Inhibition of USP10 induces myeloma cell apoptosis by promoting cyclin D3 degradation.

The cell cycle regulator cyclin D3 (CCND3) is highly expressed in multiple myeloma (MM) and it promotes MM cell proliferation. After a certain phase of cell cycle, CCND3 is rapidly degraded, which is essential for the strict control of MM cell cycle progress and proliferation. In the present study, we investigated the molecular mechanisms regulating CCND3 degradation in MM cells. By utilizing affinity purification-coupled tandem mass spectrometry, we identified the deubiquitinase USP10 interacting with CCND3 in human MM OPM2 and KMS11 cell lines. Furthermore, USP10 specifically prevented CCND3 from K48-linked polyubiquitination and proteasomal degradation, therefore enhancing its activity. We demonstrated that the N-terminal domain (aa. 1-205) of USP10 was dispensable for binding to and deubiquitinating CCND3. Although Thr283 was important for CCND3 activity, it was dispensable for CCND3 ubiquitination and stability modulated by USP10. By stabilizing CCND3, USP10 activated the CCND3/CDK4/6 signaling pathway, phosphorylated Rb, and upregulated CDK4, CDK6 and E2F-1 in OPM2 and KMS11 cells. Consistent with these findings, inhibition of USP10 by Spautin-1 resulted in accumulation of CCND3 with K48-linked polyubiquitination and degradation that synergized with Palbociclib, a CDK4/6 inhibitor, to induce MM cell apoptosis. In nude mice bearing myeloma xenografts with OPM2 and KMS11 cells, combined administration of Spautin-l and Palbociclib almost suppressed tumor growth within 30 days. This study thus identifies USP10 as the first deubiquitinase of CCND3 and also finds that targeting the USP10/CCND3/CDK4/6 axis may be a novel modality for the treatment of myeloma.

SLC38A4 functions as a tumour suppressor in hepatocellular carcinoma through modulating Wnt/ß-catenin/MYC/HMGCS2 axis.

BACKGROUND: Many molecular alterations are shared by embryonic liver development and hepatocellular carcinoma (HCC). Identifying the common molecular events would provide a novel prognostic biomarker and therapeutic target for HCC. METHODS: Expression levels and clinical relevancies of SLC38A4 and HMGCS2 were investigated by qRT-PCR, western blot, TCGA and GEO datasets. The biological roles of SLC38A4 were investigated by functional assays. The downstream signalling pathway of SLC38A4 was investigated by qRT-PCR, western blot, immunofluorescence, luciferase reporter assay, TCGA and GEO datasets. RESULTS: SLC38A4 silencing was identified as an oncofetal molecular event. DNA hypermethylation contributed to the downregulations of Slc38a4/SLC38A4 in the foetal liver and HCC. Low expression of SLC38A4 was associated with poor prognosis of HCC patients. Functional assays demonstrated that SLC38A4 depletion promoted HCC cellular proliferation, stemness and migration, and inhibited HCC cellular apoptosis in vitro, and further repressed HCC tumorigenesis in vivo. HMGCS2 was identified as a critical downstream target of SLC38A4. SLC38A4 increased HMGCS2 expression via upregulating AXIN1 and repressing Wnt/ß-catenin/MYC axis. Functional rescue assays showed that HMGCS2 overexpression reversed the oncogenic roles of SLC38A4 depletion in HCC. CONCLUSIONS: SLC38A4 downregulation was identified as a novel oncofetal event, and SLC38A4 was identified as a novel tumour suppressor in HCC.

Neuronal Apoptosis Preventive Potential of Sophocarpine via Suppression of Aß-Accumulation and Down-Regulation of Inflammatory Response.

