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Paramichelia baillonii is a rare and fast-growing tree species in subtropical China. The acidic red soil in southern China severely limits its growth as it lacks sufficient available phosphorus (P), resulting in declining soil fertility and nutrient availability. The effect of P deficiency on P. Baillonii growth, root attributes, and physiological response has not yet been reported. Understanding the adaptability of P. baillonii to low-P conditions can improve afforestation and soil management in southern China. Therefore, we conducted a pot experiment on 2-year-old saplings and treated them with different P levels. Results showed that P deficiency (0-5 mg L-1) decreased growth attributes, root morphological traits, and nutrient uptake of P. baillonii saplings compared to control (CK). Similarly, reduction in chlorophyll a, b, total chlorophyll, net photosynthetic rate (Pn), transpiration rate (Tr), and Gs were seen in low P treatment saplings compared to CK. Whereas superoxide dismutase, peroxidase, malondialdehyde, acid phosphatase activity, and soluble protein content increased with increasing P-deficiency up to 5 mg L-1, and soluble sugar showed oppsite trend. Moreover, the proteomics analysis identified 2721 proteins, 196 showing differential expression, with 90 up- and 106 down-regulated. Importantly, the metabolic activities increased in the pentose phosphate pathway, starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, and phenylpropanoid biosynthesis pathways to sustain regular plant growth under P deficiency. This study delves into the dynamic morphophysiological and proteomic changes in response to P deficiency. Overall, growth and nutrient uptake were reduced, countered by adaptive biochemical and proteomic shifts, including heightened antioxidant activities and modifications in metabolic pathways, highlighting the resilient strategies of P. baillonii saplings under P deficiency. [ABSTRACT FROM AUTHOR]

The aim of assisted reproductive technology (ART) is to select the high-quality sperm, oocytes, and embryos, and finally achieve a successful pregnancy. However, functional evaluation is hindered by intra- and inter-operator variability. Microfluidic chips emerge as the one of the most powerful tools to analyze biological samples for reduced size, precise control, and flexible extension. Herein, a systematic search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and IEEE Xplore databases until March 2023. We displayed and prospected all detection strategies based on microfluidics in the ART field. After full-text screening, 71 studies were identified as eligible for inclusion. The percentages of human and mouse studies equaled with 31.5%. The prominent country in terms of publication number was the USA (n = 13). Polydimethylsiloxane (n = 49) and soft lithography (n = 28) were the most commonly used material and fabrication method, respectively. All articles were classified into three types: sperm (n = 38), oocytes (n = 20), and embryos (n = 13). The assessment contents included motility, counting, mechanics, permeability, impedance, secretion, oxygen consumption, and metabolism. Collectively, the microfluidic chip technology facilitates more efficient, accurate, and objective evaluation in ART. It can even be combined with artificial intelligence to assist the daily activities of embryologists. More well-designed clinical studies and affordable integrated microfluidic chips are needed to validate the safety, efficacy, and reproducibility. Trial registration: The protocol was registered in the Open Science Frame REGISTRIES (identification: osf.io/6rv4a). [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is a Gram‐negative, spiral‐shaped bacterium that infects approximately 50% of the world's population and has been strongly associated with chronic gastritis, peptic ulcers, gastric mucosa‐associated lymphoma, and gastric cancer. The elimination of H. pylori is currently considered one of the most effective strategies for the treatment of gastric‐related diseases, so antibiotic therapy is the most commonly used regimen for the treatment of H. pylori infection. Although this therapy has some positive effects, antibiotic resistance has become another clinically prominent problem. Therefore, the development of a safe and efficient vaccine has become an important measure to prevent H. pylori infection. Methods: PubMed and ClinicalTrials.gov were systematically searched from January 1980 to March 2023 with search terms—H. pylori vaccine, adjuvants, immunization, pathogenesis, and H. pylori eradication in the title and/or abstract of literature. A total of 5182 documents were obtained. Based on the principles of academic reliability, authority, nearly publicated, and excluded the similar documents, finally, 75 documents were selected, organized, and analyzed. Results: Most of the candidate antigens used as H. pylori vaccines in these literatures are whole‐cell antigens and virulence antigens such as UreB, VacA, CagA, and HspA, and the main types of vaccines for H. pylori are whole bacteria vaccines, vector vaccines, subunit vaccines, nucleic acid vaccines, epitope vaccines, etc. Some vaccines have shown good immune protection in animal trials; however, few vaccines show good in clinical trials. The only H. pylori vaccine passed phase 3 clinical trial is a recombinant subunit vaccine using Urease subunit B (UreB) as the vaccine antigen, and it shows good prophylactic effects. Meanwhile, the adjuvant system for vaccines against this bacterium has been developed considerably. In addition to the traditional mucosal adjuvants such as cholera toxin (CT) and E. coli heat labile enterotoxin (LT), there are also promising safer and more effective mucosal adjuvants. All these advances made safe and effective H. pylori vaccines come into service as early as possible. Conclusions: This review briefly summarized the advances of H. pylori vaccines from two aspects, candidates of antigens and adjuvants, to provide references for the development of vaccine against this bacterium. We also present our prospects of exosomal vaccines in H. pylori vaccine research, in the hope of inspiring future researchers. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the efficacy of different exercise therapies in reducing fatigue in patients with breast cancer. Design: PubMed, Embase, Web of Science, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, China Biology Medicine, China National Knowledge Infrastructure, Database of Chinese Sci-tech Periodicals, and Wanfang databases were searched from their inception to March 2022. The authors independently screened all randomized controlled trials of exercise therapy in patients with breast cancer. A network meta-analysis was performed using Stata 16.0 software. Results: Seventy-eight studies were analyzed, with 167 comparisons and 6235 patients. The network results showed that stretching (standardized mean difference = -0.74, confidence interval = -1.43 to -0.06), yoga (standardized mean difference = -0.49, confidence interval = -0.75 to -0.22), combined exercise (standardized mean difference = -0.47, confidence interval = -0.70 to -0.24), aerobic exercise (standardized mean difference = -0.46, confidence interval = -0.66 to -0.26), and resistance exercise (standardized mean difference = -0.42, confidence interval = -0.77 to -0.08) significantly reduced fatigue. Pairwise comparisons confirmed that yoga, combined exercise, aerobic exercise, and resistance exercise were positively associated with fatigue relief. However, no significant association was identified between reduced fatigue and traditional Chinese exercises or stretching. Conclusions: The most effective exercise therapy to relieve cancer-related fatigue in patients with breast cancer was yoga, followed by combined aerobic and resistance exercises. It is expected that more randomized controlled trials will be conducted to further explore the efficacy and mechanisms of exercise. [ABSTRACT FROM AUTHOR]

