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Vehicle target recognition of synthetic aperture radar (SAR) is one of the critical tasks of image interpretation. Convolutional neural networks (CNNs) are increasingly used in SAR images and make ...

We present a study of chemistry toward 294 dense cores in 12 molecular clumps using the data obtained from the ALMA Survey of 70 $μ\rm m$ dark High-mass clumps in Early Stages (ASHES). We identified 97 protostellar cores and 197 prestellar core candidates based on the detection of outflows and molecular transitions of high upper energy levels ($E_{u}/k > 45$ K). The detection rate of the N$_{2}$D$^{+}$ emission toward the protostellar cores is 38%, which is higher than 9% for the prestellar cores, indicating that N$_{2}$D$^{+}$ does not exclusively trace prestellar cores. The detection rates of the DCO$^{+}$ emission are 35% for the prestellar cores and 49% for the protostellar cores, which are higher than those of N$_{2}$D$^{+}$, implying that DCO$^{+}$ appears more frequently than N$_{2}$D$^{+}$ in both prestellar and protostellar cores. Both N$_{2}$D$^{+}$ and DCO$^{+}$ abundances appear to decrease from the prestellar to protostellar stage. The DCN, C$_{2}$D and $^{13}$CS emission lines are rarely seen in the dense cores of early evolutionary phases. The detection rate of the H$_{2}$CO emission toward dense cores is 52%, three times higher than that of CH$_{3}$OH (17%). In addition, the H$_{2}$CO detection rate, abundance, line intensities, and line widths increase with the core evolutionary status, suggesting that the H$_{2}$CO line emission is sensitive to protostellar activity., Accepted for Publication in ApJ. 36 pages, 15 figures, 5 tables. Table 5 available at https://github.com/ShanghuoLi/70-um-dark-high-mass-clumps

Since the outbreak of COVID-19, a variety of vaccine platforms have been developed. Amongst these, inactivated vaccines have been authorized for emergency use or conditional marketing in many countries. To further enhance the protective immune responses in populations that have completed vaccination regimen, we investigated the immunogenic characteristics of different vaccine platforms and tried homologous or heterologous boost strategy post two doses of inactivated vaccines in a mouse model. Our results showed that the humoral and cellular immune responses induced by different vaccines when administered individually differ significantly. In particular, inactivated vaccines showed relatively lower level of neutralizing antibody and T cell responses, but a higher IgG2a/IgG1 ratio compared with other vaccines. Boosting with either recombinant subunit, adenovirus vectored or mRNA vaccine after two-doses of inactivated vaccine further improved both neutralizing antibody and Spike-specific Th1-type T cell responses compared to boosting with a third dose of inactivated vaccine. Our results provide new ideas for prophylactic inoculation strategy of SARS-CoV-2 vaccines.

Fermentation and chemical methods for industrial cytidine diphosphate choline (CDP-choline) catalytic production both suffer from several disadvantages such as relatively low efficiency and productivity. To overcome these problems, we applied the concept of synthetic biology to develop a new one-pot multi-enzyme system to produce CDP-choline from orotic acid. Enzymes from different sources were selected and optimized as building blocks of the system, and parameters such as oxygen supply were also optimized. This system shows a titer of 37.6 ± 1.1 mM and a reaction rate of 1.6 mM L-1 h-1, both increase 66 % from traditional processes. It also has an efficiency of energy of 25.4%, improves 2-folds. This new one-pot CDP-choline-producing system has a potential for industrial use, and the procedure to design one-pot multi-enzyme system can be applied to build other one-pot system producing energy-rich compounds.

Ultra-diffuse galaxies (UDGs) are as faint as dwarf galaxies but whose sizes are similar to those of spiral galaxies. A variety of formation mechanisms have been proposed, some of which could result in different disk thicknesses. In this study, we measure the radial profile of the HI scale height (h_g) and flaring angle (h_g/R) of AGC 242019 through the joint Poisson-Boltzmann equation based on its well spatially-resolved HI gas maps. The mean HI scale height of AGC 242019 is \approx 537.15 \pm 89.4 pc, and the mean flaring angle is \approx 0.19 \pm 0.03. As a comparison, we also derive the disk thickness for a sample of 14 dwarf irregulars. It is found that the HI disk of AGC 242019 has comparable thickness to dwarfs. This suggests that AGC 242019 is unlikely to experience much stronger stellar feedback than dwarf galaxies, which otherwise leads to a thicker disk for this galaxy., Comment: 9 pages, 7 figures. Accepted for publication in MNRAS

Both Galactic and extragalactic studies on star formation suggest that stars form directly from dense molecular gas. To trace such high volume density gas, HCN and HCO+ J=1-0 have been widely used for their high dipole moments, relatively high abundances, and often being the strongest lines after CO. However, HCN and HCO+ J=1-0 emission could be arguably dominated by the gas components at low volume densities. HCN J=2-1 and HCO+ J=2-1, with more suitable critical densities and excitation requirements, would trace typical dense gas closely related to star formation. Here we report new observations of HCN J=2-1 and HCO+ J=2-1 towards 17 nearby infrared-bright galaxies with the APEX 12-m telescope. The correlation slopes between luminosities of HCN J=2-1, and HCO+ J=2-1 and total infrared emission are 1.03 +- 0.05 and 1.00 +- 0.05, respectively. The correlations of their surface densities, normalised with the area of radio/sub-millimeter continuum, show even tighter relations (Slopes: 0.99 +- 0.03 and 1.02 +- 0.03). The eight AGN-dominated galaxies show no significant difference from the eleven star-formation dominated galaxies in above relations. The average HCN/HCO+ ratios are 1.15 +- 0.26 and 0.98 +- 0.42 for AGN-dominated and star-formation dominated galaxies, respectively, without obvious dependencies on infrared luminosity, dust temperature, or infrared pumping. The Magellanic Clouds roughly follow the same correlations, expanding to eight orders of magnitude. On the other hand, ultra-luminous infrared galaxies with active galactic nucleus (AGN) systematically lay above the correlations, indicating potential biases introduced by AGNs., 28 pages, 12 figures, 6 tables