In the current study sophocarpine was investigated in vitro for prevention of ß-amyloid induced PC12 neuronal cell damage. Exposure to ß-amyloid caused a dose-dependent suppression in growth of PC12 cells with maximum reduction at 10 µM. Sophocarpine pre-treatment reversed suppressive effect of ß-amyloid (10 µM) on PC12 cell growth in concentration-based manner. In sophocarpine pre-treated PC12 cells the ß-amyloid mediated PGE2 level elevation was attenuated significantly at 0.25-2 µM doses. Moreover, in sophocarpine pretreated PC12 cells the ß-amyloid mediated promotion of COX-2 level was also inhibited. Sophocarpine pre-treatment attenuated iNOS expression in ß-amyloid exposed PC12 cells at 0.25-2 µM doses. Pre-treatment of PC12 cells with sophocarpine suppressed NO-species generation induced by ß-amyloid exposure. In sophocarpine pretreated PC12 cells elevation of nuclear NF-κB expression induced by ß-amyloid was significantly inhibited. In summary, sophocarpine prevents reduction of PC12 cell growth induced by ß-amyloid exposure via inhibition of inflammatory processes. The preventive effect of sophocarpine on ß-amyloid induced PC12 cell damage is associated with inhibition of NF-κB nuclear translocation. Therefore, sophocarpine may be used for treatment of neurological disorders like Alzheimer's disease.

Isomeric Dibenzoheptazethrenes for Air-Stable Organic Field-Effect Transistors.

Singlet diradicaloids hold great potential as semiconductors for organic field-effect transistors (OFETs). However, their relative low material and device stabilities impede the practical applications. Here, to achieve balanced stability and performance, two isomeric dibenzoheptazethrene derivatives with singlet diradical character were synthesized in a concise manner. Benefitting from the aromatic stabilization, both compounds display a small diradical character and large singlet-triplet gap, as corroborated by variable-temperature electron paramagnetic resonance spectra, single-crystal analysis, and theoretical calculations. OFET devices based on single crystals showed a high hole mobility of 0.15 cm2 V-1 s-1 , which is the highest for zethrene-based semiconductors. Both isomers exhibited remarkable material stability in air-saturated solutions as well as excellent bias-stress and storage stability in device under ambient air.

A phase I/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

PURPOSE: Cyclin-dependent kinase-retinoblastoma (CDK-RB) pathway is dysregulated in some diffuse intrinsic pontine gliomas (DIPG). We evaluated safety, feasibility, and early efficacy of the CDK4/6-inhibitor ribociclib, administered following radiotherapy in newly-diagnosed DIPG patients. METHODS: Following radiotherapy, eligible patients received ribociclib in 28-day cycles (350 mg/m2; 21 days on/7 days off). Feasibility endpoints included tolerability for at least 6 courses, and a less than 2-week delay in restarting therapy after 1 dose reduction. Early efficacy was measured by 1-year and median overall survival (OS). Patient/parent-by-proxy reported outcomes measurement information system (PROMIS) assessments were completed prospectively. RESULTS: The study included 10 evaluable patients, 9 DIPG and 1 diffuse midline glioma (DMG)-all 3.7 to 19.8 years of age. The median number of courses was 8 (range 3-14). Three patients required dose reduction for grade-4 neutropenia, and 1 discontinued therapy for hematological toxicity following course 4. The most common grade-3/4 toxicity was myelosuppression. After 2 courses, MRI evaluations in 4 patients revealed increased necrotic volume, associated with new neurological symptoms in 3 patients. The 1-year and median OS for DIPG was 89% and 16.1 months (range 10-30), respectively; the DMG patient died at 6 months post-diagnosis. Five patients donated brain tissue and tumor; 3 were RB+ . CONCLUSIONS: Ribociclib administered following radiotherapy is feasible in DIPG and DMG. Increased tumor necrosis may represent a treatment effect. These data warrant further prospective volumetric analyses of tumors with necrosis. Feasibility and stabilization findings support further investigation of ribociclib in combination therapies. TRIAL REGISTRATION: NCT02607124.

Construction of Large-Area Ultrathin Conductive Metal-Organic Framework Films through Vapor-Induced Conversion.

On account of unique characteristics, the integration of metal-organic frameworks as active materials in electronic devices attracts more and more attention. The film thickness, uniformity, area, and roughness are all fatal factors limiting the development of electrical and optoelectronic applications. However, research focused on ultrathin free-standing films is in its infancy. Herein, a new method, vapor-induced method, is designed to construct centimeter-sized Ni3 (HITP)2 films with well-controlled thickness (7, 40, and 92 nm) and conductivity (0.85, 2.23, and 22.83 S m-1 ). Further, traditional transfer methods are tactfully applied to metal-organic graphene analogue (MOGA) films. In order to maintain the integrity of films, substrates are raised up from bottom of water to hold up films. The stripping method greatly improves the surface roughness Rq (root mean square roughness) without loss of conductivity and endows the film with excellent elasticity and flexibility. After 1000 buckling cycles, the conductance shows no obvious decrease. Therefore, the work may open up a new avenue for flexible electronic and magnetic devices based on MOGA.