Objective • Effects of Qishen Dihuang (QSDH) granules on intestinal flora of an experimental autoimmune myasthenia gravis (EAMG) model rat were investigated (CNBI:PRJNA910532). Methods • Thirty-six female Lewis rats were assigned to Control, EAMG, QSDH-low-dose, QSDH-medium-dose, QSDH-high-dose, and Prednisone groups using the random number table method (6 rats/group). A rat EAMG model was established by injecting Rα97-116 peptide antigen. Each day for 30 days, gavages were administered to rats in the Chinese medicine group (QSDH granules in different concentrations), Prednisone group (prednisone), and Control and Model groups (0.5% CMC). After 30-day gavages, rat fecal samples were collected and the microbial community composition and diversity differences between intestinal microbiota of EAMG and QSDH granule-treated groups were analyzed using 16S amplicon sequencing to explore the effect underlying QSDH granules alleviation of EAMG. Results • The clinical symptoms of rats in each treatment group improved significantly after the intervention treatment with QSDH granules. Comparison of the relative abundance of microorganisms in the gut flora of different groups with that of the EAMG group rats revealed: significantly lower phylum-level Bacteroidetes abundance and significantly greater Actinobacteria abundance in the QSDH-high-dose group and a significantly greater Firmicutes/Bacteroidetes ratio in the QSDH-medium-dose group; significantly increased family-level QSDH-high-dose group abundances of Lachnospiraceae and Trichospiraceae (Firmicutes), significantly increased QSDH-medium-dose group Lactobacillaceae abundance, and significantly increased QSDH-low-dose group Bacteroidaceae abundance; genus)level, QSDH-high-dose group Prevotella and Coprococcus abundances were significantly increased and Turicibacter and Lactobacillus abundances were significantly decreased, while QSDH-medium-dose group Akkermansia and Lactobacillus abundances were significantly increased. Greater overall community richness, diversity, and genetic diversity were observed in QSDH granules-treated groups, but differences were insignificant (P > .05). The most significant inter-group genus-level community marker differences involved Prevotella, Ruminococcus, Coprococcus, and Turicibacter. Conclusion • QSDH granules may regulate EAMG rat intestinal flora by decreasing relative abundances of Turicibacter and Clostridium and increasing relative abundances of Bifidobacterium, Lachnospiraceae, and Prevotella. [ABSTRACT FROM AUTHOR]

The article presents a study which reported a strategy to establish membrane-anchored catalysts with precise spatial control via liposome fusion-based transport (MAC-LiFT), loading bioorthogonal catalytic complexes onto either or both sides of the membrane leaflets. Topics discussed include construction of catalyst-loaded fusogenic liposome, intracellular catalysis on the outer and inner membrane leaflets, and orientation-controlled dual catalytic reactions on membrane.

In this paper, we prove the Kastler-Kalau-Walze type theorems for twisted Dirac operators on 5-dimensional manifolds with boundary. [ABSTRACT FROM AUTHOR]

The cGAS-STING pathway is essential for immune defense against microbial pathogens and malignant cells; as such, STING is an attractive target for cancer immunotherapy. However, systemic administration of STING agonists poses safety issues while intratumoral injection is limited by tumor accessibility. Here, we generated antibody-drug conjugates (ADCs) by conjugating a STING agonist through a cleavable linker to antibodies targeting tumor cells. Systemic administration of these ADCs was well tolerated and exhibited potent antitumor efficacy in syngeneic mouse tumor models. The STING ADC further synergized with an anti-PD-L1 antibody to achieve superior antitumor efficacy. The STING ADC promoted multiple aspects of innate and adaptive antitumor immune responses, including activation of dendritic cells, T cells, natural killer cells and natural killer T cells, as well as promotion of M2 to M1 polarization of tumor-associated macrophages. These results provided the proof of concept for clinical development of the STING ADCs. [ABSTRACT FROM AUTHOR]

The amyloid cascade hypothesis has always been a research focus in the therapeutic field of Alzheimer’s disease (AD) since it was put forward. Numerous researchers attempted to find drugs for AD treatment based on this hypothesis. To promote the research of anti-AD drugs development, the current hypothesis and pathogenesis were reviewed with expounding of β-amyloid generation from its precursor protein and related transformations. Meanwhile, the present drug development strategies aimed at each stage in this hypothesis were also summarized. Several strategies especially immunotherapy showed the optimistic results in clinical trials, but only a small percentage of them eventually succeeded. In this review, we also tried to point out some common problems of drug development in preclinical and clinical studies which might be settled through multidisciplinary cooperation as well as the understanding that reinforces the amyloid cascade hypothesis. [ABSTRACT FROM AUTHOR]

The article focuses on R-loops affect transcription and genome stability. Topics include examines dysregulation of R-loops is related to human diseases and considered genome wide R-loop mapping typically uses the S9.6 antibody or inactive ribonuclease H, both requiring a large number of cells with varying results observed depending on the approach applied.

Mutations in the hyperpolarization-activated nucleotidegated channel 4 (HCN4) are known to be associated with arrhythmias in which QT prolongation (delayed ventricular repolarization) is rare. Here, we identified a HCN4 mutation, HCN4-R666Q, in two sporadic arrhythmia patients with sinus bradycardia, QT prolongation, and short bursts of ventricular tachycardia. To determine the functional effect of the mutation, we conducted clinical, genetic, and functional analyses using whole-cell voltage-clamp, qPCR, Western blot, confocal microscopy, and co-immunoprecipitation. The mean current density of HEK293T cells transfected with HCN4-R666Q was lower in 24 to 36 h after transfection and was much lower in 36 to 48 h after transfection relative to cells transfected with wildtype HCN4. Additionally, we determined that the HCN4-R666Q mutant was more susceptible to ubiquitin-proteasome system-mediated protein degradation than wildtype HCN4. This decreased current density for HCN4-R666Q could be partly rescued by treatment with a proteasome inhibitor. Therefore, we conclude that HCN4-R666Q had an effect on HCN4 function in two aspects, including decreasing the current density of the channel as a biophysical effect and weakening its protein stability. Our findings provide new insights into the pathogenesis of the HCN4-R666Q mutation. [ABSTRACT FROM AUTHOR]

Wolbachia is a natural bacterium that can infect mosquitoes and reduce their ability to transmit mosquito-borne diseases, such as dengue fever, Zika, and chikungunya. Field trials and modeling studies have shown that the fraction of infection among the mosquitoes must exceed a threshold level for the infection to persist. To capture this threshold, it is critical to consider the spatial heterogeneity in the distributions of the infected and uninfected mosquitoes created by a local release of the infected mosquitoes. We develop and analyze PDE models to study the invasion dynamics of Wolbachia infection among mosquitoes in the field. Our reaction-diffusion-type models account for the complex vertical transmission and the spatial mosquito dispersion. We characterize the threshold for a successful invasion with a bubble-shaped distribution, called the \critical bubble." The critical bubble is optimal in its release size compared to other spatial profiles in a one-dimensional landscape. The fraction of infection near the release center is higher than the threshold level for the corresponding homogeneously mixing ODE models. We show that the proposed spatial models give rise to the traveling waves of Wolbachia infection when above the threshold. We quantify how the threshold condition and traveling-wave velocity depend on the diffusion coefficients and other model parameters. Numerical studies for different scenarios are presented to inform the design of release strategies. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is the most prevalent internal modification in eukaryotic RNAs. This modification is regulated by three different factors (writers, erasers, and readers) and affects multiple aspects of RNA metabolism, including RNA splicing, nuclear export, translation, stability and decay. The m6A-mediated modification plays important roles in posttranscriptional regulation of gene expression and mediates a variety of cellular and biological processes. Accordingly, deregulation in m6A modification is closely related to the occurrence and development of human diseases. The liver is the largest digestive and metabolic organ in human and recent studies have shown that m6A modification is importantly implicated in liver cellular and physiological functions and in the pathogenesis of hepatic diseases and cancers. In the current review, we summarize the functions of m6A in RNA metabolism and its roles in liver cell biology and discuss its implication in hepatic diseases and carcinogenesis. [ABSTRACT FROM AUTHOR]

