Antitumor activity and safety of camrelizumab combined with apatinib in patients with relapsed or refractory peripheral T-cell lymphoma: An open-label, multicenter, phase II study

IntroductionThe treatment for relapsed/refractory peripheral T-cell lymphoma (r/r PTCL) is suboptimal. This open-label, multicenter, single-arm study aimed to investigate the antitumor activity and safety of camrelizumab (a PD-1 blockade) plus apatinib (an antiangiogenic agent) for patients with r/r PTCL.MethodsEligible patients with r/r PTCL were enrolled and received camrelizumab 200 mg intravenously every 2 weeks and apatinib 500 or 250 mg orally once daily, 4 weeks as a cycle. The primary endpoint was overall response rate (ORR).ResultsA total of 20 patients were enrolled and received study medications in the study, with a median number of prior treatment line of 3 (range 1-6). At the cutoff date of March 4, 2022, the median follow-up was 27.2 months (range: 0.5-39.9), and three patients remained on treatment. Six patients had early discontinuation without tumor response evaluation. For all patients, the ORR was 30% (6/20) (95% confidence interval [CI], 11.9% to 54.3%), with two patients (10%) achieving complete response. The median progression-free survival (PFS) and median overall survival for all patients were 5.6 months (95% CI, 1.8 to not reached) and 16.7 months (95% CI, 2.8 to not reached), respectively. Patients with PD-L1 expression ≥50% (3 patients) had a numerically higher ORR and longer median PFS than those with PD-L1 expression < 50% (5 patients). The most commonly reported grade 3 or higher adverse events were hyperlipidemia (15%), hypokalemia (15%) and anemia (15%). No treatment-related deaths occurred.DiscussionIn this study, PD-1 inhibitors plus low-dose antiangiogenic drugs presented preliminary antitumor activity and manageable toxicity in patients with r/r PTCL

Metagenomic Analysis of Flaviviridae in Mosquito Viromes Isolated From Yunnan Province in China Reveals Genes From Dengue and Zika Viruses

More than 6,000 mosquitoes of six species from six sites were collected and tested for their virome using metagenomics sequencing and bioinformatic analysis. The identified viral sequences belonged to more than 50 viral families. The results were verified by PCR of selected viruses in all mosquitoes, followed by phylogenetic analysis. In the present study, we identified the partial dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) sequences in mosquitoes. Metagenomic analysis and the PCR amplification revealed three DENV sequences, one of which encodes a partial envelope protein. Two ZIKV sequences both encoding partial nonstructural protein 3 and one JEV sequence encoding the complete envelope protein were identified. There was variability in the viral titers of the newly isolated virus JEV-China/YN2016-1 of different passage viruses. The newly identified Zika virus gene from ZIKV-China/YN2016-1 was an Asian genotype and shared the highest nucleotide sequence identity (97.1%) with a ZIKV sequence from Thailand isolated in 2004. Phylogenetic analysis of ZIKV-China/YN2016-1 and ZIKV-China/YN2016-2 with known Flavivirus genes indicated that ZIKV has propagated in Yunnan province, China

Feasibility of Using MODIS Products to Simulate Sun-Induced Chlorophyll Fluorescence (SIF) in Boreal Forests

Solar-induced chlorophyll fluorescence (SIF) is a novel approach to gain information about plant activity from remote sensing observations. However, there are currently no continuous SIF data produced at high spatial resolutions. Many previous studies have discussed the relationship between SIF and gross primary production (GPP) and showed a significant correlation between them, but few researchers have focused on forests, which are one the most important terrestrial ecosystems. This study takes Greater Khingan Mountains, a typical boreal forest in China, as an example to explore the feasibility of using MODerate resolution Imaging Spectroradiometer (MODIS) products and Orbiting Carbon Observatory-2 (OCO-2) SIF data to simulate continuous SIF at higher spatial resolutions. The results show that there is no significant correlation between SIF and MODIS GPP at a spatial resolution of 1 km; however, significant correlations between SIF and the enhanced vegetation index (EVI) were found during growing seasons. Furthermore, the broadleaf forest has a higher SIF than coniferous forest because of the difference in leaf and canopy bio-chemical and structural characteristic. When using MODIS EVI to model SIF, linear regression models show average performance (R2 = 0.58, Root Mean Squared Error (RMSE) = 0.14 from Julian day 145 to 257) at a 16-day time scale. However, when using MODIS EVI and temperature, multiple regressions perform better (R2 = 0.71, RMSE = 0.13 from Julian day 145 to 241). An important contribution of this paper is the analysis of the relationships between SIF and vegetation indices at different spatial resolutions and the finding that the relationships became closer with a decrease in spatial resolution. From this research, we conclude that the SIF of the boreal forest investigated can mainly be explained by EVI and air temperature

Effect of microstructure evolution on mechanical property of extruded Mg–12Gd–2Er–1Zn–0.6Zr alloys

The microstructure evolution of as-cast, as-extruded and peak-aged Mg–12Gd–2Er–1Zn–0.6Zr alloys were investigated by Optical Microscope (OM), X-ray Diffraction (XRD), Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM). The mechanical performance was also tested by tensile test at room temperature in the present study. The results indicated that the lamellar 14H-LPSO structure formed during the solid solution process at 793 K for 24 h, and also existed after hot extrusion process. The dynamic recrystallization (DRX) occurred during hot extrusion. The DRXed fine grain size was ∼5 μm. Meanwhile, some un-DRXed grains contained LPSO structure had a roughly orientation along the extrusion direction. The tensile test result showed that the as-extruded alloy had a better elongation of 14% due to fine DRXed grain and fiber-like un-DRXed with LPSO structure attributed to the high elongation. Because of the precipitation of the β′-phase, the ultimate tensile strength (UTS) and yield tensile strength (YTS) increased up to 415 MPa (UTS) and 374 MPa (YTS), respectively