2D Molecular Crystal Bilayer p-n Junctions: A General Route toward High-Performance and Well-Balanced Ambipolar Organic Field-Effect Transistors.

Ambipolar organic field-effect transistors (OFETs) are vital for the construction of high-performance all-organic digital circuits. The bilayer p-n junction structure, which is composed of separate layers of p- and n-type organic semiconductors, is considered a promising way to realize well-balanced ambipolar charge transport. However, this approach suffers from severely reduced mobility due to the rough interface between the polycrystalline thin films of p- and n-type organic semiconductors. Herein, 2D molecular crystal (2DMC) bilayer p-n junctions are proposed to construct high-performance and well-balanced ambipolar OFETs. The molecular-scale thickness of the 2DMC ensures high injection efficiency and the atomically flat surface of the 2DMC leads to high-quality p- and n-layer interfaces. Moreover, by controlling the layer numbers of the p- and n-type 2DMCs, the electron and hole mobilities are tuned and well-balanced ambipolar transport is accomplished. The hole and electron mobilities reach up to 0.87 and 0.82 cm2 V-1 s-1 , respectively, which are the highest values among organic single-crystalline double-channel OFETs measured in ambient air. This work provides a general route to construct high-performance and well-balanced ambipolar OFETs based on available unipolar materials.

A Metal-Free Three-Component Reaction of trans-ß-Nitrostyrene Derivatives, Dibromo Amides, and Amines Leading to Functionalized Amidines.

A mild, metal-free, and multicomponent route for the preparation of N-acyl amidines from nitroalkene derivatives, dibromo amides, and amines has been developed that accesses an initial α,α-dibromonitroalkane intermediate that can undergo C-C bond cleavage. This protocol offers an alternative approach toward N-acyl amidines and features the rapid construction of amidine frameworks with high diversity and complexity. The procedure also accesses bisamidine and α,ß-unsaturated amidines which are challenging targets by traditional methods.

Mapping Atheroprotective Functions and Related Proteins/Lipoproteins in Size Fractionated Human Plasma.

HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, and inhibition of lipoprotein oxidation. It has been proposed that various HDL subparticles exist, each with distinct protein and lipid compositions, which may be responsible for HDL's many functions. We hypothesized that HDL functions will co-migrate with the operational lipoprotein subspecies when separated by gel filtration chromatography. Plasma from 10 healthy male donors was fractionated and the protein composition of the phospholipid containing fractions was analyzed by mass spectrometry (MS). Each fraction was evaluated for its proteomic content as well as its ability to promote cholesterol efflux and protect low density lipoprotein (LDL) from free radical oxidation. For each function, several peaks of activity were identified across the plasma size gradient. Neither cholesterol efflux or LDL antioxidation activity correlated strongly with any single protein across the fractions. However, we identified multiple proteins that had strong correlations (r values >0.7, p < 0.01) with individual peaks of activity. These proteins fell into diverse functional categories, including those traditionally associated with lipid metabolism, as well as alternative complement cascade, innate immunity and clotting cascades and immunoglobulins. Additionally, the phospholipid and cholesterol concentration of the fractions correlated strongly with cholesterol efflux (r = 0.95 and 0.82 respectively), whereas the total protein content of the fractions correlated best with antioxidant activity across all fractions (r = 0.746). Furthermore, two previously postulated subspecies (apoA-I, apoA-II and apoC-1; as well as apoA-I, apoC-I and apoJ) were found to have strong correlations with both cholesterol efflux and antioxidation activity. Up till now, very little has been known about how lipoprotein composition mediates functions like cholesterol efflux and antioxidation.

Intracerebral hemorrhage induces monocyte-related gene expression within six hours: Global transcriptional profiling in swine ICH.