Objective: To compare the safety and efficacy of Kang'ai injection combined with chemotherapy and chemotherapy alone in the treatment of non-small cell lung cancer. Methods: The related control and randomized studies from 1966 to October 01, 2022, were retrieved in the following databases: China National Knowledge Infrastructure, Wanfang databases, Value In Paper, SinoMed, PubMed, Embase and Cochrane Library. A comprehensive literature search was conducted in 7 electronic databases identifying all the relevant randomized controlled trials. Cochrane handbook 5.2.3 was applied to evaluate the quality of included trials, and the RevMan 5.3 software was used to analyze data and assess the publication bias. Results: From the 16 studies reviewed, a total of 1,398 patients were included. Compared with docetaxel + cis-platinum chemotherapy alone, Kang'ai injection combined with docetaxel + cis-platinum chemotherapy showed significant effects in improving clinical response rate (RR: 1.40, 95% confidence interval (CI) (1.25, 1.58)), quality of life score (Karnofsky score) (RR: 1.53, 95% CI (1.32, 1.78)), traditional Chinese medicine syndrome (RR: 2.01, 95% CI (1.43, 2.83)) and safety (RR: 0.62, 95% CI (0.54, 0.71)), the differences were statistically significant. Conclusion: Kang'ai injection may increase the therapeutic effectiveness, improve the quality of life, and reduce the toxicity of chemotherapy in patients with non-small cell lung cancer. These results require confirmation by further rigorously designed randomized controlled trials (PROSPERO registration number: CRD42020176917). [ABSTRACT FROM AUTHOR]

In this paper, we compute the Bott connection and their curvature on three-dimensional Lorentzian Lie groups with three different distributions, then we classify affine Ricci solitons associated to the Bott connection on the spaces under study. [ABSTRACT FROM AUTHOR]

To study the alkaloids of Solanum lyratum Thunb. ODS and silica gel column chromatography combined with HPLC were used to separate and purify the alkaloids. Seven alkaloids were identified via UHPLC-ESI-Q-TOF-MS, 1D and 2D NMR, respectively 15β-ethoxy-(3β,5α,25R)-16,23-epoxy-23,24-imino-cholestan-16,20,23(N)-triene-3β-ol-3-O-β-D-glucopyranosyl-(1→2)- β-D-glucopyranosyl-(1→4)-β-D-galactopyran-oside (1), 15β-hydroxyl-(3β,25R)-16,23-epoxy-23,24-imino-cholestan-5,16,20, 23(N)-tetraene-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactop-yranoside (2), Solalyraine A (3), Solalyraine B (4), 16,23-epoxy-22,26-imino-cholest-22(N),23,25(26)-trien-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl- (1→4)-β-D-galactopyranoside (5), N-(4-amino-butyl)-3-(3-hydroxy-4-methoxy-phenyl)-E-acrylamide (6) and magnoflorine (7). Among them, compounds 1 and 2 were two new steroidal glycoalkaloids that has not been reported in the literature, and compound 7 was isolated from S. lyratum for the first time. [ABSTRACT FROM AUTHOR]

The present article scrutinizes the text of Erythraean Sea ethnography in Book 3 of Diodorus Siculus' Bibliotheca Historica , while comparing it with Diodorus' original source—Agatharchides' On the Erythraean Sea , which is preserved in Photius' Bibliotheca. It will be argued that Diodorus, with careful modifications of his source as well as referring to, or rejecting, specific contemporary moral motifs, articulates various kinds of limitations of the Erythraean inhabitants, and therefore (re)constructs the Erythraean Sea as a static world. The different and remote world of Diodorus' protagonists serves as a mirror to reflect on moral, geographical, social and economic forms, and thus allows Diodorus to communicate with his readers: the latter are reminded of their seemingly unlimited chances in the present, which are commonly presented in contemporary literature. [ABSTRACT FROM AUTHOR]

Understanding the correlation between exposed surfaces and performances of controlled nanocatalysts can aid effective strategies to enhance electrocatalysis, but this is as yet unexplored for the nitrogen reduction reaction (NRR). Here, we first report controlled synthesis of well-defined Pt3Fe nanocrystals with tunable morphologies (nanocube, nanorod and nanowire) as ideal model electrocatalysts for investigating the NRR on different exposed facets. The detailed electrocatalytic studies reveal that the Pt3Fe nanocrystals exhibit shape-dependent NRR electrocatalysis. The optimized Pt3Fe nanowires bounded with high-index facets exhibit excellent selectivity (no N2H4 is detected), high activity with NH3 yield of 18.3 μg h−1 mg−1cat (0.52 μg h−1 cm−2ECSA; ECSA: electrochemical active surface area) and Faraday efficiency of 7.3% at −0.05 V versus reversible hydrogen electrode, outperforming the {200} facet-enclosed Pt3Fe nanocubes and {111} facet-enclosed Pt3Fe nanorods. They also show good stability with negligible activity change after five cycles. Density functional theory calculations reveal that, with high-indexed facet engineering, the Fe-3d band is an efficient d-d coupling correlation center for boosting the Pt 5d-electronic exchange and transfer activities towards the NRR. [ABSTRACT FROM AUTHOR]

Crystal phase engineering is a powerful strategy for regulating the performance of electrocatalysts towards many electrocatalytic reactions, while its impact on the nitrogen electroreduction has been largely unexplored. Herein, we demonstrate that structurally ordered body‐centered cubic (BCC) PdCu nanoparticles can be adopted as active, selective, and stable electrocatalysts for ammonia synthesis. Specifically, the BCC PdCu exhibits excellent activity with a high NH3 yield of 35.7 μg h−1 mg−1cat, Faradaic efficiency of 11.5 %, and high selectivity (no N2H4 is detected) at −0.1 V versus reversible hydrogen electrode, outperforming its counterpart, face‐centered cubic (FCC) PdCu, and most reported nitrogen reduction reaction (NRR) electrocatalysts. It also exhibits durable stability for consecutive electrolysis for five cycles. Density functional theory calculation reveals that strong orbital interactions between Pd and neighboring Cu sites in BCC PdCu obtained by structure engineering induces an evident correlation effect for boosting up the Pd 4d electronic activities for efficient NRR catalysis. Our findings open up a new avenue for designing active and stable electrocatalysts towards NRR. [ABSTRACT FROM AUTHOR]