An emergy analysis is used to assess the sustainability of urban agglomerations’ eco-economic systems, which are generally measured by emergy–value sustainability indicators using a combination of several system indicators. However, this assessment approach is not applicable to economically developed high-density urban agglomerations. The application of the traditional entropy value evaluation method needs to be expanded to further strengthen the sustainability of the complex eco-economic–social relationships in megacity cluster regions. In this study, taking the Guangdong–Hong Kong–Macau Greater Bay Area (GBA) as a case study, we study a new evaluation method for evaluating the sustainable development capacity of cities. This method is based on the entropy power method and is used to construct the evaluation system of all indicators of the social–economic–natural subsystems of the eco-economic system, and it couples the development degree with the coordination degree. (1) This study shows that the new method is applicable for the sustainability assessment of high-density megacity clusters and is more accurate and comprehensive. The sustainability rankings are provided for Zhaoqing, Jiangmen, Huizhou, Guangzhou, Macau, Foshan, Zhongshan, Dongguan, Zhuhai, and Shenzhen. Hong Kong is the most representative, with a high sustainability index, but has the lowest level of coordination and a clear incoherence within the system. (2) The current emergy structure of the GBA city cluster is extremely unreasonable. The GBA city cluster is a resource-consuming city with a common characteristic of a low level of coordinated development. Although urban clusters have some potential in terms of renewable emergy and resources, the recycling rate of waste is low, and the consumption rate of nonrenewable resources is high. The effective use of land resources has become an important factor in the bottlenecking of sustainable development, and all other cities face such problems, except Zhaoqing, Jiangmen, and Huizhou. (3) The GBA city cluster can be divided into three categories according to the new method. Category 1 mainly includes Hong Kong, Shenzhen, Dongguan, and Zhuhai, which have coordinated development degrees ranging between 0.0 and 0.135 and the highest emergy density (ED) values but are extremely dependent on external emergy. They have high levels of emergy use per capita (EUC), high living standards, and high quality of life. The effective use of land resources severely restricts sustainable economic development, resulting in extreme ecological and environmental carrying pressure. Category 2 includes Guangzhou, Macau, Foshan, and Zhongshan, whose coordinated development degrees range from 0.143 to 0.179. The sustainable development capacity of these cities is at the middle level amongst the whole GBA. Their main emergy characteristics are emergy flow and subsystem evaluation indices that are between category 1 and category 3, but each has its own characteristics. The category 3 cities include Zhaoqing, Jiangmen, and Huizhou, whose coordinated development degrees are between 0.192 and 0.369. These cities are characterized by relatively low ED and EUC values, living standards, and quality, but their land resources have certain potential. These cities have a high emergy self-sufficiency rate (ESR) and natural environmental support capacity, but their environmental loading ratio (ELR) is still much higher than the national average. In terms of the economic development and innovation development levels, these cities are ranked as category 1 > category 2 > category 3. In terms of the ecological and environmental conditions and blue–green space protection, these cities are ranked as category 1 < category 2 < category 3. The results of this study can provide cities in the GBA with more scientific and consistent directions for the coordinated development of their ecological–economic–social systems to provide sustainable development decision-making services for megacity cluster systems.

The outbreak of COVID-19 has posed a huge threat to global health and economy. Countermeasures have revolutionized norms for working, socializing, learning, and travel. Importantly, vaccines have been considered as most effective tools to combat with COVID-19. As of the beginning of 2021, >200 COVID-19 vaccine candidates, covering nearly all existing technologies and platforms, are being research and development (R&D) by multiple manufacturers worldwide. This has posed a huge obstacle to the quality control and evaluation of those candidate vaccines, especially in China, where five vaccine platforms are deployed in parallel. To accelerate the R&D progress of COVID-19 vaccines, the guidances on R&D of COVID-19 vaccine have been issued by National Regulatory Authorities or organizations worldwide. The Center for Drug Evaluation and national quality control laboratory in China have played a leading role in launching the research on quality control and evaluation in collaboration with relevant laboratories involved in the vaccine R&D, which greatly supported the progression of vaccines R&D, and accelerated the approval for emergency use and conditional marketing of currently vaccine candidates. In this paper, the progress and experience gained in quality control and evaluation of COVID-19 vaccines developed in China are summarized, which might provide references for the R&D of current and next generation of COVID-19 vaccines worldwide.

Verruciform xanthoma (VX) is a rare, benign, mucocutaneous, verrucous, papillary lesion. This paper retrospectively summarizes clinical and pathologic features of 32 vulvar verruciform xanthoma reported from China and abroad. The skin lesions are generally single, mainly in labia minora, clitoris and fourchette with partly extending to the groin, buttocks and anus. The possible inducing factors include long-term scratching, local itching, severe lymphedema or lymphangioma circumscriptum. Severe cutaneous trauma and chronic inflammation may be the main causes. Clinically, it can easily be misdiagnosed as condylomata acuminata, squamous cell carcinoma, bowenoid papulosis, etc. It is reported to be related to underlying disorders. The main treatment is complete resection.

Our previous study demonstrated that pentacyclic triterpenoids from the fruits of Chaenomeles speciosa had prominent treatment functions on gastric damage patients and animals. However, little has been known about the pharmacological activity and mechanism of its each triterpene component (oleanolic acid, maslinic acid, betulinic acid, ursolic acid, 3-O-acetyl ursolic acid, 3-O-acetyl pomolic acid, tormentic acid (TA)). In current study, we found that TA possessed stronger cell protective effect and promoted proliferation activity on IND-damaged GES-1 cells than other triterpenoids from the fruits of Chaenomeles speciose by bioscreening. Therefore, we selected TA for further research. The results demonstrated that TA might ameliorate the gastric mucosal injury induced by IND, which was associated with accelerating the damaged GES-1 cell proliferation and migration, meliorating the injured rat GBF, ulcer inhibitor, ulcer area and pathologic changes of gastric mucous tissue, reducing the total acidity and volume of the gastric effluents, and raising the gastric pH; Further empirical research indicated that TA dramatically suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expressions, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expressions. these data demonstrated that TA avoided gastric mucosal injury by suppressing miR-139 expression and activating the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway, thereby boosting the epithelial cell proliferation and migration, and promoting the gastric damaged healing.

We present sensitive observations of NH2D at 110.153599 GHz toward 50 Galactic massive star-forming regions with IRAM 30-m telescope. The NH2D transition is detected toward 36 objects, yielding a detection rate of 72%. Column densities of NH2D, HC3N and C18O for each source are derived by assuming local thermal equilibrium conditions with a fixed excitation temperature. The deuterium ratio of NH$_3$, defined as the abundance ratio of NH2D to NH3, for 19 sources is also obtained with the information of NH3 from the literature. The range of deuterium fractionation bends to be large in the late-stage star-forming regions in this work, with the value from 0.043 to 0.0006. The highest deuterium ratio of NH3 is 0.043 in G081.75+00.78 (DR21). We also find that the deuterium ratio of NH3 increases with the Galactocentric distances and decreases with the line width., Accepted for publication in MNRAS. 16 pages, 12 figures, 3 tables

