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Five undescribed indole alkaloids, fusarindoles A-E, together with seven known compounds were obtained from the marine-derived fungus Fusarium equiseti LJ-1. Their chemical structures and absolute configurations were determined by comprehensive analysis of the NMR, HRMS, UV, IR, ECD calculation and single-crystal X-ray diffraction data. The possible biosynthetic pathways of fusarindoles C-E were proposed. The cytotoxicities of eleven compounds, including fusarindoles A-E and six known compounds, against five human cancer cell lines A549, CNE2, SUNE1, HepG2 and QGY7701 were evaluated.

Anemoside B4 (AB4) is reported to prevent acute colitis when given via intraperitoneal injection by two recent studies. However, whether oral AB4 protects against chronic colitis which resembles the clinical phenotype of ulcerative colitis (UC) and its mechanism of action are largely unknown.To systemically investigate the effects of oral AB4 against chronic colitis and illustrate the underlying mechanism of action.The preventive, therapeutic, and dose-dependent effects of AB4 against UC were examined in mice with acute or chronic relapsing colitis induced by dextran sulfate sodium (DSS). The inflammatory responses, colonic transcriptome, and 16S rDNA sequencing of the intestinal content of mice were analyzed.Oral administration of AB4 alleviated disease severity and colon shortening in mice with chronic relapsing colitis in a dose-dependent manner. The effects of AB4 were comparable to those of two positive-control compounds: tofacitinib and berberine. Unlike tofacitinib, AB4 did not have a deleterious effect on DSS-induced splenic swelling and anemia. Furthermore, AB4 inhibited the inflammatory responses of colitis, as evidenced by in-vivo, ex-vivo, and in-vitro studies. Transcriptomics revealed that AB4 treatment reversed the DSS-mediated decrease in the expression of colonic Pelo, B3gat2 and Mir8010. In addition, AB4 reversed DSS-induced alterations in the intestinal microbiome in mice. Through fecal microbiota transplantation, we proved that AB4 partially exerted its anti-colitis effects by modulating the gut microbiota.We demonstrated for the first time that AB4 has dose-dependent therapeutic effects against chronic relapsing colitis by modulating the inflammatory response, colonic gene expression, and intestinal microbiota.

A biopolymer-inorganic hybrid system (MSN@PBLGF) is designed and fabricated from mesoporous silica nanoparticles (MSNs) and folic acid (FA)-terminated temperature-sensitive synthetic polypeptide, i.e., poly(γ-benzyl- l -glutamate) (PBLG) derivative, through a thiol-disulfide exchange reaction, where MSNs with high drug loading capacity serve as drug nanocarriers and the biocompatible PBLG biopolymer brushes installed on MSN surface through disulfide bonds endow the system with tumor-specific recognition ability and GSH/temperature dual-stimuli responsiveness. Controlled drug release experiments indicate that DOX can be tightly hosted in the system with limited premature release, but efficiently released in response to an increased concentration of GSH and/or an elevated temperature. Intracellular experiments demonstrate that the DOX-loaded MSN@PBLGF nanohybrid shows outstanding cellular uptake and cell-growth inhibition effects on human lung cancer cell line A549 in comparison with healthy human cells such as hepatocyte cells LO2.

Single cone bit is frequently used in slim-hole drilling field. To solve the problems of the spherical single cone bit during drilling process, a new type of single cone bit is designed, and field test is carried out. In this paper, the statistical analysis of tooth wear is done, and the causes of cutting tooth wear and protects radial tooth eccentric wear are analyzed in detail. In order to figure out the causes of tooth failure, the tooth load of non-spherical single cone bit was measured by experiment method and the change regularity of tooth load was statistically analyzed. The results show that the axial load is greater than the tangential load and radial load during drilling process. The axial load increase is more obvious with increase of weight on bit (WOB), but the tangential load and radial load change less. With increase of axle tilt angle of bit axis, the axial load and tangential load is reduced at the end of cone, but the radial load is increase. However, the axial load, tangential load and radial load of other's tooth is increase with increase of axle tilt angle of bit axis. The experiment results explained the cause of tooth wear, and it was important to understand the mechanism of tooth wear, optimize the structure parameters of bit, and understand the movement of bit in the well.

For an integral self-affine spectral measure, if the zeros of its Fourier transform are all integral vectors, it is proven that any its spectrum has a tree structure. For any subset with such tree structure, a sufficient condition and a necessary condition for the subset to be a spectrum are given, respectively. Applications are given to some known results as special cases.

