mTOR agonists MHY1485 and 3BDO restored the migratory deficit caused by Mid1 depletion. Conclusion: Our data suggests that Mid1 regulates effector T cell migration to the central nervous system via mTOR/microtubule pathway in EAE, and thus may serve as a potential therapeutic target for the treatment of MS.

A helicase-independent role of DHX15 promotes MYC stability and acute leukemia cell survival.

DHX15 has been implicated in RNA splicing and ribosome biogenesis, primarily functioning as an RNA helicase. To systematically assess the cellular role of DHX15, we conducted proteomic analysis to investigate the landscape of DHX15 interactome, and identified MYC as a binding partner. DHX15 co-localizes with MYC in cells and directly interacts with MYC in vitro. Importantly, DHX15 contributes to MYC protein stability at the post-translational level and independent of its RNA binding capacity. Mechanistic investigation reveals that DHX15 interferes the interaction between MYC and FBXW7, thereby preventing MYC polyubiquitylation and proteasomal degradation. Consequently, the abrogation of DHX15 drastically inhibits MYC-mediated transcriptional output. While DHX15 depletion blocks T cell development and leukemia cell survival as we recently reported, overexpression of MYC significantly rescues the phenotypic defects. These findings shed light on the essential role of DHX15 in mammalian cells and suggest that maintaining sufficient MYC expression is a significant contributor to DHX15-mediated cellular functions.

A molecular networking-assisted automatic database screening strategy for comprehensive annotation of small molecules in complex matrices.

Liquid chromatography-tandem with high-resolution mass spectrometry (LCHRMS) has proven challenging for annotating multiple small molecules within complex matrices due to the complexities of chemical structure and raw LCHRMS data, as well as limitations in previous literatures and reference spectra related to those molecules. In this study, we developed a molecular networking assisted automatic database screening (MN/auto-DBS) strategy to examine the combined effect of MS1 exact mass screening and MS2 similarity analysis. We compiled all previously reported compounds from the relevant literatures. With the development of a Python software, the in-house database (DB) was created by automatically calculating the m/z and data from experimental MS1 hits were rapid screened with DB. We then performed a feature-based molecular network analysis on the auto-MS2 data for supplementary identification of unreported compounds, including clustered FBMN and annotated GNPS compounds. Finally, the results from both strategies were merged and manually curated for correct structural assignment. To demonstrate the applicability of MN/auto-DBS, we selected the Huangqi-Danshen herb pair (HD), commonly used in prescriptions or patent medicines to treat diabetic nephropathy and cerebrovascular disease. A total of 223 compounds were annotated, including 65 molecules not previously reported in HD, such as aromatic polyketides, coumarins, and diarylheptanoids. Using MN/auto-DBS, we can profile and mine a wide range of complex matrices for potentially new compounds.

An Interactive Framework of Cross-Lingual NLU for In-Vehicle Dialogue.

As globalization accelerates, the linguistic diversity and semantic complexity of in-vehicle communication is increasing. In order to meet the needs of different language speakers, this paper proposes an interactive attention-based contrastive learning framework (IABCL) for the field of in-vehicle dialogue, aiming to effectively enhance cross-lingual natural language understanding (NLU). The proposed framework aims to address the challenges of cross-lingual interaction in in-vehicle dialogue systems and provide an effective solution. IABCL is based on a contrastive learning and attention mechanism. First, contrastive learning is applied in the encoder stage. Positive and negative samples are used to allow the model to learn different linguistic expressions of similar meanings. Its main role is to improve the cross-lingual learning ability of the model. Second, the attention mechanism is applied in the decoder stage. By articulating slots and intents with each other, it allows the model to learn the relationship between the two, thus improving the ability of natural language understanding in languages of the same language family. In addition, this paper constructed a multilingual in-vehicle dialogue (MIvD) dataset for experimental evaluation to demonstrate the effectiveness and accuracy of the IABCL framework in cross-lingual dialogue. With the framework studied in this paper, IABCL improves by 2.42% in intent, 1.43% in slot, and 2.67% in overall when compared with the latest model.

ZrTe2 Compound Dirac Semimetal Contacts for High-Performance MoS2 Transistors.