Crystal phase engineering is a powerful strategy for regulating the performance of electrocatalysts towards many electrocatalytic reactions, while its impact on the nitrogen electroreduction has been largely unexplored. Herein, we demonstrate that structurally ordered body‐centered cubic (BCC) PdCu nanoparticles can be adopted as active, selective, and stable electrocatalysts for ammonia synthesis. Specifically, the BCC PdCu exhibits excellent activity with a high NH3 yield of 35.7 μg h−1 mg−1cat, Faradaic efficiency of 11.5 %, and high selectivity (no N2H4 is detected) at −0.1 V versus reversible hydrogen electrode, outperforming its counterpart, face‐centered cubic (FCC) PdCu, and most reported nitrogen reduction reaction (NRR) electrocatalysts. It also exhibits durable stability for consecutive electrolysis for five cycles. Density functional theory calculation reveals that strong orbital interactions between Pd and neighboring Cu sites in BCC PdCu obtained by structure engineering induces an evident correlation effect for boosting up the Pd 4d electronic activities for efficient NRR catalysis. Our findings open up a new avenue for designing active and stable electrocatalysts towards NRR. [ABSTRACT FROM AUTHOR]

Among patients with intensive care unit-acquired weakness (ICUAW), skeletal muscle strength often decreases significantly. The present study aimed to explore the effects of testosterone propotionate on skeletal muscle using rat model of sepsis. Male SD rats were randomly divided into experimental group, model control group, sham operation group and blank control group. Rats in experimental group were given testosterone propionate two times a week, 10 mg/kg for 3 weeks. Maximal contraction force, fatigue index and cross-sectional area of the extensor digitorum longus (EDL) were measured. Myosin, IGF-1, p-AKT and p-mTOR levels in EDL were detected by Western blot. Histological changes of the testis and prostate were detected by hematoxylin and eosin staining. We found that maximal contraction force and fatigue index of EDL in experimental group were significantly higher than in model control group. Cross-sectional area of fast MHC muscle fiber of EDL in group was significantly higher than in model control group. The levels of myosin, IGF-1, p-AKT and p-mTOR of EDL in experimental group were significantly higher than in model control group. In addition, no testicle atrophy and prostate hyperplasia were detected in experimental group. In conclusion, these results suggest that testosterone propionate can significantly improve skeletal muscle strength, endurance and volume of septic rats, and the mechanism may be related to the activation of IGF-1/AKT pathway. Moreover, testosterone propionate with short duration does not cause testicular atrophy and prostate hyperplasia in septic rats. Therefore, testosterone propionate is a potential treatment for muscle malfunction in ICUAW patients. [ABSTRACT FROM AUTHOR]

This work introduces a cluster-based structural optimization (CBSO) method for the design of categorical multimaterial structures subjected to crushing, dynamic loading. The proposed method consists of three steps: conceptual design generation, design clustering, and Bayesian optimization. In the first step, a conceptual design is generated using the hybrid cellular automaton (HCA) algorithm. In the second step, threshold-based cluster analysis yields a lower-dimensional design. Here, a cluster validity index for structural optimization is introduced in order to qualitatively evaluate the clustered design. In the third step, the optimal design is obtained through Bayesian optimization, minimizing a constrained expected improvement function. This function allows to impose soft constraints by properly redefining the expected improvement based on the maximum constraint violation. The Bayesian optimization algorithm implemented in this work has the ability to search over (i) a real design space for sizing optimization, (ii) a categorical design space for material selection, or (iii) a mixed design space for concurrent sizing optimization and material selection. With the proposed method, materials are optimally selected based on multiple attributes and multiple objectives without the need for material ranking. The effectiveness of this approach is demonstrated with the design for crashworthiness of multimaterial plates and thin-walled structures. [ABSTRACT FROM AUTHOR]

The design and development of non‐noble metal alternatives with superior performance and promising long‐term stability that is comparable or even better than those of noble‐metal‐based catalysts is a significant challenge. Here, we report the thermal‐induced phase engineering of non‐noble‐metal‐based nanowires with superior electrochemical activity and stability for the methanol oxidation reaction (MOR) under alkaline conditions. The optimized Cu–Ni nanowires deliver an unprecedented mass activity of 425 mA mg−1, which is 4.3 times higher than that of the untreated one. Detailed catalytic investigations show that the enhanced performance is due to the large active area, the increased number of active sites (NiOOH), and fast methanol electrooxidation kinetics. In addition, the generated hollow feature in the nanowires provides a unique void space to release the volume expansion, where the activity can be maintained for 5 h without a distinct activity decay. The present work emphasizes the importance of precisely phase modulating of nanomaterials for the design of non‐noble metal electrocatalysts towards the MOR, which opens up a new pathway for the design of cost‐effective electrocatalysts with promising activity and long‐term stability. [ABSTRACT FROM AUTHOR]

A series of novel alkyl amine-substituted icariside II (ICA II) derivatives were synthesized by Mannich reactions at the 6-C position (compounds 4a-d) and changing the carbon chain length at the 7-OH position (compounds 7a-h), and their in vitro antitumor activity towards human breast cancer lines (MCF-7 and MDA-MB-231) and human hepatoma cell lines (HepG2 and HCCLM3-LUC) were evaluated by the MTT assay. Compared with ICA II, most of the twelve derivatives showed good micromole level activity and a preliminary structure-activity relationship (SAR) for the anticancer activity was obtained. Compound 7g showed the most potent inhibitory activity for the four cancer cell lines (13.28 µM for HCCLM3-LUC, 3.96 µM for HepG2, 2.44 µM for MCF-7 and 4.21 µM for MDA-MB-231), which was 2.94, 5.54, 12.56 and 7.72-fold stronger than that of ICA II. The preliminary SAR showed that the introduction of a alkyl amine substituent at 6-C was not favorable for the anticancer activity, while most of the 7-O-alkylamino derivatives exhibited good antitumor activity and the anticancer activity 7-O-alkylamino derivatives were influenced by the alkyl chain length and the different terminal amine substituents. Furthermore, the effects of compound 7g on apoptosis and cell cycle of MCF-7 cells were further investigated, which showed that compound 7g triggered apoptosis and arrested the cell cycle at the G0/G1 phase in MCF-7 cells. Our findings indicate that compound 7g may be a promising anticancer drug candidate lead. [ABSTRACT FROM AUTHOR]

This article finds that the innovative practice of involving social workers in settling petition disputes in Shanghai is a kind of "flexible governance" stressing affective care and multi-pronged means of dispute resolution to relieve petition pressures and maintain social stability in the authoritarian state. [ABSTRACT FROM AUTHOR]