Even with a long lifetime of 25–30 years of green energy production, end-of-life treatment of solar photovoltaic modules can negatively impact the environment if not handled properly. This is particularly urgent when the use of photovoltaics has grown at an unprecedented rate, generating clean energy all over the world. Therefore, it is essential to develop commercially viable end-of-life recycling technologies to guarantee a sustainable future for the photovoltaic technology. Silicon photovoltaic modules, the most popular photovoltaic technology, have been shown to be economically unattractive for recycling - the materials are mixed and difficult to separate, and have low value, so that the cost of recycling is hardly recovered. In this paper, we review the state-of-art recycling technology and associate it with a quantitative economic assessment to breakdown the cost structure and better understand the presented economic barrier. The techno-economic review allows us to identify essential framework and technology changes required to overcome the current barrier to implementing commercial-scale recycling. (i) The authority may impose price signal to impress direct landfill of end-of-life modules while proactively establish an effective collection network. (ii) The local recyclers may aim at value recovery as a step beyond mass recovery, especially targeting at recovery of intact silicon wafers and silver to guarantee the recycling revenue. Meanwhile, efforts should be put on reducing the recycling processing cost. (iii) Photovoltaic module manufacturers may take end-of-life responsibilities and up-design the product to facilitate end-of-life recycling, which includes features for simple disassembly, recycling, and reducing or eliminating the use of toxic components.

Two strategies for the design of new pillar[5]arene-based mechanically self-interlocked molecules (MSMs) are reported here. The first strategy is based on the construction of an intermediate pseudo[1]rotaxane followed by the desired bis-[1]rotaxane. The other one is based on the construction of the desired bis-[1]rotaxane directly via a condensation reaction through host-guest interactions between a mono-functionalized pillar[5]arene and the axle. The newly synthesized bis-[1]rotaxane BR was characterized by 1H NMR, 13C NMR, 2D NMRs (1H-13C HSQC, 1H-1H COSY and NOESY) and LC-ESI-MS, which indicated compound BR displayed an self-interlocked structure in CDCl3. Surprisingly, the results of SEM, TEM and DLS showed that the compound BR could assemble into spherical nanoparticles in MeOH.

Anemoside B4 (AB4) is a representative component of Pulsatilla decoction that is used in traditional Chinese medicine for treating inflammatory conditions. It is not known whether AB4 has beneficial effects on multiple sclerosis (MS).In the present study, we examined the preventative and therapeutic effects of AB4, and the possible mechanism by which it protects female mice against experimental autoimmune encephalomyelitis (EAE).Preventative treatment with AB4 (given orally at 100 and 200 mg/kg for 18 days) reduced the clinical severity of EAE significantly (from 3.6 ± 1.3 to 1.8 ± 1.5 and 1.6 ± 0.6, respectively), and inhibited demyelination and inflammatory infiltration of the spinal cord. In the therapeutic protocol, oral administration of 200 mg/kg AB4 for 21 days after initiation of EAE significantly alleviated disease severity (from 2.6 ± 1.3 to 0.9 ± 0.6) and was as effective as the clinically used drug fingolimod (0.3 ± 0.6). Furthermore, both doses of AB4 significantly inhibited mRNA expression of TNF-α, IL-6, and IL-17, and STAT3 activation, in the spinal cord; and the ex vivo and iv vitro AB4 treatment markedly inhibited secretion of the three cytokines from lymphocytes of EAE mice upon in vitro restimulation. In addition, AB4 reversed the changes in the composition of the intestinal microbiome observed in EAE mice.We reveal for the first time that AB4 protects against EAE by modulating inflammatory responses and the gut microbiota, demonstrating that AB4 may have potential as a therapeutic agent for treating MS in humans.