Intracerebral hemorrhage (ICH) is a severe neurological disorder with no proven treatment. Our prior research identified a significant association with monocyte level and ICH mortality. To advance our understanding, we sought to identify gene expression after ICH using a swine model to test the hypothesis that ICH would induce peripheral blood mononuclear cell (PBMC) gene expression. In 10 pigs with ICH, two PBMC samples were drawn from each with the first immediately prior to ICH induction and the second six hours later. RNA-seq was performed with subsequent bioinformatics analysis using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity® Pathway Analysis (IPA). There were 182 significantly upregulated and 153 significantly down-regulated differentially expressed genes (DEGs) after ICH. Consistent with findings in humans, significant GO and KEGG pathways were primarily related to inflammation and the immune response. Five genes, all upregulated post-ICH and known to be associated with monocyte activation, were repeatedly DEGs in the significant KEGG pathways: CD14, TLR4, CXCL8, IL-18, and CXCL2. In IPA, the majority of upregulated disease/function categories were related to inflammation and immune cell activation. TNF and LPS were the most significantly activated upstream regulators, and ERK was the most highly connected node in the top network. ICH induced changes in PBMC gene expression within 6 h of onset related to inflammation, the immune response, and, more specifically, monocyte activation. Further research is needed to determine if these changes affect outcomes and may represent new therapeutic targets.

Network-Based Analysis on Orthogonal Separation of Human Plasma Uncovers Distinct High Density Lipoprotein Complexes.

High density lipoprotein (HDL) particles are blood-borne complexes whose plasma levels have been associated with protection from cardiovascular disease (CVD). Recent studies have demonstrated the existence of distinct HDL subspecies; however, these have been difficult to isolate and characterize biochemically. Here, we present the first report that employs a network-based approach to systematically infer HDL subspecies. Healthy human plasma was separated into 58 fractions using our previously published three orthogonal chromatography techniques. Similar local migration patterns among HDL proteins were captured with a novel similarity score, and individual comigration networks were constructed for each fraction. By employing a graph mining algorithm, we identified 183 overlapped cliques, among which 38 were further selected as candidate HDL subparticles. Each of these 38 subparticles had at least two literature supports. In addition, GO function enrichment analysis showed that they were enriched with fundamental biological and CVD protective functions. Furthermore, gene knockout experiments in mouse model supported the validity of these subparticles related to three apolipoproteins. Finally, analysis of an apoA-I deficient human patient's plasma provided additional support for apoA-I related complexes. Further biochemical characterization of these putative subspecies may facilitate the mechanistic research of CVD and guide targeted therapeutics aimed at its mitigation.

A comparison of the mouse and human lipoproteome: suitability of the mouse model for studies of human lipoproteins.

Plasma levels of low density lipoproteins (LDL) and high density lipoproteins (HDL) exhibit opposing associations with cardiovascular disease in human populations and mouse models have been heavily used to derive a mechanistic understanding of these relationships. In humans, recent mass spectrometry studies have revealed that the plasma lipoproteome is significantly more complex than originally appreciated. This is particularly true for HDL which contains some 90 distinct proteins, a majority of which play functional roles that go beyond those expected for simple lipid transport. Unfortunately, the mouse lipoproteome remains largely uncharacterized-a significant gap given the heavy reliance on the model. Using a gel filtration chromatography and mass spectrometry analysis that targets phospholipid-bound plasma proteins, we compared the mouse lipoproteome and its size distribution to a previous, identical human analysis. We identified 113 lipid associated proteins in the mouse. In general, the protein diversity in the LDL and HDL size ranges was similar in mice versus humans, though some distinct differences were noted. For the majority of proteins, the size distributions, that is, whether a given protein was associated with large versus small HDL particles, for example, were also similar between species. Again, however, there were clear differences exhibited by a minority of proteins that may reflect metabolic differences between species. Finally, by correlating the lipid and protein size profiles, we identified five proteins that closely track with the major HDL protein, apolipoprotein A-I across both species. Thus, mice have most of the minor proteins identified in human lipoproteins that play key roles in inflammation, innate immunity, proteolysis and its inhibition, and vitamin transport. This provides support for the continued use of the mouse as a model for many aspects of human lipoprotein metabolism.