Core-shell structures are of particular interest in the development of advanced composite materials as they can efficiently bring different components together at nanoscale. The advantage of this structure greatly relies on the crucial design of both core and shell, thus achieving an intercomponent synergistic effect. In this report, we show that decorating semiconductor nanocrystals with a boronate polymer shell can easily achieve programmable core-shell interactions. Taking ZnO and anatase TiO2 nanocrystals as inner core examples, the effective core-shell interactions can narrow the band gap of semiconductor nanocrystals, change the HOMO and LUMO levels of boronate polymer shell, and significantly improve the carrier density of core-shell particles. The hole mobility of core-shell particles can be improved by almost 9 orders of magnitude in comparison with net boronate polymer, while the conductivity of core-shell particles is at most 30-fold of nanocrystals. The particle engineering strategy is based on two driving forces: catechol-surface binding and B-N dative bonding and having a high ability to control and predict the shell thickness. Also, this approach is applicable to various inorganic nanoparticles with different components, sizes, and shapes. [ABSTRACT FROM AUTHOR]

Design, materials, and performance are important factors in the research of bone tissue scaffolds. This work briefly describes the bone scaffolds and their anatomic structure, as well as their biological and mechanical characteristics. Furthermore, we reviewed the characteristics of metal materials, inorganicmaterials, organic polymermaterials, and compositematerials. The importance of the bionic design in preoperative diagnosis models and customized bone scaffolds was also discussed, addressing both the bionic structure design (macro and micro structure) and the bionic performance design (mechanical performance and biological performance). Materials and performance are the two main problems in the development of customized bone scaffolds. Bionic design is an effective way to solve these problems, which could improve the clinical application of bone scaffolds, by creating a balance between mechanical performance and biological performance. Abstract: Design, materials, and performance are important factors in the research of bone tissue scaffolds. This work briefly describes the bone scaffolds and their anatomic structure, as well as their biological and mechanical characteristics. Furthermore, we reviewed the characteristics of metal materials, inorganic materials, organic polymer materials, and composite materials. The importance of the bionic design in preoperative diagnosis models and customized bone scaffolds was also discussed, addressing both the bionic structure design (macro and micro structure) and the bionic performance design (mechanical performance and biological performance). Materials and performance are the two main problems in the development of customized bone scaffolds. Bionic design is an effective way to solve these problems, which could improve the clinical application of bone scaffolds, by creating a balance between mechanical performance and biological performance. [ABSTRACT FROM AUTHOR]

The horizontal and vertical distributions of aerosol optical properties over China in 2013-2015 were investigated using RAMS (Regional Atmospheric Modeling System)-CMAQ (Models-3 Community Multiscale Air Quality) simulations and CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) observations. To better understand the performance of the RAMS-CMAQ model over China, comparisons with the ground-based Sun photometers AERONET (Aerosol Robotic Network), MODIS (Moderate Resolution Imaging Spectroradiometers) data and the on-board Lidar CALIOP were used for comprehensive evaluations, which could characterize the abilities of the model to simulate the spatial and vertical distributions of the AOD (Aerosol Optical Depth) as well as the optical properties for four seasons. Several high value areas (e.g., the Sichuan Basin, Taklamakan Desert, North China Plain, and Yangtze River Delta) were found over China during the study period, with the maximum mean AOD (CALIOP: ~0.7; RAMS-CMAQ: >1) in the Sichuan district. Compared with AODs of AERONET, both the CALIOP and RAMS-CMAQ AODs were underestimated, but the RAMS-CMAQ data show a better correlation with AERONET (AERONET vs. RAMS-CMAQ R: 0.69, AERONET vs. CALIOP R: 0.5). The correlation coefficients between RAMS-CMAQ and CALIOP are approximately 0.6 for all four seasons. The AEC (Aerosol Extinction Coefficient) vertical profiles over major cities and their cross sections exhibit two typical features: (1) most of the AEC peaks occurred in the lowest ~0.5 km, decreasing with increasing altitude; and (2) the RAMS-CMAQ AEC underestimated the region with high AODs in the northwest of China and overestimated the region with high AODs in the east-central plain and the central basin regions. The major difference in the AEC values of RAMS-CMAQ and CALIOP is mainly caused by the level of relative humidity and the hygroscopic growth effects of water-soluble aerosols, especially, in the Sichuan district. In general, both the column and vertical RAMS-CMAQ aerosol optical properties could be supplemented efficiently when satellite observations are not available or invalid over China in the applications of climate change and air pollution. [ABSTRACT FROM AUTHOR]

A newly emerged pseudorabies virus (PRV) variant has been identified in many Bartha-K61-vaccinated pig farms. This variant has caused great economic losses to the swine industry in China since 2011. Sequence analysis demonstrated that the gB gene of the emerging PRV variant JS-2012 had multiple variations compared with the vaccine strain Bartha-K61. In the study, a specific CRISPR/Cas9 system combined with homologous recombination was used to construct two recombinant viruses, BJB (Bartha-K61 + JS-2012gB) and JBJ (JS-2012-ΔgE/gI + Bartha-K61gB), by interchanging the full-length gB genes between Bartha-K61 and JS-2012-ΔgE/gI. The two recombinant viruses showed similar characteristics in growth kinetics in vitro and similar pathogenicity in mice, as compared to their parental strains. Immunization of mice with inactivated BJB or JBJ followed by challenge of JS-2012 showed that BJB could increase protective efficacy to 80%, compared to only 40% protection by the parental Bartha-K61 strain. JBJ had a decreased protective efficacy of 65%, as compared to 90% protection by its parental JS-2012-ΔgE/gI strain. Exchange of the gB gene markedly altered the immunogenicity of the recombinant PRV. These data suggest that variations in gB might play an important role in the virulence of the reemergent PRV variant in China. Our results demonstrate the importance of gB in protective immunity and suggest that the recombinant virus BJB could be a promising vaccine candidate for eradication of the PRV variant. [ABSTRACT FROM AUTHOR]

There is growing evidence that wildlife conservation measures have mixed effects on the emergence and spread of zoonotic disease. Wildlife conserva- tion has been found to have both positive (dilution) and negative (contagion) effects. In the case of avian influenza H5N1 in China, the focus has been on negative effects. Lakes and wetlands attracting migrating waterfowl have been argued to be disease hotspots. We consider the implications of water- fowl conservation for H5N1 infections in both poultry and humans between 2004 and 2012. We model both environmental and economic risk factors. Environmental risk factors comprise the conditions that structure interaction between wild and domesticated birds. Economic risk factors comprise the cost of disease, biosecurity measures and disease risk mitigation. We find that H5N1 outbreaks in poultry populations are indeed sensitive to the exist- ence of wild-domesticated bird mixing zones, but not in the way we would expect from the literature. We find that risk is decreasing in protected migratory bird habitat. Since the number of human cases is increasing in the number of poultry outbreaks, as expected, the implication is that the pro- tection of wetlands important for migratory birds offers unexpected human health benefits. This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'. [ABSTRACT FROM AUTHOR]