Background Coronavirus disease 2019 (COVID-19) is a public health emergency of international concern and has caused traumatic experience for nurses worldwide. However, the prevalence of depression and anxiety symptoms in nurses, and how psychosocial factors influence nurses in this public crisis are unknown. Objectives To determine the effect of COVID-19 on the mental health of nurses and the prevalence of anxiety and depression symptoms among nurses in China during the outbreak. Design A cross-sectional study. Settings and participants A total of 3,228 nurses in Sichuan Province and Wuhan City were selected by convenience sampling. All participants were invited to complete the questionnaire through WeChat from January 27 to February 3, 2020. Methods A self-reported questionnaire combining depression and anxiety scale was used to collect data anonymously. Binary and multivariate logistic regression was applied to measure the odds of psychosocial factors of anxiety and depression and perceived health, respectively. Results The total incidence of depression (34.3%) and anxiety (18.1%) during the COVID-19 outbreak was lower than that during the SARS outbreak; however, the rate of depression in our study (47.1%) was high and similar in a recent study (50.4%) about the health care workers exposed to COVID-19 in China. The results indicated that COVID-19-related stress, relationship quality with family, and demographic characteristics were associated with depression, anxiety, and perceived health status. Furthermore, the prevalence of depression was similar between nurses working in low-risk COVID-19 wards was as high as working in high-risk COVID-19 wards (OR, 1.078; 95% CI, 0.784–1.481). Conclusions Our study revealed the high prevalence of depression and anxiety among nurses during the outbreak of COVID-19. COVID-19 factors and psychosocial factors were associated with mental health of nurses. The results suggest that hospitals should implement effective mental health promotion programs focused on occupational safety and family support to improve the well-being of nurses.

Interleukin-2 (IL-2) benefits some cancer patients by promoting the proliferation of cytotoxic effector T cells, but this process is limited by the expansion of regulatory T cells (Tregs). Low-dose cyclophosphamide (CTX) can inhibit the number and function of Tregs. We treated carcinoma-bearing mice with Vehicle, CTX, IL-2 and CTX + IL-2 to investigate the effects of low-dose CTX combined with IL-2 in antitumor treatment. In comparison to monotherapy, CTX + IL-2 significantly limited tumor growth, via tumor cell proliferation inhibition and increased apoptosis. The infiltration of CD8

The global need for improved fuels has promoted the development of the renewable photovoltaic industry. However, a significant amount of diamond wire saw silicon powder (DWSSP, ∼300,000 t/a) is produced during the process of solar cell manufacturing. Thus, there is a significant need for strategies to recycle and utilize DWSSP for increased sustainability and protection of the environment. Here, nano-porous silicon composites materials derived from silicon cutting waste were used to fabricate lithium-ion anodes with high capacity and stable cycling performance. DWSSP was chemically crushed using nano-copper-assisted etching. Next, porous silicon/Ag composites (PSi/Ag) were prepared by nano-silver-assisted etching, using dopamine as a source of organic for surface coating. Carbon-coated porous silicon/Ag nanocomposites (PSi/Ag/C) exhibited excellent cycling performance with retained discharge capacity of 1092.9 mAh g-1 after 300 cycles at 1000 mA/g, with a capacity retention rate of 80%. These results indicate that PSi/Ag/C from DWSSP can be used to prepare functional lithium-ion battery anodes. This work describes the high-value utilization of an abundant waste material produced in the solar industry and provides an effective strategy to produce porous materials for energy storage.

In this paper, a necessary and sufficient condition for a class of Moran-type self-similar measures with consecutive digits to be spectral is given, which partially answers Lai and Wang's conjecture in [16] .

Plating has long been recognized as a promising alternative to screen printing in commercial PV metallization due to its cost-saving and scaling-up potential. In this paper, we investigated the laser doping effects on plated contact formation. Critical parameters, such as laser power, focal position, and scanning speed, have been systematically analyzed by comparing their impacts on surface morphology, electrical properties, and plating results. Moreover, it was found the LD openings made by different laser resources would need different plating strategies. We have also successfully developed a baseline procedure integrating laser doping and hydrogenation passivation for bifacial plated PERC solar cells. Despite severe technical challenges in experimental conditions, up to 20.4% cell efficiency has been achieved, which evidentially demonstrates the commercial potential of plated contacts.

The non-spherical single cone bit is a new type of cone bit designed on the basis of the spherical single cone bit; the new cone bit performs rock breaking by shocking and scraping to achieve a good effect on hard strata. Mechanics analysis is performed, and the kinetic equations are established in the drilling process to study the law of rock breaking of the bit. The tooth load of the bit, which is linked to the bit dynamic equation, is tested using a full-scale drilling test bench for different weight on bit (WOB) and rock. The test results demonstrate that the tooth is most easily damaged when the end of cone tooth-row tooth has the highest peak load. Axial force is greater than the tangential force and the radial force on the same tooth. The tooth load increases approximately linearly with the WOB increasing. The tooth load when drilling into sandstone is lower than that when drilling into limestone under the same WOB. In the process of the tooth rock breaking, the directions of the axial force and the tangential force remain constant, whereas the radial force direction changes. The study not only deepens the understanding of the rock breaking mechanism of a non-spherical single cone bit but also offers some guidance on the design of the bit.

