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[Display omitted] Reactive oxygen species (ROS)-centered chemodynamic therapy (CDT) holds significant potential for tumor-specific treatment. However, insufficient endogenous H 2 O 2 and extra glutathione within tumor microenvironment (TME) severely deteriorate the CDT's effectiveness. Herein, rich-Zn-Co 3 O 4 / N -doped porous carbon (Zn-Co 3 O 4 /NC) was fabricated by two-step pyrolysis, and applied to build high-efficiency nano-platform for synergistic cancer therapy upon combination with glucose oxidase (GOx), labeled Zn-Co 3 O 4 /NC-GOx for clarity. Specifically, the multiple enzyme-like activities of the Zn-Co 3 O 4 /NC were scrutinously investigated, including peroxidase-like activity to convert H 2 O 2 to O 2 ∙−, catalase-like activity to decompose H 2 O 2 into O 2 , and oxidase-like activity to transform O 2 to O 2 ∙−, which achieved the CDT through the catalytic cascade reaction. Simultaneously, GOx reacted with intracellular glucose to produce gluconic acid and H 2 O 2 , realizing starvation therapy. In the acidic TME, the Zn-Co 3 O 4 /NC-GOx rapidly caused intracellular Zn2+ pool overload and disrupted cellular homeostasis for ion-intervention therapy. Additionally, the Zn-Co 3 O 4 /NC exhibited glutathione peroxidase-like activity, which consumed glutathione in tumor cells and reduced the ROS consumption for ferroptosis. The tumor treatments offer some constructive insights into the nanozyme-mediated catalytic medicine, coupled by avoiding the TME limitations. [ABSTRACT FROM AUTHOR]

We report a surface modified and sulfide electrolyte-infiltrated LiNi 0.6 Co 0.2 Mn 0.2 O 2 cathode to inhibit the interface side reactions and enhance the physical contact. The Li 10 GeP 2 S 12 -infiltrated electrode using LiNi 0.6 Co 0.2 Mn 0.2 O 2 cathode with Li 1.5 Al 0.5 Ge 1.5 (PO 4) 3 coating exhibits outstanding rate performance, excellent capacity retention and low interface impedance. [Display omitted] Sulfide-based all-solid-state lithium batteries (ASSLBs) with high-voltage Ni-rich layered cathodes have shown great potential in energy storage systems. However, the application of ASSLBs is hindered by severe interface issues and poor solid–solid contact between cathodes and sulfide electrolytes. In this work, a suitably thin Li 1.5 Al 0.5 Ge 1.5 (PO 4) 3 (LAGP) coating (0.41 mS cm−1) is introduced onto the surface of single-crystal LiNi 0.6 Co 0.2 Mn 0.2 O 2 particles to mitigate interface side reactions. Subsequently, sheet-type electrodes are fabricated by the infiltration of Li 10 GeP 2 S 12 to fill the voids and achieve highly dense solid–solid contact, thus preventing contact loss. The Li 10 GeP 2 S 12 -infiltrated ASSLBs with a LAGP buffer layer display a high initial discharge capacity of 141.5 mAh g−1 at 0.05 C and ultrastable cycling for 100 cycles at 0.1 C. An effective fabrication method for highly dense electrodes is proposed in this work, which provides a new direction for scalable industrial production. [ABSTRACT FROM AUTHOR]

The kinetics knowledge of lignocellulosic biomass decomposition is essential to develop efficient thermochemical conversion technology. However, the simplification of reaction mechanisms in existing oxidative pyrolysis studies largely compromises the application of kinetic models. To explore more exact kinetic parameters and reaction mechanism of lignocellulosic biomass oxidative pyrolysis, an updated oxidative pyrolysis kinetic model (seven-step reaction combined kinetics model) coupled with an optimization algorithm is proposed. Based on a series of thermogravimetric experiments in an air atmosphere, the extra oxidative pyrolysis kinetic parameters are obtained by the Shuffled Complex Evolution method. The proposed kinetic model is validated based on the degradation process of each component (hemicellulose, cellulose, and lignin). Furthermore, the obtained kinetic parameters are applied to predict the oxidative pyrolysis behavior, and the predicted mass loss rate is in good agreement with the experimental data. Eventually, according to the key combined kinetics parameters, it is found that the oxidative pyrolysis mechanisms of hemicellulose, cellulose, and lignin correspond to the power law, nucleation & growth, and chemical reaction order, respectively, while the combustion of char corresponds to the reaction order mechanism. • A seven-step reaction combined kinetics model is proposed. • The model is coupled with combined kinetics and Shuffled Complex Evolution. • Hemicellulose and cellulose correspond to power law and nucleation & growth. • Lignin and char correspond to chemical reaction order and reaction order. [ABSTRACT FROM AUTHOR]

Microbes and microbial metabolites/molecules-induced resistance is known to protect plants from several invaders, including viruses. We studied a water extract of dry mycelium of Penicillium chrysogenum (DMP)-induced defense responses and determined whether this extract protects tobacco from Tobacco Mosaic Virus (TMV). Transcripts of four genes – PAL , 4CL , C4H and LPO that are involved in the synthesis of secondary metabolites and the contents of phenolic compounds, scopoletin and lignin, were rapidly induced in DMP-treated BY-2 cell suspensions that were derived from Nicotiana tabacum L. cv. Bright Yellow-2, indicating a DMP-induced resistance in BY-2 cells. Transcripts of the salicylic acid (SA)-dependent gene PR-1a were rapidly induced after DMP treatment, indicating the activation of SA-dependent signaling pathway. The expression of the jasmonic acid (JA)-responsive gene PDF1.2 suggests that DMP might induce distinct signaling pathways simultaneously. A 30B vector carrying the green fluorescent protein gene (30B:GFP) was used to monitor the replication of the virus vector in BY-2 cells and tobacco plants. The spread of the virus vector was impaired both in DMP-pretreated BY-2 cells and tobacco plants, indicating that DMP helped protect tobacco against TMV. Our data suggest that the DMP activates defense responses in tobacco BY-2 cell suspensions, including the accumulation of secondary metabolites and the expression of defense responses genes, and protects tobacco from TMV. [ABSTRACT FROM AUTHOR]