Recent investigations reveal elemental semimetal (Bi and Sb) contacts fabricated with conventional deposition processes exhibit a remarkable capacity of approaching the quantum limit in two-dimensional (2D) semiconductor contacts, implying it might be an optimal option to solve the contact issue of 2D semiconductor electronics. Here, we demonstrate novel compound Dirac semimetal ZrTe2 contacts to MoS2 constructed by a nondestructive van der Waals (vdW) transfer process, exhibiting excellent ohmic contact characteristics with a negligible Schottky barrier. The band hybridization between ZrTe2 and MoS2 was verified. The bilayer MoS2 transistor with a 250 nm channel length on a 20 nm thick hexagonal boron nitride (h-BN) exhibits an ION/IOFF current ratio over 105 and an on-state current of 259 µA µm-1. The current results reveal that 2D compound semimetals with vdW contacts can offer a diverse selection of proper semimetals with adjustable work functions for the next-generation 2D-based beyond-silicon electronics.

Berberine ameliorates iron levels and ferroptosis in the brain of 3 × Tg-AD mice.

BACKGROUND: Berberine (BBR) is a natural alkaloid extracted from the herb Coptis chinensis. This compound has the ability to penetrate the blood-brain barrier (BBB) and exhibit neuroprotective value in the treatment of Alzheimer's disease (AD). AD is a neurodegenerative disease characterized by ß-amyloid (Aß) deposition, hyperphosphorylated tau and other characters. Iron accumulation and ferroptosis were also detected in AD brain, which can result in neuronal damage. However, it is still unclear whether BBR can suppress ferroptosis in AD and alleviate its underlying pathology. PURPOSE: This study investigated whether BBR may affect ferroptosis and related signaling pathways in triple transgenic AD (3 × Tg-AD) mice. METHODS: Four-month-old 3 × Tg-AD mice received oral administration of BBR at a dose of 50 mg/kg for 7.5 months. Cognitive function and anxiety levels in mice were assessed using the morris water maze test, open field test, and novel object recognition test. Western blot, immunohistochemistry, and ICP-MS were employed to assess the pathology of AD, brain iron metabolism, and ferroptosis signaling pathways. Transmission electron microscopy was used to detect mitochondrial changes. The synergistic effects of BBR combined with Nrf2 were investigated using molecular docking programs and surface plasmon resonance technology. Co-inmunoprecipitation assay was used to examine the effect of BBR on the binding ability of Nrf2 and Keap1. RESULTS: The results indicated that chronic treatment of BBR mitigated cognitive disorders in 3 × Tg-AD model mice. Reductions in Aß plaque, hyperphosphorylated tau protein, neuronal loss, and ferroptosis in the brains of 3 × Tg-AD mice suggested that BBR could alleviate brain injury. In addition, BBR treatment attenuated ferroptosis, as evidenced by decreased levels of iron, MDA, and ROS, while enhancing SOD, GSH, GPX4, and SLC7A11. Consistent with the in vivo assay, BBR inhibited RSL3-induced ferroptosis in N2a-sw cells. BBR increased the expression levels of GPX4, FPN1 and SLC7A11 by regulating Nrf2 transcription levels, thereby inhibiting ferroptosis. Molecular docking programs and surface plasmon resonance technology demonstrated the direct combination of BBR with Nrf2. Co-inmunoprecipitation analysis showed that BBR inhibited the interaction between Keap1 and Nrf2. CONCLUSION: For the first time, these results showed that BBR could inhibit iron levels and ferroptosis in the brains of 3 × Tg-AD model mice and partially protect against RSL3-induced ferroptosis via the activation of Nrf2 signaling.

Research progress on the mechanism of ferroptosis and its role in diabetic retinopathy.

Ferroptosis is iron-dependent regulatory cell death (RCD). Morphologically, ferroptosis is manifested as mitochondrial atrophy and increased mitochondrial membrane density. Biochemically, ferroptosis is characterized by the depletion of glutathione (GSH), the inactivation of glutathione peroxidase 4 (GPX4), and an increase in lipid peroxides (LPO)and divalent iron ions. Ferroptosis is associated with various diseases, but the relationship with diabetic retinopathy(DR) is less studied. DR is one of the complications of diabetes mellitus and has a severe impact on visual function. The pathology of DR is complex, and the current treatment is unsatisfactory. Therefore, exploring pathogenesis is helpful for the clinical treatment of DR. This paper reviews the pathological mechanism of ferroptosis and DR in recent years and the involvement of ferroptosis in the pathology of DR. In addition, we propose problems that need to be addressed in this research field. It is expected to provide new ideas for treating DR by analyzing the role of ferroptosis in DR.