Leukemia remains a fatal disease for most patients and novel therapeutic strategies are urgently needed. Aberrant DNA methylation is an epigenetic modification that is important in the initiation and progression of leukemia. Here, we demonstrated NCL/miR-221/NFκB/DNMT1 axis as a new molecular pathway promoting aggressive acute myeloid leukemia (AML) leukemogenesis and successfully designed and prepared a nuclear localization signal (NLS) peptide-targeted gold nanoparticles with co-loaded anti-221 and AS1411 (NPsN-AS1411/a221), which can specifically target NCL/miR-221/NFκB/DNMT1 signaling pathway in AML. NPsN-AS1411/a221 synergistically abrogate endogenous miR-221 promoting cancerous growth by inhibiting the expression of p27Kip1 suppressor gene, as well as effectively deregulate the DNMT1 expression through NFκB signaling which led to a reduction of global DNA methylation and the restoration of tumor suppressor p15INK4B via its promoter DNA hypomethylation. Functionally, NPsN-AS1411/a221 remarkably blockage leukemia proliferation and clonogenic potential in NCL/miR-221/NFκB/DNMT1 positive AML cell lines. More importantly, NPsN-AS1411/a221 cooperatively extend the overall survival, lower the white blood cells, reverse splenomegaly, inhibit blasts in bone marrow and metastatic to lung in a preclinical AML animal model. Altogether, our studies provide a proof of concept for multiple-functional drug delivery system that based on the specific gene network involved in tumor growth, and highlight the clinical potential of NCL/miR-221/NFκB/DNMT1-targeted AML nanotherapy.

The expression levels of glycans on the surfaces of cancer and normal cells show different, however, this difference is not noticeable enough to distinguish them directly. So, herein, based on the targeted molecular recognition of the glycans on cell surfaces by 4-mercaptophenyl boronic acid (MPBA), a novel surface-enhanced Raman scattering (SERS) nanoprobe (glucose-MPBA@AgNPs) was prepared by inducing controllable assembly of MPBA decorated Ag nanoparticles (MPBA@AgNPs) in a certain level via the bridge of glucose to amplify such a limited difference in SERS measurements. On the basis of the aggregation-induced 3D SERS hot spot effect, this multi-particle nanoprobe possesses over 10 times stronger SERS enhancement ability than the individual MPBA@AgNPs. As the different sialic acid (SA) expression on the surfaces of cancer and normal cells led to the different accumulation of glucose-MPBA@AgNPs, the results we obtained (mean intensities recorded from five cells) indicate the SA amounts on two kinds of cells can provide 5-7 times signal contrast grade in SERS band intensities (P < 0.001). Compared with the monodispersed nanoprobe, our developed nanoprobe amplifies the SA expression difference on cell surfaces and supports high sensitivity for cancer cell recognition, which might be useful in providing highly effective recognition of the edges of tumor tissues in clinic field.

The morphology, size and surface roughness of the nucleating agent significantly affect the nucleation effect for foaming in the polymer. In this work, four nucleating agents with different morphologies, namely DE, MS, OMMT and β- CD as heterogeneous nucleation agents were selected for a polypropylene (PP) foaming injection molding process to explore nucleation mechanism. A theoretical assumption (cavity nucleation) in polymer foaming had been put forward about how to enhance the efficiency of bubble nucleation based on classical nucleation theory (CNT). Subsequently, the cavity nucleation was validated by chemical core-back injection foaming molding and in-situ visualization and elaborated by establishing a formula. Finally, designed petals shape particles as nucleating agents to further test this theory. The confirmation of this theory effectively improved the nucleation efficiency and foaming quality, which has important guiding significance to the development of lightweight products.

Single-cone bit are an important tool for slim-hole drilling. In view of the problems of drilling with a spherical single-cone bit, a new non-spherical single-cone bit is designed that breaks rock by impacting and scraping. The field experiment test show that the tooth at the small end of the cone was severely worn, and the tooth at the large end of the cone was minimally worn. To determine the cause of the eccentric bit wear, the tooth breaking rock was simulated using the finite element method. The tooth load, the cutting trajectory shape of each tooth, and the contact time between the tooth and rock were analysed. The theoretical model of tooth wear calculation was derived and compared with experimental results. The results showed that the tooth load at the large end of the cone was greater than the tooth load at the small end of the cone, but the contact time at the small end of the cone was longer. The field test results showed that the No. 6 tooth wear was small, and No.1, No.4 and No.5 was smaller. The No.3 tooth was the most severely worn. The results from theoretical model were consistent with the field test results indicating that the tooth wear theory formula can predict tooth wear.

