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Background: Aggregation of α-synuclein (α-syn) is a prominent feature of Parkinson’s disease (PD) and other synucleinopathies. In these diseases, the extracellular spreading of misfolded α-syn significantly contributes to the cell-to-cell propagation of the α-syn misfolding pathology in a prion-like fashion. Therefore, extracellular α-syn aggregates are considered primary targets both for diagnostics and for novel disease modifying therapies. Currently, α-syn seed amplification assays (SAAs) using cerebrospinal fluid (CSF) represent the most promising diagnostic tools for synucleinopathies. However, CSF itself contains several compounds that can modulate the aggregation of α-syn in a patient-dependent manner, potentially sabotaging unoptimized α-syn SAAs and preventing seed quantification. Methods: In this study, we characterized the inhibitory effect of CSF on in vitro α-syn aggregation by means of CSF fractionation, mass spectrometry, dot-blot, Western blot, transmission electron microscopy, solution nuclear magnetic resonance spectroscopy, a highly accurate and standardized diagnostic SAA, and different in vitro aggregation conditions to evaluate spontaneous aggregation of α-syn. Results: We found the high-molecular weight fraction of CSF (>100,000 Da) to be highly inhibitory and identified lipoproteins to be the main drivers of this effect. We evaluated direct interaction between lipoprotein and α-syn and observed lipoprotein-α-syn complexes by transmission electron microscopy. Direct interaction between lipoproteins and monomeric α-syn was not detected by solution nuclear magnetic resonance spectroscopy, suggesting interaction between lipoproteins and oligomeric/proto-fibrillary α-syn intermediates instead. Lastly, we observed significantly slower amplification of α-syn seeds in PD CSF when lipoproteins were added to the reaction mix of a highly accurate diagnostic SAA. Conclusions: Our results describe a novel interaction between lipoproteins and α-syn aggregates that inhibits the formation of α-syn fibrils and could have relevant biological and translational implications. Indeed, the donor-specific inhibition of CSF on α-syn aggregation explains the lack of quantitative results so far obtained by the analysis of SAA-derived kinetic parameters. Furthermore, our data show that apolipoproteins are the main inhibitory components of CSF, suggesting that lipoprotein concentration measurements could be incorporated into data analysis models to eliminate the confounding effects of CSF milieu on α-syn quantification efforts.

Terpenoids are the most diverse class of plant primary and specialized metabolites, and

Joint communication and sensing (JCAS) is a very promising 6G technology, which attracts more and more research attention. Compared with communication, radar has many unique features in terms of waveform design criteria, self-interference cancellation (SIC), aperture-dependent resolution, and virtual aperture. This paper proposes a novel waveform design named max-aperture radar slicing (MaRS) to gain a large time-frequency aperture, which is generated by orthogonal frequency division multiplexing (OFDM) and occupies only a tiny fraction of OFDM resources. The proposed MaRS keeps the radar advantages of constant modulus, zero auto-correlation sequence, and simple SIC. As MaRS consumes much less resources, conventional processing methods fail, and novel angle-Doppler map based methods are proposed to obtain the range-velocity-angle information from MaRS echos and strong clutters. To avoid complex full-duplex communication, this paper proposes a hybrid-duplex JCAS scheme composed of half-duplex communication and full-duplex radar. The half-duplex communication antenna array is reused, and a small sensing-dedicated antenna array is added. Using these two arrays, a large space-domain sensing aperture is virtually formed to greatly improve the angle resolution. The numerical results show that the proposed MaRS and hybrid duplex can achieve a high sensing resolution with only 0.4% OFDM resources, which reduces the overheads of conventional methods to less than one tenth., in IEEE Internet of Things Journal