Research on corona characteristics and type selection of fittings in extra high voltage alternating current substation

In order to eliminate the energy loss and electromagnetic interference caused by corona discharge, the size selection and design of fittings under different voltage levels and different altitudes are studied in this paper. The corona discharge phenomena of several extra high voltage (EHV) alternating current (AC) substations are observed by ultraviolet (UV) imager. It is found that the areas with serious corona discharge in EHV AC substations are mainly concentrated on the shielding ring of terminal insulator string and shielding ball of conductor. The electric field calculation model is established for two typical fittings with serious corona discharge in COMSOL multiphysics software, and the distribution of electric field intensity on the surface of different sizes of fittings under the voltage level of 500 kV and 750 kV is calculated based on the finite element method. The results show that the maximum electric field intensity (MEFI) on the surface of the shielding ring of the terminal insulator string appears at the connection between the arc and the straight line of the shielding ring; the MEFI on the surface of the shielding ball appears in the ball head. Compare the numerical values of the corona onset field intensity (COFI) of the fittings at different sizes and altitudes calculated by using the physical calculation model of the COFI, so as to determine the size selection of the fittings at different altitudes and different voltage levels. The corona onset tests of fittings carried out in low altitude areas and high altitude areas verify the applicability of the size selection design of fittings at different altitudes and different voltage levels. The results show that the size selection design of fittings for 500 kV high altitude substation shall refer to the size selection of fittings for 750 kV plain substation

Electrochemical Oxygen Reduction to Hydrogen Peroxide via a Two-Electron Transfer Pathway on Carbon-Based Single-Atom Catalysts

Electrochemical reduction of oxygen is considered as a new strategy to achieve decentralized preparation of hydrogen peroxide (H2O2) in a green manner. As a promising new type of catalytic material, carbon-based single-atom catalysts can achieve wide-range adjustments of the electronic structure of the active metal centers while also maximize the utilization of metal atoms, toward electrochemical production of H2O2 from the selective two-electron transfer oxygen reduction reaction (ORR). Herein, starting from the reviewing of characterizing methods and reaction mechanisms of ORR via two-electron and four-electron transfer pathways, the vital role of binding strength between OOH intermediate and active sites in determining the activity and selectivity towards H2O2 production is revealed and illustrated. Currently reported carbon-based single-atom catalysts for H2O2 production are systematically summarized and critically reviewed. Moreover, with the underpinning chemistry to improve the overall efficiency, three aspects concerning the central metal atoms, coordinated atoms, and environmental atoms are comprehensively analyzed. Based on the understanding of the most current progresses, some predictions for future H2O2 production via electrochemical routes are offered, which include catalyst designs at atomic levels, new synthesis strategies and characterization techniques, as well as interfacial superwetting interaction engineering at electrode and device levels

Ag85a-S2 Activates cGAS-STING Signaling Pathway in Intestinal Mucosal Cells

Brucellosis is a zoonotic disease caused by Gram-negative bacteria. Most of the brucellosis vaccines in the application are whole-bacteria vaccines. Live-attenuated vaccines are widely used for brucellosis prevention in sheep, goats, pigs, and cattle. Thus, there is also a need for an adjuvanted vaccine for human brucellosis, because the attenuated Brucella vaccines now utilized in animals cause human illness. Here, we developed a live-attenuated Brucella suis strain 2 vaccine (S2) adjuvanted with Ag85a (Ag85a-S2). We found that Ag85a-S2 activated cGAS-STING pathways both in intestinal mucosal cells in vivo and in the BMDM and U937 cell line in vitro. We demonstrated that the cGAS knockout significantly downregulated the abundance of interferon and other cytokines induced by Ag85a-S2. Moreover, Ag85a-S2 triggered a stronger cellular immune response compared to S2 alone. In sum, Ag85a-S2-mediated enhancement of immune responses was at least partially dependent on the cGAS-STING pathway. Our results provide a new candidate for preventing Brucella pathogens from livestock, which might reduce the dosage and potential toxicity compared to S2

Electrochemical oxygen reduction to hydrogen peroxide via a two‐electron transfer pathway on carbon‐based single‐atom catalysts

Electrochemical reduction of oxygen is considered as a new strategy to achieve decentralized preparation of hydrogen peroxide (H2O2) in a green manner. As a promising new type of catalytic material, carbon‐based single‐atom catalysts can achieve wide‐range adjustments of the electronic structure of the active metal centers while also maximize the utilization of metal atoms, toward electrochemical production of H2O2 from the selective two‐electron transfer oxygen reduction reaction (ORR). Herein, starting from the reviewing of characterizing methods and reaction mechanisms of ORR via two‐electron and four‐electron transfer pathways, the vital role of binding strength between OOH intermediate and active sites in determining the activity and selectivity towards H2O2 production is revealed and illustrated. Currently reported carbon‐based single‐atom catalysts for H2O2 production are systematically summarized and critically reviewed. Moreover, with the underpinning chemistry to improve the overall efficiency, three aspects concerning the central metal atoms, coordinated atoms, and environmental atoms are comprehensively analyzed. Based on the understanding of the most current progresses, some predictions for future H2O2 production via electrochemical routes are offered, which include catalyst designs at atomic levels, new synthesis strategies and characterization techniques, as well as interfacial superwetting interaction engineering at electrode and device levels