Sialoglycan expression is critical for assessing various diseases progression. Especially, its abnormal levels are commonly believed to be associated with tumor and metastatic cancer types. While, complicated structures, multiple types and dynamic distributions make it challenging for in situ investigating sialoglycans at the physiological status. Herein, we developed a 4-mercaptophenylboronic acid (MPBA)-based surface-enhanced Raman scattering (SERS) nanosensor to in situ study sialoglycan levels and dynamic expression processes of different cell types based on molecular recognition between phenylboronic acid and sialoglycans at physiological condition. This nanosensor is designed by the MPBA decorated silver nanoparticle (AgNP), which is unique and multifunctional because of its three-in-one role involving the Raman signal enhancer (AgNP), the sensing reporter of MPBA and the target receptor based on the recognition of phenylboronic acid and sialoglycans. When this nanosensor binds to sialoglycans, the molecular vibrational modes of MPBA will change, which can be traced by ultrasensitive SERS technique. The superiority of this study is that we built the relation between the spectral changes of MPBA (relative intensities) in molecular recognition with the sialoglycan dynamic expression of cells. We believe that our SERS strategy could be further extended to explore crucial physiological processes and significant biological system that glycans are involved in.

Both experiments and numerical simulations of the mixing and discharging processes of two-sized particles in a truck mixer were carried out. The discharged particles were divided into 10 groups of samples with same weight. By comparing the big particle content (BPC) in discharged samples and the discharging time, the presented discrete element method (DEM) model was validated first. Then, DEM simulations were further performed to investigate quantitatively the transition of axial segregation and the distribution of the BPC in the 10 discharged samples which is almost impossible by conventional physical experiments of state-of-art. In the numerical analysis of axial segregation transition, the mixed particles are also divided into 10 groups of samples with same weight according to their x positions. Numerical results reveal that the size difference of particles and the structure of the drum cause the occurrence and transition of axial segregation during the mixing process. Small particles readily fill in among the big particle clusters or the similarly size gap more easily, thus the small particles force the big particles out from the drum bottom, ultimately facilitating the axial segregation occurs and band of small particles is observed at the drum bottom (Sample 10) and widen to Sample 9 as mixing. The big particles being crowed out gradually move toward drum mouth causing the increase of BPC in other samples. During the mixing process, the relative movements are positively associated with the axial segregation: the stronger the relative moments are, the larger the speed and extent of the axial segregation are; the speed of total axial segregation decreases as mixing progresses, but the degree of axial segregation increases. The discharging process can somehow restrain and improve the axial segregation of the discharged samples. The falling back and feeding forward movements of the big particles make the BPC in discharged Samples 1 to 5 almost be consistent with the relevant mixed samples, whereas the BPC in discharged Samples 6 to 8 decreases and discharged Samples 9 and 10 increases. The transition of axial segregation during the mixing and discharging processes determines the BPC distribution in discharged samples following a parabola law.

The mixing processes of equal-sized acrylonitrile butadiene Styrene copolymers beads in a rotating drum were simulated using the Discrete Element Method (DEM) at different rotational speeds and filling degrees. The contacting parameters of the DEM models were determined by a series of experiments including high rebound test, friction and wear test, stacking angle test and L-box test. The validity of the DEM simulations was confirmed by comparing the numerical results with the experimental ones. Quantitative criteria of particles mixing performance which is characterized by the mixing degree and mixing time were proposed based on the mathematical statistical analysis of simulation results. A new parameter C which is defined as the ratio of the active region area to the whole bed area was suggested to describe the active region in the mixing process. Our numerical results reveal that the parameter C has a significant influence on the mixing time but little influence on the mixing degree. With the increase of the rotational speed and the decrease of the filling degree, the parameter C increases but the mixing time decreases.

A simple and effective method has been developed to reflect the growth of bacteria CH-1 via the potential of the solution. The results indicate that during the bacterial cultivation, the biomass increases and the potential of the solution decreases over time. The relationship between biomass and potential of the solution could be expressed by the equation with constants of a and b which are all related to species, batch, number, and growth environment of bacterial. When the initial pH value is 10 and the initial biomass is 6.55×10 7 cell/mL, the correlated equation of the biomass and the potential of the solution could be divided into two segments. The growth of bacteria CH-1 is different under various experimental conditions, but the biomass is directly related to the potential of the solution regardless of the conditions of different initial pH values and bacteria number.