The purpose of this study was to determine the sensitivity and specificity of α-synuclein seed amplification assay (αSyn-SAA) in antemortem and postmortem cerebrospinal fluid (CSF) of autopsy-confirmed patients with different distributions of pathological αSyn, co-pathologies, and clinical diagnoses.The αSyn-SAA was used to test antemortem CSF samples from 119 subjects with a variety of clinical syndromes and standardized neuropathological examinations from Oregon Health and Science University (OHSU) and University of California San Diego (UCSD; 56 additional postmortem CSF samples available). The αSyn-SAA was also applied to frontal cortex and amygdala homogenates. Sensitivity and specificity were compared across distributions of αSyn pathology. Clinical data and co-pathologies were compared across αSyn-SAA positive and negative groups.Fifty-three individuals without and 66 with αSyn-pathology (neocortical [n = 38], limbic [n = 7], and amygdala-predominant [n = 21]) were included. There was a sensitivity of 97.8% and specificity of 98.1% of the αSyn-SAA to identify patients with limbic/neocortical pathology from antemortem CSF. Sensitivity to detect amygdala-predominant pathology was only 14.3%. Postmortem CSF and brain tissue αSyn-SAA analyses also showed higher assay positivity in samples from limbic/neocortical cases.CSF αSyn-SAA reliably identifies αSyn seeds in patients with diffuse αSyn pathology in the context of co-pathology and non-Lewy body disease (LBD) diagnoses. The analysis of brain homogenates suggests that pathological αSyn in the amygdala might differ from pathological αSyn in the frontal cortex. The αSyn-SAA might facilitate the differential diagnosis of dementias with mixed pathologies. ANN NEUROL 2022;92:650-662.

With the rapid growth of China's economy, the increase in water demand has threatened the sustainable development of groundwater. Construction of the South-to-North Water Diversion Project alleviated this problem. Zhengzhou, with a large population and high-intensity energy consumption, is a water-receiving city of the South-to-North Water Diversion Central Line Project (CLP). A series of ecological risks caused by the excessive exploitation of groundwater have been exposed. It is urgent to strengthen the assessment and management of groundwater to ensure sustainable development. In this study, the multi-criteria decision analysis (MCDA) underpinned the assessment of the sustainable groundwater development (ASGD) framework. Eight assessment factors were established based on the resource supply function (RSF) and eco-environment stability function (ESF). The novelty of this study lies in the integration of ASGD results with the impact of the CLP on the evolution of groundwater levels in Zhengzhou. Thus, more comprehensive and scientific management suggestions for groundwater development in Zhengzhou were obtained. GIS technology was integrated with the ASGD framework to identify five visualized areas: centralized groundwater supply area (8.61%), decentralized groundwater supply area (27.91%), vulnerable eco-environment area (14.34%), recharge protection area (45.67%), and unsuitable exploitation area (3.47%). The CLP changed the groundwater evolution pattern in Zhengzhou. The results showed that the operation of the CLP effectively slowed the decline in groundwater levels, thus confirming that the CLP has a positive impact on the rational utilization of groundwater. The disuse of two groundwater sources (G1 and G9) were able to enhance sustainable groundwater development. Meanwhile, five groundwater sources in the plain area proved unsuitable. Overall, this study provides a scientific basis for groundwater management in Zhengzhou City, while generating new ideas for sustainable groundwater development in cities affected by large-scale hydraulic projects worldwide.

This study was aimed to investigate whether ginsenoside Rb1 (GS-Rb1) from the cardioprotective Chinese medicine ginseng can reduce hypoxia-reoxygenation (HR)-induced damage to cardiomyocytes by protecting the mitochondria. Mitochondria-mediated apoptosis plays a key role during myocardial ischemia-reperfusion injury (MIRI). When MIRI occurs, the continuous opening of the mitochondrial permeability transition pore (mPTP) causes mitochondrial damage and ultimately leads to apoptosis. We treated H9c2 cells, derived from rat embryonic cardiomyoblasts, with GS-Rb1, diazoxide, and 5-hydroxydecanoate (5-HD), using HR to simulate MIRI. We found that GS-Rb1 can reduce mPTP by stabilizing the mitochondrial membrane potential (MMP) and by reducing reactive oxygen species (ROS) during HR. This protects the mitochondria by reducing the release of cytochrome c and the expression of cleaved-caspase-3 in the cytoplasm, ultimately reducing apoptosis. During this process, GS-Rb1 and diazoxide showed similar effects. These findings provide some evidence for a protective effect of GS-Rb1 treatment on MIRI.