Cloning and Tissue-Specific Expression of a Chitin Deacetylase Gene from Helicoverpa armigera (Lepidoptera: Noctuidae) and Its Response to Bacillus thuringiensis.

Chitin deacetylases (CDAs) convert chitin into chitosan, the N-deacetylated form of chitin, which influences the mechanical and permeability properties of structures such as the cuticle and peritrophic matrices. In this article, a new CDA encoding gene, Hacda2, was cloned by reverse transcription-polymerase chain reaction method in Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), with an open reading frame of 1,611 bp. The deduced protein composed of 536 amino acid residues with a signal peptide, a chitin-binding domain, a low-density lipoprotein receptor class A domain, and a polysaccharide deacetylase-like catalytic domain. The highest expression level of Hacda2 was detected in fat body among tissues tested in the fifth-instar larvae using real-time quantitative polymerase chain reaction method. Feeding of Bacillus thuringiensis (Bt) (Bacillales: Bacillaceae) diet changed the expression level of Hacda1, Hacda2, Hacda5a, and Hacda5b significantly and differentially in the third-instar larvae. Hacda5a and Hacda5b expression were initially down-regulated and then up-regulated, whereas, the expression level of Hacda1 and Hacda2 was suppressed constantly postfeeding on Bt diet. These results suggested that HaCDAs may be involved in the response of H. armigera larvae to Bt and may be helpful to elucidate the roles of HaCDAs in the action of Bt cry toxin. The potential of HaCDAs to be used as synergists of Bt insecticidal protein needs to be further tested.

Bruceine B Displays Potent Antimyeloma Activity by Inducing the Degradation of the Transcription Factor c-Maf.

The oncogenic transcription factor c-Maf has been proposed as an ideal therapeutic target for multiple myeloma (MM), a not-yet-curable malignancy of plasma cells. In the present study, we establish a c-Maf-based luciferase screen system and apply it to screen a homemade library composed of natural products from which bruceine B (BB) is identified to display potent antimyeloma activity. BB is a key ingredient isolated from the Chinese traditional medicinal plant Brucea javanica (L.) Merr. (Simaroubaceae). BB inhibits MM cell proliferation and induces MM cell apoptosis in a caspase-3-dependent manner. The mechanism studies showed that BB inhibits c-Maf transcriptional activity and downregulates the expression of CCND2 and ITGB7, the downstream genes typically modulated by c-Maf. Moreover, BB induces c-Maf degradation via proteasomes by inducing c-Maf for K48-linked polyubiquitination in association with downregulated Otub1 and USP5, two proven deubiquitinases of c-Maf. We also found that c-Maf activates STAT3 and BB suppresses the STAT3 signaling. In the in vivo study, BB displays potent antimyeloma activity and almost suppresses the growth of myeloma xenografts in 7 days but shows no overt toxicity to mice. In conclusion, this study identifies BB as a novel inhibitor of c-Maf by promoting its degradation via the ubiquitin-proteasomal pathway. Given the safety and the successful clinical application of bruceine products in traditional medicine, BB is ensured for further investigation for the treatment of patients with MM.

High Tribocatalytic Performance of FeOOH Nanorods for Degrading Organic Dyes and Antibiotics.

Tribocatalysis is vitally important for electrochemistry, energy conservation, and water treatment. Exploring eco-friendly and low-cost tribocatalysts with high performance is crucial for practical applications. Here, the highly efficient tribocatalytic performance of FeOOH nanorods is reported. The factors related to the tribocatalytic activity such as nanorod diameter, surface area, and surface roughness are investigated, and the diameter of the FeOOH nanorods is found to have a significant effect on their tribocatalytic performance. As a result, under ultrasonic excitation, the optimized FeOOH nanorods exhibit superior tribocatalytic degradation toward rhodamine B (RhB), acid orange 7, methylene blue, methyl orange dyes, and their mixture. The RhB and mixed dyes are effectively degraded within 20 min (k = 0.179 min-1 ) and 35 min (k = 0.089 min-1 ), respectively, with the FeOOH nanorods showing excellent reusability. Moreover, antibiotics, such as tetracycline hydrochloride, phenol, and bisphenol A are efficiently degraded. Investigation of the catalytic mechanism reveals that the friction-generated h+ as well as these yielded •OH and •O2 - active radicals participate in the catalytic reaction. This work not only shed light on the design of high-performance tribocatalyst but also demonstrates that by harvesting mechanical energy, the FeOOH nanorods are promising materials for removing organic contaminants in wastewater.