Preparation and application of high-brightness red carbon quantum dots for pH and oxidized L-glutathione dual response.

Carbon dots (CDs) with red fluorescence emission are highly desirable for use in bioimaging and trace- substance detection, with potential applications in biotherapy, photothermal therapy, and tumor visualization. Most CDs emit green or blue fluorescence, thus limiting their applicability. We report a novel fluorescent detection platform based on high-brightness red fluorescence emission carbon dots (R-CDs) co-doped with nitrogen and bromine, which exhibit pH and oxidized L-glutathione (GSSG) dual-responsive characteristics. The absolute quantum yield of the R-CDs was as high as 11.93%. We discovered that the R-CDs were able to detect acidic pH in live cells and zebrafish owing to protonation and deprotonation. In addition, GSSG was detected in vitro over a broad linear range (8-200 µM) using the R-CDs with excitation-independent emission. Furthermore, cell imaging and bioimaging experiments demonstrated that the R-CDs were highly cytocompatible and could be used as fluorescent probes to target lysosomes and nucleolus. These studies highlight the promising prospects of R-CDs as biosensing tools for bioimaging and trace-substance detection applications.

Pantethine Ameliorates Recognition Impairment in a Mouse Model of Alzheimer's Disease by Modulating Cholesterol Content and Intestinal Flora Species.

SCOPE: As a natural dietary low-molecular-weight thiol, pantethine helps maintain brain homeostasis and function in Alzheimer's disease (AD) mice. The current study aims to investigate the protective effects and underlying mechanisms of pantethine on the mitigation of cognitive deficits and pathology in a triple transgenic AD mouse model. METHODS AND RESULTS: Compared to control mice, oral administration of pantethine improve spatial learning and memory ability, relieve anxiety, and reduce the production of amyloid-ß (Aß), neuronal damage, and inflammation in 3×Tg-AD mice. Pantethine reduces body weight, body fat, and the production of cholesterol in 3×Tg-AD mice by inhibiting sterol regulatory element-binding protein (SREBP2) signal pathway and apolipoprotein E (APOE) expression; lipid rafts in the brain, which are necessary for the processing of the Aß precursor protein (APP), are also decreased. In addition, pantethine regulates the composition, distribution, and abundance of characteristic flora in the intestine; these floras are considered protective and anti-inflammatory in the gastrointestinal tract, suggesting a possible improvement in the gut flora of 3×Tg-AD mice. CONCLUSION: This study highlights the potential therapeutic effect of pantethine in AD by reducing cholesterol and lipid raft formation and regulating intestinal flora, suggesting a new option for the development of clinical drugs for AD.

Nitrogen-doped orange emitting carbon dots for ß-carotene detection and lysosomal imaging.

ß-Carotene is a natural antioxidant that has an indispensable effect on the growth and immunity of the human body. For intracellular and in vitro detection of ß-carotene, N-doped carbon quantum dots (O-CDs) were prepared by co-heating carbonization of 1,5-naphthalenediamine and nitric acid in ethanol solvent for 2 h at 200 °C. O-CDs have longer wavelength orange light emission, with an optimal excitation peak of 470 nm and an optimal emission peak of 590 nm. According to the principle of the internal filtering effect on which the detection system is based, O-CDs present a good linear relationship with ß-carotene within a wide range of 0-2000 µM, and the R2 coefficient of the linear regression equation is 0.999. In addition, O-CDs showed targeting of lysosomes in cell imaging and could be used to detect intracellular lysosomal movement. These experiments show that O-CDs can be used for in vivo and in vitro detection of ß-carotene and can serve as a potential substitute to commercial lysosome targeting probes.

Untargeted Metabolomics Revealed Potential Biomarkers of Small Yellow Follicles of Chickens during Sexual Maturation.

