A Novel Optimization of Water-Soluble Compound Polysaccharides from Chinese Herbal Medicines by Quantitative Theory and Study on Its Characterization and Antioxidant Activities

The present study optimized the extraction characterization and antioxidant activities of water-soluble compound polysaccharides (CPs) from hawthorn, lotus leaf, Fagopyrum tataricum, semen cassiae, Lycium barbarum, and Poria cocos Chinese herbal medicines that have mass ratios of 4 : 2 : 2 : 1.5 : 1 : 1. The CPs yield equation was predicted using quantitative theory, to which a maximum CPs yield of 7.18±0.24 % under the following optimal extraction conditions: a water-to-raw material ratio of 30 mL/g, an extraction temperature of 65 °C, an extraction time of 45 min, and extraction mode ultrasonic-assistant extraction. CPs were consisted of Ara, Gal, Glc, Xyl, Man, GalA and GlcA in a molar ratio of 3.1 : 2.6 : 50.6 : 1.7 : 20.4 : 17.2 : 4.2. The HPGPC profiles and FT-IR spectra implied that CPs were heterogeneous acidic polysaccharides and possessed the β-d -pyranose configuration. Congo red test, CD spectrum and SEM revealed that CPs with three helix conformation showed a flocculent, granulous or sheet-like appearance. Furthermore, the relationships between antioxidant activity and concentration of CPs displayed significant positive correlation, and the scavenging abilities for DPPH, hydroxyl radical, ABTS, superoxide-anion radical and reducing power of CPs were 93.56±2.51 %, 84.03±1.69 %, 83.29±1.93 %, 37.49±1.93 % and 0.467±0.006 at a concentration of 4.0 mg/mL. Therefore, CPs could be applied as a potential natural antioxidant in pharmaceutical or functional food fields.     

Similarity Ratio Analysis for Early Stage Fault Detection with Optical Emission Spectrometer in Plasma Etching Process

A Similarity Ratio Analysis (SRA) method is proposed for early-stage Fault Detection (FD) in plasma etching processes using real-time Optical Emission Spectrometer (OES) data as input. The SRA method can help to realise a highly precise control system by detecting abnormal etch-rate faults in real-time during an etching process. The method processes spectrum scans at successive time points and uses a windowing mechanism over the time series to alleviate problems with timing uncertainties due to process shift from one process run to another. A SRA library is first built to capture features of a healthy etching process. By comparing with the SRA library, a Similarity Ratio (SR) statistic is then calculated for each spectrum scan as the monitored process progresses. A fault detection mechanism, named 3-Warning-1-Alarm (3W1A), takes the SR values as inputs and triggers a system alarm when certain conditions are satisfied. This design reduces the chance of false alarm, and provides a reliable fault reporting service. The SRA method is demonstrated on a real semiconductor manufacturing dataset. The effectiveness of SRA-based fault detection is evaluated using a time-series SR test and also using a post-process SR test. The time-series SR provides an early-stage fault detection service, so less energy and materials will be wasted by faulty processing. The post-process SR provides a fault detection service with higher reliability than the time-series SR, but with fault testing conducted only after each process run completes.     

Xinnaokang improves cecal microbiota and lipid metabolism to target atherosclerosis

This study aims to explore the potential mechanisms of Xinnaokang in atherosclerosis treatment. Firstly, the active components of Xinnaokang were analysed by HPLC, which contains ginsenoside Rg1, puerarin, tanshinone, notoginsenoside R1, ammonium glycyrrhizate and glycyrrhizin. Network pharmacology analysis showed there were 145 common targets of Xinnaokang, including the chemical stress, lipid metabolite, lipopolysaccharide, molecules of bacterial origin, nuclear receptor and fluid shear stress pathways. Then, the animal experiment showed that Xinnaokang reduced the body weight and blood lipid levels of atherosclerotic mice. Vascular plaque formation was increased in atherosclerotic mice, which was markedly reversed by Xinnaokang. In addition, Xinnaokang reduced CAV-1 expression and increased ABCA1, SREBP-1 and LXR expressions in the vasculature. Xinnaokang promoted SREBP-2 and LDLR expressions in the liver but decreased IDOL and PCSK9 expressions, indicating that Xinnaokang regulated lipid transport-related protein expression. Cecal microbiota diversity was reduced in atherosclerotic mice but increased after Xinnaokang treatment. Xinnaokang treatment also improved gut microbiota communities by enriching Actinobacteria, Bifidobacteriales and Bifidobacteriaceae abundances. Metabolic profile showed that Xinnaokang significantly reduced homogentisate, phenylacetylglycine, alanine and methionine expressions in the liver of atherosclerotic mice. Xinnaokang effectively alleviated atherosclerosis, and this effect might be linked with the altered features of the liver metabolite profiles and cecal microbiota.     