Supersonic motions are common in molecular clouds. (Sub)sonic turbulence is usually detected toward dense cores and filaments. However, it remains unknown whether (sub)sonic motions at larger scales ($\gtrsim$1~pc) can be present in different environments or not. Located at a distance of about 110 pc, Ophiuchus North 1 (Oph N1) is one of the nearest molecular clouds that allows in-depth investigation of its turbulence properties by large-scale mapping observations of single-dish telescopes. We carried out the $^{12}$CO ($J=1-0$) and C$^{18}$O ($J=1-0$) imaging observations toward Oph N1 with the Purple Mountain Observatory 13.7 m telescope. The observations have an angular resolution of $\sim$55\arcsec (i.e., 0.03~pc). Most of the whole C$^{18}$O emitting regions have Mach numbers of $\lesssim$1, demonstrating the large-scale (sub)sonic turbulence across Oph N1. Based on the polarization measurements, we estimate the magnetic field strength of the plane-of-sky component to be $\gtrsim$9~$\mu$G. We infer that Oph N1 is globally sub-Alfv{\'e}nic, and is supported against gravity mainly by the magnetic field. The steep velocity structure function can be caused by the expansion of the Sh~2-27 H{\scriptsize II} region or the dissipative range of incompressible turbulence. Our observations reveal a surprising case of clouds characterised by widespread subsonic turbulence and steep size-linewidth relationship. This cloud is magnetized where ion-neutral friction should play an important role., Comment: 16 pages, 12 figures, accepted for publication in A&A

Along with the rising of the development of CAR-T therapy, the biodistribution and in vivo proliferation of CAR-T cells which are the basis of their effectiveness and safety, have aroused much attention. For IND application, the biodistribution characteristics of CAR-T cells are required to be determined using at least two methods (both quantitative and qualitative evaluation could be applicable) for a comprehensively understanding of their potential target organs/tissues. This chapter takes the CD19 targeted CAR-T cell as an example, to introduce the most commonly used experimental procedure and technical points of using tumor-bearing NSG mice to perform biodistribution research based on in vivo optical imaging, flow cytometry, histopathology/immunochemistry and real-time quantitative PCR. Although these protocols are not fully standardized and could be further optimized, the data obtained from these approaches has been accepted by U.S. Food and Drug Administration and China Food and Drug Administration.

Ischemia/reperfusion (I/R) injury is a serious clinical condition characterized by high morbidity and mortality rates. Donepezil plays a neuroprotective role in I/R‑associated diseases. The aim of the present study was to investigate the role and the potential mechanism of action of donepezil in I/R‑induced myocardial microvascular endothelial cell dysfunction. An I/R model was simulated using oxygen‑glucose deprivation/reoxygenation (OGD/R) injury in human cardiac microvascular endothelial cells (CMECs). Cell viability and lactate dehydrogenase release were examined following treatment with donepezil. Commercial kits were used to evaluate cell apoptosis, cell permeability and caspase‑3 activity. The expression levels of apoptosis‑associated proteins, as well as proteins found in tight junctions or involved in the poly(ADP‑ribose) polymerase 1 (PARP1)/NF‑κB pathway, were measured using western blotting. These parameters were also examined following PARP1 overexpression. The results demonstrated that donepezil increased cell viability and reduced toxicity in OGD/R‑treated CMECs. The apoptotic rate, caspase‑3 activity and protein expression levels of Bax and cleaved caspase‑3 were significantly reduced following donepezil treatment, which was accompanied by Bcl‑2 upregulation. Moreover, cell permeability was notably reduced, coupled with a marked increase in the expression of tight junction‑associated proteins. The expression levels of proteins related to PARP1/NF‑κB signaling were significantly downregulated in CMECs following donepezil treatment. However, the protective effects of donepezil on OGD/R‑induced CMEC injury were reversed following PARP1 overexpression. In conclusion, donepezil suppressed OGD/R‑induced CMEC dysfunction via PARP1/NF‑κB signaling. This finding provided insight into the mechanism underlying myocardial I/R injury.

Supernovae and their remnants provide energetic feedback to the ambient interstellar medium (ISM), which is often distributed in multiple gas phases. Among them, warm molecular hydrogen (H$_2$) often dominates the cooling of the shocked molecular ISM, which has been observed with the H$_2$ emission lines at near-infrared wavelengths. Such studies, however, were either limited in narrow filter imaging or sparsely sampled mid-infrared spectroscopic observations with relatively poor angular resolutions. Here we present near-infrared ($H$- and $K$-band) spectroscopic mosaic observations towards the A, B, C, and G regions of the supernova remnant (SNR) IC 443, with the K-band Multi-Object Spectrograph (KMOS) onboard the Very Large Telescope (VLT). We detected 20 ro-vibrational transitions of H$_2$, one H line (Br$\gamma$), and two [Fe II] lines, which dominate broadband images at both $H$- and $K$-band. The spatial distribution of H$_2$ lines at all regions are clumpy on scales from $\sim 0.1$ pc down to $\sim 0.008$ pc. The fitted excitation temperature of H$_2$ is between 1500 K and 2500 K, indicating warm shocked gas in these regions. The multi-gas-phase comparison shows stratified shock structures in all regions, which explains the co-existence of multiple types of shocks in the same regions. Last, we verify the candidates of young stellar objects previously identified in these regions with our spectroscopic data, and find none of them are associated with young stars. This sets challenges to the previously proposed scenario of triggered star formation by SNR shocks in IC~443., Comment: 21 pages, 17 figures. Accepted by MNRAS

International audience; We show the first experiment of a transverse laser interference for electron injection into the laser plasma accelerators. Simulations show such an injection is different from previous methods, as electrons are trapped into later acceleration buckets other than the leading ones. With optimal plasma tapering, the dephasing limit of such unprecedented electron beams could be potentially increased by an order of magnitude. In simulations, the interference drives a relativistic plasma grating, which triggers the splitting of relativistic-intensity laser pulses and wakefield. Consequently, spatially dual electron beams are accelerated, as also confirmed by the experiment.

Ions (e.g., H$_3^+$, H$_2$O$^+$) have been used extensively to quantify the cosmic-ray ionization rate (CRIR) in diffuse sightlines. However, measurements of CRIR in low-to-intermediate density gas environments are rare, especially when background stars are absent. In this work, we combine molecular line observations of CO, OH, CH, and HCO$^+$ in the star-forming cloud IC~348, and chemical models to constrain the value of CRIR and study the response of the chemical abundances distribution. The cloud boundary is found to have an $A_{\rm V}$ of approximately 4 mag. From the interior to the exterior of the cloud, the observed $^{13}$CO line intensities drop by an order of magnitude. The calculated average abundance of $^{12}$CO (assuming $^{12}$C/$^{13}$C = 65) is (1.2$\pm$0.9) $\times$10$^{-4}$, which increases by a factor of 6 from the interior to the outside regions. The average abundance of CH (3.3$\pm$0.7 $\times$ 10$^{-8}$) is in good agreement with previous findings in diffuse and translucent clouds ($A_{\rm V}$ $, Comment: 21 pages, 11 figures. Submitted to ApJ

