Histone deacetylase 6 deficiency protects the liver against ischemia/reperfusion injury by activating PI3K/AKT/mTOR signaling.

Liver transplantation (LT) is the only effective method to treat end-stage liver disease. Hepatic ischemia-reperfusion injury (IRI) continues to limit the prognosis of patients receiving LT. Histone deacetylase 6 (HDAC6) is a unique HDAC member involved in inflammation and apoptosis. However, its role and mechanism in hepatic IRI have not yet been reported. We examined HDAC6 levels in liver tissue from LT patients, mice challenged with liver IRI, and hepatocytes subjected to hypoxia/reoxygenation (H/R). In addition, HDAC6 global-knockout (HDAC6-KO) mice, adeno-associated virus-mediated liver-specific HDAC6 overexpressing (HDAC6-LTG) mice, and their corresponding controls were used to construct hepatic IRI models. Hepatic histology, inflammatory responses, and apoptosis were detected to assess liver injury. The molecular mechanisms of HDAC6 in hepatic IRI were explored in vivo and in vitro. Moreover, the HDAC6-selective inhibitor tubastatin A was used to detect the therapeutic effect of HDAC6 on liver IRI. Together, our results showed that HDAC6 expression was significantly upregulated in liver tissue from LT patients, mice subjected to hepatic I/R surgery, and hepatocytes challenged by hypoxia/reoxygenation (H/R) treatment. Compared with control mice, HDAC6 deficiency mitigated liver IRI by inhibiting inflammatory responses and apoptosis, whereas HDAC6-LTG mice displayed the opposite phenotype. Further molecular experiments show that HDAC6 bound to and deacetylated AKT and HDAC6 deficiency improved liver IRI by activating PI3K/AKT/mTOR signaling. In conclusion, HDAC6 is a key mediator of hepatic IRI that functions to promote inflammation and apoptosis via PI3K/AKT/mTOR signaling. Targeting hepatic HDAC6 inhibition may be a promising approach to attenuate liver IRI.

Exploring Infantile Epileptic Spasm Syndrome: A Proteomic Analysis of Plasma Using the Data-Independent Acquisition Approach.

This study aimed to identify characteristic proteins in infantile epileptic spasm syndrome (IESS) patients' plasma, offering insights into potential early diagnostic biomarkers and its underlying causes. Plasma samples were gathered from 60 patients with IESS and 40 healthy controls. Data-independent acquisition proteomic analysis was utilized to identify differentially expressed proteins (DEPs). These DEPs underwent functional annotation through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Gene set enrichment analysis (GSEA) was employed for both GO (GSEA-GO) and KEGG (GSEA-KEGG) analyses to examine the gene expression profiles. Receiver operating characteristic (ROC) curves assessed biomarkers' discriminatory capacity. A total of 124 DEPs were identified in IESS patients' plasma, mainly linked to pathways, encompassing chemokines, cytokines, and oxidative detoxification. GSEA-GO and GSEA-KEGG analyses indicated significant enrichment of genes associated with cell migration, focal adhesion, and phagosome pathways. ROC curve analysis demonstrated that the combination of PRSS1 and ACTB, PRSS3, ACTB, and PRSS1 alone exhibited AUC values exceeding 0.7. This study elucidated the significant contribution of cytokines, chemokines, oxidative detoxification, and phagosomes to the IESS pathogenesis. The combination of PRSS1 and ACTB holds promise as biomarkers for the early diagnosis of IESS.

Ion Transport Behavior in van der Waals Gaps of 2D Materials.

2D materials, with advantages of atomic thickness and novel physical/chemical characteristics, have emerged as the vital building blocks for advanced lamellar membranes which possess promising potential in energy storage, ion separation, and catalysis. When 2D materials are stacked together, the van der Waals (vdW) force generated between adjacent layered nanosheets induces the construction of an ordered lamellar membrane. By regulating the interlayer spacing down to the nanometer or even sub-nanometer scale, rapid and selective ion transport can be achieved through such vdW gaps. The further improvement and application of qualified 2D materials-based lamellar membranes (2DLMs) can be fulfilled by the rational design of nanochannels and the intelligent micro-environment regulation under different stimuli. Focusing on the newly emerging advances of 2DLMs, in this review, the common top-down and bottom-up synthesis approaches of 2D nanosheets and the design strategy of functional 2DLMs are briefly introduced. Two essential ion transport mechanisms within vdW gaps are also involved. Subsequently, the responsive 2DLMs based on different types of external stimuli and their unique applications in nanofluid transport, membrane-based filters, and energy storage are presented. Based on the above analysis, the existing challenges and future developing prospects of 2DLMs are further proposed.