Estrogen drives key transcriptional changes in breast cancer and stimulates breast cancer cells' growth with multiple mechanisms to coordinate transcription and translation. In addition to protein-coding transcripts, estrogen can regulate long non-coding RNA (lncRNA) transcripts, plus diverse non-coding RNAs including antisense, enhancer, and intergenic. LncRNA genes comprise the majority of human genes. The accidental, or regulated, translation of their short open reading frames by ribosomes remains a controversial topic. Here we report for the first time an integrated analysis of RNA abundance and ribosome occupancy level, using Ribo-seq combined with RNA-Seq, in the estrogen-responsive, estrogen receptor α positive, human breast cancer cell model MCF7, before and after hormone treatment. Translational profiling can determine, in an unbiased manner, which fraction of the genome is actually translated into proteins, as well as resolving whether transcription and translation respond concurrently, or differentially, to estrogen treatment. Our data showed specific transcripts more robustly detected in RNA-Seq than in the ribosome-profiling data, and vice versa, suggesting distinct gene-specific estrogen responses at the transcriptional and the translational level, respectively. Here, we showed that estrogen stimulation affects the expression levels of numerous lncRNAs, but not their association with ribosomes, and that most lncRNAs are not ribosome-bound. For the first time, we also demonstrated the transcriptional and translational response of expressed pseudogenes to estrogen, pointing to new perspectives for drug-target development in breast cancer in the future. • Estrogen distinctly regulates lncRNAs transcription in breast cancer cells. • Estrogen distinctly regulates lncRNAs translation in breast cancer cells. • Estrogen distinctly regulates pseudogenes transcription in breast cancer cells. • Estrogen distinctly regulates pseudogenes translation in breast cancer cells. [ABSTRACT FROM AUTHOR]

• The research took IL-4/STAT6 pathway as the entry point to observe the effects of moxibustion on the expression of macrophages and related inflammatory factors in RA rats. • The study starts with the polarization of macrophages to explore the anti-inflammatory mechanism of moxibustion. To observe the effects of moxibustion on "Shenshu" and "Zusanli" on macrophage polarization and IL-4/STAT6 signaling pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA. The rats' right hind paws were injected with freund's complete adjuvant (FCA) to establish the model of RA. Seven days after the injection of FCA, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. The researchers measured the thickness of the foot pad. ELISA and Histological Analysis were performed to observe the anti-inflammatory effect of moxibustion. Then researchers detected the expression of macrophage phenotype and the expression of IL-4/STAT6 signaling pathway related molecules. It was observed that after the injection of FCA, the rats' feet showed obvious symptoms of redness and swelling. But the symptoms were significantly improved when moxibustion was employed. The study found lower IL-23 and higher IL-4 level in the serum of FCA-injected rats after moxibustion treatment. HE staining showed that the synovium of the RA group was hyperemia and edema, with a large number of inflammatory cells infiltration and vascular dilatation. In the moxibustion group, the degree of synovial hyperemia and edema was improved, and the infiltration of inflammatory cells and vascular dilation were reduced. The study also found that there wer differences among the expressions of macrophage phenotypes in RA, and this was shown by the high expression of CD86 and low expression of CD206. However, the polarization of macrophages in the moxibustion group changed, and that was manifested by enhanced M2-polarized Mφs and inhibited M1-polarized Mφs. Meanwhile, moxibustion suppressed the activation of JAK1, JAK3 and STAT6 in the IL-4/STAT6 signaling pathway, which contributed to the polarization of M2. The results demonstrate that moxibustion not only suppresses the polarization of M1, but also promotes the polarization of M1. The anti-inflammatory effect of moxibustion may be related to the regulation of macrophage polarization through IL-4/STAT6 signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: Background: Substantial evidence suggests that the expansion of regulatory T cells (Tregs) plays a pivotal role in immunological evasion of tumors. Recent studies have demonstrated that a majority of tumor cells overexpress B7-H1, and this overexpression is associated with poor disease prognosis. Although an increase of Tregs and B7-H1 has been revealed in several malignancies, their correlation in gastric cancer has not been studied. Methods: Tumor sections from 111 gastric cancer patients were stained for FOXP3 and B7-H1 by immunohistochemistry. The expression levels of these two molecules were statistically associated with various factors involved in disease progression and prognosis. The correlation between their expression levels was analyzed. Results: The infiltration of FOXP3+ Tregs and expression of B7-H1 were observed in gastric cancer tissues, and there was a highly significant correlation between these two molecules (P<0.01). The expression of FOXP3+ Tregs and B7-H1 was associated with lymph node metastasis and the clinicopathological stage and prognosis of gastric cancer patients. The expression levels of these two determinants in patients with lymph node metastasis and an advanced clinicopathological stage were distinctly higher (P<0.05). The patients with enhanced expression of FOXP3+ Tregs and B7-H1 exhibited a lower overall survival rate and a worse prognosis (P<0.05). Conclusions: Increased expression of FOXP3+ Tregs and B7-H1 was observed in gastric cancer tissues; the two molecules were closely correlated with each other, suggesting that they might be used as new biomarkers to predict the disease progression and prognosis. Combinatorial immunotherapeutic approaches based on depleting the Tregs and blocking B7-H1 might improve therapeutic efficacy in gastric cancer. [Copyright &y& Elsevier]

Abstract: The performance of edible coating is influenced by the properties of coating materials and execution methods. In this study, three different coating materials (chitosan, sodium alginate, and soy protein isolate) and four different coating application methods (dipping, enrobing, spraying and electrostatic spraying) were investigated on their performance for coating Mozzarella cheese. The properties of coating solutions, morphology and basic quality changes of the cheese during storage at 4 °C were evaluated. Results showed that sodium alginate solution was the most viscous (η = 0.155 Pa s) and had small contact angle on hydrophobic substrate surface indicating its better spreadability on cheese. Film thickness displayed obvious differences based on the coating methods (ranging from 30.6 to 83.3 μm), with two spraying methods leading to thinner coatings. Sodium alginate coated cheese possessed the best overall physicochemical properties during storage whereas the preservation effects were not significantly different among four coating methods. This study provided valuable new information about the effective coating application methods for different coating materials. [Copyright &y& Elsevier]

Abstract: The impact of high hydrostatic-pressure (HHP) processing on the volatile profile of cooked Japonica rice (Wuchang) and Jasmine rice (Complete Wheel) was investigated by SPME–GC/MS. Presoaked samples were treated at 200, 400 and 600 MPa for 10 min and then cooked for volatile compound analysis. Seventy-seven compounds were identified in two cooked rice varieties: 20 aldehydes, 16 alcohols, 14 ketones, 9 arenes, 7 esters, 5 alkanes, 3 olefins and 3 hetero-cycle compounds. Results showed that both pressure level (P < 0.01) and rice variety (0.01 < P < 0.05) significantly impact the volatile compounds in rice and there is also an interaction between pressure and rice variety (P < 0.01). Overall, HPP decreased the amount of aldehydes more obviously in Complete Wheel rice than that in Wuchang variety. Both 200 and 400 MPa increased the levels of alcohols, ketones, esters and olefins, but reduced those of heterocycles, alkanes and arenes. Similar volatile change trends were found at 600 MPa except the concentration of each component was closer to that of control group. Based on the changes in the three key flavor compounds in rice (aldehydes, alcohols and ketones), the HPP process could be a suitable alternative to traditional pretreatment for improving flavor in cooked rice. [Copyright &y& Elsevier]