A pilot project has been proceeded to map 1 deg$^2$ on the Galactic plane for radio recombination lines (RRLs) using the Five hundred meter Aperture Spherical Telescope (FAST). The motivation is to verify the techniques and reliabilities for a large-scale Galactic plane RRL survey with FAST aiming to investigate the ionized environment in the Galaxy. The data shows that the bandpass of the FAST 19 beam L-band is severely affected by radio frequency interferences (RFIs) and standing wave ripples, which can hardly be corrected by traditional low order polynomials. In this paper, we investigate a series of penalized least square (PLS) based baseline correction methods for radio astronomical spectra that usually contain weak signals with high level of noise. Three promising penalized least squares based methods, AsLS, arPLS, and asPLS are evaluated. Adopting their advantages, a modified method named rrlPLS is developed to optimize the baseline fitting to our RRL spectra. To check their effectiveness, the four methods are tested by simulations and further verified using observed data sets. It turns out that the rrlPLS method, with optimized parameter $\lambda = 2 \times 10^8$ , reveals the most sensitive and reliable emission features in the RRL map. By injecting artificial line profiles into the real data cube, a further evaluation of profile distortion is conducted for rrlPLS. Comparing to simulated signals, the processed lines with low signal-to-noise ratio are less affected, of which the uncertainties are mainly caused by the rms noise. The rrlPLS method will be applied for baseline correction in future data processing pipeline of FAST RRL survey. Configured with proper parameters, the rrlPLS technique verified in this work may also be used for other spectroscopy projects., Comment: accepted for publication in PASA

Although enormous success has been achieved with anti-PD-1/PD-L1 and anti-CTLA-4 monoclonal antibodies (mAbs), their unsatisfactory response rate in cancer patients has been driving the research and development of novel immune checkpoint inhibitors (ICIs). Anti-LAG-3 mAbs, as one of the most promising candidates, are now being tested for various human cancers at different stages of clinical trials. Here, we describe the development and validation of a reporter gene assay (RGA) to measure the bioactivity of anti-LAG-3 mAbs. We established the bioassay based on parental Raji cells and a Jurkat cell line stably transfected with human LAG-3 gene and luciferase reporter elements controlled by nuclear factor of activated T cell (NFAT) from the IL-2 promoter. After optimization of key parameters, the established RGA showed excellent precision, specificity, accuracy, and stability. The mechanism of action (MOA) relatedness and the excellent assay performance make the RGA suitable for the characterization, lot release, and stability test of anti-LAG-3 mAbs.

We present CO observations toward a sample of six HI-rich Ultra-diffuse galaxies (UDGs) as well as one UDG (VLSB-A) in the Virgo Cluster with the IRAM 30-m telescope. CO 1-0 is marginally detected at 4sigma level in AGC122966, as the first detection of CO emission in UDGs. We estimate upper limits of molecular mass in other galaxies from the non-detection of CO lines. These upper limits and the marginal CO detection in AGC122966 indicate low mass ratios between molecular and atomic gas masses. With the star formation efficiency derived from the molecular gas, we suggest that the inefficiency of star formation in such HI-rich UDGs is likely caused by the low efficiency in converting molecules from atomic gas, instead of low efficiency in forming stars from molecular gas., Comment: accepted by MNRAS letters

In this work, we studied the kinetics and behavior of wood panel wastes containing ureaformaldehyde resins. For this purpose, we used a TG-FTIR coupled system to analyze the gaseous products of the pyrolysis. With the results, we obtained the models that provide theoretical evidence and data support for the studied reactions. According to our findings, the pyrolysis of the ureaformaldehyde components displayed two stages, and the second stage presented a higher intensity. At a temperature of 900 °C, the gas generation rate for hard UF (UF1) was 32.6% higher than that for soft UF (UF2). When temperature increased from 600 °C to 900 °C, the increase of the gas generation rate was relatively small. In addition, the reaction order was obtained using the CoatsRedfern method, which provided a value for the reaction order of 1.4. The activation energy of UF1 was slightly higher than that of UF2. The FTIR analysis indicated that the main gaseous products of the pyrolysis of the urea-formaldehyde resin samples were CO2, H2O, and other compounds containing the C–H and the N–H bond as well as carbonyl groups. In addition, it was determined that Nitrogen was mainly present in the form of hydronitrogen compounds but not as nitrogen oxides. These last may represent a higher degree of pollution.

The low carbon metallurgy technology based on the high-value utilization of biomass is considered as the key development orientation of green ironmaking. In this paper, a pyrolysis coupling technology of biomass tar and iron ore powder is proposed for the reduction of iron ore. Tar is degraded efficiently due to the synergy effects respectively through oxidation of iron oxides and the catalytic action of reduced iron, and simultaneously the reduction of iron oxide to metallic iron. Representative tar components including vanillin, naphthalene, and catechol were selected as tar model compounds. The various reaction conditions on the reduction degree of iron ores was investigated, which include the type of tar component, the pyrolysis temperature, and the ratio of reactants. According to the results, the optimal relationship between tar degradation and reduction of iron ore was identified. It can be found that under the catalytic effects of iron ore fines, the degradation efficiency of the three model compounds followed the following order: naphthalene > vanillin > catechol. Naphthalene owned the better reduction ability. The highest reduction degree of the product reached to 78.5% at 800 °C for 30 min.

In the present research, TG and FTIR were used to study the effect of chemical activation pretreatment on sludge pyrolysis. The results showed that both acidic and alkaline activation promoted sludge pyrolysis. KOH inhibited the elimination of crystallization water and promoted the release of volatiles. On the other hand, H2SO4 favored the separation of crystallization water and the release of volatiles. Low concentrations of the activator promoted the production of combustible gas and inhibited the generation of CO2. By analyzing the activation energy of the pyrolysis process using the Coats-Redfern method, it was found that both, KOH and H2SO4, were able to reduce the pyrolysis activation energy. When H2SO4 was used, the effect was more significant.

Our previous studies have demonstrated that trametenolic acid B (TAB) extracted from the Laetiporus sulphureus (Fr.) Murrill owned effective anti-proliferation of HepG2/2.215 cells and induced autophagy activity. The present aim was to further investigate its mechanisms involved by proteomic analysis. The iTRAQ of TAB on HepG2/2.215 was carried out and the western blot was used to verify the results of the proteomics analysis. According to the peptide segment quantitative standard (FDR ≤ 1%), a total of 5324 proteins were identified in HepG2/2.215 by proteomic analysis. The results identified that the major up-regulated proteins were HSP90AA4P, MYB, SERPINE1, and down-regulated proteins were Rho C, SERPINA1, and PIK3R4, which were related to PI3K/Akt signaling pathway, cell metastasis, and autophagy. HSP90AA4P and Rho C’s proteomics analysis were further confirmed by the western blot. The proteomic results demonstrated that the anti-hematoma effect of TAB was closely related to the increase of HSP90AA4P protein expressions and autophagy, which may be a critical target of TAB, which was expected to be a candidate drug for the treatment liver cancer.