Precise Atomic Structure Regulation of Single-Atom Platinum Catalysts toward Highly Efficient Hydrogen Evolution Reaction.

Noble metal single-atom-catalysts (SACs) have demonstrated significant potential to improve atom utilization efficiency and catalytic activity for hydrogen evolution reaction (HER). However, challenges still remain in rationally modulating active sites and catalytic activities of SACs, which often results in sluggish kinetics and poor stability, especially in neutral/alkaline media. Herein, precise construction of Pt single atoms anchored on edge of 2D layered Ni(OH)2 (Pt-Ni(OH)2-E) is achieved utilizing in situ electrodeposition. Compared to the single-atom Pt catalysts anchored on the basal plane of Ni(OH)2 (Pt-Ni(OH)2-BP), the Pt-Ni(OH)2-E possesses superior electron affinity and high intrinsic catalytic activity, which favors the strong adsorption and rapid dissociation toward water molecules. As a result, the Pt-Ni(OH)2-E catalyst requires low overpotentials of 21 and 34 mV at 10 mA cm-2 in alkaline and neutral conditions, respectively. Specifically, it shows the high mass activity of 23.6 A mg-1 for Pt at the overpotential of 100 mV, outperforming the reported catalysts and commercial Pt/C. This work provides new insights into the rational design of active sites for preparing high-performance SACs.

CgADAR1 involved in regulating the synthesis of interferon-like protein in Crassostrea gigas.

Adenosine deaminases acting on RNA 1 (ADAR1) is a dsRNA adenosine (A)-to-inosine (I) editing enzyme that regulates the innate immune response against virus invasion. In the present study, a novel CgADAR1 was identified from the oyster Crassostrea gigas. The open reading frame (ORF) of CgADAR1 was of 3444 bp encoding a peptide of 1147 amino acid residues with two Zα domains, one dsRNA binding motif (DSRM) and one RNA adenosine deaminase domain (ADEAMc). The mRNA transcripts of CgADAR1 were detected in all the examined tissues, with higher expression levels in mantle and gill, which were 7.11-fold and 4.90-fold (p < 0.05) of that in labial palp, respectively. The mRNA transcripts of CgADAR1 in haemocytes were significantly induced at 24 h and 36 h after Poly (A: U) stimulation, which were 6.03-fold (p < 0.01) and 1.37-fold (p < 0.001) of that in control group, respectively. At 48 h after Poly (A:U) stimulation, the mRNA expression of CgRIG-Ⅰ, CgIRF8 and CgIFNLP significantly increased, which were 4.36-fold (p < 0.001), 1.82-fold (p < 0.05) and 1.92-fold (p < 0.05) of that in control group. After CgADAR1 expression was inhibited by RNA interference (RNAi), the mRNA expression levels of CgMDA5, CgRIG-Ⅰ, CgTBK1, CgIRF8 and CgIFNLP were significantly increased, which were 11.88-fold, 11.51-fold, 2.22-fold, 2.85-fold and 2.52-fold of that in control group (p < 0.001), and the phosphorylation level of CgTBK1 was also significantly increased. These results suggested that CgADAR1 played a regulation role in the early stages of viral infection by inhibiting the synthesis of interferon-like protein.

Application of the mild behavioral impairment checklist in Chinese patients with the behavioral variant of frontotemporal dementia.