Bta-miR-200b promotes endometrial epithelial cell apoptosis by targeting MYB in cattle.

Embryonic mortality is considered to be one of the main reasons for reduced conception rates in the cattle industry. Insufficient endometrial receptivity is a major factor resulting in embryo implantation failure and losses. Apoptosis of endometrial epithelial cells is an important process during establishment of uterine receptivity and embryo implantation. The aim of this study was to explore the role of bta-miR-200b on endometrial epithelial cell apoptosis in cattle. Overexpression of bta-miR-200b upregulated the expression of proapoptotic gene BCL2 associated X, apoptosis regulator (BAX) and endometrial receptivity marker gene osteopontin (OPN) at mRNA and protein level in bovine endometrial epithelial cells. Moreover, overexpression of bta-miR-200b was able to inhibit proliferation and promote apoptosis of bovine endometrial epithelial cells by arresting the cell cycle at the G0/G1 phase. MYB Proto-Oncogene (MYB) was verified to be a target of bta-miR-200b in bovine endometrial epithelial cells using dual-luciferase reporter assay. Transfection of bta-miR-200b mimics decreased the mRNA and protein expression of MYB. Overexpression of MYB decreased the effect of bta-miR-200b on apoptosis of bovine endometrial epithelial cells. Our findings suggest that bta-miR-200b can affect the apoptosis of endometrial epithelial cells in cattle by targeting the MYB gene.

Melatonin Suppresses Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Signaling and Delays the Development of Hearing Loss in the C57BL/6J Presbycusis Mouse Model.

Melatonin supplementation has been shown to delay age-related hearing loss (ARHL) progression. Previously, melatonin was found to inhibit neuronal mitochondrial DNA (mtDNA) release, as well as inhibit cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling, thereby delaying the onset of central nervous system diseases. Therefore, we hypothesized that melatonin may delay the progression of hearing loss in the C57BL/6J presbycusis mouse model by inhibiting cGAS-STING signaling in the auditory pathway. Oral melatonin at 10 mg/kg/d was administered to 3-month-old C57BL/6J mice until 12 months of age. The auditory brainstem response (ABR) threshold was used to assess their hearing ability. By real-time polymerase chain reaction and Western blot analysis, the levels of cytosolic mtDNA, cGAS/STING, and cytokines were examined in the mouse cochlea, inferior colliculus, and auditory cortex. We found that the 12-month-old control mice exhibited significant hearing loss, increased cytosolic mtDNA, increased expression of inflammatory factors TNF-α, IL-6, IFN-ß, Cxcl10, and Ifit3, up-regulated cGAS and STING expression, and enhanced interferon regulatory factor 3 (IRF3) phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. Melatonin treatment significantly improved hearing, decreased cytosolic mtDNA, suppressed the expression of inflammatory cytokines TNF-α, IL-6, IFN-ß, Ifit3, and Cxcl10, down-regulated cGAS and STING expression, and attenuated IRF3 phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. This study suggested that melatonin had a protective effect on auditory function in the C57BL/6J presbycusis mouse model, which may be mediated through reducing mtDNA release, inhibiting the cGAS-STING signaling pathway in the auditory pathway.

Jiedu Yizhi Formula Improves Cognitive Function by Regulating the Gut Dysbiosis and TLR4/NF-κB Signaling Pathway.