Objectives Aspidin BB, a typical phloroglucinol derivative from Dryopteris fragrans, possesses significant antifungal property. This study aimed to investigate potential mechanism of antifungal activity of Aspidin BB against Trichophyton rubrum which is the most common pathogens responsible for chronic dermatophytosis. Methods The minimum inhibitory concentration (MIC) of Aspidin BB against strains was determined by broth microdilution. The effects of Aspidin BB on ergosterol biosynthesis were investigated by content determination based on UPLC method. Besides, the effects of drugs on squalene epoxidase (SE) in T. rubrum cell membrane were analyzed. Results MIC value of Aspidin BB against T. rubrum was 25.0 μg/mL. Aspidin BB reduced ergosterol content significantly, but no notable effect on squalene epoxidase activity. Conclusion The results suggested that Aspidin BB inhibited ergosterol biosynthesis. However, it was not squalene epoxidase but other components may sever as possible targets in ergosterol biosynthesis pathway.

Background: For patients hospitalized with severe influenza A, morbidity and mortality remain high. MHAA4549A, a human monoclonal antibody targeting the influenza A hemagglutinin stalk, has demonstrated pharmacological activity in animal studies and in a human influenza A challenge study. We evaluated the safety and efficacy of MHAA4549A plus oseltamivir (OS) against influenza A infection in hospitalized patients. Methods: The CRANE trial was a phase 2b, randomized, double-blind, placebocontrolled study of single intravenous (IV) doses of placebo, 3600-mg, or 8400-mg MHAA4549A, all in combination with oral oseltamivir (+OS) in patients hospitalized with severe influenza A. Patients were enrolled across 68 clinical sites in 18 countries and randomized 1:1:1 into the three cohorts. The primary endpoint was the median time to normalization of respiratory function defined as the time to removal of supplemental oxygen support to maintain a stable SpO2 ≥ 95%. Findings: 166 patients were randomized and analyzed during a preplanned interim analysis (placebo+OS: 56; 3600-mg MHAA4549A+OS: 55; 8400-mg MHAA4549A+OS: 47). Compared to placebo+OS, MHAA4549A+OS did not significantly affect the time to normalization of respiratory function (placebo+OS: 4·28 days (80% CI: 3·06, 6·60); 3600-mg MHAA4549A+OS: 2·78 days (80% CI: 2·52, 4·20); 8400-mg MHAA4549A+OS: 2·65 days (80% CI: 1·58, 4·52). Patient deaths comprised 4 of 9, 6 of 13, and 4 of 9 study discontinuations in each of those treatment arms, respectively. Frequency of adverse events between treatment arms was not significantly different (placebo+OS: 45 (80·4%); 3600-mg MHAA4549A+OS: 37 (67·3%); 8400-mg MHAA4549A+OS: 35 (74·5%)). Interpretation: In hospitalized patients with influenza A, MHAA4549A did not improve clinical outcomes over oseltamivir alone. Variability in patient removal from oxygen supplementation limited the utility of the primary endpoint. Validated endpoints are needed to assess novel treatments for severe influenza A. Trial Registration: This completed trial was registered under ClinicalTrials.gov #NCT02293863 and EudraCT #2014- 000461-43. Funding Statement: Genentech, Inc. provided funding for this study. Declaration of Interests: JJL, PK, JMM, RD, CL, XY, AN, PH, MM, AC, MCP, JG, TC, EMN, and JAT were employees of Genentech, Inc., a member of the Roche group, and own/owned Roche stock and/or options at the time this study was performed. Genentech, Inc. provided research funding to the institutions of ACN, MS, and NA for the conduct of this study. AC is currently an employee of Calico Life Sciences, LLC. Ethics Approval Statement: The CRANE trial was conducted in full conformance with the International Council for Harmonisation (ICH) E6 guideline for Good Clinical Practice (GCP) and the principles of the Declaration of Helsinki, or the laws and regulations of the country in which the research is conducted, whichever afforded the greater protection to the individual. The study complied with the requirements of the ICH E2A guideline (Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). Studies conducted in the European Union (EU) or European Economic Area complied with the EU Clinical Trial Directive (2001/20/EC). All patients or their legally authorized representative provided written, informed consent.