Studies in mice using resting-state functional magnetic resonance imaging (rs-fMRI) have provided opportunities to investigate the effects of pharmacological manipulations on brain function and map the phenotypes of mouse models of human brain disorders. Mouse rs-fMRI is typically performed under anaesthesia, which induces both regional suppression of brain activity and disruption of large-scale neural networks. Previous comparative studies using rodents investigating various drug effects on long-distance functional connectivity (FC) have reported agent-specific FC patterns, however, effects of regional suppression are sparsely explored. Here we examined changes in regional connectivity under six different anaesthesia conditions using mouse rs-fMRI with the goal of refining the framework of understanding the brain activation under anaesthesia at a local level. Regional homogeneity (ReHo) was used to map local synchronization in the brain, followed by analysis of several brain areas based on ReHo maps. The results revealed high local coherence in most brain areas. The primary somatosensory cortex and caudate-putamen showed agent-specific properties. Lower local coherence in the cingulate cortex was observed under medetomidine, particularly when compared to the combination of medetomidine and isoflurane. The thalamus was associated with retained local coherence across anaesthetic levels and multiple nuclei. These results show that anaesthesia induced by the investigated anaesthetics through different molecular targets promote agent-specific regional connectivity. In addition, ReHo is a data-driven method with minimum user interaction, easy to use and fast to compute. Given that examination of the brain at a local level is widely applied in human rs-fMRI studies, our results show its sensitivity to extract information on varied neuronal activity under six different regimens relevant to mouse functional imaging. These results, therefore, will inform future rs-fMRI studies on mice and the type of anaesthetic agent used, and will help to bridge observations between this burgeoning research field and ongoing human research across analytical scales. [ABSTRACT FROM AUTHOR]

We present a rigorous finite element method to calculate circular dichroism (CD) in various systems consisting of nanostructures and oriented chiral molecules with electric quadrupole transitions. The interaction between oriented molecule materials, which are regarded as anisotropic chiral media, and metallic nanostructures has been investigated. Our results show that the plasmon-induced CD is sensitive to the orientations of the molecules. In many cases, the contribution of molecular electric quadrupole transitions to the total CD signal can play a key role. More interesting, we have demonstrated that both the quadrupole- and dipole-based CD signals can be improved greatly by matching the phases for the electromagnetic fields and their gradients at different regions around the nanostructures, which are occupied by the oriented chiral molecules. Different regions might produce CD of opposite sign. When integrating over regions with only one side of the proposed nanostructure, we find that the CD peak may be nearly hundreds-fold over the case of integrating both sides. We believe that these findings would be helpful for realizing ultrasensitive probing of chiral information for oriented molecules by plasmon-based nanotechnology. [ABSTRACT FROM AUTHOR]

Based on a perturbative approach, we propose a simple and efficient method to engineer the topological edge states in two dimensional magnetic photonic crystals. The topological edge states in the microstructures can be constructed and varied by altering the parameters of the microstructure according to the field-energy distributions of the Bloch states at the related Bloch wave vectors. The validity of the proposed method has been demonstrated by exact numerical calculations through three concrete examples. Our method makes the topological edge states "designable." [ABSTRACT FROM AUTHOR]

Emerging pseudorabies virus (PRV) variant have led to pseudorabies outbreaks in Chinese pig farms. The commercially available PRV vaccine provides poor protection against the PRV variant. In this study, a gE/gI deleted PRV strain JS-2012-△gE/gI was generated from a PRV variant strain using homologous DNA recombination. Compared to the parental strain JS-2012, JS-2012-△gE/gI grew slowly and showed small plaque morphology on Vero cells. The safety and immunological efficacy of JS-2012-△gE/gI was evaluated as a vaccine candidate. JS-2012-△gE/gI was avirulent to suckling piglets, but was able to provide full protection for young piglets against challenge with both the classical virulent PRV and the emerging PRV variant. After sows were vaccinated with the gE/gI-deleted strain, their suckling offspring were resistant to an otherwise lethal challenge with the classical and the variant PRVs. Piglets inoculated with JS-2012-△gE/gI did not develop PRV-specific gE-ELISA antibodies. Thus, JS-2012-△gE/gI appears to be a promising marker vaccine candidate to control PRV variant circulating in pig farms in China. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus, a gram-positive pathogen, causes many human infections. Methicillin-resistant S. aureus (MRSA) is the most common drug-resistance bacteria. Nearly all MRSA bacteria are resistant to several drugs. Specific antibodies are the main components of the host's humoral immunity, and play a significant role in the process of the host's resistance to bacterial infection. Results: A single-chain variable fragment (scFv) library was constructed using mRNA from the peripheral blood mononuclear cells of S. aureus infected volunteers. After the scFv library DNA was transformed into Escherichia coli TG1, ~1.7 × 107 independent clones with full-length scFv inserts. The scFv library was screened by phage display for three rounds using S. aureus as an antigen. The single clones were chosen at random and the scFvs were expressed for enzyme-linked immunosorbent assay (ELISA) assessment. Approximately 50 % of the clones were positive with good binding activity to S. aureus. To improve the stability of scFvs, scFv-fragment crystallizable regions (-Fcs) were constructed and expressed in E. coli DH5α. The expressed scFv-Fcs were purified and identified by western blot. These antibodies were further characterized and analyzed for bioactivity. The results showed that the expression level and folding of scFv-Fcs induced at 25 °C without isopropyl β-D-1-thiogalactopyranoside (IPTG) were higher than that induced at 32 °C with 1.0 mmol/L IPTG. scFv-Fcs had good bioactivity and could specifically bind with S. aureus. Conclusion: scFv-Fcs against S. aureus were successfully constructed and are good candidates for the development of future adjunctive therapy for severe S. aureus infections. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the expression of legumain in uveal melanoma (UM) cell lines and primary UM specimens, and to determine the possible association between legumain expression and clinical as well as pathological characteristics to reveal its impact on the prognosis of patients with UM. Records of primary UM cases treated at Beijing Tongren Hospital and Tianjin Eye Hospital between 1996 and 2005 were retrieved for analysis and a total of 82 patients with uveal melanoma were included in the study. The expression of legumain in the formalin-fixed and paraffin-embedded surgical specimens of these 82 patients was determined using immunohistochemical analysis. In addition, the expression of legumain was examined in two uveal melanoma cell lines using polymerase chain reaction and western blot analyses. The association of legumain expression with clinical/pathological characteristics was analyzed using the X2 and Fisher's exact test. In addition, the impact of legumain on the prognosis of patients with uveal melanoma was examined. Upregulation of legumain was more predominant in the highly invasive uveal melanoma cell line MUM-2B compared with that in the MUM-2C with low invasiveness. Of 82 primary uveal melanoma tissues, 35 exhibited high expression of legumain, while the other 47 specimens exhibited low or negative expression of legumain. High legumain expression was primarily associated with local invasion of UM. Overall survival analysis revealed that the patients with high legumain expression exhibited poorer survival than patients with low/negative legumain expression. These findings suggested that upregulation of legumain is associated with malignant behavior of UM and that legumain may be used as an negative prognostic factor as well as a therapeutic target. [ABSTRACT FROM AUTHOR]