BACKGROUND: The mild behavioral impairment checklist (MBI-C) designed to capture neuropsychiatric symptoms in the whole spectrum of elder with or without dementia, have been verified in mild behavioral impairment, mild cognitive impairment and Alzheimer's Disease, but never used in the behavioral variant of frontotemporal dementia (bvFTD). METHODS: Fifty-two patients with bvFTD (mild, n = 30; moderate-severe, n = 22) and 82 community-dwelling elderly individuals (HCs) were enrolled. All subjects were assessed with a full neuropsychological scale including the MBI-C, Neuropsychiatric Inventory Questionnaire (NPI-Q), and Frontal Behavioral Inventory (FBI). Receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the MBI-C, NPI-Q, and FBI, and cutoff points were determined using the Youden index. RESULTS: The MBI-C and domain scores in all patients with bvFTD were significantly higher than those in HCs. The most common symptoms of bvFTD were apathy (82.7%) and impulse dyscontrol (80.8%). The MBI-C score was positively correlated with the NPI-Q, FBI, and Activities of Daily Living. For differentiating patients with both bvFTD and mild bvFTD from HCs, the optimal MBI-C cutoff point was 5.5 with a sensitivity of 100% and specificity of 82%, and its sensitivity was higher than that of the NPI-Q and FBI. CONCLUSION: The MBI-C is a sensitive tool for screening behavioral and psychological symptoms in patients with bvFTD, even in the early stages of the disease.

First Report of Filipino ß0-Thalassemia/ß-Thalassemia in a Chinese Family.

A pregnant woman living in Fujian Province, southeastern China, presented due to a risk of having a baby with ß-thalassemia major, during her second pregnancy, since she and her husband were suspected as ß-thalassemia carriers and their affected daughter was a transfusion-dependent patient. Using the common α-thalassemia and ß-thalassemia genotypes test, the pregnant woman was diagnosed as a ß-thalassemia carrier with ßIVS-2 - 654 (C→T)/ßN genotype and her daughter had a homozygosity for IVS - 2 - 654 (C→T) mutation, however, no abnormalities were detected in her husband. SMRT identified a Filipino ß0-deletion in her husband, and MLPA also revealed an unknown deletion in the HBB gene. Electrophoresis showed approximately 350 bp of the PCR product, and the ß-Filipino genotype presented novel fracture fragments ranging from 5,112,884 to 5,231,358 bp, and lacked a 118,475 bp fragment relative to the wild-type sequence. The daughter was therefore diagnosed with the ßIVS-2 - 654 (C→T)/ßFilipino genotype. Prenatal diagnosis with umbilical cord blood at 27th week of gestation showed heteroztgosity for IVS - 2 - 654 (C→T) mutation in the fetus and continued pregnancy was recommended. In conclusion, we identified the Filipino ß0-deletion in a Chinese family, from Fujian area, for the first time, during prenatal screening.

Twisted Bilayer Graphene Induced by Intercalation.

Twisted bilayer graphene (tBLG) has gained significant attention due to its unique physical and electronic properties. However, efficient fabrication of high-quality tBLG with diverse twist angles is crucial to expedite research on angle-dependent physics and potential applications. In this study, an intercalation strategy utilizing organic molecules, such as 1,2-dichloroethane, is developed to weaken the interlayer interaction and induce slide or rotation of the topmost graphene layer for tBLG fabrication. The proportion of tBLGs in the resulting 1,2-dichloroethane-treated BLG (dtBLG) reaches up to 84.4% for twist angles ranging from 0° to 30°, surpassing previously reported methods using chemical vapor deposition (CVD). Moreover, the twist angle distribution is not uniform and tends to concentrate in the ranges of 0-10° and 20-30°. This facile and rapid intercalation-based methodology provides a practical solution for studying angle-dependent physics and advancing the utilization of twisted two-dimensional materials.

Additives improve the fermentation quality, anthocyanin content, and biological activity of purple Napier grass silage.

BACKGROUND: Purple Napier grass (PNG), a widely used grass rich in anthocyanin, is commonly employed in the production of silage. However, there is currently limited research on the retention of anthocyanin with or without additives during ensiling. Therefore, this study aimed to investigate the effect of different additives (Lactiplantibacillus plantarum CCZZ1 (LP), glucose, acetic acid, and dried soybean curd residue) on fermentation quality, anthocyanin content, and microbial community structure of PNG silage. RESULTS: Ensiling PNG without additives led to poor fermentation quality and rapid degradation of anthocyanin, resulting in a decline in antioxidant activity and the persistence of harmful microorganisms with high relative abundance. The use of additives, especially LP, effectively increased the relative abundance of L. plantarum, enhancing fermentation quality, the retention of anthocyanin (up to 166% increase rate) and antioxidant activity, while reducing the relative abundance of harmful microorganisms during ensiling for 30 days. Additionally, prolonged ensiling negatively affected the preservation of anthocyanin. Based on both fermentation quality and bioactivity, PNG should be ensiled for 30 days with LP inoculation. CONCLUSION: The employment of additives, especially LP, improved the fermentation quality, anthocyanin retention, and microbial community structure in PNG silage. To optimize both fermentation quality and bioactivity, it is recommended that PNG be ensiled for 30 days with LP inoculation. © 2024 Society of Chemical Industry.