Bioactive gibberellins (GAs or diterpenes) are essential hormones in land plants that control many aspects of plant growth and development. In flowering plants, 13-OH GAs (having low bioactivity-for example, GA1) and 13-H GAs (having high bioactivity-for example, GA4) frequently coexist in the same plant. However, the identity of the native Arabidopsis thaliana 13-hydroxylase GA and its physiological functions remain unknown. Here, we report that cytochrome P450 genes (CYP72A9 and its homologues) encode active GA 13-hydroxylases in Brassicaceae. Plants overexpressing CYP72A9 exhibited semi-dwarfism, which was caused by significant reduction in GA4 levels. Biochemical assays revealed that recombinant CYP72A9 protein catalysed the conversion of 13-H GAs to the corresponding 13-OH GAs. CYP72A9 was expressed predominantly in developing seeds in Arabidopsis. Freshly harvested seeds of cyp72a9 mutants germinated more quickly than the wild type, whereas stratification-treated seeds and seeds from long-term storage did not. The evolutionary origin of GA 13-oxidases from the CYP72A subfamily was also investigated and discussed here.

To fulfill challenging requirements of 6G, cell- free massive MIMO can be used to provide ubiquitous connectivity for multiple users. There are two kinds of cell-free schemes: centralized and distributed. Centralized schemes suffer from high fronthaul loading, while distributed schemes have some performance degradation. This paper proposes a cooperative scheme to avoid these drawbacks. Unlike conventional schemes, the proposed scheme employs a spatial combining jointly using access points and central processing unit. A novel cooperative regularized zero-forcing (C-RZF) algorithm is employed, which derives from minimum-meansquare-error processing. Simulation results show that the proposed scheme is able to gain a performance close to centralized MMSE using a fronthaul cost as low as simple distributed schemes, which makes it very suitable for practical implementations.

Terpenoids are the most diverse class of plant primary and specialized metabolites, and trans-prenyltransferases (trans-PTs) are the first branch point to synthesize precursors of various chain lengths for further metabolism. Whereas the catalytic mechanism of the enzyme is known, there is no reliable method for precisely predicting the functions of trans-PTs. With the exponentially increasing number of available trans-PTs genes in public databases, an in silico functional prediction method for this gene family is urgently needed. Here, we present PTS-Pre, a web tool developed on the basis of the “three floors” model, which shows an overall 86% prediction accuracy for 141 experimentally determined trans-PTs. The method was further validated by in vitro enzyme assays for randomly selected trans-PTs. In addition, using this method, we identified nine new GFPPSs from different plants which are beyond the previously reported Brassicaceae clade, suggesting these genes may have occurred via convergent evolution and are more likely lineage-specific. The high accuracy of our blind prediction validated by enzymatic assays suggests that PTS-Pre provides a convenient and reliable method for genome-wide functional prediction of trans-PTs enzymes and will surely benefit the elucidation and metabolic engineering of terpenoid biosynthetic pathways.

Despite some progress have been made in social media based suicide risk detection. However, visual information form post is often ignored when doing suicide risk detection. In this study, we propose a dual attention mechanism to capture the implicit correlation between text and image from the same post and utilize the visual information to improve the performance on social media based suicide risk detection. Experimental results on 5,000 Sina Weibo users show that with dual attention mechanism, our suicide risk detection model (DAM) can obtain 90% high accuracy.