Sexual maturation provides economically important traits in poultry production. Research on the initiation mechanism of sexual maturity is of great significance for breeding high-yield laying hens. However, the underlying mechanisms are not fully clear. Here, one hundred and fifty Chahua No. 2 laying hens (the CH2 group, which has precocious puberty) and one hundred and fifty Wu Liang Shan black-bone laying hens (the WLS group, a late-maturing chicken breed) with similar weights and ages were randomly selected. ELISA was used to determine the secretion levels of luteinizing hormone (LH), estradiol (E2), and progesterone (P4) in 150-day-old serum and small yellow follicle (SYF) tissues. A histology examination, immunohistochemistry, and quantitative real-time PCR (qPCR) were used to explore the molecular mechanism of how some genes related to oxidative stress affect sexual maturation. The results showed that the secretion levels of LH, E2, and P4 in the CH2 group serum and SYF were higher than those in the WLS group. The results of the real-time PCR of all genes showed that the expression levels of cytochrome P450 family 11 subfamily A member 1, steroidogenic acute regulatory protein, follicle-stimulating hormone receptor, and cytochrome P450 family 19 subfamily A member 1 in the CH2 group were significantly higher than those in the WLS groups (p < 0.001). Untargeted metabolomics combined with multivariate statistical analysis was used to identify biomarkers of SYF tissues in the CH2 and WLS groups. A trajectory analysis of the principal component analysis (PCA) results showed that the samples within the group were clustered and that the samples were dispersed between the CH2 and the WLS groups, indicating that the results of the measured data were reliable and could be used for further research. Further analysis showed that a total of 319 metabolites in small yellow follicles of the CH2 and WLS groups were identified, among which 54 downregulated differential metabolites were identified. These 54 metabolites were found as potential CH2 biomarkers compared with WLS at 150 days, and the different expressions of L-arginine, L-prolinamide, (R)-4-hydroxymandelate, glutathione, and homovanillic acid were more significant. Twenty metabolic pathways were found when significantly differential metabolites were queried in the KEGG database. According to the impact values of the metabolic pathways, eighteen differential metabolites belonged to the mTOR signaling pathway, glutathione metabolism, ABC transporters, the cell ferroptosis pathway, and D-arginine and D-ornithine metabolism. Interestingly, we identified that the cell ferroptosis pathway played an important role in chicken follicle selection for the first time. The histology and immunohistochemistry of SYF showed that the number of granulosa cells increased in the CH2 groups and the expression levels of glutathione peroxidase 4, tumor protein p53, ribosomal protein S6 kinase, and sterol regulatory element binding protein 1 in the granulosa cell layer were upregulated in the CH2 group at the time of sexual maturation. Furthermore, we also speculated that the antioxidant system may play an indispensable role in regulating sexual maturity in chickens. Overall, our findings suggest differentially expressed metabolites and metabolic pathways between CH2 and WLS chickens, providing new insights into the initiation mechanism of sexual maturation.

High-Performance Aqueous Zinc-Ion Batteries Enabled by Binder-Free and Ultrathin V2O5-x@Graphene Aerogels with Intercalation Pseudocapacitance.

As a result of the absence of solid-state diffusion limitation, intercalation pseudocapacitance behavior is emerging as an attractive charge-storage mechanism that can greatly facilitate the ion kinetics to boost the rate capability and cycle stability of batteries; however, related research in the field of zinc-ion batteries (ZIBs) is still in the initial stage and only found in limited cathode materials. In this study, a novel V2O5-x@rGO hybrid aerogel consisting of ultrathin V2O5 nanosheets (∼1.26 nm) with abundant oxygen vacancies (Vö) and a three-dimensional (3D) graphene conductive network was specifically designed and used as a freestanding and binder-free electrode for ZIBs. As expected, the ideal microstructure of both the material and the electrode enable fast electron/ion diffusion kinetics of the electrode, which realize a typical intercalation pseudocapacitance behavior as demonstrated by the simulation calculation of cyclic voltammetry (CV), ex situ X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and first-principles density functional theory (DFT) calculation. Thanks to the elimination of solid-state diffusion limitation, the V2O5-x@rGO electrode delivers a high reversible rate capacity of 153.9 mAh g-1 at 15 A g-1 and 90.6% initial capacity retention at 0.5 A g-1 after 1050 cycles in ZIBs. The intercalation pseudocapacitance behavior is also realized in the assembled soft-pack battery, showing promising practical application prospects.