Effect of different mouthwashes on ventilator-related outcomes and mortality in intensive care unit patients: A network meta-analysis.

BACKGROUND: Ventilator-associated pneumonia is a common and life-threatening complication in intensive care unit (ICU) patients. Maintaining oral hygiene is crucial for reducing ventilator-associated pneumonia incidence. Various mouthwash solutions are used for oral care in ICU settings, but their comparative effectiveness remains unclear. This study aims to systematically evaluate and compare the efficacy and safety of commonly used mouthwashes for oral care in mechanically ventilated ICU patients. METHODS: We searched PubMed, Web of Science, Embase, and Cochrane Library for randomised controlled trials (RCTs) comparing saline, chlorhexidine, sodium bicarbonate, oxidising agents, herbal extracts, and povidone-iodine for oral care in ventilated ICU patients. Outcomes included ventilator-associated pneumonia incidence, ICU mortality, duration of ventilation, and Escherichia coli fixed value. A network meta-analysis (NMA) was conducted to synthesise direct and indirect evidence. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols, 2023120028. RESULTS: FourteenRCTs with 1644 participants were included. Oxidising agents showed a trend towards reducing the incidence of VAP compared to the control group (risk ratio: 0.24, 95% confidence interval: 0.05-1.10). Administration of saline was associated with a notable reduction in ICU mortality (risk ratio: 0.18, 95% confidence interval: 0.04-0.88) versus no mouthwash. No significant differences were observed in the duration of mechanical ventilation between chlorhexidine, povidone-iodine, and the control group. CONCLUSIONS: Antimicrobial mouthwashes, especially chlorhexidine, pose potential risks in ICU patients; oxidising solutions demonstrate relative safety. Saline solution emerges as a promising alternative, associated with a significant reduction in mortality rates. However, the need for large, high-quality RCTs remains paramount to substantiate these findings and establish evidence-based oral-care protocols in ICU settings. REGISTRATION: This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols, 2023120028.

Identification and Characterization of DNA-Oxaliplatin Adducts through α-hemolysin Nanopores.

The antitumor effect of Pt-based drugs is determined by their binding activity with deoxyribonucleic acid (DNA), and understanding the reaction process in a systematic manner is crucial. However, existing assays used for DNA-Pt research suffer from several issues, such as complicated sample preparation, preamplification, and expensive instruments, which dramatically limit their practical application. In this study, a novel method was presented to investigate the adducts of DNA and oxaliplatin using an α-hemolysin nanopore sensor. This approach allows for real-time monitoring of the DNA-oxaliplatin condensation process through the detection of nanopore events associated with DNA-oxaliplatin adducts. Specifically, type I and II signals exhibiting specific current characteristics were observed during the process. Typical signals with high frequency were obtained by recording the designed DNA sequence. Furthermore, the production of these signals was confirmed to be independent of homologous adducts. This finding suggests that the DNA-oxaliplatin adduct can serve as a potential sensor for detecting oxaliplatin lesions and multiple types of molecules.

Paxillin interactome identified by SILAC and label-free approaches coupled to TurboID sheds light on the compositions of focal adhesions in mouse embryonic stem cells.