Class I terpene synthase (TPS) generates bioactive terpenoids with diverse backbones. Sesterterpene synthase (sester-TPS, C25), a branch of class I TPSs, was recently identified in Brassicaceae. However, the catalytic mechanisms of sester-TPSs are not fully understood. Here, we first identified three nonclustered functional sester-TPSs (AtTPS06, AtTPS22, and AtTPS29) in Arabidopsis thaliana. AtTPS06 utilizes a type-B cyclization mechanism, whereas most other sester-TPSs produce various sesterterpene backbones via a type-A cyclization mechanism. We then determined the crystal structure of the AtTPS18–FSPP complex to explore the cyclization mechanism of plant sester-TPSs. We used structural comparisons and site-directed mutagenesis to further elucidate the mechanism: (1) mainly due to the outward shift of helix G, plant sester-TPSs have a larger catalytic pocket than do mono-, sesqui-, and di-TPSs to accommodate GFPP; (2) type-A sester-TPSs have more aromatic residues (five or six) in their catalytic pocket than classic TPSs (two or three), which also determines whether the type-A or type-B cyclization mechanism is active; and (3) the other residues responsible for product fidelity are determined by interconversion of AtTPS18 and its close homologs. Altogether, this study improves our understanding of the catalytic mechanism of plant sester-TPS, which ultimately enables the rational engineering of sesterterpenoids for future applications., Sesterterpenoids, a relatively new group of terpenoids, are structurally diverse and widely distributed in bacteria, fungi, and the plant kingdom. However, the enzymatic mechanism of sesterterpene synthase (sester-TPS), the first committed biosynthesis step, remains obscure. This study reveals the critical amino acids controlling the substrate and product specificity of plant sester-TPS by determining the first crystal structure of the sester-TPS–FSPP complex.

Terpenes, the largest group of plant-specialized metabolites, have received considerable attention for their highly diverse biological activities. Monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and triterpenes (C30) have been extensively investigated at both the biochemical and molecular levels over the past two decades. Sesterterpenes (C25), an understudied terpenoid group, were recently described by plant scientists at the molecular level. This review summarizes the plant species that produce sesterterpenes and describes recent developments in the field of sesterterpene biosynthesis, placing a special focus on the catalytic mechanism and evolution of geranylfarnesyl diphosphate synthase and sesterterpene synthase. Finally, we propose several questions to be addressed in future studies, which may help to elucidate sesterterpene metabolism in plants., This review introduces the sesterterpenes (C25), including the plant species that produce them and their potential bioactivities. Then, recent findings in plant sesterterpene biosynthesis are reviewed, with a particular focus on geranylfarnesyl diphosphate synthase and sesterterpene synthase.

A novel bootstrap method is proposed, which can significantly reduce the clock feedthrough effect and the dynamic power consumption. An ESL a-IGZO TFTs based gate driver using this technique is designed. It is shown that the ripple voltage and the power consumption of the proposed driver are only 22.9% and 23.86% of those of the earlier driver.

Triterpenoids possess versatile biological activities including antiviral, anticancer, and hepatoprotective activities. They are widely used in medicine and other health-related fields. However, current production of such compounds relies on plant culture and extraction, which brings about concerns for environmental, ecological, and infield problems. With increasing awareness of environmental sustainability, various microbes have been engineered to produce natural products, in which yeast turned out to be feasible for the heterologous biosynthesis of triterpenoids on account of its inherent advantages such as the robustness, safety, and sufficient precursor supplementation. This review has focused on recent progress regarding the biosynthesis of triterpenoids in yeast. The key enzymes to reconstruct the triterpenoid pathways in yeast, include: oxidosqualene cyclases, cytochrome P450s and UDP-glycosyltransferases are systematically presented. We then discuss recent metabolic engineering strategies and future prospects of protein engineering, pathway compartmentalization, product transportation, and other aspects for triterpenoid production in yeast.

Land plants co-speciate with a diversity of continually expanding plant specialized metabolites (PSMs) and root microbial communities (microbiota). Homeostatic interactions between plants and root microbiota are essential for plant survival in natural environments. A growing appreciation of microbiota for plant health is fuelling rapid advances in genetic mechanisms of controlling microbiota by host plants. PSMs have long been proposed to mediate plant and single microbe interactions. However, the effects of PSMs, especially those evolutionarily new PSMs, on root microbiota at community level remain to be elucidated. Here, we discovered sesterterpenes in Arabidopsis thaliana, produced by recently duplicated prenyltransferase-terpene synthase (PT-TPS) gene clusters, with neo-functionalization. A single-residue substitution played a critical role in the acquisition of sesterterpene synthase (sesterTPS) activity in Brassicaceae plants. Moreover, we found that the absence of two root-specific sesterterpenoids, with similar chemical structure, significantly affected root microbiota assembly in similar patterns. Our results not only demonstrate the sensitivity of plant microbiota to PSMs but also establish a complete framework of host plants to control root microbiota composition through evolutionarily dynamic PSMs.

