The rice leaf folder Cnaphalocrocis medinalis Güenée is a serious insect pest of rice in Asia. This pest occurs in summer, and it is sensitive to high temperature. However, the larvae exhibit heat ...acclimation/adaptation. To understand the underlying mechanisms, we established a heat-acclimated strain via multigenerational selection at 39 °C. After heat shock at 41 °C for 1 h, the transcriptomes of the heat-acclimated (S-39) and unacclimated (S-27) larvae were sequenced, using the unacclimated larvae without exposure to 41 °C as the control.
Five generations of selection at 39 °C led larvae to acclimate to this heat stress. Exposure to 41 °C induced 1160 differentially expressed genes (DEGs) between the heat-acclimated and unacclimated larvae. Both the heat-acclimated and unacclimated larvae responded to heat stress via upregulating genes related to sensory organ development and structural constituent of eye lens, whereas the unacclimated larvae also upregulated genes related to structural constituent of cuticle. Compared to unacclimated larvae, heat-acclimated larvae downregulated oxidoreductase activity-related genes when encountering heat shock. Both the acclimated and unacclimated larvae adjusted the longevity regulating, protein processing in endoplasmic reticulum, antigen processing and presentation, MAPK and estrogen signaling pathway to responsed to heat stress. Additionally, the unacclimated larvae also adjusted the spliceosome pathway, whereas the heat-acclimated larvae adjusted the biosynthesis of unsaturated fatty acids pathway when encountering heat stress. Although the heat-acclimated and unacclimated larvae upregulated expression of heat shock protein genes under heat stress including HSP70, HSP27 and CRYAB, their biosynthesis, metabolism and detoxification-related genes expressed differentially.
The rice leaf folder larvae could acclimate to a high temperature via multigenerational heat selection. The heat-acclimated larvae induced more DEGs to response to heat shock than the unacclimated larvae. The changes in transcript level of genes were related to heat acclimation of larvae, especially these genes in sensory organ development, structural constituent of eye lens, and oxidoreductase activity. The DEGs between heat-acclimated and unacclimated larvae after heat shock were enriched in the biosynthesis and metabolism pathways. These results are helpful to understand the molecular mechanism underlying heat acclimation of insects.
The cyclization reactions of propargylic alcohols and propargylic amines with CO2 are important in industrial applications, but it was a great challenge that non‐noble‐metal catalysts catalyzed both ...reactions under mild conditions. Herein, the catalyst Cu2O@ZIF‐8 was prepared by encapsulating Cu2O nanoparticles into robust ZIF‐8, and it can effectively catalyze the cyclization of both propargylic alcohols and propargylic amines with CO2 into valuable α‐alkylidene cyclic carbonates and oxazolidinones with turnover numbers (TONs) of 12.1 and 19.6, which can be recycled at least five times. The mechanisms were further uncovered by NMR, FTIR, 13C isotope‐labeling experiments and DFT calculations, in which Cu2O and DBU can synergistically activate the C≡C bond and the hydroxy/amino group of substrates. Importantly, it is the first example of a noble‐metal‐free catalyst that can catalyze both propargylic alcohols and propargylic amines with CO2 simultaneously.
The noble‐metal‐free catalyst Cu2O@ZIF‐8 with a yolk–shell structure was synthesized, and it represents the first noble‐metal‐free catalyst that can effectively catalyze both propargylic alcohols and propargylic amines with CO2 under mild conditions.
G-protein-coupled receptors (GPCRs) are critically regulated by β-arrestins, which not only desensitize G-protein signalling but also initiate a G-protein-independent wave of signalling. A recent ...surge of structural data on a number of GPCRs, including the β2 adrenergic receptor (β2AR)-G-protein complex, has provided novel insights into the structural basis of receptor activation. However, complementary information has been lacking on the recruitment of β-arrestins to activated GPCRs, primarily owing to challenges in obtaining stable receptor-β-arrestin complexes for structural studies. Here we devised a strategy for forming and purifying a functional human β2AR-β-arrestin-1 complex that allowed us to visualize its architecture by single-particle negative-stain electron microscopy and to characterize the interactions between β2AR and β-arrestin 1 using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and chemical crosslinking. Electron microscopy two-dimensional averages and three-dimensional reconstructions reveal bimodal binding of β-arrestin 1 to the β2AR, involving two separate sets of interactions, one with the phosphorylated carboxy terminus of the receptor and the other with its seven-transmembrane core. Areas of reduced HDX together with identification of crosslinked residues suggest engagement of the finger loop of β-arrestin 1 with the seven-transmembrane core of the receptor. In contrast, focal areas of raised HDX levels indicate regions of increased dynamics in both the N and C domains of β-arrestin 1 when coupled to the β2AR. A molecular model of the β2AR-β-arrestin signalling complex was made by docking activated β-arrestin 1 and β2AR crystal structures into the electron microscopy map densities with constraints provided by HDX-MS and crosslinking, allowing us to obtain valuable insights into the overall architecture of a receptor-arrestin complex. The dynamic and structural information presented here provides a framework for better understanding the basis of GPCR regulation by arrestins.
