Search

Breast cancer (BC) is one of the frequently diagnosed cancers, and the leading cause of cancer-related death among women worldwide. The roles of protein L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) in human cancer have been exploring, but the clinical significance and biological function of PCMT1 in BC are not yet clear. In this study, based on the TCGA-BRCA data set, the results showed that high expression of PCMT1 gene was significantly correlated with shorter overall survival (OS), disease specific survival (DSS) and progress free suvival (PFS) of BC patients. Utilizing the immunohistochemical assay, we found that PCMT1 protein was located in the cytoplasm of BC cells, and PCMT1 expression was only obviously correlated with progesterone receptor expression of patients (p

Vermicompost is a commonly used organic fertilizer that can effectively improve the fertility and structure of saline soil. However, the effect of vermicompost on the growth of halophytes in coastal saline soil, especially under flooding conditions, is obscure. We conducted two greenhouse experiments in which seeds and seedlings, respectively, of the Suaeda salsa were subjected to no flooding, episodic flooding, or continuous flooding, crossed with or without vermicompost addition, in a factorial design. Continuous flooding decreased seed germination and seedling biomass of S. salsa. Under no flooding or episodic flooding, vermicompost addition significantly increased seed germination and seedling growth in S. salsa, but vermicompost addition had no significant effects under continuous flooding. Vermicompost addition increased the stability of soil aggregates and decreased soil electrical conductivity, thereby improving the soil quality. Our results suggest that vermicompost addition could be an effective strategy for enhancing the population growth of S. salsa in saline soil and benefit the restoration of the S. salsa community in the Yellow River Delta, China.

Background The Janus kinase (JAK) pathway mediates the activity of many asthma-relevant cytokines, including IL-4 and IL-13. GDC-0214 is a potent, inhaled, small-molecule JAK inhibitor being developed for the treatment of asthma. Objective We sought to determine whether GDC-0214 reduces fractional exhaled nitric oxide (F eno ), a JAK1-dependent biomarker of airway inflammation, in patients with mild asthma. Methods We conducted a double-blind, randomized, placebo-controlled, phase 1 proof-of-activity study in adults with mild asthma and F eno higher than 40 parts per billion (ppb). Subjects were randomized 2:1 (GDC-0214:placebo) into 4 sequential ascending-dose cohorts (1 mg once daily [QD], 4 mg QD, 15 mg QD, or 15 mg twice daily). All subjects received 4 days of blinded placebo, then 10 days of either active drug or placebo. The primary outcome was placebo-corrected percent reduction in F eno from baseline to day 14. Baseline was defined as the average F eno during the blinded placebo period. Pharmacokinetics, safety, and tolerability were also assessed. Results Thirty-six subjects (mean age, 28 years; 54% females) were enrolled. Mean F eno at baseline across all subjects was 93 ± 43 ppb. At day 14, placebo-corrected difference in F eno was −23% (95% CI, −37.3 to −9) for 15 mg QD and −42% (95% CI, −57 to −27.4) for 15 mg twice daily. Higher plasma exposure was associated with greater F eno reduction. No dose-limiting adverse events, serious adverse events, or treatment discontinuations occurred. There were no major imbalances in adverse events or laboratory findings, or evidence of systemic JAK inhibition. Conclusions GDC-0214, an inhaled JAK inhibitor, caused dose-dependent reductions in F eno in mild asthma and was well tolerated without evidence of systemic toxicity.

High interleukin (IL)-6 levels are associated with more severe clinical manifestations in patients hospitalized with COVID-19, but the complex role of IL-6 in antiviral and inflammatory processes has made it difficult to decipher its involvement in the disease. IL-6 receptor blockade by tocilizumab (anti-IL6R; Actemra) is used globally for the treatment of severe COVID-19, yet a molecular understanding of the therapeutic benefit remains unclear. We characterized the immune profile and identified cellular and molecular pathways directly modified by tocilizumab in peripheral blood samples collected from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial that assessed the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19 pneumonia. We identified factors predicting disease severity and clinical outcomes, including markers of inflammation, lymphopenia, myeloid dysregulation, and organ injury. Proteomic analysis confirmed a pharmacodynamic effect for tocilizumab in addition to identifying novel pharmacodynamic biomarkers. Transcriptomic analysis revealed that tocilizumab treatment leads to faster resolution of lymphopenia and myeloid dysregulation associated with severe COVID-19, indicating greater anti-inflammatory activity relative to standard of care and potentially leading to faster recovery in patients hospitalized with COVID-19.One sentence summaryInterleukin-6 receptor blockade with tocilizumab accelerated resolution of myeloid dysfunction and lymphopenia in patients hospitalized with COVID-19

Polymeric nanoreactors in water fabricated by the self-assembly of amphiphilic copolymers have attracted much attention due to their good catalytic performance without using organic solvents. However, the disassembly and instability of relevant nanostructures often compromise their potential applicability. Herein, the preparation of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-containing nanoreactors by the self-assembly of amphiphilic bottlebrush copolymers has been demonstrated. First, a macromonomer having a norbornenyl polymerizable group was prepared by RAFT polymerization of hydrophobic and hydrophilic monomers. The macromonomer was further subjected to ring-opening metathesis polymerization to produce an amphiphilic bottlebrush copolymer. Further, TEMPO, as a catalyst, was introduced into the hydrophobic block through the activated ester strategy. Finally, TEMPO-functionalized polymeric nanoreactors were successfully obtained by self-assembly in water. The nanoreactors exhibited excellent catalytic activities in selective oxidation of alcohols in water. More importantly, the reaction kinetics showed that the turnover frequency is greatly increased compared to that of the similar nanoreactor prepared from liner copolymers under the same conditions. The outstanding catalytic activities of the nanoreactors from bottlebrush copolymers could be attributed to the more stable micellar structure using the substrate concentration effect. This work presents a new strategy to fabricate stable nanoreactors, paving the way for highly efficient organic reactions in aqueous solutions.