We present 1 and 3 mm observations of the 13C- and 15N-bearing isotopologues of dense gas tracers towards eight nearby infrared-bright galaxies. With the Institut de Radioastronomie Millimétrique 30-m telescope, we observed the J = 1–0 transitions of H13CN, HC15N, H13CO+, HN13C, and H15NC towards M 82, NGC 3079, IC 694, Mrk 231, and NGC 6240. The J = 3–2 transition of H13CN was obtained in M 82, NGC 3079, NGC 3504, NGC 4418, NGC 6240, and NGC 6946, using the 10-m Submillimeter Telescope (SMT). We report the first detections of HN13C J = 1–0 and H13CN J = 3–2 in M 82, and H13CN J = 3–2 in NGC 6240 and NGC 3079. We find different line profiles between the J = 1–0 and 3–2 transitions of H13CN in both M 82 and NGC 3079. The optical depths of HCN show significant variations among the sample, indicating that dense gas masses estimated from the line luminosities of HCN J = 1–0 and 3–2 should be treated with caution for individual galaxies. Optical depth of HCN J = 3–2 is found to be higher than that of HCN J = 1–0 in M 82, NGC 3079, NGC 4418, and NGC 6240, which indicates that ground state transitions of dense gas tracers might better trace the star-forming gas than the high-J transitions. Based on the H13CN/HC15N line ratios, with the double-isotopic method, low 14N/15N abundance ratios of 120 and 140 are found in NGC 3079 and Mrk 231, respectively.

We performed high-sensitivity mapping observations of several complex organic molecules around Sagittarius B2 with ARO 12m telescope at 3-mm wavelength. Based on their spatial distribution, molecules can be classified as either "extended" that detected not only in Sgr B2(N) and Sgr B2(M), or "compact" that only detected toward or near to Sgr B2(N) and Sgr B2(M). The "extended" molecules including glycolaldehyde (CH2OHCHO), methyl formate (CH3OCHO), formic acid (t-HCOOH), ethanol (C2H5OH) and methyl amine (CH3NH2), while the "compact" molecules including dimethyl ether (CH3OCH3), ethyl cyanide (C2H5CN), and amino acetonitrile (H2NCH2CN). These "compact" molecules are likely produced under strong UV radiation, while "extended" molecules are likely formed under low-temperature, via gas-phase or grain surface reactions. The spatial distribution of "warm" CH2OHCHO at 89 GHz differ from the spatial distribution of "cold" CH2OHCHO observed at 13 GHz. We found evidence for an overabundance of CH2OHCHO compared to that expected from the gas-phase model, which indicates that grain-surface reactions are necessary to explain the origin of CH2OHCHO in Sagittarius B2. Grain-surface reactions are also needed to explain the correlation between the abundances of "cold" CH2OHCHO and C2H5OH. These results demonstrate the importance of grain-surface chemistry in the production of complex organic molecules., Comment: 11 pages, accepted by MNRAS

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). SFTS is mainly characterized by severe fever with thrombocytopenia and has a high mortality rate. The virus has been found in China, South Korea, and Japan. Effective antiviral drugs or vaccines still have been unavailable. Now, two vaccine manufacturers in China are actively engaged in the development of the vaccine. To promote the development of SFTS vaccines and ensure their effective quality control, we developed national antigen and antibody references. We collaborative calibrated the standards; evaluated the homogeneity and stability of the national SFTS standards. The national SFTS vaccine antigen and antibody references met the Chinese national standards and can be used to standardize quality control for the manufacture of SFTS vaccines. And also can be used into the study the dose-response relationship of SFTS vaccines, determine clinical doses, and evaluate vaccine immunogenicity.

Background Patient delay in seeking help has been reported to be a major factor that related to delay in care of acute myocardial infarction (AMI). Lack the knowledge of symptoms may translate to behavioral deficiencies which lead up to failing to seek medical assistant at early stage of AMI. Purpose The aim of present study is to investigate the awareness of AMI symptoms and the emergency responses among community residents over 35 years old. Methods The sample was proportionally distributed by age according to the national census data. The sex ratio was 1:1. The sample size is calculated according to the significance level of 0.05, the allowable error of 0.1, and the estimated Excellent awareness level of 10%. The final sample size is adjusted to 4200, considering non-response rate of 20%. Multi-stage stratified random sampling was used. On the first stage, two districts each in urban and rural regions were randomly selected. On the second stage, 3–10 community health service centers were randomly selected in each district. On the third stage, residents over 35 managed by the community health service center were proportionally sampled to be interviewed. A structured questionnaire was used and the survey was conducted in a face-to-face interview by clinical physicians. Logistic regression was applied to analyze factors related to Good knowledge. Results The top three symptom recognized by public is “pain or discomfort in the chest” (71.3%), followed by “difficulty breathing” (65.1%) and “pain or discomfort in the jaw, neck, or back” (60.9%). 85.0% chose to call an ambulance as first response when witness others having an AMI. Those who lives alone (OR=1.408; 95% CI, 1.005–1.972) and whose immediate family had been diagnosed with AMI (OR=1.510; 95% CI, 1.040–2.192) has better knowledge. A significant positive correlation was observed for those with hypertension (OR=1.199; 95% CI, 1.007–1.429), while a negative correlation was observed for those with diabetes (OR=0.788; 95% CI, 0.626–0.992). Public education could improve Good knowledge (OR=1.662; 95% CI, 1.388–1.990), while doctoral advise has been shown negative impact (OR=0.824; 95% CI, 0.691–0.984). Conclusions Our data provide first population-based estimates of public awareness in our country. Further promotional strategies to increase overall awareness in general public are seriously needed. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Major Science and Technology Projects of Tianjin Science and Technology Commission Multivariable logistic regression

We present high-sensitivity CH 9 cm ON/OFF observations toward 18 extra-galactic continuum sources that have been detected with OH 18 cm absorption in the Millennium survey with the Arecibo telescope. CH emission was detected toward six of eighteen sources. The excitation temperature of CH has been derived directly through analyzing all detected ON and OFF velocity components. The excitation temperature of CH 3335 MHz transition ranges from $-54.5$ to $-0.4$ K and roughly follows a log-normal distribution peaking within [$-$5, 0] K, which implies overestimation by 20% to more than ten times during calculating CH column density by assuming the conventional value of $-60$ or $-10$ K. Furthermore, the column density of CH would be underestimated by a factor of $1.32\pm 0.03$ when adopting local thermal equilibrium (LTE) assumption instead of using the CH three hyperfine transitions. We found a correlation between the column density of CH and OH following log$N$(CH) = (1.80$\pm$ 0.49) log$N$(OH) $-11.59 \pm 6.87$. The linear correlation between the column density of CH and H$_2$ is consistent with that derived from visible wavelengths studies, confirming that CH is one of the best tracers of H$_2$ component in diffuse molecular gas., 15 pages, 9 figures, accepted by ApJS