Dapper Antagonist of Catenin-1 Cooperates with Dishevelled-1 during Postsynaptic Development in Mouse Forebrain GABAergic Interneurons

Synaptogenesis has been extensively studied along with dendritic spine development in glutamatergic pyramidal neurons, however synapse development in cortical interneurons, which are largely aspiny, is comparatively less well understood. Dact1, one of 3 paralogous Dact (Dapper/Frodo) family members in mammals, is a scaffold protein implicated in both the Wnt/β-catenin and the Wnt/Planar Cell Polarity pathways. We show here that Dact1 is expressed in immature cortical interneurons. Although Dact1 is first expressed in interneuron precursors during proliferative and migratory stages, constitutive Dact1 mutant mice have no major defects in numbers or migration of these neurons. However, cultured cortical interneurons derived from these mice have reduced numbers of excitatory synapses on their dendrites. We selectively eliminated Dact1 from mouse cortical interneurons using a conditional knock-out strategy with a Dlx-I12b enhancer-Cre allele, and thereby demonstrate a cell-autonomous role for Dact1 during postsynaptic development. Confirming this cell-autonomous role, we show that synapse numbers in Dact1 deficient cortical interneurons are rescued by virally-mediated re-expression of Dact1 specifically targeted to these cells. Synapse numbers in these neurons are also rescued by similarly targeted expression of the Dact1 binding partner Dishevelled-1, and partially rescued by expression of Disrupted in Schizophrenia-1, a synaptic protein genetically implicated in susceptibility to several major mental illnesses. In sum, our results support a novel cell-autonomous postsynaptic role for Dact1, in cooperation with Dishevelled-1 and possibly Disrupted in Schizophrenia-1, in the formation of synapses on cortical interneuron dendrites.     

Failed Stabilization for Long-Term Potentiation in the Auditory Cortex of Fmr1 Knockout Mice

Fragile X syndrome is a developmental disorder that affects sensory systems. A null mutation of the Fragile X Mental Retardation protein 1 (Fmr1) gene in mice has varied effects on developmental plasticity in different sensory systems, including normal barrel cortical plasticity, altered ocular dominance plasticity and grossly impaired auditory frequency map plasticity. The mutation also has different effects on long-term synaptic plasticity in somatosensory and visual cortical neurons, providing insights on how it may differentially affect the sensory systems. Here we present evidence that long-term potentiation (LTP) is impaired in the developing auditory cortex of the Fmr1 knockout (KO) mice. This impairment of synaptic plasticity is consistent with impaired frequency map plasticity in the Fmr1 KO mouse. Together, these results suggest a potential role of LTP in sensory map plasticity during early sensory development.     

A High-Order,Symplectic, Finite-Difference Time-Domain Scheme for Bioelectromagnetic Applications within the Mother/Fetus Model

An explicit high-order, symplectic, finite-difference time-domain (SFDTD) scheme is applied to a bioelectromagnetic simulation using a simple model of a pregnant woman and her fetus. Compared to the traditional FDTD scheme, this scheme maintains the inherent nature of the Hamilton system and ensures energy conservation numerically and a high precision. The SFDTD scheme is used to predict the specific absorption rate (SAR) for a simple model of a pregnant female woman (month 9) using radio frequency (RF) fields from 1.5 T and 3 T MRI systems (operating at approximately 64 and 128 MHz, respectively). The results suggest that by using a plasma protective layer under the 1.5 T MRI system, the SAR values for the pregnant woman and her fetus are significantly reduced. Additionally, for a 90 degree plasma protective layer, the SAR values are approximately equal to the 120 degree layer and the 180 degree layer, and it is reduced relative to the 60 degree layer. This proves that using a 90 degree plasma protective layer is the most effective and economical angle to use.     