A power-on-reset (POR) circuit, which is an important block in mixed-signal integrated circuits, is used for the correct initialization of critical logic states in digital blocks of mixed-signal circuits. A POR circuit with precisely triggered threshold voltages is proposed. The circuit is designed in a 0.18 μm CMOS technology with a maximum 4 μA quiescent current. The output signal of the proposed circuit is also used to precisely detect whether the power supply is power-on or brown-out. The proposed POR circuit is insensitive to the power ramping time and tolerant to process variations. At typical corner, the proposed circuit reduces the quiescent current by more than 10x and layout area by 38% compared to the previously published designs.

A 27.6 MHz 297 μW relaxation oscillator is presented in this paper by using an 180-nm CMOS technology. The proposed oscillator employs an adjustable temperature compensation feedforward scheme, in which the charging current can be set steady by a four-bit digital trimming signal. We have demonstrated a frequency variation lower than 33.5 ppm/°C which could be close to 0 ppm/°C in theory if the precision is high enough. In practical production, it is effective to calibrate the mismatching and deviation of fabrication because of the novel adjustable temperature compensation scheme.

Pseudogenes have long been marked as “false” genes, which are similar with real genes but have no apparent function. The 3′UTR is well-known to regulate gene expression post-transcriptionally. Our recent evidence, however, indicates novel functional roles of pseudogene CYP4Z2P 3′UTR (Z2P-UTR). We found that ectopic expression of Z2P-UTR in breast cancer cells significantly increased the expression of VEGF-A without affecting cell proliferation in vitro. Meanwhile, conditioned medium (CM) from Z2P-UTR overexpression cells enhanced proliferation, migration and tube formation of HUVEC, and promoted angiogenesis in ex vivo models. Also, CM increased the expression of VEGFR2 in HUVEC. Our data suggest that Z2P-UTR can promote breast cancer angiogenesis partly via paracrine pathway of VEGF-A/VEGFR2.

Grafting is becoming more popular in cucurbit crop production for soil-borne disease control. The correct choice of rootstock can have a vital role in the success of grafting. An improved understanding of the genetic diversity and potential of rootstock germplasm can be expected to contribute to more efficient breeding for improved rootstocks. Cucurbita spp. (squash and pumpkins) are major sources of rootstocks for grafting cucumbers, melons, and watermelons. The genetic diversity and relatedness of 25 commercial Cucurbita rootstock cultivars and 10 inbred lines were assessed using 80 simple sequence repeat (SSR) markers in this study. Forty-one SSR loci yielded 94 polymorphic alleles, with an average of 2.29 alleles per locus. The polymorphism information content values ranged from 0.16 to 0.60, with an average of 0.36. Cluster analysis and principal coordinate analysis showed that the majority of commercial Cucurbita rootstocks are interspecific hybrids, C. maxima × C. moschata , and these hybrids are closely related. By contrast, the C. moschata inbreds exhibit considerably greater genetic diversity, suggesting that they could be useful for rootstock improvement.

This work introduced an eco-friendly approach for the synthesis of sliver nanoparticles (AgNPs) with a water-soluble fraction of polysaccharides extracted from the roots of Astragalus membranaceus (AMWP). AMWP mediated AgNPs (AMWP-AgNPs) were successfully synthesized using 1.0mM AgNO3 and 1.25mg/mL AMWP, reacting in aqueous environment at 25°C for 6h. The synthesized AMWP-AgNPs exhibited a broad surface plasmon resonance peak (SPR) at 445nm in Ultraviolet-visible (UV-vis) spectrum, which was characteristic of a poly-dispersed AMWP-AgNPs. Transmission electron microscopy (TEM) and Dynamic light scattering (DLS) analysis revealed that the AMWP-AgNPs were almost spherical shaped with an average diameter of 65.08nm. The antibacterial activities of AMWP-AgNPs were assessed on four strains of clinical isolated multidrug resistant (MDR) bacteria and four relative reference strains using modified agar disk diffusion and tetrazolium methods. All strains, especially the resistant strains, were significantly inhibited by AMWP-AgNPs at comparatively low concentration (minimum inhibition concentrations (MICs) ranging from 0.032 to 0.063mg/mL). Therefore, we propose that the AMWP-AgNPs will have a great potential in anti-MDR bacterial applications.