Prediction of protein-protein interaction sites in intrinsically disordered proteins.

Intrinsically disordered proteins (IDPs) participate in many biological processes by interacting with other proteins, including the regulation of transcription, translation, and the cell cycle. With the increasing amount of disorder sequence data available, it is thus crucial to identify the IDP binding sites for functional annotation of these proteins. Over the decades, many computational approaches have been developed to predict protein-protein binding sites of IDP (IDP-PPIS) based on protein sequence information. Moreover, there are new IDP-PPIS predictors developed every year with the rapid development of artificial intelligence. It is thus necessary to provide an up-to-date overview of these methods in this field. In this paper, we collected 30 representative predictors published recently and summarized the databases, features and algorithms. We described the procedure how the features were generated based on public data and used for the prediction of IDP-PPIS, along with the methods to generate the feature representations. All the predictors were divided into three categories: scoring functions, machine learning-based prediction, and consensus approaches. For each category, we described the details of algorithms and their performances. Hopefully, our manuscript will not only provide a full picture of the status quo of IDP binding prediction, but also a guide for selecting different methods. More importantly, it will shed light on the inspirations for future development trends and principles.

[Tongdu Xingshen acupuncture and moxibustion combined with cognitive training in treatment of post-stroke mild cognitive impairment: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect of Tongdu Xingshen (promoting the governor vessel and regaining consciousness) acupuncture and moxibustion combined with cognitive training and the simple cognitive training for post-stroke mild cognitive impairment (PSMCI). METHODS: Eighty-four patients with PSMCI were randomly divided into an observation group and a control group, with 42 cases in each group (3 cases in the observation group and 2 cases in the control group dropped off). The observation group was treated by Tongdu Xingshen acupuncture and moxibustion combined with cognitive training, acupuncture was given at Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), etc., and moxibustion was given at Shenting (GV 24) , Baihui (GV 20), Shendao (GV 11), Fengfu (GV 16) and Xinshu (BL 15). The control group was only given cognitive training. All the above treatment was given once a day, 5 times a week, for 4 consecutive weeks. The scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), activity of daily living (ADL) and stroke-specific quality of life (SS-QOL) were compared between the two groups before treatment, after treatment, 4 weeks and 12 weeks after treatment. RESULTS: After treatment, 4 weeks and 12 weeks after treatment, the MoCA, MMSE and SS-QOL scores of the two groups were all higher than those before treatment (P<0.05), and the ADL scores were lower than those before treatment (P<0.05). In the observation group, the MoCA and MMSE scores were higher than those of the control group after treatment, 4 weeks and 12 weeks after treatment (P<0.05), and the SS-QOL score was higher than that of the control group 12 weeks after treatment (P<0.05). CONCLUSION: Both Tongdu Xingshen acupuncture and moxibustion combined with cognitive training and simple cognitive training can improve cognitive function, daily living ability and quality of life in patients with PSMCI, and the combined therapy is superior to simple cognitive training in improving cognitive function and long-term quality of life in patients with PSMCI.

Tunneling Magnetoresistance in Noncollinear Antiferromagnetic Tunnel Junctions.

Antiferromagnetic (AFM) spintronics has emerged as a subfield of spintronics driven by the advantages of antiferromagnets producing no stray fields and exhibiting ultrafast magnetization dynamics. The efficient method to detect an AFM order parameter, known as the Néel vector, by electric means is critical to realize concepts of AFM spintronics. Here, we demonstrate that noncollinear AFM metals, such as Mn_{3}Sn, exhibit a momentum dependent spin polarization which can be exploited in AFM tunnel junctions to detect the Néel vector. Using first-principles calculations, we predict a tunneling magnetoresistance (TMR) effect as high as 300% in AFM tunnel junctions with Mn_{3}Sn electrodes, where the junction resistance depends on the relative orientation of their Néel vectors and exhibits four nonvolatile resistance states. We argue that the spin-split band structure and the related TMR effect can also be realized in other noncollinear AFM metals like Mn_{3}Ge, Mn_{3}Ga, Mn_{3}Pt, and Mn_{3}GaN. Our work provides a robust method for detecting the Néel vector in noncollinear antiferromagnets via the TMR effect, which may be useful for their application in AFM spintronic devices.