Self-renewal and differentiation of mouse embryonic stem cells (mESCs) are greatly affected by the extracellular matrix (ECM) environment; the composition and stiffness of which are sensed by the cells via integrin-associated focal adhesions (FAs) which link the cells to the ECM. Although FAs have been studied extensively in differentiated cells, their composition and function in mESCs are not as well elucidated. To gain more detailed knowledge of the molecular compositions of FAs in mESCs, we adopted the proximity-dependent biotinylation (BioID) proteomics approach. Paxillin, a known FA protein (FAP), is fused to the promiscuous biotin ligase TurboID as bait. We employed both SILAC- and label-free (LF)-based quantitative proteomics to strengthen as well as complement individual approach. The mass spectrometry data derived from SILAC and LF identified 38 and 443 proteins, respectively, with 35 overlapping candidates. Fifteen of these shared proteins are known FAPs based on literature-curated adhesome and 7 others are among the reported "meta-adhesome", suggesting the components of FAs are largely conserved between mESCs and differentiated cells. Furthermore, the LF data set contained an additional 18 literature-curated FAPs. Notably, the overlapped proteomics data failed to detect LIM-domain proteins such as zyxin family proteins, which suggests that FAs in mESCs are less mature than differentiated cells. Using the LF approach, we are able to identify PDLIM7, a LIM-domain protein, as a FAP in mESCs. This study illustrates the effectiveness of TurboID in mESCs. Importantly, we found that application of both SILAC and LF methods in combination allowed us to analyze the TurboID proteomics data in an unbiased, stringent and yet comprehensive manner.

Anti-Inflammatory Effects of New Naphthyridine from Sponge Aaptos suberitoides in LPS-Stimulated RAW 264.7 Macrophages via Regulation of MAPK and Nrf2 Signaling Pathways.

Two new naphthyridine compounds, 4-methoxycarbonyl-5-oxo-1,6-naphthyridine (1) and 5-methoxycarbonyl-4-oxo-1,6-naphthyridine (2) were obtained from the MeOH extracts of sponge Aaptos suberitoides. Their structures were determined by spectroscopic methods, including HR-ESI-MS, 1D-NMR (1 H-NMR, 13 C-NMR), 2D-NMR (COSY, HSQC, HMBC). The structure of compound 1 was further confirmed via single crystal X-ray diffraction analysis. Compound 1 was found to reduce NO production in LPS-induced RAW 264.7 macrophages with IC50 value of 0.15 mM. In addition, it decreased the mRNA expression levels of pro-inflammatory mediators, such as the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) in LPS-induced macrophages. It also decreased the protein expression of iNOS and COX-2 in LPS-induced macrophages. Mechanistic studies further revealed that compound 1 inhibited the mitogen-activated protein kinase (MAPK), and activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathways in LPS-induced RAW 264.7 macrophages.

Preparation of a novel photocatalytic catalyst PW9@ZnO/Ag and the photocatalytic degradation of butyl xanthate under visible light.

Photocatalytic technology is attracting considerable attention for the advantages of low cost and environmentally friendly properties. In this study, a novel photocatalyst PW9@ZnO/Ag (PZA) was synthesized hydrothermally and characterized by a variety of means. The results indicated that ZnO and Ag NPs were successfully decorated and uniformly dispersed on PW9 to form the composites. The prepared PZA was applied in the degradation of simulated butyl xanthate (BX) beneficiation wastewater both under the UV light and the xenon lamp, and a maximum degradation of 99.83% was obtained under the visible light with 10% ZnO loading, 1 g/L PZA, initial BX concentration of 20 mg/L, and pH 5.5. The PZA was recovered and reused for 5 times, and the degradation rates remained above 70%. Superoxide radical (·O2-) was the main active species for the photocatalytic degradation of BX. The experimental results demonstrate that PZA is a promising photocatalyst, making it a prospective strategy to overcome current challengers in the use of xanthate degradation and beneficiation wastewater treatment under visible light.

Antidepressant effects of cherry leaf decoction on a chronic unpredictable mild stress rat model based on the Glu/GABA-Gln metabolic loop.