A marine-derived actinomycete (Streptomyces sp. WBF16) exhibiting antitumor activities was investigated. The strain was identified using morphological, biochemical and genetic techniques. 16S rDNA sequence of the isolate indicated that it was most closely related to Streptomyces coelicolor A3 (2). Furthermore, a new aureolic acid (Chromomycin B, 1), along with Chromomycin A(2) (2) and Chromomycin A(3) (3) were isolated from its secondary metabolites. Their structures were determined by chemical and spectroscopic methods including 1D, 2D NMR and HRMS. Compounds 1-3 showed strong cytotoxicity against SGC7901, HepG2, A549, HCT116 and COC1 and HUVEC.

Two new anthraquinone glycosides Strepnoneside A ( 1 ) and Strepnoneside B ( 2 ), together with Chromomycin A 3 ( 3 ), were isolated from cultures of the marine Streptomyces sp. strain. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. Compound 3 exhibited cytotoxic activities against HCT 116 cell lines (IC 50 = 300 ± 11 pM).

Fine particle strontium and iron substituted lanthanum gallates La0.4Sr0.6Ga1−yFeyO3−δ, and La0.6Sr0.4Ga1−yFeyO3−δ, where y=0.4, 0.6, and 0.8, have been synthesized by a modified citrate method. The membranes were prepared by pressing the powders using a uniaxial pressing machine to form a disc (13 mm diameter, 1 mm thickness) and sintering at 1250–1380 °C for 10 h. Formation of these powders and membranes were confirmed by the X-ray powder diffraction and scanning electron microscopy. The membranes remained the cubic structure under the sintering temperature below 1400 °C with the above 90% of theoretical density. Oxygen permeabilities of the as high as 1.5 cm3/min cm2 was obtained for LSGF4646 at 925 °C.

Ding Qu,1 Yihua Ma,1 Wenjie Sun,1,2 Yan Chen,1 Jing Zhou,1 Congyan Liu,1 Mengmeng Huang1 1Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 2Department ofPharmaceutics, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China Abstract: A microemulsion-based synergistic dual-drug codelivery system was developed for enhanced cell apoptosis by transporting coix seed oil and etoposide into A549 (human lung carcinoma) cells simultaneously. Results obtained by dynamic light scattering showed that an etoposide (VP16)-loaded coix seed oil microemulsion (EC-ME) delivery system had a small size around 35 nm, a narrow polydispersity index, and a slightly negative surface charge. The encapsulating efficiency and total drug loading rate were 97.01% and 45.48%, respectively, by high-performance liquid chromatography. The release profiles at various pH values showed an obvious pH-responsive difference, with the accumulated amount of VP16 released at pH 4.5 (and pH 5.5) being 2.7-fold higher relative to that at pH 7.4. Morphologic alteration (particle swelling) associated with a mildly acidic pH environment was found on transmission electron microscopy. In the cell study, the EC-ME system showed a significantly greater antiproliferative effect toward A549 cells in comparison with free VP16 and the mixture of VP16 and coix seed oil. The half-maximal inhibitory concentration of the EC-ME system was 3.9-fold and 10.4-fold lower relative to that of free VP16 and a mixture of VP16 and coix seed oil, respectively. Moreover, fluorescein isothiocyanate and VP16 (the green fluorescent probe and entrapped drug, respectively) were efficiently internalized into the cells by means of coix seed oil microemulsion through intuitive observation and quantitative measurement. Importantly, an EC-ME system containing 20 µg/mL of VP16 showed a 3.3-fold and 3.5-fold improvement in induction of cell apoptosis compared with the VP-16-loaded microemulsion and free VP16, respectively. The EC-ME combination strategy holds promise as an efficient drug delivery system for induction of apoptosis and treatment of lung cancer. Keywords: microemulsion, synergistic effect, dual-drug codelivery, coix seed oil, apoptosis induction