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•Biochars are potential sustainable precursors for activated carbon production.•Physical activation and chemical activation are applied in the production process.•Production ...parameters affect the properties of resultant activated carbon.•Multiple applications in environmental protection and energy storage are reviewed.•Future perspectives about biochar activation and applications are highlighted.
There is a growing interest of the scientific community on production of activated carbon using biochar as potential sustainable precursors pyrolyzed from biomass wastes. Physical activation and chemical activation are the main methods applied in the activation process. These methods could have significantly beneficial effects on biochar chemical/physical properties, which make it suitable for multiple applications including water pollution treatment, CO2 capture, and energy storage. The feedstock with different compositions, pyrolysis conditions and activation parameters of biochar have significant influences on the properties of resultant activated carbon. Compared with traditional activated carbon, activated biochar appears to be a new potential cost-effective and environmentally-friendly carbon materials with great application prospect in many fields. This review not only summarizes information from the current analysis of activated biochar and their multiple applications for further optimization and understanding, but also offers new directions for development of activated biochar.
A retrospective cohort study was conducted to collect 465 patients with hepatitis B-related hepatocellular carcinoma who had undergone radical hepatectomy from January 1, 2012, to August 31, 2018, at ...the First Affiliated Hospital of the University of Science and Technology of China. The clinical, pathological, and follow-up information was collected to compare the basic characteristics of death and nondeath after radical resection. Kaplan–Meier curves were used for survival analysis and male and female subgroup analysis. The multivariate Cox proportional-hazards regression model was used to analyze independent risk factors related to postoperative death. Of the 465 patients with radical resection of hepatitis B-related hepatocellular carcinoma, 132 died, and 1-, 3-, and 5-year cumulative survival rates after operation were 92.1%, 78%, and 64%, respectively. In the male and female subgroup, 115 and 17 patients died, respectively. The 1-, 3-, and 5-year cumulative survival rates were 92.6%, 77.0%, and 62.6%, respectively, in men, and 89.6%, 78.8%, and 70.2%, respectively, in women. Multivariate Cox proportional-hazards regression analysis showed that microvascular invasion (MVI), Edmondson III/IV, BCLC stage B, and total bilirubin (TB) > 20.5 μmol/L were independent risk factors in patients with hepatitis B-related hepatocellular carcinoma after radical hepatectomy.
Behavioral thermoregulation is a key strategy for insects to cope with heat stress.The rice leaf folder Cnaphalocrocis medinalis Guenée (Lepidoptera: Pyralidae) larvae usually fold one leaf to ...construct a leaf shelter. The larvae are vulnerable to heat stress, and the temperature in summer is often beyond the optimal range of them. Shelters confer protection against environmental stress but unclear whether larvae will alter shelter-building behavior when encountering heat stress. We observed the shelter-building behavior of larvae during and after heat shock, and then examined the shape and structure of shelters. Larvae spent more time in selecting a site and building a shelter during and after heat shock than at the optimal temperature. More than 70% of larvae folded two or three leaves to build a shelter during and after heat shock, but more than 60% of larvae only folded one leaf at the optimal temperature. Larvae built more single-leaf longitudinal shelters at the optimal temperature, but they built more multileaf overlapping shelters during and after heat stress. Larvae constructed a short leaf shelter using a small amount of silk binds when they were exposed to 40°C for 4 h. The rice leaf folder larvae can alter their shelter-building behavior and shelter structure in response to heat stress.