The growing photovoltaic industry produces a mass of silicon cutting waste each year. How to effectively manage the resulting silicon cutting waste is essential from an environmental and an economic perspective. In this study, a new strategy was developed to utilize silicon cutting waste and fabricate high-performance lithium-ion battery anode materials . This study combines nanocopper-assisted chemical etching technology with graphite and carbon nanotubes (CNTs) coating technology . The resulting Si/nano-Cu/CNTs/C composite show an excellent reversible capacity of 1750 mAh/g and 64% capacity retention rate after 100 cycles at 200 mA/g. Different current charging and discharging tests were applied, and good rate performance achieved. When the current was switched from 2000 mA/g to 100 mA/g, the discharge capacity returned to the original 1750 mAh/g, demonstrating excellent rate performance. Furthermore, the higher ion diffusion coefficient improved the conductivity of the electrode, and the combination of silicon and carbon is beneficial to the electrode stability, which was verified by simulation calculation. Our work indicates that the silicon waste can be a cost-effective silicon source in the preparation of high-performance Si/C anode material by the simple and economical manufacturing method.

For an arbitrary self-affine measure defined by a self-affine iterated function system and a family of probability weights, it is proven in this article that, if a self-affine measure is a spectral measure, then the probability weights must be equal and measure non-overlap holds in a weaker sense. In particular, all spectral integral self-affine measures satisfy the OSC.

The E and Z isomeric intermediates based on ethyl/methyl-2-cyano-3-(5-formyl-1-(4-iodo-phenyl)-1H-pyrrol-2-yl)acrylate have been synthesized and these intermediates (E or Z) were further stereo-selectively converted into their respective E, E or E, Z isomers of diethyl/dimethyl-3,3'-(1-(4-iodophenyl)-1H-pyrrole-2,5-diyl)bis (2-cyanoacrylate) at the first time. The E, E isomers of both 2a and 3a, in solid state displayed higher quantum efficiency with longer fluorescent lifetime as compared to E, Z isomers. Notably, the E, E isomers proved to be better AIEs while, E, Z isomer of 2a has eminent anticancer activity against human nasopharyngeal carcinoma. A simple and straight forward strategy has been firstly developed to utilize the impact of configuration on fluorescence and anti-cancer activity.

Objective To explore the effect of electroacupuncture at conception vessel and governor vessel on correlative signals of inflammatory response stress-injury-repair in cerebral ischemia reperfusion rats. Methods A total of 216 rats were included in the experiment, of which 192 rats were randomly divided into four groups, including sham operation group (group A), model group (group B), governor vessel group (group C), and conception vessel and governor vessel group (group D), 48 rats in each group. The rats in each group were further divided into six sub-groups, including 12 h group, 24 h group, 48 h group, 72 h group, 96 h group and 144 h group. MCAO operation course was simulated in group A, and the common carotid artery, internal carotid artery and external carotid artery on the right side were exposed, without insertion of suture or treatment. After completion of modeling in group B, treatment was not conducted. After completion of modeling in group C, “Shuigōu ( GV 26)”, “Baihui ( GV 20)” and “Dazhuī ( GV 14)” of governor vessel were selected, and electroacupuncture device was connected with “GV 14” and “GV 20”. After completion of modeling in group D, “GV 26”, “GV 20” and “GV 14” of governor vessel, and “Qihai ( CV 6)”, “Guānyuan ( CV 4)” and “Chengjiāng ( CV 24)” of conception vessel were selected; electroacupuncture device was connected with “GV 14” and “GV 20”, “CV 4” and “CV 6”. Neurological severity score was conducted. Enzyme linked immunosorbent assay (ELISA) was applied to determine the concentration of peripheral serum adrenocorticotropic hormone (ACTH) of rats, and immunohistochemical method was adopted to detect the expression levels of tumor necrosis factor α (TNF-α) and transforming growth factor β1 (TGF-β1) in brain tissue of rats. The other 24 rats were also randomly divided into four groups mentioned above, 6 rats in each group, to detect cerebral ischemie volume. Results Compared with group B, the ischemia volume in brain tissue at 144 h after cerebral ischemia reperfusion decreased significantly in group C and group D (P Conclusion Electroacupuncture at conception vessel and governor vessel can protect brain through the intervention of the expression of correlative signals of inflammatory response stress-injury-repair of cerebral ischemia reperfusion.