Wenjie Sun,1,2,* Ding Qu,1,* Yihua Ma,1 Yan Chen,1,2 Congyan Liu,1 Jing Zhou11Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 2Department of Pharmaceutics, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workAbstract: Silver nanoparticles (AgNPs) are widely used as antibacterial products in various fields. Recent studies have suggested that AgNPs need an appropriate stabilizer to improve their stability. Some antibacterial traditional Chinese medicines (TCMs) contain various reductive components, which can not only stabilize AgNPs but also enhance their antimicrobial activity. In this study, we developed a series of novel AgNPs using a TCM extract as a stabilizer, reducing agent, and antimicrobial agent (TCM-AgNPs). A storage stability investigation of the TCM-AgNPs suggested a significant improvement when compared with bare AgNPs. Further, conjugation of TCMs onto the AgNP surface resulted in stronger antimicrobial potency on antibacterial evaluation using Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus with minimum inhibitory concentration 50% (MIC50) ratios (and minimum bactericidal concentration 90% [MBC90] ratios) of AgNPs to respective TCM-AgNPs as assessment indices. Among these, P. cuspidatum Sieb. et-conjugated AgNPs (P.C.-AgNPs) had the advantage of a combination of TCMs and AgNPs and was studied in detail with regard to its synthesis and characterization. The extraction time, reaction temperature, and concentrations of AgNO3 and Polygonum cuspidatum Sieb. et extract were critical factors in the preparation of P.C.-AgNPs. Further, the results of X-ray diffraction and Fourier transform infrared spectroscopy indicated successful preparation of P.C.-AgNPs. In representative studies, P.C.-AgNPs showed a well-defined spherical shape, a homogeneous small particle size (36.78 nm), a narrow polydispersity index (0.105), and a highly negative zetapotential (-23.6 mV) on transmission electron microscopy and dynamic light scattering. These results indicate that TCM-AgNPs have a potential role as antibacterial agents in the clinic setting.Keywords: traditional Chinese medicine, extract, silver nanoparticles, stability, antibacterial, Polygonum cuspidatum Sieb. et

Emodin, a natural anthraquinone isolated from the traditional Chinese medicine Radix rhizoma Rhei, can induce apoptosis in many kinds of cancer cells. This study demonstrated that emodin induces apoptosis in human colon cancer HCT116 cells by provoking oxidative stress, which subsequently triggers a p53-mitochondrial apoptotic pathway. Emodin induced mitochondrial transmembrane potential loss, increase in Bax and decrease in Bcl-2 expression and mitochondrial translocation and release of cytochrome c to cytosol in HCT116 cells. In response to emodin-treatment, ROS increased rapidly, and subsequently p53 was overexpressed. Pretreatment with the antioxidant NAC diminished apoptosis and p53 overexpression induced by emodin. Transfecting p53 siRNA also attenuated apoptosis induced by emodin, Bax expression and mitochondrial translocation being reduced compared to treatment with emodin alone. Taken together, these results indicate that ROS is a trigger of emodin-induced apoptosis in HCT116 cells, and p53 expression increases under oxidative stress, leading to Bax-mediated mitochondrial apoptosis.

A new water-soluble polysaccharide (SEP-2), with a molecular weight of 6.78 × 10(5)Da, was isolated from Strongylocentrotus nudus eggs under the extraction conditions optimized by response surface methodology (RSM). Preliminary characterization of SEP-2 was performed by HPSEC and GC-MS, indicating that SEP-2 could be a D-glucan containing a (1 → 4)-linked D-Glcp backbone with (1 → 3)-linked D-Glcp side chains. In subsequent immunostimulatory studies, significantly enhanced ROS level, NO production and inflammatory cytokines secretion (IL-1β, IL-6, and TNF-α) were observed in SEP-2 treated murine macrophage cell line RAW264.7. These results suggest that SEP-2 might have the capability to enhance the microbicidal activity and killing function of macrophages through the polarization toward the pro-inflammatory M1 state.