Cherry leaves (Prunus pseudocerasus Lindl. [Rosaceae]), a traditional Chinese herbal medicine, can regulate the factors closely related to depression including inflammatory cytokines, oxidative stress and blood glucose level. However, the antidepressant effects of cherry leaves and underlying neuromodulatory mechanisms remain relatively have not been elucidated explicitly. The present study investigated the antidepressant effects of cherry leaf decoction (CLD). The underlying neuromodulatory mechanism was explored by examining the glutamate (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. The chronic unpredictable mild stress (CUMS) rodent model was used in this study. The main flavonoids components of CLD were identified using high-performance liquid chromatography (HPLC). The antidepressant effects of CLD were assessed throughout behavioural tests including the bodyweight, sucrose preference test (SPT), forced swimming test (FPT) and tail suspension test (TST). Moreover, The baseline levels of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were quantified. The expression of proteins integrally involved in the Glu/GABA-Gln metabolic loop were observed and quantified by Western blotting, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. This study found that CLD ameliorated depressive-like behaviours induced by CUMS. The increase of serum ACTH and CORT baseline levels induced by CUMS was also reversed after CLD intervention. Furthermore, CUMS reduced the expression of GAD65, GAD67, GLT-1, GS and GABAA and increased NMDAR1 levels in the rat hippocampus, which was normalized by CLD treatment. The findings demonstrated that CLD could ameliorate the depression-like behaviours induced by CUMS, potentially through the inhibition of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and the regulation of Glu/GABA-Gln metabolic loop.

Liquiritigenin protects against myocardial ischemic by inhibiting oxidative stress, apoptosis, and L-type Ca2+ channels.

Liquiritigenin (Lq) offers cytoprotective effects against various cardiac injuries, but its beneficial effects on myocardial ischemic (MI) injury and the related mechanisms remain unclear. In the in vivo study, an animal model of MI was induced by intraperitoneal injection of isoproterenol (Iso, 85 mg/kg). ECG, heart rate, serum levels of CK and CK-MB, histopathological changes, and reactive oxygen species (ROS) levels were all measured. In vitro, H9c2 cells were divided into four groups and treated for 24 hr with liquiritigenin (30 µmol/L and 100 µmol/L) followed with CoCl2 (800 µmol/L) for another 24 hr. Cell viability, apoptosis, mitochondrial membrane potential, and intracellular Ca2+ concentration ([Ca2+ ]i ) were then assessed. The L-type Ca2+ current (ICa-L ) was detected using a patch clamp technique on isolated rat ventricular myocytes. The myocyte contraction and Ca2+ transients were measured using an IonOptix detection system. The remarkable cardiac injury and generation of intracellular ROS induced by Iso were alleviated via treatment with Lq. CoCl2 administration induced cell apoptosis, mitochondrial dysfunction, and Ca2+ overload in H9c2; Lq reduces these deleterious effects of CoCl2 . Meanwhile, Lq blocked ICa-L in a dose-dependent manner. The half-maximal inhibitory concentration of Lq was 110.87 µmol/L. Lq reversibly reduced the amplitude of cell contraction as well as the Ca2+ transients. The results show that Lq protects against MI injury by antioxidation, antiapoptosis, counteraction mitochondrial dysfunction, and inhibition of ICa-L , thus damping intracellular Ca2+ .

Multi-GNSS Combined Orbit and Clock Solutions at iGMAS.

Global navigation services from the quad-constellation of GPS, GLONASS, BDS, and Galileo are now available. The international GNSS monitoring and assessment system (iGMAS) aims to evaluate the navigation performance of the current quad systems under a unified framework. In order to assess impact of orbit and clock errors on the positioning accuracy, the user range error (URE) is always taken as a metric by comparison with the precise products. Compared with the solutions from a single analysis center, the combined solutions derived from multiple analysis centers are characterized with robustness and reliability and preferred to be used as references to assess the performance of broadcast ephemerides. In this paper, the combination method of iGMAS orbit and clock products is described, and the performance of the combined solutions is evaluated by various means. There are different internal precisions of the combined orbit and clock for different constellations, which indicates that consistent weights should be assigned for individual constellations and analysis centers included in the combination. For BDS-3, Galileo, and GLONASS combined orbits of iGMAS, the root-mean-square error (RMSE) of 5 cm is achieved by satellite laser ranging (SLR) observations. Meanwhile, the SLR residuals are characterized with a linear pattern with respect to the position of the sun, which indicates that the solar radiation pressure (SRP) model adopted in precise orbit determination needs further improvement. The consistency between combined orbit and clock of quad-constellation is validated by precise point positioning (PPP), and the accuracies of simulated kinematic tests are 1.4, 1.2, and 2.9 cm for east, north, and up components, respectively.