Abstract: Dietary carotenoids have been shown to be beneficial to health by decreasing the risk of many diseases. Attempts to enhance carotenoids in food crops have been successful although higher plants appear to resist big changes of carotenoid biosynthesis by metabolic engineering. Here we report the generation of a more nutritious tomato by modifying the intrinsic carotenes to astaxanthin, a high-value ketocarotenoid rarely found in plants. This was achieved by co-expression of the algal β-carotene ketolase from Chlamydomonas reinhardtii and β-carotene hydroxylase from Haematococcus pluvialis, a unique pair of enzymes identified to co-operate perfectly in converting β-carotene to astaxanthin by functional complementation in Escherichia coli. Expression of the two enzymes in tomato up-regulated most intrinsic carotenogenic genes, and efficiently directed carbon flux into carotenoids, leading to massive accumulations of mostly free astaxanthin in leaves (3.12mg/g) but esterified astaxanthin in fruits (16.1mg/g) and a 16-fold increase of total carotenoid capacity therein without affecting the plant normal growth and development. This study opened up the possibility of employing crop plants as green factories for economical production of astaxanthin. [Copyright &y& Elsevier]

Control of viral diseases using systemic resistance-inducing microbes and microbial metabolites/molecules is an established alternative strategy for inhibiting plant viruses. However, the mechanisms whereby virus infection is inhibited and restricted in plants expressing systemic resistance remains poorly understood. We have previously reported that an aqueous extract of the dry mycelium of Penicillium chrysogenum (DMP) can be used to protect tobacco plants against Tobacco mosaic virus (TMV). In this study, we investigated the effect of crude peptides derived from DMP (PDMP) in protecting Nicotiana glutinosa against TMV. The number and diameter of TMV lesions in plants pre-treated with PDMP were fewer and smaller, respectively, than those in control plants. The elevated expressions of PAL , PTI5 , PR-1a , NPR1 , PR-1b, and PDF1.2 detected in the induced and systemic leaves following PDMP treatment indicated that the PDMP induced basal and systemic resistance in N. glutinosa. Callose deposition and TMV- N gene-triggered hypersensitive response (HR) at the site of the TMV infection were identified as key factors restricting the movement of viruses. The levels of N gene transcripts, as well as those of the TMV- N gene-triggered HR-related genes HSR203J , AOXa , SIPK, and ZFT1 increased more rapidly after being challenged with TMV in N. glutinosa plants pre-treated with PDMP compared with the control plants. However, we detected no significant difference between PDMP-treated and control plants with respect to TMV-induced callose deposition, indicating that PDMP enhances the resistance of N. glutinosa against TMV by accelerating TMV- N gene-triggered-HR rather than by priming callose deposition. • Penicillium chrysogenum activates defense responses to tobacco mosaic virus (TMV). • It induced systemic resistance via both SA and JA/ET signaling pathways. • It also accelerated TMV- N gene-triggered-HR without primed callose deposition. [ABSTRACT FROM AUTHOR]

The utilization of photothermal agents (PTAs) in photothermal therapy (PTT) is faced with challenges such as immune clearance and inadequate concentration, which consequently result in residual tumors and an increased risk of recurrence and metastasis. Conversely, excessive treatment can lead to heightened inflammation and inevitable harm to adjacent healthy tissues. To address these issues, we developed a nanosystem (M@PB) consisting of Prussian blue coated with tumor cell membrane for precise photothermal therapy (PTT) and subsequent reduction of inflammation. This system not only evades immune attack due to the homologous biological characteristics of the encapsulating cell membrane but also exhibits active targeting capabilities towards homologous tumors. Furthermore, it effectively reduces excessive phototoxicity by leveraging the distinctive photothermal and anti-inflammatory characteristics of PB nanoparticles. The resulting M@PB nanosystem demonstrates effective photothermal ablation under 808 nm laser irradiation while mitigating the inflammatory response through inhibiting of local production of inflammatory mediators. Our study provides valuable insights into achieving targeted PTT with high efficiency while minimizing post-treatment inflammatory responses. [Display omitted] • A tumor cell membrane-coated Prussian blue nanosystem (M@PB) was constructed. • M@PB exhibits effective targeting photothermal ablation capabilities. • Prussian blue can reduce inflammatory response caused by photothermal therapy. [ABSTRACT FROM AUTHOR]

Plants are often primed to enhanced resistance upon recognizing certain microbes and microbial metabolites/molecules. We investigated the effect of PDMP, the peptides extract of dry mycelia of Penicillium chrysogenum , on defense of Nicotiana benthamiana to Tobacco mosaic virus (TMV). The 30B vector harboring the green fluorescent protein gene (30B:GFP) was used to monitor virus movement. Movement of the virus vector was limitied in PDMP-pretreated tobacco, in which significant callose accumulation was observed after challenge inoculation with the TMV vector. Callose accumulation was absent in plants pretreated with both the PDMP and callose synthesis inhibitor, resulting in elimination of PDMP-induced inhibition of TMV spread. Transcripts of the defense-related genes were significantly accumulated after challenge inoculation with TMV in PDMP-pretreated tobacco. Interestingly, PDMP treatment or TMV inoculation alone did neither induce callose deposition, nor enhance the transcript abundance of the defense-related genes, indicating that PDMP was more likely to promote tobacco to a primed state than induce defense responses directly. The primed callose accumulation plays a crucial role in restricting TMV spread in PDMP-pretreated tobacco. The present results provide evidence of PDMP can promote N. benthamiana to a primed state of enhance defense against TMV. Image 1 • PDMP induced resistance to the cell-to-cell and systemic movement of TMV. • PDMP led to primed callose deposition in leaves challenge-inoculated with TMV. • PDMP influences the expression of defense-related genes. [ABSTRACT FROM AUTHOR]