Objective: To explore the electroencephalogram (EEG) characteristics in patients with chronic fatigue syndrome (CFS) using brain electrical activity mapping (BEAM) and EEG nonlinear dynamical analysis. Methods: Forty-seven outpatients were selected over a 3-month period and divided into an observation group (24 outpatients) and a control group (23 outpatients) by using the non-probability sampling method. All the patients were given a routine EEG. The BEAM and the correlation dimension changes were analyzed to characterize the EEG features. Results: 1) BEAM results indicated that the energy values of δ, θ, and α1 waves significantly increased in the observation group, compared with the control group (P<0.05, P<0.01, respectively), which suggests that the brain electrical activities in CFS patients were significantly reduced and stayed in an inhibitory state; 2) the increase of δ, θ, and α1 energy values in the right frontal and left occipital regions was more significant than other encephalic regions in CFS patients, indicating the region-specific encephalic distribution; 3) the correlation dimension in the observation group was significantly lower than the control group, suggesting decreased EEG complexity in CFS patients. Conclusion: The spontaneous brain electrical activities in CFS patients were significantly reduced. The abnormal changes in the cerebral functions were localized at the right frontal and left occipital regions in CFS patients. [ABSTRACT FROM AUTHOR]

Pseudorabies virus (PRV) causes Pseudorabies (PR), an economically important disease in domestic swine. PR outbreaks on pig farms caused by PRV variant strains in Bartha-K61-vaccinated pigs have resulted in considerable economic losses in China since 2011. In this study, the pathogenicity of the PRV variant JS-2012 strain to pigs was investigated by experimentally inoculating piglets of different ages in comparison with a classic virulent PRV SC strain. The JS-2012 strain caused an earlier onset of clinical signs and higher mortality in 15, 30, and 60-day-old pigs, as compared with a classic virulent PRV SC strain. The Bartha-K61 vaccination provided complete protection against challenge with classical virulent PRV, but only partial protection against challenge with the JS-2012 strain in piglets. In conclusion, the increased virulence of the PRV variant may have partly contributed to the PR outbreak in China. [ABSTRACT FROM AUTHOR]

Organometallic macrocycles based on bridge ligands with terminal imidazole groups show the formation of various patterns. The end imidazolyl finishes the conjugated system on the back bone and can freely twist or rotate just like the joints of a human body such as the knee and wrist. [ABSTRACT FROM AUTHOR]

Background: Recent global genomic analyses identified 69 gene sets and 12 core signaling pathways genetically altered in pancreatic cancer, which is a highly malignant disease. A comprehensive understanding of the genetic signatures and signaling pathways that are directly correlated to pancreatic cancer survival will help cancer researchers to develop effective multi-gene targeted, personalized therapies for the pancreatic cancer patients at different stages. A previous work that applied a LASSO penalized regression method, which only considered individual genetic effects, identified 12 genes associated with pancreatic cancer survival. Results: In this work, we integrate pathway information into pancreatic cancer survival analysis. We introduce and apply a doubly regularized Cox regression model to identify both genes and signaling pathways related to pancreatic cancer survival. Conclusions: Four signaling pathways, including Ion transport, immune phagocytosis, TGFβ (spermatogenesis), regulation of DNA-dependent transcription pathways, and 15 genes within the four pathways are identified and verified to be directly correlated to pancreatic cancer survival. Our findings can help cancer researchers design new strategies for the early detection and diagnosis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Osteoblast proliferation and osteogenic differentiation (OGD) are regulated by complex mechanisms. The roles in cell proliferation and OGD of RNA‐binding proteins in the insulin‐like growth factor 2 mRNA‐binding protein (IGF2BP) family remain unclear. To elucidate this, we examined the differential expression of IGF2BP2 in OGD and osteoporosis, and the expression profile of IGF2BP2‐binding RNA in vitro. We screened the GEO database for differential expression of IGF2BP in OGD and osteoporosis, and verified the RNAs interacting with IGF2BP2 via RNA immunoprecipitation sequencing assays. The proliferation and OGD of IGF2BP2‐ and serum response factor (SRF)‐treated cells, and their regulatory mechanisms, were examined. IGF2BP2 was differentially expressed in OGD and osteoporosis. The RNA immunoprecipitation sequencing assay identified all of the RNAs that bind with IGF2BP2, and revealed SRF as a target of IGF2BP2. IGF2BP2 and SRF inhibition impaired MC3T3‐E1 cell growth but promoted OGD. The mRNA stability analysis revealed that IGF2BP2 enhanced SRF mRNA stability against degradation. In summary, IGF2BP2 is a potential biomarker and therapeutic target for osteoporosis and OGD. [ABSTRACT FROM AUTHOR]

Highly pathogenic porcine reproductive and respiratory syndrome virus PRRSV (HP-PRRSV) was one of the most devastating diseases of the pig industry, among various strategies, vaccination was one of the most useful tools for PRRS control. Attenuated live vaccine was used worldwide, however, the genetic basis of HP-PRRSV virulence change during attenuation remain to be determined. Here, to identify virulence associated regions of HP-PRRSV during attenuation in vitro, six full-length infectious cDNA clones with interchanges of 5′UTR + ORF1a, ORF1b, and ORF2-7 + 3′UTR regions between HP-PRRSV strain HuN4-F5 and its attenuated vaccine strain HuN4-F112 were generated, and chimeric viruses were rescued. Piglets were inoculated with chimeric viruses and their parental viruses, and rectal temperature were recorded daily, and serum were collected for future experiments. Our results showed that ORF1a played an important role on virus replication, cytokine response and lung damage, the exchange of ORF1b and ORF2-7 in different backbone led to different exhibition on virus replication in vivo/vitro and cytokine response. Among 9 PRRSV attenuated series, consistent amino acid changes during PRRSV attenuation were found in NSP4, NSP9, GP2, E, GP3 and GP4. Our study provides a fundamental data for the investigation of PRRSV attenuation, the different results of the virulence change among different studies indicated that different mechanisms might be used during PRRSV virulence enhancement in vivo and attenuation in vitro. [ABSTRACT FROM AUTHOR]

Carbon materials have become a focal point in supercapacitors (SCs) due to their perfect charge–discharge behavior, relatively low cost, and excellent electrochemical stability, but the limited electrochemical activity restricts their further development. MXenes (Ti3C2Tx) combine high electrical conductivity, hydrophilicity, and abundance surface functional groups, which contribute to high energy density when compounded with carbon materials. In this work, carbon material derived from mineral water bottles is modified with cetyltrimethylammonium bromide (CTAB) that spontaneously forms into porous heterogeneous structures with Ti3C2Tx under electrostatic interactions. The carbon material hinders the reaggregation of Ti3C2Tx, while Ti3C2Tx increases the electrochemical activity on the surface of the carbon material. A hierarchical porous carbon with a large specific surface area of 1754.3 m2 g−1, promoting the electrolyte migration kinetics and high specific capacitance in 6 m KOH electrolyte (404.1 F g−1 at 1 A g−1). The symmetric SC made as‐prepared carbon electrode shows an extended voltage window (1.8 V), an optimal energy density (31.19 Wh kg−1 at a power density of 450 W kg−1) and a low capacitance decay (1% after 15 000 cycles) in 1.5 m Na2SO4. The preparation of electrode material with a unique structure provides a practical and innovative strategy for the value‐added utilization of waste plastics. [ABSTRACT FROM AUTHOR]