Aaptamine - a dual acetyl - and butyrylcholinesterase inhibitor as potential anti-Alzheimer's disease agent.

CONTEXT: Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are promising therapeutic targets for AD. OBJECTIVE: To evaluate the inhibitory effects of aaptamine on two cholinesterases and investigate the in vivo therapeutic effect on AD in a zebrafish model. MATERIALS AND METHODS: Aaptamine was isolated from the sponge Aaptos suberitoides Brøndsted (Suberitidae). Enzyme inhibition, kinetic analysis, surface plasmon resonance (SPR) and molecular docking assays were used to determine its inhibitory effect on AChE and BuChE in vitro. Zebrafish were divided into six groups: control, model, 8 µM donepezil, 5 , 10 and 20 µM aaptamine. After three days of drug treatment, the behaviour assay was performed. RESULTS: The IC50 values of aaptamine towards AChE and BuChE were 16.0 and 4.6 µM. And aaptamine directly inhibited the two cholinesterases in the mixed inhibition type, with Ki values of 6.96 ± 0.04 and 6.35 ± 0.02 µM, with Kd values of 87.6 and 10.7 µM. Besides, aaptamine interacts with the crucial anionic sites of AChE and BuChE. In vivo studies indicated that the dyskinesia recovery rates of 5 , 10 and 20 µM aaptamine group were 34.8, 58.8 and 60.0%, respectively, and that of donepezil was 63.7%. DISCUSSION AND CONCLUSIONS: Aaptamine showed great potential to exert its anti-AD effects by directly inhibiting the activities of AChE and BuChE. Therefore, this study identified a novel medicinal application of aaptamine and provided a new structural scaffold for the development of anti-AD drugs.

HDAC6 regulates antibody-dependent intracellular neutralization of viruses via deacetylation of TRIM21.

Tripartite motif-containing protein 21 (TRIM21) is a cytosolic antibody receptor that targets the internalized virus-antibody complex to the proteasome for degradation. However, the precise mechanism regulating TRIM21 activity is unknown. Here we show that TRIM21 is a substrate of histone deacetylase 6 (HDAC6) and that its function is regulated by acetylation. HDAC6 interacts with TRIM21 through its PRYSPRY motif and deacetylates TRIM21 at lysine 385 and lysine 387, thus promoting its homodimerization. Inhibiting HDAC6 activity increases TRIM21 acetylation, and hyperacetylation blocks TRIM21 dimerization and ubiquitination, preventing its binding to the virus-antibody complex and its degradation via the ubiquitin-proteasome pathway. HDAC6 depletion or inhibition increases virus accumulation in cells, indicative of an impaired capacity for antibody-dependent intracellular neutralization of viruses, whereas TRIM21 acetylation-deficient K385/387R mutant rescues HDAC6 depletion-caused ADIN impairment. These findings provide evidence for HDAC6 as a novel regulator of TRIM21-mediated intracellular innate immunity.

Ni(OH)2 Templated Synthesis of Ultrathin Ni3 S2 Nanosheets as Bifunctional Electrocatalyst for Overall Water Splitting.

Ultrathin nickel (Ni)-based sulfide nanosheets have been reported as excellent electrocatalysts for overall water splitting; however, the uncontrollability over thickness due to the nonlayered structure still hampers its practical application. Herein, a simple topochemical conversion strategy is employed to synthesize cobalt-doped Ni3 S2 (Co-Ni3 S2 ) ultrathin nanosheets on Ni foam. The Co-Ni3 S2 nanosheets are controlled synthesized by using Co-Ni(OH)2 ultrathin nanosheets as templates with anneal and sulfurization treatment, showing exceptional electrocatalytic activity. This template-assisted method can also be applied to obtain Ni, NiO, and NiPx nanosheets, providing a universal strategy to synthesize ultrathin nanosheets of nonlayered materials. The overall water splitting of this Co-Ni3 S2 ultrathin nanosheets achieves a low voltage of 1.54 V at a current density of 10 mA cm-2 and high durability in 1 m KOH, comparable to the best performance of electrochemical water splitting ever reported. The detailed structural transformation of Ni-based sulfides in the catalytic process and its mechanism are further explored both experimentally and theoretically.