To establish an animal model of delayed intravenous resuscitation following seawater immersion after hemorrhagic shock (HS). Adult male SD rats were randomly divided into three groups: group NI (HS with no immersion), group SI (HS with skin immersion), and group VI (HS with visceral immersion). Controlled HS in rats was induced by withdrawing 45% of the calculated total blood volume within 30 min. In SI group, immediately after blood loss, 0.5 cm below the xiphoid process was immersed in artificial seawater, at (23 ± 1) °C, for 30 min. In VI group, the rats were performed by laparotomy and the abdominal organs were immersed in (23 ± 1) °C seawater for 30 min. Two hours after seawater immersion, the extractive blood and lactated Ringer's solution were delivered intravenously. The mean arterial pressure (MAP), lactate, and other biological parameters were investigated in different time points. The survival rate of 24 h after HS was recorded. After seawater immersion following HS, MAP and abdominal viscera blood flow decreased significantly, and the plasma levels of lactate and the organ function parameters were increased than the baseline. The above changes in VI group were more serious than those in SI and NI group, especially in myocardial and small intestine damage. The hypothermia, hypercoagulation, and metabolic acidosis were also observed after seawater immersion; the injury was more severely in VI group than that of SI group. However, the plasma levels of sodium, potassium, chlorine, and calcium in VI group were significantly higher than those before injury and in the other two groups. In the VI group, the level of plasma osmolality in instant, 2 h, and 5 h after immersion was 111%, 109%, and 108% of the SI group, respectively, all P < 0.01. The 24-h survival rate of VI group was 25%, which was significantly lower than that of SI group (50%) and NI group (70%), P < 0.05. The model fully simulated the key damage factors and field treatment conditions, reflected the effects of low temperature and hypertonic damage caused by seawater immersion on the severity and prognosis of naval combat wounds, and provided a practical and reliable animal model for the study of field treatment technology of marine combat shock. [ABSTRACT FROM AUTHOR]

[Display omitted] • A cheap and binderless CuFe NPs@N C/NF electrocatalyst was prepared. • Electrode with Cu/Fe molar ratio of 1:2 exhibited the highest NO 3 – removal. • N 2 selectivity of the CuFe NPs@N C/NF cathode electrochemical system reached 94.0%. • CuFe NPs@N C/NF had long-term durability for NO 3 – conversion. • The mechanism of electrochemical denitrification on CuFe NPs@N C/NF was proposed. Electrocatalytic denitrification is an attractive and effective method for complete elimination of nitrate (NO 3 –). However, its application is limited by the activity and stability of the electrocatalyst. In this work, a novel bimetallic electrode was synthesized, in which N-doped graphitized carbon sealed with Cu and Fe nanoparticles and immobilized them on nickel foam (CuFe NPs@N C/NF) without any chemical binder. The immobilized Cu-Fe nanoparticles not only facilitated the adsorption of the reactant but also enhanced the electron transfer between the cathode and NO 3 –, thus promoting the electrochemical reduction of NO 3 –. Therefore, the as-prepared electrode exhibited enhanced electrocatalytic activity for NO 3 – reduction. The composite electrode with the Cu/Fe molar ratio of 1:2 achieved the highest NO 3 – removal (79.4 %) and the lowest energy consumption (0.0023 kW h mg−1). Furthermore, the composite electrode had a robust NO 3 – removal capacity under various conditions. Benefitting from the electrochlorination on the anode, this electrochemical system achieved nitrogen (N 2) selectivity of 94.0 %. Moreover, CuFe NPs@N C/NF exhibited good stability after 15 cycles, which should be attributed to the graphitized carbon layer. This study confirmed that CuFe NPs@N C/NF electrode is a promising and inexpensive electrode with long-term stability for electrocatalytic denitrification. [ABSTRACT FROM AUTHOR]

[Display omitted] • A suspected older new taxa has been discovered. • This new taxa involves the production of a large number of hybrid offspring. • Hybridization is the main driving force of poplar evolution in Tibet Plateau. • A new hypothesis of "Hybrid Species Exterminating Their Ancestral Species" is proposed. While the diversity of species formation is broadly acknowledged, significant debate exists regarding the universal nature of hybrid species formation. Through an 18-year comprehensive study of all Populus species on the Qinghai-Tibet Plateau, 23 previously recorded species and 8 new species were identified. Based on morphological characteristics, these can be classified into three groups: species in section Leucoides , species with large leaves, and species with small leaves in section Tacamahaca. By conducting whole-genome re-sequencing of 150 genotypes from these 31 species, 2.28 million single nucleotide polymorphisms (SNPs) were identified. Phylogenetic analysis utilizing these SNPs not only revealed a highly intricate evolutionary network within the large-leaf species of section Tacamahaca but also confirmed that a new species, P. curviserrata , naturally hybridized with P. cathayana, P. szechuanica, and P. ciliata , resulting in 11 hybrid species. These findings indicate the widespread occurrence of hybrid species formation within this genus, with hybridization serving as a key evolutionary mechanism for Populus on the plateau. A novel hypothesis, "Hybrid Species Exterminating Their Ancestral Species (HSEAS)," is introduced to explain the mechanisms of hybrid species formation at three different scales: the entire plateau, the southeastern mountain region, and individual river valleys. [ABSTRACT FROM AUTHOR]

• The first web server for in silico identification of m6A m sites from the primary sequences of RNA. • Optimized model with eXtreme Gradient Boosting with Dart algorithm (XgbDart) and EIIP-PseEIIP encoding scheme. • Considerably high accuracy achieved in terms of Sensitivity, Specificity, and AUC. N6,2′-O-dimethyladenosine (m6A m) is a reversible modification widely occurred on varied RNA molecules. The biological function of m6A m is yet to be known though recent studies have revealed its influences in cellular mRNA fate. Precise identification of m6A m sites on RNA is vital for the understanding of its biological functions. We present here m6AmPred, the first web server for in silico identification of m6A m sites from the primary sequences of RNA. Built upon the eXtreme Gradient Boosting with Dart algorithm (XgbDart) and EIIP-PseEIIP encoding scheme, m6AmPred achieved promising prediction performance with the AUCs greater than 0.954 when tested by 10-fold cross-validation and independent testing datasets. To critically test and validate the performance of m6AmPred, the experimentally verified m6A m sites from two data sources were cross-validated. The m6AmPred web server is freely accessible at: https://www.xjtlu.edu.cn/biologicalsciences/m6am , and it should make a useful tool for the researchers who are interested in N6,2′-O-dimethyladenosine RNA modification. [ABSTRACT FROM AUTHOR]