Fluid shear stress regulates HepG2 cell migration though time-dependent integrin signaling cascade

Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear. In this study, hepatocellular carcinoma HepG2 cells were exposed to 1.4 dyn/cm² FSS for transient duration (15s and 30s), short duration (5 min, 15 min and 30 min) and long duration (1h, 2h and 4h), respectively. The expression and translocation of Integrins induced FAK-Rho GTPases signaling events were examined. Our results showed that FSS endowed HepG2 cells with higher migration ability via reorganizing cellular F-actin and disrupting intercellular tight junctions. We further demonstrated that FSS regulated the expression and translocation of Integrins and their downstream signaling cascade in time-dependent patterns. The FSS downregulated focal adhesion components (Paxillin, Vinculin and Talin) while upregulated the expression of Rho GTPases (Cdc42, Rac1 and RhoA) in long durations. These results indicated that FSS enhanced tumor cell migration through Integrins-FAK-Rho GTPases signaling pathway in time-dependent manners. Our in vitro findings shed new light on the role of FSS acting in physiologic and pathological processes during tumor progression, which has emerged as a promising clinical strategy for liver carcinoma.     

Gut microbiota in wild and captive Guizhou snub‐nosed monkeys,Rhinopithecus brelichi

Many colobine species—including the endangered Guizhou snub‐nosed monkey (Rhinopithecus brelichi) are difficult to maintain in captivity and frequently exhibit gastrointestinal (GI) problems. GI problems are commonly linked to alterations in the gut microbiota, which lead us to examine the gut microbial communities of wild and captive R. brelichi. We used high‐throughput sequencing of the 16S rRNA gene to compare the gut microbiota of wild (N = 7) and captive (N = 8) R. brelichi. Wild monkeys exhibited increased gut microbial diversity based on the Chao1 but not Shannon diversity metric and greater relative abundances of bacteria in the Lachnospiraceae and Ruminococcaceae families. Microbes in these families digest complex plant materials and produce butyrate, a short chain fatty acid critical to colonocyte health. Captive monkeys had greater relative abundances of Prevotella and Bacteroides species, which degrade simple sugars and carbohydrates, like those present in fruits and cornmeal, two staples of the captive R. brelichi diet. Captive monkeys also had a greater abundance of Akkermansia species, a microbe that can thrive in the face of host malnutrition. Taken together, these findings suggest that poor health in captive R. brelichi may be linked to diet and an altered gut microbiota.     

Intravenous injection of the oncolytic virus M1 awakens antitumor T cells and overcomes resistance to checkpoint blockade

Reversing the highly immunosuppressive tumor microenvironment (TME) is essential to achieve long-term efficacy with cancer immunotherapy. Despite the impressive clinical response to checkpoint blockade in multiple types of cancer, only a minority of patients benefit from this approach. Here, we report that the oncolytic virus M1 induces immunogenic tumor cell death and subsequently restores the ability of dendritic cells to prime antitumor T cells. Intravenous injection of M1 disrupts immune tolerance in the privileged TME, reprogramming immune-silent (cold) tumors into immune-inflamed (hot) tumors. M1 elicits potent CD8⁺ T cell-dependent therapeutic effects and establishes long-term antitumor immune memory in poorly immunogenic tumor models. Pretreatment with M1 sensitizes refractory tumors to subsequent checkpoint blockade by boosting T-cell recruitment and upregulating the expression of PD-L1. These findings reveal the antitumor immunological mechanism of the M1 virus and indicated that oncolytic viruses are ideal cotreatments for checkpoint blockade immunotherapy.Subject terms: Cancer microenvironment, Targeted therapies