Internet of Things is considerably increasing the levels of convenience at homes. The smart door lock is an entry product for smart homes. This work used Raspberry Pi, because of its low cost, as the main control board to apply face recognition technology to a door lock. The installation of the control sensing module with the GPIO expansion function of Raspberry Pi also improved the antitheft mechanism of the door lock. For ease of use, a mobile application (hereafter, app) was developed for users to upload their face images for processing. The app sends the images to Firebase and then the program downloads the images and captures the face as a training set. The face detection system was designed on the basis of machine learning and equipped with a Haar built-in OpenCV graphics recognition program. The system used four training methods: convolutional neural network, VGG-16, VGG-19, and ResNet50. After the training process, the program could recognize the user’s face to open the door lock. A prototype was constructed that could control the door lock and the antitheft system and stream real-time images from the camera to the app.

To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding.A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle.A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P0.05).The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

Besides their wide existence in various industrial processes, nanoscale particle suspensions are also the important media for some emerging technologies such as photocatalytic hydrogen production. The circulating flow properties of the nanoparticles in the fluid are of great concern for their practical use. In our study, a modified experimental system was set up based on Malvern laser particle analyzer that can estimate the nanoparticle concentration and size distribution in a laminar nanoparticle circulating flow. We found that the particle concentration and size distribution were periodical oscillation with time in such flow. Understanding the oscillation mechanism is capable of promote the energy efficiency of photocatalytic hydrogen production. A simulation based on Discrete Element Method (DEM) was conducted to understand this particular oscillation mechanism by studying the single particle movement and trajectory properties in the solid-liquid suspension. The simulation results agree well with the tendency obtained by the experimental results and are capable of better understanding the oscillation characteristics. The simulation results also reveal that the nanoparticles tend to gather in the middle region (the higher velocity region) of the tube after several cycles. Moreover the gravity is of great significance in the circulating flow of solid-liquid suspension because the particle swarms tend to distribute a little below the axial center line of the straight tube. These obtained results are credible for understanding the nanoscale particle transport phenomenon in many natural or industrial processes. In particular, our results are helpful for the understanding and effective control of the movement and distribution of photocatalyst particles in the tubular photocatalytic reactor, which is believed to significantly affect the incident radiation distribution and finally the energy conversion efficiency of the photocatalytic process.

China experienced a 47% expansion in higher education enrolment between 1998 and 1999 and a sixfold expansion in the decade to 2008. Using a fuzzy discontinuity in the months of births, we show tha...

Alzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly, and the mechanisms of AD are not fully defined. MicroRNAs (miRNAs) have been shown to contribute to memory deficits in AD. In this study, we identified that miR-204-3p was downregulated in the hippocampus and plasma of 6-month-old APPswe/PS1dE9 (APP/PS1) mice. miR-204-3p overexpression attenuated memory and synaptic deficits in APP/PS1 mice. The amyloid levels and oxidative stress were decreased in the hippocampus of APP/PS1 mice after miR-204-3p overexpression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4) was a target of miR-204-3p, and Nox4 inhibition by GLX351322 protected neuronal cells against Aβ(1–42)-induced neurotoxicity. Furthermore, GLX351322 treatment rescued synaptic and memory deficits, and decreased oxidative stress and amyloid levels in the hippocampus of APP/PS1 mice. These results revealed that miR-204-3p attenuated memory deficits and oxidative stress in APP/PS1 mice by targeting Nox4, and miR-204-3p overexpression and/or Nox4 inhibition might be a potential therapeutic strategy for AD treatment.

CO2 valorization into valuable chemicals has attracted much attention, among which carboxylative cyclization represents an appealing transformation strategy to synthesize heterocyclic compounds. Conventionally, the carboxylative cyclization comprises CO2 capture and subsequent nucleophilic attack of the resulting carboxylic anion to an unsaturated bond, by which the monofunctionalization of the unsaturated bond is realized and the heterocyclic compounds, such as 5-/6-membered cyclolactone, cyclocarbonate, and oxazolidinone, are accordingly generated. Nowadays, the CO2-participated multicomponent carboxylative cyclizations have evoked intense interest due to their ability to perform the bifunctionalization of the unsaturated bond in the ring-closing step, thus assembling complex molecules. Up to now, by activating the unsaturated bonds with functionalized reagents and designing cascade reactions of organometallic compounds, substituents including iodine, trifluoromethyl, perfluoroalkyl, alkyl, cyanoalkyl, allyl, aryl, phenoxy, allenyl, selenyl, amino, and phosphonyl groups have been incorporated into the cyclocarbonate or oxazolidinone compounds successfully through the multicomponent carboxylative cyclizations. Given the tremendous utility of this synthetic strategy in heterocyclic compound synthesis, this review summarizes the progress of multicomponent carboxylative cyclizations to spur the further development of this field.