[Display omitted] • A true sense of global smoothing approach for compact linear toolpath is presented. • Computational efficient geometric and motion smoothing methods are included. • The geometric smoothing generates global smoothed path without unwanted undulation. • The motion smoothing yields jerk-limited feed-axis trajectories by FIR filtering. The toolpaths for curved surfaces generated by most existing computer-aided-manufacturing applications are always consisted by short line segments. Due to the first-order discontinuity of the short line segment toolpath, the precise following of them must result in frequent acceleration/decelerations, which is easy to excite structural vibration of the machine tools, thus degrading the machining quality. To solve this problem, local corner rounding approaches are widely researched, however, most areas on the toolpath after corner rounding remains linear segments, unlike the global smoothing method who replaces all short line segments to spline curves thus obtaining smoother feed motion. Compared with the local corner rounding method, the global smoothing always requires iterative computes to satisfy the accuracy requirement, which makes it so time consuming that can hardly be utilized in CNC systems. To deal with above problem, this paper proposes a highly stable global smoothing method which does not need iterative computations. This is realized by a control-point-assigning-based global geometric smoothing algorithm and a FIR (Finite Impulse Response) filtering-based global motion smoothing algorithm. During global geometric smoothing, the short line segment toolpath is replaced by piecewise B-spline curve segments whose control points are directly assigned under the error tolerance constraint. During the global motion smoothing, a fast spline interpolation method based on FIR filtering is provided to generate smooth axial position references of the piecewise B-spline curve segments under the axial drive constraint. The whole global smoothing approach does not require pre-processing or iterative computation, which makes it easy to be applied. Extensive illustrations including numerical tests and experimental verification/comparison tests demonstrate the favorable effects of the proposed method in real-time capability and motion smoothing performance. Comparing with typical local corner rounding approach, the proposed global smoothing approach results in shorter motion time and better smoothness. Comparing with typical existing global smoothing method, the proposed method performs better in no required pre-processing and high-order motion smoothness. [ABSTRACT FROM AUTHOR]

[Display omitted] • Three new taxa of the sect. Leucoides were discovered. • The three new taxa all originated from distant hybridization between different sections. • The three new taxa had stronger adaptability than the ancient ancestor species. • A universal model of hybrid speciation process is proposed. Although numerous studies have been conducted on hybrid speciation, our understanding of this process remains limited. Through an 18-year systematic investigation of all taxa of Populus on the Qinghai-Tibet Plateau, we discovered three new taxa with clear characteristics of sect. Leucoides. Further evidence was gathered from morphology, whole-genome bioinformatics, biogeography, and breeding to demonstrate synthetically that they all originated from distant hybridization between sect. Leucoides and sect. Tacamahaca. P. gonggaensis originated from the hybridization of P. lasiocarpa with P. cathayana , P. butuoensis from the hybridization of P. wilsonii with P. szechuanica , and P. dafengensis from the hybridization of P. lasiocarpa with P. szechuanica. Due to heterosis, the three hybrid taxa possess greater ecological adaptability than their ancestral species. We propose a hybrid speciation process model that incorporates orthogonal, reverse, and backcrossing events. This model can adequately explain some crucial evolutionary concerns, such as the nuclear-cytoplasmic conflict on phylogeny and the extinction of ancestral species within the distribution range of hybrid species. [ABSTRACT FROM AUTHOR]

A novel in-situ N-doped carbon nanoparticles (NCNs) was prepared through direct pyrolysis of N-rich polyaniline (PANI) without using external N-containing precursor and the as-prepared materials were employed as metal-free peroxydisulfate (PDS) activator for bisphenol A (BPA) degradation. The catalyst derived from PANI carbonization at 900 °C (NCNs-9) displayed the excellent catalytic activity to activate PDS, resulting in 96.0% BPA degradation efficiency within 20 min. The catalytic activity of NCNs was closely related to their structure-composition, and higher graphitic N content and larger BET surface area were beneficial to the generation of reactive oxygen species (ROS). The quenching tests and electron paramagnetic resonance (EPR) demonstrated that BPA degradation in PDS/NCNs system was accomplished via non-radical (1O 2) and radical (·OH, SO 4 ·−, and O 2 ·−) pathways, in which O 2 ·− was the main ROS. The origin of O 2 ·− was the conversion of dissolved oxygen and the activation of PDS. The possible degradation pathways of BPA were also proposed. This study might provide inspirations to design in-situ N-doped carbon nanoparticles as the PDS activator for efficient degradation of persistent organic compound via advanced oxidation processes (AOPs). [ABSTRACT FROM AUTHOR]

Hyperlipidemia-induced retinal vascular dysfunction is a complex pathological process. circRNAs are important regulators of biological processes and disease progression. However, the expression pattern of circRNAs in hyperlipidemia-induced retinal vascular dysfunction remains unclear. Herein, we used a murine model of hyperlipidemia and identified 317 differentially expressed circRNAs between hyperlipidemic retinas and normolipidemic retinas by circRNA microarrays. GO analysis indicated that the host genes of dysregulated circRNAs were targeted to cell differentiation (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis revealed that circRNAs-mediated network was mostly enriched in focal adhesion signaling. Notably, circLDB1 was significantly up-regulated in the serum of coronary artery disease patients and aqueous humor of age-related macular degeneration patients. circLDB1 regulated endothelial cell viability, proliferation, and apoptosis in vitro. Thus, circRNAs are the promising targets for the prediction and diagnosis of hyperlipidemia-induced vascular diseases. • 317 differentially expressed circRNAs between hyperlipidemic retinas and normolipidemic retinas. • circLDB1 was up-regulated in the serum of CAD patients. • circLDB1 was up-regulated in the aqueous humor of AMD patients. • circLDB1 regulated endothelial cell viability, proliferation, and apoptosis. [ABSTRACT FROM AUTHOR]

Iridovirus of Taiwan (TGIV) has been threatening the grouper farming since 1997, effective prophylaxis method is urgently needed. Subunit vaccine was proved to be useful to against the virus. Bath is the simplest method of vaccination and easy to be administrated without any stress to fish. In this research, we constructed a prokaryotic expression vector of TGIV's major capsid protein (MCP) to acquire the vaccine. Single-walled carbon nanotubes (SWCNTs) were used as the carrier to enhance the protective effect of bath vaccination for juvenile pearl gentian grouper (bath with concentrations of 5, 10, 20 mg/L for 6 h). Virus challenge was done after 28 days. Survival rates were calculated after 14 days. The level of antibody, activities of related enzymes in serums and expression of immune-related genes in kidneys and spleens were test. The results showed that vaccine with SWCNTs as carrier induced a higher level of antibody than that without. In addition, the activities of related enzymes (acid phosphatase, alkaline phosphatase, superoxide dismutase) and the expression of immune-related genes (Mx1, IgM, TNFαF, Lysozyme, CC chemokine 1, IL1-β, IL-8) had a significantly increase. What's more, higher survival rates (42.10%, 77.77%, 89.47%) were provided by vaccine with SWCNTs than vaccine without SWCNTs (29.41%, 38.09%, 43.75%). This study suggests that the protective effect of vaccine that against TGIV with the method of bath vaccination could be enhanced by SWCNTs and SWCNTs could be a potential carrier for other subunit vaccines. • SWCNTs enhance the immune protective effect of bath subunit vaccine. • SWCNTs-MCP enhances the immunological activity against TGIV infection. • SWCNTs-MCP provides a good protection for pearl gentian grouper against TGIV. [ABSTRACT FROM AUTHOR]