The effects of phloridzin (PHL), main component of Malus hupehensis (MH) tea leaves, on blood glucose (BG) and glucose-6-phosphatase (G-6-Pase) were investigated to provide a basis for finding a scheme of stabilizing BG. Glucose uptake of insulin resistant HepG2 cells was measured by glucose oxidase method. Glucose tolerance, fasting BG (FBG) and postprandial BG (PBG) were determined by BG test strips. The expression of G-6-Pase was detected by Western blot. The results showed that glucose uptake was enhanced and the expression of G-6-Pase was inhibited by PHL in insulin resistant HepG2 cells. Glucose tolerance was enhanced, FBG level was increased and PBG level was decreased by PHL in mice. The expression of G-6-Pase in the liver was enhanced under fasting state, and was inhibited by the low and medium dose under postprandial state. It indicated that PHL has a positive effect on stabilizing BG in mice, which is related to bidirectional regulation of G-6-Pase activity. PRACTICAL APPLICATIONS: Malus hupehensis, edible and medicinal plant, which has been proved by long-term application and experiments that it has a good effect on stabilizing blood glucose, preventing diabetes and adjuvant treatment. Its effect is closely related to its main component PHL. Thus, MH can be used as a dietary regulating drink for daily life to maintain blood glucose. Its main ingredient is PHL, which can be developed as a candidate drug for diabetes treatment.

Malus hupehensis (Pamp.) Rehd (MH) is a dual-purpose plant used as medicine and food, which possesses various biological activities including hepatoprotective effect. In this study, the hepatoprotective activity of extracts of MH (MHE) against RFP + INH-induced liver injury was investigated. Animals in model group were given saline and INH + RFP. Animals in MHE groups were given MHE and INH + RFP. Animals in normal control group were given equal volume of saline. Subsequently, blood and liver samples were collected and assessed. MHE significantly alleviated the liver injury, as evidenced by decreased activities of the ALT, AST, TBIL, MDA and GSH-ST, and increased levels of SOD and GSH. MHE also effectively reduced the pathological tissue damage. Moreover, the CYP450 levels, and expression of CYP3A4, CYP2C9 and NADPH4 protein were inhibited by MHE. MHE exerts a protective effect against RFP + INH-induced liver injury in mice, and could be developed as a liver protectant for treatment of DILI.

Dense gas is the key for understanding star formation in galaxies. We present high resolution ($\sim3''$) observations of CN 2-1 and CS 5-4 as dense gas tracers toward Arp 299, a mid stage major merger of galaxies, with the Submillimeter Array (SMA). The spatial distribution of CN 2-1 and CS 5-4 are generally consistent with each other, as well as HCN 1-0 in literature. However, different line ratios of CS 5-4 and CN 2-1 are found in A, B, and C regions, with highest value in B. Dense gas fraction decreases from IC 694 (A), to NGC 3690 (B) and the overlap starburst region (C and C$'$), which indicates that circum-nuclear upcoming starburst in A and B will be more efficient than that in the overlap region of Arp 299., 6pages, 2 Figures

CTLA-4 is an important immune checkpoint for the regulation of T cell activation, and anti-CTLA-4 monoclonal antibodies (mAbs) are being developed as mono- or combination therapy for various tumors with reliable clinical efficacy. Ipilimumab is the first approved inhibitor of immune checkpoint, and many other anti-CTLA-4 mAbs, including ipilimumab biosimilars, are in different stages of clinical trials. However, due to the immunomodulating nature of the mAbs targeting CTLA-4, mode of action (MoA) and cell-based bioassay to determine their bioactivities as the lot release or stability test has been a great challenge to quality control laboratories. In this study, we have developed and validated a reporter gene assay (RGA), in which two kinds of cell lines were engineered to measure the bioactivity of anti-CTLA-4 mAbs. Raji cells were stably transfected with the membrane-anchored anti-CD3 single chain antibody fragment (scFv) as antigen-presenting cells (APCs, Raji-CD3scFv cells), while Jurkat cells were stably transfected with CTLA-4 with Y201V mutation and NFAT controlled luciferase as the effector cells (Jurkat-CTLA-4-NFAT-luc cells). The ligation of CD80/CD86 on the APCs with CTLA-4 could reduce the luciferase expression accompanied with the activation of effector cells, while the anti-CTLA-4 mAb could reverse the reduction, which resulted in good dose response curve to determine its bioactivity. After optimizing various assay conditions, we performed full validation according to ICH-Q2 (R1), which demonstrated the excellent specificity, accuracy, precision, linearity, and the cell passage stability. The satisfied performance characteristics render the RGA a good bioassay in the bioactivity determination of anti-CTLA-4 mAbs, as applied in characterization, batch release control, stability study, and biosimilar assessment.

We have identified 453 compact dense cores in 3 mm continuum emission maps in the ATOMS (ALMA Three-millimeter Observations of Massive Star-forming regions) survey, and compiled three catalogues of high-mass star forming cores. One catalogue, referred to as H/UC-HII catalogue, includes 89 cores that enshroud hyper/ultra compact (H/UC) HII regions as characterized by associated compact H40alpha emission. A second catalogue, referred to as pure s-cHMC, includes 32 candidate Hot Molecular Cores (HMCs) showing rich spectra (N>20lines) of complex organic molecules (COMs) but not associated with H/UC-HII regions. The third catalogue, referred to as pure w-cHMC, includes 58 candidate HMCs with relatively low levels of COM richness and not associated with H/UC-HII regions. These three catalogues of dense cores provide an important foundation for future studies of the early stages of high-mass star formation across the Milky Way. We also find that nearly half of H/UC-HII cores are candidate HMCs. From the number counts of COM-containing and H/UC-HII cores, we suggest that the duration of high-mass protostellar cores showing chemically rich features is at least comparable to the lifetime of H/UC-HII regions. For cores in the H/UC-HII catalogue, the width of the H40alpha line increases as the core size decreases, suggesting that the non-thermal dynamical and/or pressure line-broadening mechanisms dominate on the smaller scales of the H/UC-HII cores., 17 pages, five tables, and 11 figures. Accepted for publication at MNRAS

Herbicide resistance to chemical herbicide is a global issue that presents an ongoing threat to grain production. Though it has been frequently implicated that the production of detoxification enzymes increased in resistance development, the mechanisms for overexpression of these genes employed by herbicide-resistant weeds remain complicated. In this study, a mesosulfuron-methyl resistant Beckmannia syzigachne population (R) was found to be cross-resistant to another herbicide pyriminobac-methyl. No known target-site mutations were detected in the R population. In contrast, the decreased uptake and enhanced metabolic rates of mesosulfuron-methyl were detected in the R than the susceptible (S) population. Two candidate ATP-binding cassette (ABC) transporter genes (ABCB25 and ABCC14) that were constitutively up-regulated in the R population were identified by RNA-sequencing and validated by RT-qPCR. Alteration of antioxidant enzyme activities and gene expressions implied that mesosulfuron-methyl-induced antioxidant defenses provoked reactive oxygen species (ROS) burst. ROS scavenger assay showed that ROS induces ABCB25 and ABCC14 expression. This study reported for the first time that ABC transporters mediated non-target-site resistance contributes to mesosulfuron-methyl resistance in a B. syzigachne population, and implicated that ROS burst might be involved in the overexpression of ABC transporter genes in weeds.