Objective: The objective of this study was to explore the neuroprotective mechanism of JDYZF in treating AD from the perspective of inflammation and intestinal microflora. Methods: A total of 24 APP/PS1 mice were randomly divided into four groups: model (n = 6), JDYZF low-dose (n = 6), JDYZF high-dose (n = 6), and positive drug (n = 6), six C57 mice were used as the control group. The body weights and diets of all mice were examined daily. After 8 weeks of administration, the learning and memory of mice were evaluated by the Morris water maze test. The histopathological changes of hippocampus, liver and kidney in mice were observed by HE staining after being euthanized. The expression of p-tau in hippocampus tissue was detected by immunohistochemistry. After that, 16S rDNA sequencing was used to investigate the relationship between JDYZF and intestinal microbiota. Finally, a comparison of TLR4, p65, p-p65, iκB, p-iκB, and IL-1ß protein expression in the hippocampus tissue of mice in each group was measured by Western blot. Results: The results showed that APP/PS1 mice taking JDYZF orally were generally in good condition. Compared with the control group, JDYZF significantly improved learning and memory ability in ethology. Histology showed that JDYZF improved the hippocampal structure of mice and inhibited the deposition of p-tau. JDYZF treatment could regulate the gut microbiota of APP/PS1 mice by increasing the richness of Lachnospiraceae, Ruminococcaceae, and Actinobacteria and reducing that of Alistipes and Muribaculaceae. It also significantly inhibited the activation of the TLR4/NF-κB signaling pathway in the brain. In addition, no obvious toxic reactions were found in the liver and kidney of APP/PS1 mice after taking JDYZF for 8 weeks. Conclusion: The findings revealed that JDYZF improved cognitive ability and alleviated the TLR4/NF-κB signaling pathway in APP/PS1 mice, and the modulating the gut microbiota presented here may help illuminate its activation mechanism.

High-Contrast Bidirectional Optoelectronic Synapses based on 2D Molecular Crystal Heterojunctions for Motion Detection.

Light-stimulated optoelectronic synaptic devices are fundamental compositions of the neuromorphic vision system. However, there are still huge challenges to achieving both bidirectional synaptic behaviors under light stimuli and high performance. Herein, a bilayer 2D molecular crystal (2DMC) p-n heterojunction is developed to achieve high-performance bidirectional synaptic behaviors. The 2DMC heterojunction-based field effect transistor (FET) devices exhibit typical ambipolar properties and remarkable responsivity (R) of 3.58×104 A W-1 under weak light as low as 0.008 mW cm-2 . Excitatory and inhibitory synaptic behaviors are successfully realized by the same light stimuli under different gate voltages. Moreover, a superior contrast ratio (CR) of 1.53×103 is demonstrated by the ultrathin and high-quality 2DMC heterojunction, which transcends previous optoelectronic synapses and enables application for the motion detection of the pendulum. Furthermore, a motion detection network based on the device is developed to detect and recognize classic motion vehicles in road traffic with an accuracy exceeding 90%. This work provides an effective strategy for developing high-contrast bidirectional optoelectronic synapses and shows great potential in the intelligent bionic device and future artificial vision.

Seroprevalence of Toxoplasma gondii infection among patients of a tertiary hospital in Guangzhou, Guangdong province, PR China.

PURPOSE: This study aimed to explore the prevalence of Toxoplasma gondii (T. gondii) among patients in Guangzhou city, South China, and to identify susceptible patient populations and analyze the causes of infection differences. METHODS: From May 2020 to May 2022, a total of 637 sera were collected from patients, and 205 sera were collected from health participants as health control. All sera were examined by colloidal gold kits to detect the positivity of antibodies against T. gondii. And the positivity of antibodies in sera was confirmed with ARCHITECT i2000SR system. RESULTS: The prevalence of T. gondii infection in patients was 7.06% (45/637), which was lower than the prevalence in health participants 4.88% (10/205). Among patients, 34 (5.34%) were positive only for IgG, 10 (1.57%) were only for IgM, and 1 (0.16%) was positive for both IgG and IgM. There was a significant difference in prevalence between male and female patients, but not among different age groups or diseases groups. The prevalence of T. gondii infection in diseases groups varied. The prevalence was relatively high in patients with the disorders of thyroid gland and the malignant neoplasms of digestive organs, which suggests that caution should be taken to avoid T. gondii infection in these patients. Surprisingly, the prevalence was quite low in diffuse Large B-cell Lymphoma (DLBC) patients. This may be due to the overexpression of TNF-α in tumor tissues of DLBC patients and the higher protein level of TNF-α in sera of DLBC patients. CONCLUSION: This study provides a systematic exploration of the prevalence of T. gondii infection in patients in a tertiary hospital. Our data contributes to a better understanding of the epidemic investigation of T. gondii among patients in South China, which can help the prevention and treatment of the disease caused by T. gondii infection.