• An electromagnetic modeling approach for damaged fiber-based laminates is presented. • The presented approach generates the accurate (thus benchmark) solution. • Missing, displaced, shrunk, and expanded fibers and circular inclusions are modeled as equivalent sources inside undamaged fibers. • The field solution is a summation of responses due to the exterior illuminating source and equivalent ones. • The proposed approach bridges the field solution of damaged laminates and corresponding undamaged ones. As a prerequisite to nondestructive testing of damaged fibered laminates, the Green's function, corresponding with an undamaged structure, and the electromagnetic fields associated with the damaged one are investigated herein. For the undamaged fibered laminate, benefiting from the periodicity of the fibers within each layer, the field solution follows the scattering-matrix-based method using the Floquet theorem. Yet, the periodicity is destroyed by the analytical source (for the Green's function) or by damages, and the Floquet theorem cannot be directly applied to compute the associated scattering matrices. The array scanning method is introduced to that effect. Inserting fictitious sources to get a quasi-periodic source array, the modeling approach for undamaged laminates can be used to compute the field with the source array, the integration of which cancels the effects of the fictitious sources and yields the Green's function. With the multipole method, field disturbances by damages, which include missing, displaced, shrunk, and expanded fibers and circular inclusions inside fibers, are accurately modeled by setting equivalent sources inside sound fibers, and the array scanning method applies. Modeling accuracy and efficiency of the approaches are illustrated by numerical simulations. [ABSTRACT FROM AUTHOR]

Diabetic neuropathic pain is one of the most common complications of diabetes. Mechanisms underlying the central modulation are still unclear. Here, we investigated the role of the neuron-restricted silencing factor (NRSF/REST) in diabetic-related neuropathic pain. Mechanical allodynia and thermal hyperalgesia were assessed to evaluate painful behaviors. Our results found that in the anterior cingulate cortex (ACC) of db/db mice, NRSF/REST levels increased significantly. Reduction of NRSF/REST improved the painful sensation. Meanwhile, in vitro study found that high glucose and high palmitic acid treatment induced elevation of NRSF/REST and its cofactors (mSin3A, CoREST and HDAC1), whereas downregulation of GluR2 and NMDAR2B. Knockdown of NRSF/REST could attenuate the LDH release and partially reversed the expression changes of HDAC1 and NMDAR2B. Our results suggested that the elevation of NRSF/REST in the ACC area of db/db mice is one of the key mediators of diabetic neuropathic pain. • NRSF/REST level increases in diabetic mice or under high glucose and fatty acid treatment. • Knockdown of NRSF/REST in the ACC area alleviates diabetes painful neuropathy. • Knockdown of NRSF/REST reverses the expression changes of HDAC1 and NMDAR2B under high glucose and palmitic acid treatment. [ABSTRACT FROM AUTHOR]

Layered molybdenum disulfide (MoS 2) has received significant attention due to various applications, such as catalysis, supercapacitors, batteries, and polymer nanocomposites. However, developing highly effective MoS 2 -based polymer nanocomposites with superior dispersion resulting in improved thermal and flame retardant properties still remains a huge challenge. Herein, a kind of MoS 2 hybrid was synthesized by the reaction of exfoliated MoS 2 nanosheets with (4-carboxybutyl) triphenylphosphonium bromide (TPP) via a cost-effective method, where TPP serves as a synergistic agent to further improve the dispersion and flame retardant efficiency of MoS 2. Then the TPP-MoS 2 hybrid was added to epoxy resin (EP) matrix to improve its fire safety properties. The hybrid was characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA). The TPP-MoS 2 hybrid was uniformly dispersed in the matrix, leading to significant improvement of fire safety. After the addition of 2 wt% TPP-MoS 2 , the char residue of the EP nanocomposites was increased by 46% compared with that of pure EP, while the peak heat release rate (PHRR) and total smoke release (TSR) were reduced by 26% and 21%, respectively. The superior dispersion of the hybrid improved the physical barrier effect of MoS 2 nanosheets thereby delaying the diffusion of volatile pyrolysis products and the transmission of heat and oxygen to underlying material. [ABSTRACT FROM AUTHOR]

Abstract Persulfate (PS)-based advanced oxidation processes have aroused considerable attentions due to their higher efficiency and wider adaptability to the degradation of bio-recalcitrant organic contaminants. In this study, Cu-Fe layered doubled hydroxide (CuFe-LDH) was employed to degrade Methyl Violet (MV) through heterogeneous photo-activation of PS under visible-light irradiation. The reaction kinetics, degradation mechanism, catalyst stability were investigated in detail. Under the conditions of CuFe-LDH (3:1) dosage 0.2 g/L, PS concentration 0.2 g/L and without initial pH adjustment, 20 mg/L MV was almost completely degraded within 18 min. Electron Spin Resonance (ESR) test and radical quenching experiment indicated that sulfate radicals (SO 4 -) were the dominant reactive oxidants for the MV decolorization, while hydroxyl radicals (OH) were also involved. The CuFe-LDH/PS/Vis system was applicable at wide range of pH level (3–9). However, extreme pH level would lead to the reduction or transformation of SO 4 -. The catalyst CuFe-LDH exhibited excellent stability and maintained relatively high catalytic activity to PS even after four recycles. Mechanism study revealed that the redox cycle of Fe3+/Fe2+ and Cu2+/Cu3+ assisted by visible-light irradiation accounted for the enhanced generation of radicals in CuFe-LDH/PS/Vis system, resulting in the improved degradation of organic contaminants. Overall, the CuFe-LDH/PS/Vis process could be a promising approach for the removal of refractory organic pollutants in wastewater. Graphical abstract Image 1 Highlights • A visible-light-responsive catalyst CuFe-LDH was prepared via co-precipitation method. • The introduction of visible light and CuFe-LDH effectively accelerated PS activation. • Superior photoactivation efficiency was maintained at wide range of pH level. • The main active species were SO 4 - and OH. • Enhanced mechanism for CuFe-LDH/PS/Vis system was elucidated. [ABSTRACT FROM AUTHOR]