A marine actinomycete, designated strain BM-17, was isolated from a sediment sample collected in the Arctic Ocean. The strain was identified as Nocardia dassonvillei based on morphological, cultural, physiological, biochemical characteristics, along with the cell wall analysis and 16S rDNA gene sequence analysis. A new secondary metabolite (1), N-(2-hydroxyphenyl)-2-phenazinamine (NHP), and six known antibiotics (2-7) have been isolated from the saline culture broth of the stain by sequentially purification over macroporous resin D101, silica gel, Sephadex LH-20 column chromatography and preparative HPLC after the stain was incubated in soy bean media at 28°C for 7 days. The chemical structures of the compounds were elucidated on the basis of spectroscopic analysis, including two-dimensional (2D) NMR and HR-ESI-MS data. The new compound showed significant antifungal activity against Candida albicans, with a MIC of 64 μg/ml and high cancer cell cytotoxicity against HepG2, A549, HCT-116 and COC1 cells.

S-thanatin, an analog of thanatin, was synthesized by substituting the 15th amino acid of threonine with serine, which showed a broad antimicrobial activity against bacteria. We reported earlier that membrane phospholipid was found to be the target for S-thanatin with different mechanism from other antimicrobial peptides. In this study, we have performed its structural characterization by circular dichroism (CD) spectroscopy. The CD analysis showed that S-thanatin retained its overall conformation β-sheet in aqueous buffer, β-turn in 50% trifluoroethanol (TFE) and β-hairpin in 0.4 mM POPC-LUVs. In hemolysis assay, S-thanatin exhibited low hemolytic activity and bacteria selectivity. We investigated the effect of the presence of 33 mol percent cholesterol on the interactions of the antimicrobial peptide S-thanatin with phosphatidylcholine (PC) model membrane systems. The results showed that S-thanatin was more potent at disrupting cholesterol-free bacterial than cholesterol-containing eukaryotic membranes. Thus, in all respects, fluorescence dye leakage experiments indicated that cholesterol inhibited the S-thanatin-induced permeabilization of PC vesicles. Finally, flow cytometry was used to monitor changes in bacterial cell membrane potential and cell membrane integrity, with specific fluorescent dyes DiBAC 4 (3) and PI. Adding the respiratory poison CCCP seemed to prevent peptide-induced membrane damage, which suggested that S-thanatin acted at the metabolic level on respiratory chain. These findings might explain why S-thanatin was selective toxicity towards bacteria, but low toxicity towards erythrocytes. It might be due to three factors at least: electrostatic interaction (namely anionic phospholipids); cholesterol; respiratory chain.

The experiment about ramie fabrics processed by oxygen plasma was introduced. The mass spectrum of residual gas was measured by QMS, and quantities of hydrogen, carbon, oxygen and its compounds was observed from vacuum residual gas. The microcosmic characteristic of ramie treated by oxygen plasma show that the surface of the ramie fibre was effectively eroded by energetic particle and active molecules. It can be obviously seen from X-Ray diffraction analysis that the crystalline-indices of ramie fibre were slightly reduced after processing in oxygen plasma. Experiment results reveal that, with the increase of the processing time and power, the physical chemical properties such as wettability and dyeability were obviously improved.

Spectroscopic ellipsometry has been used to examine the pH-responsive interfacial adsorption of a series of biocompatible diblock copolymers incorporating 2-methacryloyloxyethyl phosphorylcholine-based (MPC) residues and 2-(dialkylamino)ethyl methacrylate residues, with a specific focus on 2-(diethylamino)ethyl groups (referred to as MPCm-DEAn, where m and n refer to the mean degrees of polymerization of each block) at the hydrophilic silicon oxide/water interface. For all the copolymers studied the surface excess shows only weak concentration dependence. Increasing the length of the DEA block has little effect on the dynamic or equilibrated adsorption at pH 7, indicating that the DEA block adopts a flat conformation on the silicon oxide surface at this pH. With increasing pH, however, the surface excess shows a dramatic increase, followed by a subsequent decline. The observed maximum in surface excess represents a balance between charge over-compensation of the copolymer with the oppositely charged surface and the subsequently reduced charge density of the copolymer. Variations in the observed maxima for various MPCm-DEAn diblock copolymers indicate different surface conformations at high pH. Salt addition does not affect copolymer adsorption. This behavior is attractive for biomedical applications in which the ionic strength is variable. It was also found that the preadsorbed diblock copolymers immobilized DNA from solution to an extent that is proportional to the relative charge ratio between the anionic DNA and the cationic DEA block of the copolymer.