Polycomb repressive complex 2 (PRC2)-mediated histone H3 lysine 27 (H3K27) methylation is vital for Polycomb gene silencing, a classic epigenetic phenomenon that maintains transcriptional silencing throughout cell divisions. We report that PRC2 activity is regulated by the density of its substrate nucleosome arrays. Neighboring nucleosomes activate the PRC2 complex with a fragment of their H3 histones (Ala31 to Arg42). We also identified mutations on PRC2 subunit Su(z)12, which impair its binding and response to the activating peptide and its ability in establishing H3K27 trimethylation levels in vivo. In mouse embryonic stem cells, local chromatin compaction occurs before the formation of trimethylated H3K27 upon transcription cessation of the retinoic acid-regulated gene CYP26a1. We propose that PRC2 can sense the chromatin environment to exert its role in the maintenance of transcriptional states. [ABSTRACT FROM AUTHOR]

Background: Since progressive intracranial haemorrhage (PIH) was introduced in neurosurgical literatures, several studies have been performed. PIH has been shown to be associated with a high increase in the risk of clinical worsening and related to morbidity and mortality as well. So, early detection and prediction of PIH is practically important in a clinical situation. Objectves: To investigate the risk factors related to PIH in patients with acute traumatic brain injury (TBI) and analyse their clinical significances. Methods: PIH was confirmed by comparing the first and repeated CT scans. Data compared included gender, age, mechanism of injury, Glasgow Coma Score (GCS) at admission, timing from injury to the first CT, the signs of the initial CT scan, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fg), thrombin time (TT), platelet (PLT) and D-dimer (D-D) values. Logistic regression analysis was used to show the risk factors related to PIH. Results: A cohort of 498 patients with TBI was evaluated, and there were 139 (27.91%) patients who suffered from PIH. The differences between PIHs and non-PIHs were significant in age, GCS at admission, the signs of the initial CT scan (fracture, subarachnoid haemorrhage, brain contusion and primary haematoma), PT, Fg and D-D values ( p < 0.001). Logistic regression analysis was used to identify that CT scans (subarachnoid haemorrhage, brain contusion and primary haematoma) and plasma D-D values as the most important predictors of PIH ( p < 0.001). Conclusions: For patients with the initial CT scan showing subarachnoid haemorrhage, brain contusion and primary haematoma with abnormal D-D levels, an earlier and dynamic CT scan should be performed, for the detection of PIH as early as possible and the medical intervention would be enforced in time. [ABSTRACT FROM AUTHOR]

Introduction: Since progressive hemorrhagic injury (PHI) was introduced in neurosurgical literatures, several studies have been performed, the results of which have influenced doctors but do not define guidelines for the best treatment of PHI. PHI may be confirmed by a serial computerized tomography (CT) scan, and it has been shown to be associated with a fivefold increase in the risk of clinical worsening and is a significant cause of morbidity and mortality as well. So, early detection of PHI is practically important in a clinical situation. Methods: To analyze the early CT signs of progressive hemorrhagic injury following acute traumatic brain injury (TBI) and explore their clinical significances, PHI was confirmed by comparing the first and repeated CT scans. Data were analyzed and compared including times from injury to the first CT and signs of the early CT scan. Logistic regression analysis was used to show the risk factors related to PHI. Results: A cohort of 630 TBI patients was evaluated, and there were 189 (30%) patients who suffered from PHI. For patients with their first CT scan obtained as early as 2 h post-injury, there were 116 (77.25%) cases who suffered from PHI. The differences between PHIs and non-PHIs were significant in the initial CT scans showing fracture, subarachnoid hemorrhage (SAH), brain contusion, epidural hematoma (EDH), subdural hematoma (SDH), and multiple hematoma as well as the times from injury to the first CT scan ( P < 0.01). Logistic regression analysis showed that early CT scans (EDH, SDH, SAH, fracture, and brain contusion) were predictors of PHI ( P < 0.01). Conclusion: For patients with the first CT scan obtained as early as 2 h post-injury, a follow-up CT scan should be performed promptly. If the initial CT scan shows SAH, brain contusion, and primary hematoma with brain swelling, an earlier and dynamic CT scan should be performed for detection of PHI as early as possible and the medical intervention would be enforced in time. [ABSTRACT FROM AUTHOR]

The protein kinase Akt (also known as protein kinase B) is a critical signaling hub downstream of various cellular stimuli such as growth factors that control cell survival, growth, and proliferation. The activity of Akt is tightly regulated, and the aberrant activation of Akt is associated with diverse human diseases including cancer. Although it is well documented that the mammalian target of rapamycin complex 2 (mTORC2)-dependent phosphorylation of the Akt hydrophobic motif (Ser-473 in Akt1) is essential for full Akt activation, it remains unclear whether this phosphorylation has additional roles in regulating Akt activity. In this study, we found that abolishing Akt Ser-473 phosphorylation stabilizes Akt following agonist stimulation. The Akt Ser-473 phosphorylation promotes a Lys-48-linked polyubiquitination of Akt, resulting in its rapid proteasomal degradation. Moreover, blockade of this proteasomal degradation pathway prolongs agonist-induced Akt activation. These data reveal that mTORC2 plays a central role in regulating the Akt protein life cycle by first stabilizing Akt protein folding through the turn motif phosphorylation and then by promoting Akt protein degradation through the hydrophobic motif phosphorylation. Taken together, this study reveals that the Akt Ser-473 phosphorylation-dependent ubiquitination and degradation is an important negative feedback regulation that specifically terminates Akt activation. [ABSTRACT FROM AUTHOR]

S-8300, a small (8200.901 Da) antidiabetic peptide, was purified and characterized from shark livers (Chiloscyllium plagiosum ). It was isolated by extraction of the water-soluble fraction, dialysis, ultrafiltration and dicthylaminoethyl Sepharose, Bio-Gel P-10 and fast protein liquid chromatography monoQ chromatography. The new peptide (S-8300) contained 17 amino acids and the 15 N-terminal amino acid residues of S-8300 were NH2-Met-Leu-Val-Gly-Pro-Ile-Gly-Ala-Ala-Lys-Val-Val-Tyr-Glu-Gln-. The new peptide was stable at 95C for 30 min and stable between pH 3.0 and 9.0. It was not inactivated by DNase and RNase, but totally inactivated by trypsin and proteinase K digestion. In addition, S-8300 could remarkably protect the structure integrity and recover the damage of NIT-1 cell after exposure to the toxin of streptozotocin. Homology search of NH2-terminal sequence showed that S-8300 was a totally new protein. PRACTICAL APPLICATIONS The experiments suggested that S-8300 could reduce the adverse effect of β-cell toxins and protect the structure integrity and mitigate the damage. S-8300 could markedly decrease the level of fasting plasma glucose, glycohemoglobin-A1, triglyceride, cholesterol, free fatty acid and malondialdehyde, increased the activity of superoxide dismutase and attenuated the injury of β-cell in pancreatic islet. Therefore, S-8300 has a significant protective effect on diabetes in mice. These might indicate that S-8300 could have clinical therapy significance. [ABSTRACT FROM AUTHOR]