Glioblastoma has been extensively studied due to its high mortality and short survival. The evolution mechanism of tumor-associated macrophages (TAMs) to Glioma-associated microglia and macrophages (GAMs) in the tumor microenvironment (TME) remains to be elucidated. The tumor cell-to-cell interaction patterns have not been well defined yet. The EF-Hand Domain Family Member D2 (EFHD2) has been reported to be differentially expressed as an immunomodulatory molecule in a variety of cancers. But large-scale clinical data from multiple ethnic communities have not been used to investigate the role of EFHD2 in glioma. RNA-seq data from 313 or 657 glioma patients from the Chinese Glioma Genome Atlas (CGGA) database and 603 glioma patients from the Cancer Genome Atlas (TCGA) database were analyzed retrospectively. Cell localization was performed using single-cell sequencing data from the CGGA database and the GSE131928 dataset. Mouse glioma cell lines and primary macrophages isolated from Efhd2 knockout mice were co-cultured to validate the immunomodulatory effects of EFHD2 on macrophages and the remodeling of TME of glioblastoma. EFHD2 is enriched in high-grade gliomas, isocitrate dehydrogenase wild-type, and 1p/19q non-co-deficient gliomas. It is a potential biomarker of glioma-proneuronal subtypes and an independent prognostic factor for overall survival in patients with malignant glioblastoma. EFHD2 regulates the monocyte-macrophage system function and positively correlates with immunosuppressive checkpoints. Further experimental data demonstrates that Efhd2 influences the polarization state of GAMs and inhibits the secretion of TGF-β1. In vitro experiments have revealed that macrophages lacking Efhd2 suppress the vitality of two glioma cell lines and decelerate the growth of glioma xenografts. In conclusion, EFHD2 promises to be a key target for TME-related immunotherapy. • EFHD2 is an independent prognostic factor for glioblastoma. • EFHD2 affects the polarization state of tumor-associated macrophage. • A promising target for tumor microenvironment-related immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract The dry mycelium of Penicillium chrysogenum (DMP) induces systemic acquired resistance (SAR), which enhances defenses in plants. To understand the molecular mechanisms involved in DMP-mediated signaling pathways, we examined the mRNA levels in Arabidopsis with jasmonic acid (JA), DMP or salicylic acid (SA) treatment compared with a control. RNA-Seq based transcriptome analysis revealed that the differentially expressed genes (DEGs) after DMP treatment were significantly enriched in three metabolism pathways shared by SA treatment and one additional pathway shared by JA treatment. Key DEGs, including PR1 , EIN3 and FRK1 , in the SA, JA/ethylene (ET) and pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) pathways for inducing resistance were significantly regulated. Further quantitative real-time PCR (qRT-PCR) analysis revealed that DMP-mediated signaling cross-talked with JA and SA signaling and associated with PAMP-triggered immunity. SA accumulated significantly after DMP treatment. However some known small molecules inducing SA accumulation were not found in DMP. Together, we demonstrated that DMP treatment activated defense in SAR via gene regulation in the JA and SA pathways. These results provide molecular evidence for the mechanisms in the DMP induced SAR and could guide the further identification of the activators. Highlights • Shared gene expressions in Arabidopsis treated with DMP, SA and JA. • Crosstalk between SA, JA pathway in Arabidopsis treated with DMP was found. • Total SA was significantly accumulated in Arabidopsis treated with DMP. • DMP induced gene regulation of the SA signaling pathway by activating PTI. • Neither SA nor chemical activators that can induced SAR were found in the DMP. [ABSTRACT FROM AUTHOR]

Aims The present study aimed to investigate the hepatoprotective effects of Methyl ferulic acid (MFA) against oxidative stress and apoptosis as well as inflammation in mice with liver injury induced by alcohol and its underlying mechanisms. Methods C57BL/6 mice were divided into a control group,a model group, and Methyl ferulic acid with high dosage (20 mg/kg), moderate dosage (10 mg/kg) and low dosage (5 mg/kg) groups. The general condition and organ index of each group were investigated. Histopathological analysis was performed to determine the degree of hepatic injury. Biochemical analyses of functional liver enzymes, lipid peroxidation enzymes and lipid content in each group. The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The mechanisms were investigated by detecting levels of NADPH Oxidase 4 (NOX4),p22phox, cytochrome P4502E1 (CYP2E1),Bax,B-cell lymphoma 2 (Bcl-2),cleaved-caspase 3 and 9 and phosphorylated extracellular regulated protein kinases(ERK),phosphorylated c-Jun N-terminal kinase (JNK), and phosphorylated p38 mitogen-activated protein kinase (MAPK) using real-time polymerase chain reaction (PCR) and Western blotting. Results MFA treatment significantly decreased serum enzymatic activities of alanine aminotransferase (ALT) and aspartate aminotransaminase (AST). MFA markedly increased levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px) and total antioxidative capacity (T-AOC), and reduced the concentration of malondialdehyde (MDA) and reactive oxygen species (ROS). Histopathological examination of livers showed that MFA reduced cytoplasmic vacuolisation necrosis and inflammatory cell infiltration in alcohol-treated mice. MFA treatment remarkably reduced the levels of trigyceride (TG), total cholesterol (TC) and low-density lipoprotein (LDL), decreasing the levels of high-density lipoprotein (HDL), alcohol dehydrogenase(ADL) and aldehyde dehydrogenase (ALDH). MFA treatment remarkably inhibited the expression of inflammatory factors tumour necrosis factor (TNF)-α, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-1β and IL-6. MFA attenuated both mRNA and protein expression of NOX4,p22phox,CYP2E1,Bax/Bcl-2. In addition, MFA inhibited the activation of caspase 3 and 9 and downregulated the levels of p -JNK,p-p38 MAPK and p -ERK in liver. Conclusion MFA has a protective effect on alcohol-induced liver injury, which may be related to its antioxidant,anti-inflammatory,lipid-eliminating properties and its ability to regulate the NOX4/ROS-MAPK signalling pathway. [ABSTRACT FROM AUTHOR]