We present one of the first Shanghai Tian Ma Radio Telescope (TMRT) K Band observations towards a sample of 26 infrared dark clouds (IRDCs). We observed the (1,1), (2,2), (3,3), and (4,4) transitions of NH together with CCS (2–>1) and HCN J = 2–1, simultaneously. The survey dramatically increases the existing CCS-detected IRDC sample from 8 to 23, enabling a better statistical study of the ratios of carbon-chain molecules (CCM) to N-bearing molecules in IRDCs. With the newly developed hyperfine group ratio (HFGR) method of fitting NH inversion lines, we found the gas temperature to be between 10 and 18 K. The column density ratios of CCS to NH for most of the IRDCs are less than 10, distinguishing IRDCs from low-mass star-forming regions. We carried out chemical evolution simulations based on a three-phase chemical model NAUTILUS. Our measurements of the column density ratios between CCM and NH are consistent with chemical evolutionary ages of ≲10 yr in the models. Comparisons of the data and chemical models suggest that CCS, HCN, and NH are sensitive to the chemical evolutionary stages of the sources. © 2021, Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature., This work was supported by the National Natural Science Foundation of China (Grant Nos. 11988101, 11725313, 11911530226, and 11403041), and the Chinese Academy of Sciences International Partnership Program (Grant No. 114A11KYSB20160008). The authors would like to thank the referees for the many constructive comments. Jinjin Xie would like to thank the support and help from the TMRT operating team and the co-observer Yaoting Yan during her observations at Shanghai Tian Ma Radio Telescope. Jinjin Xie would also like to thank Xintong Lu and Yongxiong Wang for correcting the English in this paper. Gary A. Fuller acknowledges financial support from the State Agency for Research of the Spanish MCIU through the AYA2017-84390-C2-1-R grant (co-funded by FEDER) and through the "Center of Excellence Severo Ochoa" award for the Instituto de AstrofÍsica de Andalucia (Grant No. SEV-2017-0709). Gary A. Fuller also acknowledges support from the Collaborative Research Centre 956, funded by the Deutsche Forschungsgemeinschaft (Grant No. 184018867).

A grid of equidistant electron stripes is generated during the collision of two laser pulses under a small angle in underdense plasma. Due to the oblique incidence, transverse standing wave in plasma is observed, in addition to the longitudinal traveling wave of the compound laser field. This standing wave results in the generation of plasma density grating. The ratio of the peak stripe density to background density can reach the value of 20:1. The grating period is determined by the interaction angle. Analytical theory of the compound electric fields is provided for plane waves. The grating formation is then verified via particle-in-cell simulations for short Gaussian laser pulses with typical experimental parameters. In addition, the interference pattern was also observed during experiments with Diocles laser. The results presented here are relevant for many laser-plasma applications, such as Raman scattering, inertial confinement fusion, plasma photonic crystals and laser wakefield acceleration.

Glyphosate is the most widely used herbicide in world agriculture and for general vegetation control in a wide range of situations. Global and often intensive glyphosate selection of very large weedy plant populations has resulted in widespread glyphosate resistance evolution in populations of many weed species. Here, working with a glyphosate-resistant (GR) Echinochloa colona population that evolved in a Western Australia agricultural field, we identified an ATP-binding cassette (ABC) transporter (EcABCC8) that is consistently up-regulated in GR plants. When expressed in transgenic rice, this EcABCC8 transporter endowed glyphosate resistance. Equally, rice, maize, and soybean overexpressing the EcABCC8 ortholog genes were made resistant to glyphosate. Conversely, CRISPR/Cas9-mediated knockout of the EcABCC8 ortholog gene OsABCC8 increased rice susceptibility to glyphosate. Subcellular localization analysis and quantification of glyphosate cellular levels in treated ABCC8 transgenic rice plants and isolated leaf protoplasts as well as structural modeling support that EcABCC8 is likely a plasma membrane–localized transporter extruding cytoplasmic glyphosate to the apoplast, lowering the cellular glyphosate level. This is a report of a membrane transporter effluxing glyphosate in a GR plant species, and its function is likely conserved in crop plant species.

The world has entered the second wave of the COVID-19 pandemic, and its intensity is significantly higher than that of the first wave of early 2020. Many countries or regions have been forced to start the second round of lockdowns. To respond rapidly to this global pandemic, dozens of COVID-19 vaccine candidates have been developed and many are undergoing clinical testing. Evaluating and defining effective vaccine candidates for human use is crucial for prioritizing vaccination programs against COVID-19. In this review, we have summarized and analyzed the efficacy, immunogenicity and safety data from clinical reports on different COVID-19 vaccines. We discuss the various guidelines laid out for the development of vaccines and the importance of biological standards for comparing the performance of vaccines. Lastly, we highlight the key remaining challenges, possible strategies for addressing them and the expected improvements in the next generation of COVID-19 vaccines.

We present 3 mm and 2 mm band simultaneously spectroscopic observations of HCN 1-0, HCO$^{+}$ 1-0, HNC 1-0, and CS 3-2 with the IRAM 30 meter telescope, toward a sample of 70 sources as nearby galaxies with infrared luminosities ranging from several 10$^{5}L_{\odot}$ to more than 10$^{12}L_{\odot}$. After combining HCN 1-0, HCO$^{+}$ 1-0 and HNC 1-0 data from literature with our detections, relations between luminosities of dense gas tracers (HCN 1-0, HCO$^{+}$ 1-0 and HNC 1-0) and infrared luminosities are derived, with tight linear correlations for all tracers. Luminosities of CS 3-2 with only our observations also show tight linear correlation with infrared luminosities. No systematic difference is found for tracing dense molecular gas among these tracers. Star formation efficiencies for dense gas with different tracers also do not show any trend along different infrared luminosities. Our study also shows that HCN/HCO$^{+}$ line ratio might not be a good indicator to diagnose obscured AGN in galaxies., 25 pages, 5 figures, 3 tables. Accepted for publication in MNRAS