This paper proposes a three-phase bidirectional ac/dc converter with Y-Δ connected transformers. The converter achieves both buck-boost ac/dc bidirectional conversion and electrical isolation with ...the single-stage structure. By introducing three dc-dc transformers, the total power is distributed and the current stress of the rectifier stage decreases. The Y-Δ connected transformers provide extra step-down conversion ratio and facilitate the converters' application in buck conversion. The circuit derivation, operation principles, and control strategy with the SVPWM algorithm are presented. A 3-kW prototype with 380-V dc and a 1.6-kW prototype with 48-V dc were built in the lab and experimental results verify the theoretical analysis well.
This paper proposes a three-phase isolated bidirectional ac/dc converter. The converter achieves buck-boost ac/dc bidirectional conversion, sinusoidal ac current, and high-frequency electrical ...isolation with single-stage structure. The traditional SVPWM algorithm should be modified to keep the voltage-second balance of the transformer. The circuit derivation, operation principles, and SVPWM algorithm are presented specifically. The solution for shoot-through problem is proposed, which does not need extra dead time. To verify the theoretical analysis, the proposed converter was simulated by MATLAB/SIMULINK and a 3 kW prototype was built in the lab. The simulation and experimental results show the high power factor and the low harmonic distortion characteristics of the circuit.
Immune checkpoint blockade has shown significant clinical benefit in multiple cancer indications, but many patients are either refractory or become resistant to the treatment over time. HER2/neu ...oncogene overexpressed in invasive breast cancer patients associates with more aggressive diseases and poor prognosis. Anti-HER2 mAbs, such as trastuzumab, are currently the standard of care for HER2-overexpressing cancers, but the response rates are below 30% and patients generally suffer relapse within a year. In this study we developed a bispecific antibody (BsAb) simultaneously targeting both PD1 and HER2 in an attempt to combine HER2-targeted therapy with immune checkpoint blockade for treating HER2-positive solid tumors. The BsAb was constructed by fusing scFvs (anti-PD1) with the effector-functional Fc of an IgG (trastuzumab) via a flexible peptide linker. We showed that the BsAb bound to human HER2 and PD1 with high affinities (EC
values were 0.2 and 0.14 nM, respectively), and exhibited potent antitumor activities in vitro and in vivo. Furthermore, we demonstrated that the BsAb exhibited both HER2 and PD1 blockade activities and was effective in killing HER2-positive tumor cells via antibody-dependent cellular cytotoxicity. In addition, the BsAb could crosslink HER2-positive tumor cells with T cells to form PD1 immunological synapses that directed tumor cell killing without the need of antigen presentation. Thus, the BsAb is a new promising approach for treating late-stage metastatic HER2-positive cancers.
A novel avian influenza A (H7N9) virus has caused great morbidity as well as mortality since its emergence in Eastern China in February 2013. However, the possible risk factors for death are not yet ...fully known.
Patients with H7N9 virus infection between March 1 and August 14, 2013 in Jiangsu province were enrolled. Data were collected with a standard form. Mean or percentage was used to describe the features, and Fisher's exact test or t-test test was used to compare the differences between fatal and nonfatal cases with H7N9 virus infection. A total of 28 patients with H7N9 virus infection were identified among whom, nine (32.1%) died. The median age of fatal cases was significant higher than nonfatal cases (P<0.05). Patients with older age were more strongly associated with increased odds of death (OR = 30.0; 95% CI, 2.85-315.62). Co-morbidity with chronic lung disease and hypertension were risk factors for mortality (OR = 14.40; 95% CI, 1.30-159.52, OR = 6.67; 95% CI, 1.09-40.43, respectively). Moreover, the presence of either bilateral lung inflammation or pulmonary consolidation on chest imaging on admission was related with fatal outcome (OR = 7.00; 95%CI, 1.10-44.61). Finally, dynamic monitoring showed that lymphopenia was more significant in fatal group than in nonfatal group from day 11 to week five (P<0.05). The decrease in oxygenation indexes were observed in most cases and more significantly in fatal cases after week three (P<0.05), and the value of nearly all fatal cases were below 200 mmHg during our evaluation period.
Among cases with H7N9 virus infection, increased age accompanied by co-morbidities was the risk of death. The severity of lung infection at admission, the persistence of lymphocytopenia, and the extended duration of lower oxygenation index all contributed to worsened outcomes of patients with H7N9 virus infection.
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