DNA methylation is an important epigenetics, which occurs in the early stages of tumor formation. And it also is of great significance to find the relationship between DNA methylation and cancer. This paper proposes a novel model, iCancer-Pred, to identify cancer and classify its types further. The datasets of DNA methylation information of 7 cancer types have been collected from The Cancer Genome Atlas (TCGA). The coefficient of variation firstly is used to reduce the number of features, and then the elastic network is applied to select important features. Finally, a fully connected neural network is constructed with these selected features. In predicting seven types of cancers, iCancer-Pred has achieved an overall accuracy of over 97% accuracy with 5-fold cross-validation. For the convenience of the application, a user-friendly web server: http://bioinfo.jcu.edu.cn/cancer or http://121.36.221.79/cancer/ is available. And the source codes are freely available for download at https://github.com/Huerhu/iCancer-Pred. • A high accurate predictor is proposed to classify cancer and its type. • A feature selection mold is designed to choose the significate DNA methylation sites related cancer. • Discovering genes related cancer. [ABSTRACT FROM AUTHOR]

Activated fibroblasts continue to proliferate at injury sites, leading to progressive muscular fibrosis in Duchenne muscular dystrophy (DMD). TGF-β1 is a dominant profibrotic mediator thought to play a critical role in muscle fibrosis; however, the implicated mechanisms are not fully understood. Here we showed that TGF-β1 increased the resistance to apoptosis and stimulated cell cycle progression in dystrophic muscle fibroblasts under serum deprivation conditions in vitro . TGF-β1 treatment activated the canonical NF-κB pathway; and we found that pharmacological inhibition of IKKβ with IMD-0354 and RelA gene knockdown with siRNA attenuated these effects of TGF-β1 on dystrophic muscle fibroblasts. Collectively, our data suggest that TGF-β1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: Background: CXCL16 has been shown to be involved in atherosclerotic lesion development, but its role in preexisting lesions is still unclear. This study aims to assess the effect of CXCL16 on the stability of preexisting lesions. Methods: We firstly measured plasma CXCL16 level in Apolipoprotein E–Knockout (ApoE KO) mice with either high-cholesterol diet (HCD) or normal diet (ND) by enzyme-linked immunosorbent assay (ELISA). Then, silastic collars were placed around the carotid arteries in HCD-ApoE KO mice to accelerate atherosclerotic lesions. Five weeks later, CXCL16 was overexpressed by intravenous injection of lentivirus carrying CXCL16 transgene. Two weeks after infection, lesions were stained with hematoxylin and eosin (HE) and with oil red O. Biomarkers in the lesions, such as MMPs, CCL2, VCAM-1 and TNF-α were measured by real-time polymerase chain reaction (RT-PCR), which indicate the instability of plaques. Results: The level of CXCL16 in plasma was higher in HCD-ApoE KO mice as compared to ND-ApoE KO mice. Circulating CXCL16 overexpression does not affect the size of preexisting plaques, but it leads to vulnerable plaque morphology and increases the expression of markers of plaque destabilization. Conclusion: Systemic CXCL16 becomes much higher in atherosclerosis, and it could be a potential atherogenic biomarker. Overexpression of CXCL16 promotes the evolution of preexisting lesions to vulnerable plaques in ApoE KO mice. [Copyright &y& Elsevier]

Abstract: A considerable number of cells expressing typical immature neuronal markers including doublecortin (DCX+) are present around layer II in the cerebral cortex of young and adult guinea pigs and other larger mammals, and their origin and biological implication await further characterization. We show here in young adult guinea pigs that these DCX+ cells are accompanied by in situ cell division around the superficial cortical layers mostly in layer I, but they co-express proliferating cell nuclear antigen (PCNA) and an early neuronal fate determining factor, PAX6. A small number of these DCX+ cells also colocalize with BrdU following administration of this mitotic indicator. Cranial X-ray irradiation causes a decline of DCX+ cells around layer II, and novel environmental exploration induces c-Fos expression among these cells in several neocortical areas. Together, these data are compatible with a notion that DCX+ cortical neurons around layer II might derive from proliferable neuronal precursors around layer I in young adult guinea pig cerebrum, and that these cells might be modulated by experience under physiological conditions. [ABSTRACT FROM AUTHOR]

Abstract: HIV-1-infected brains are characterized by increased amyloid deposition. To study the influence of HIV-1 on amyloid beta (Aβ) homeostasis at the blood–brain barrier (BBB) level, we employed a model of brain microvascular endothelial cells exposed to HIV-1 in the presence or absence of Aβ. HIV-1 markedly increased endogenous Aβ levels and elevated accumulation of exogenous Aβ. Simvastatin, the HMG-CoA reductase inhibitor, blocked these effects. We next evaluated the effects of HIV-1 and/or simvastatin on expression of the receptor for lipoprotein related protein (LRP1) and the receptor for advanced glycation end products (RAGE), known to regulate Aβ transport across the BBB. LRP1 expression was not affected by HIV-1; however, it was increased by simvastatin. Importantly, simvastatin attenuated HIV-1-induced RAGE expression. These results suggest that HIV-1 may directly contribute to Aβ accumulation at the BBB level. In addition, statins may protect against increased Aβ levels associated with HIV-1 infection in the brain. [Copyright &y& Elsevier]

Emerging evidence implicates gut microbiota have an important role in ulcerative colitis (UC). Previous study indicated that Evodiamine (EVO) can alleviate colitis through downregulating inflammatory pathways. However, specific relationship between EVO-treated colitis relief and regulation of gut microbiota is still unclear. Here, our goal was to determine the potential role of gut microbiota in the relief of UC by EVO. By using pathology-related indicators, 16S rRNA sequencing and metabolomics profiling, we assessed the pharmacological effect of EVO on dextran sulfate sodium (DSS)-induced colitis rats as well as on the change of gut microbiota and metabolism. Fecal derived from EVO-treated rats was transplanted into colitis rats to verify the effect of EVO on gut microbiota, and 'driver bacteria' was found and validated by 16S rRNA sequencing, metagenome and qRT-PCR. The effect of Lactobacillus acidophilus (L. acidophilus) was investigated by vivo experiment, microbiota analysis, Short-chain fatty acids (SCFAs) quantification and colon transcriptomics. EVO reduced the susceptibility to DSS-induced destruction of epithelial integrity and severe inflammatory response, and regulated the gut microbiota and metabolites. Fecal Microbiota Transplantation (FMT) alleviated DSS-induced colitis, increased the abundance of L. acidophilus and the level of acetate. Furthermore, gavaged with L. acidophilus reduced pro-inflammatory cytokines, promoted the increase of goblet cells and the secretion of antimicrobial peptides, regulated the ratio of Firmicutes/Bacteroidetes and increased the level of acetate. Our results indicated that EVO mitigation of DSS-induced colitis is associated with increased in L. acidophilus and protective acetate production, which may be a promising strategy for treating UC. [ABSTRACT FROM AUTHOR]