We performed observations of the HC$_3$N (24-23, 17-16, 11-10, 8-7) lines towards a sample consisting of 19 Galactic massive star-forming regions with the Arizona Radio Observatory 12-m and Caltech Submillimeter Observatory 10.4-m telescopes. HC$_3$N (24-23, 17-16, 11-10, 8-7) lines were detected in sources except for W44, where only HC$_3$N (17-16, 11-10) were detected. Twelve of the nineteen sources showed probable line wing features. The excitation temperatures were estimated from the line ratio of HC$_3$N (24-23) to HC$_3$N (17-16) for 18 sources and are in the range 23-57 K. The line widths of higher-$J$ transitions are larger than lower-$J$ ones for most sources. This indicates that the inner dense warm regions have more violent turbulence or other motions (such as rotation) than outer regions in these sources. A possible cutoff tendency was found around $L_{\rm IR}$ $\sim$ 10$^{6}$ $L_\odot$ in the relation between $L_{\rm IR}$ and full width at half maximum line widths., Accepted for publication in PASJ

The high global burden of tuberculosis (TB) underscores the urgent need for an effective TB vaccine since the only licensed Bacillus Calmette-Guérin (BCG) vaccine is ineffective in preventing adult pulmonary TB and affords no protection against latent TB infection (LTBI). Herein we investigated the potential of Mycobacterium tuberculosis (Mtb) antigen proteins AEC comprised of Ag85b and ESAT6-CFP10 proteins in conjunction with aluminum (Al) and polyriboinosinic-polyribocytidylic acid (poly-IC) as a novel subunit vaccine against TB. The immunogenicity and protection induced by the adjuvanted vaccine were evaluated in two animal models. Mice vaccinated with AEC/Al/poly-IC exhibited significant antigen-specific humoral immune responses and cell-mediated immunity as determined by immunoassay and multicolor flow cytometric assay, and the protective effect of the vaccine was demonstrated in a guinea pig model of latent Mtb infection. Compared to the control group, the mean pathological scores and bacterial loads in lungs and spleens of AEC/Al/poly-IC-immunized guinea pigs were significantly reduced. These data indicate that the AEC/Al/poly-IC is highly immunogenic in mice and can effectively protect guinea pigs against latent Mtb infection; it may represent a promising candidate vaccine for the control of latent TB.

Influenza vaccine potency is determined by the quantification of immunologically active hemagglutinin capable of eliciting neutralizing antibodies upon immunization. Currently, the single radial immunodiffusion (SRID) method is the standard in vitro potency assay used for lot release of seasonal inactivated influenza vaccines. Despite the proven usage of SRID, significant limitations such as the time-consuming preparation of reagents and limited dynamic range warrant the need for the development of alternative potency assays. Such alternative approaches need to discriminate and quantify relevant hemagglutinin material, provide strain identity, and be independent of strain-specific and seasonal reagents. Herein, we present a proof of concept method that combines the capture of conformationally well-folded hemagglutinin via a sialic acid binding step with the resolving power of reversed-phase high-performance liquid chromatography for strain identity and determination. Details of the protocol for the selective capture of receptor-binding hemagglutinin, its release from the receptor, and its relative determination are presented. This approach was found to provide flexibility for the reagents to be used and was adaptable to varying strain compositions of influenza vaccines. This proof of concept approach was developed as an antibody-independent methodology.

Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that causes substantial morbidity and mortality in livestock and humans. To date, there are no licensed human vaccines or therapeutics available. Here, we report the isolation of monoclonal antibodies from a convalescent patient, targeting the RVFV envelope proteins Gn and Gc. The Gn-specific monoclonal antibodies exhibited much higher neutralizing activities in vitro and protection efficacies in mice against RVFV infection, compared to the Gc-specific monoclonal antibodies. The Gn monoclonal antibodies were found to interfere with soluble Gn binding to cells and prevent infection by blocking the attachment of virions to host cells. Structural analysis of Gn complexed with four Gn-specific monoclonal antibodies resulted in the definition of three antigenic patches (A, B and C) on Gn domain I. Both patches A and B are major neutralizing epitopes. Our results highlight the potential of antibody-based therapeutics and provide a structure-based rationale for designing vaccines against RVFV. The isolation and characterization of glycoprotein-specific monoclonal antibodies from a patient with Rift Valley fever (RVF) provide insights into the humoral immune responses elicited by the RVF virus as well as the therapeutic potential of antibody-based strategies.

Sludge gasification for the production of hydrogen-rich gas is a promising technology. In this paper, a pilot study on the hydrogen-rich gas production by sludge gasification using waste heat of blast furnace slag was carried out, and the mass and energy balance of gasification process using waste heat from blast furnace slag were evaluated. The results show that the higher the gasification temperature, the higher the hydrogen content in the gas. When the gasification temperature reaches 880 °C, the hydrogen content in the gas reaches the maximum,35.3%. The technology of sludge gasification combined with waste heat recovery of high furnace slag is feasible. Its efficiency of heat recovery can reach up to 64.35%, and the gasification efficiency and energy consumption ratio can reach to 42.30% and 3.67, respectively.

Adoptive cell therapy using chimeric antigen receptor T (CAR-T) cells, which is a promising cancer immunotherapy strategy, has been developing very rapidly in recent years. CAR-T cells are genetically modified T cells that can specifically recognize tumor specific antigens on the surface of tumor cells, and then effectively kill tumor cells. At present, exciting results are being achieved in clinical applications of CAR-T cells for patients with hematological malignancies. The research and development of CAR-T cells for various targets and for the treatment of solid tumors have become a hot topic worldwide, so an increasing number of investigational new drug applications (INDAs) and new drug applications (NDAs) of CAR-T cell products are expected to be submitted in future. The quality control and nonclinical research of these products are of great significance in ensuring the safety and effectiveness of these products; however, they also present great challenges and difficulties. This article discusses the general principles of and key issues regarding the quality control and nonclinical research of CAR-T cell products based on their product characteristics and on relevant guidelines for gene and cell therapy products. Keywords: Chimeric antigen receptor T cells, Quality control, Nonclinical research, Safety, Efficacy, Clinical trials, Cancer immunotherapy

RANKL (receptor activator of nuclear factor κB ligand) plays a key role in the differentiation, activation and survival of osteoclasts. Denosumab, which targets RANKL, is approved for osteoporosis or bone loss that has a high risk for fracture and bone metastases from solid tumors. Bioactivity determination is essential for the safety and efficacy of therapeutic antibodies. At present, the mechanism of action (MOA) based bioassay for anti-RANKL monoclonal antibodies (mAbs) is the measurement of tartrate resistant acid phosphatase (TRAP) activity, which takes about five days and has complex operation and relatively high variation. In this study, we developed a reporter gene assay (RGA) based on a RAW264.7 cell line stably expressing luciferase reporter under the control of nuclear factor-κB (NF-κB) response elements. After optimizing the key parameters, the validation results based on ICH-Q2 not only show superior specificity, precision, linearity, accuracy and passage stability, but also a short duration and simple operation. These results demonstrate the RGA based on the RANKL-RANK-NF-κB pathway can be an excellent alternative for measuring the bioactivity of anti-RANKL mAbs.