The presence and/or generation mechanism of a mantle plume associated with early Permian rifting on the northern margin of Gondwana are topics of debate. Here we report LA–ICP–MS U–Pb zircon ages, whole-rock geochemistry, and Sr–Nd isotope data for high-Ti mafic dykes from southern Qiangtang, Tibet, with the aim of assessing if a mantle plume formed in this region during the early Permian. Zircon U–Pb dating of diabase dykes yielded ages of 290.6 ± 3.5 Ma and 290.1 ± 1.5 Ma, indicating they were emplaced during the early Permian. Whole-rock geochemistry shows that these mafic dykes are alkaline (Nb/Y = 0.73–0.99), have high TiO2 (3.6%–4.8%), and have ocean-island basalt (OIB)-like trace element patterns with enrichments in Nb, Ta, and Ti. Whole-rock Sr–Nd isotope data show a relatively narrow range of eNd(t) (+ 2.29 to + 3.53), similar to basalts produced by a mantle plume (e.g., Emeishan continental flood basalts (ECFB)). Elemental and isotope data suggest that the dykes have undergone fractionation crystallization of mafic minerals and have experienced negligible crustal contamination. These mafic rocks show an affinity to OIB and may have been generated by partial melting of an OIB-type, garnet-bearing asthenospheric mantle source. On the basis of a similar emplacement age to the Panjal Traps basalts in the Himalayas, combined with a tectonic reconstruction of Gondwana in the early to middle Permian, our work suggests that the high-Ti mafic dykes in the Southern Qiangtang terrane and the coeval Panjal Traps basalts in the Himalayas together comprise a ca. 290 Ma large igneous province linked to a mantle plume, which probably played an active role in early Permian rifting on the northern margin of Gondwana and was related to circum-Pangea subduction.

For a class of Sierpinski-type self-affine measures on R 2 , a characterization for all maximal orthogonal sets of exponentials is given. By this characterization, a sufficient condition for a maximal orthogonal set to be a basis of L 2 ( μ ) is given.

ObjectiveTo explore the protection and molecular mechanism of histone deacetylase inhibitors (HDACIs) on the spleen of rats with hemorrhagic shock.MethodsA total of 60 SPF male SD rats were selected for the modeling of severe hemorrhagic shock using the method of arterial and venous cannulation with the time-divided bleeding. The measurement of mean arterial blood pressure and blood lactic acid was used to verify the modeling. The modeled rats were randomly divided into shock group, shock + suberoylanilide hydroxamic acid (SAHA) group, shock + autogenous transfusion group and shock + SAHA + autogenous transfusion group. Three hours after the treatment, the spleen of rats was collected and TUNEL method was employed to detect the apoptosis of spleen cells in each group. The statistical analysis was performed. Afterwards, real-time PCR and western blot were employed to detect the expression of BCL-2, BAX and caspass3 in the spleen of rats in each group.ResultsA total of 53 rats had successful modeling of severe hemorrhagic shock, with success rate of 88%. Cell apoptosis in the severe hemorrhagic model group was the most serious. After the intervention of HDACIs and the autogenous transfusion, the tissue injury was a bit recovered. Cell apoptosis was least in the shock + SAHA + autogenous transfusion group (P

Pulsatilla Decoction (Bai-Tou-Weng-Tang) has been used medically in China for thousands of years for the treatment of diseases caused by bacteria. In recent decades, Pulsatilla Decoction is becoming a well-known formula prescription used for the treatment of ulcerative colitis in traditional Chinese medicine. Pulsatilla chinensis is the chief herbal source of Pulsatilla Decoction, and it is rich in triterpenoid saponins, such as anemoside B4, anemoside A3, and 23-hydroxybetulinic acid. Anemoside B4 is the most abundant of that group and has been used as a quality control marker for Pulsatilla chinensis. As the major active component of Pulsatilla chinensis, anemoside B4 has also received attention as a pure compound for its therapeutic potential. In this review, we systematically analyze the findings on triterpenoid saponins, especially anemoside B4, anemoside A3 and 23-hydroxybetulinic acid, included in Pulsatilla chinensis and Pulsatilla Decoction. We discuss the pharmacokinetics and tissue distribution of these triterpenoid saponins as well as their biological activities. We also summarize the pharmacological effects of anemoside B4 and its two possible metabolites, anemoside A3 and 23-hydroxybetulinic acid, as pure compounds. In summary, this review sketches a profile of the state of existing knowledge with regard to the pharmacological effects of anemoside B4, especially its anti-inflammatory and immunomodulatory effects. These findings point to the possibility that anemoside B4 has potential to be studied further as a natural compound-originated immunomodulatory agent for the treatment of inflammatory diseases such as ulcerative colitis and thus, may represent one of the most important active components of Pulsatilla Decoction responsible for its anti-ulcerative colitis efficacy.