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Due to variations in gravity, temperature, and external disturbances, the optical axes of a telescope’s primary mirrors can shift and, consequently, become misaligned with the light path. Such misalignment significantly reduces image quality; thus, the position and orientation of primary mirror (POPM) control systems must maintain the optical axis in an ideal position. Therefore, in this paper, we proposes a novel high-accuracy electrohydraulic control system for the position and orientation of the primary mirror (POPM) of a large telescope. To this end, a POPM control system with five electrohydraulic partitions is adopted, and a mathematical model of the POPM is derived. In addition, a mathematical model of each partition of the electrohydraulic system is derived for the telescope controller design. A linear active disturbance rejection controller (LADRC) and a sliding mode controller (SMC) are adopted in each electro-hydraulic partition to ensure positioning accuracy. Experiments are carried out on 4 and 1.2 m large telescopes. The corresponding results show that by both keeping constant and varying the elevation of the large telescopes, the position error of the primary mirror can be limited to less than 1 μm, and the orientation of the primary mirror can be maintained with an error of less than 0.05 arcsec, even in the presence of external disturbances. This control accuracy can guarantee both the inalterability of the optical axis of the primary mirror and the possibility to adjust the light according to the requirement in order to obtain high-resolution images.

FeOOH on the real catalytic interface for the oxygen evolution reaction (OER) is chemically unstable to dissolve in alkaline media. Herein, based on the perspective of the dynamically stable interface, we purposely design the well-dispersed nanorod arrays of CoMoO4 as a host on activated iron foam (IF) to realize the optimal redeposition of FeOOH, constructing a self-sacrificial template rich in the FeOOH surface. Notably, at long-time oxidation potential, the precatalyst FeOOH-CoMoO4 can realize MoO42- dissolution and redeposition of Co oxyhydroxides on FeOOH host simultaneously, constructing a dynamically stable Fe(Co)OOH interface. The introduction of CoOOH improves conductivity and provides synergistic effect with FeOOH to lower the energy barrier for OER and maintain long-time stability, eventually exhibiting a low overpotential of 298 mV to reach the current density of 100 mA cm-2 and high stability over 60 h. This work demonstrates the feasibility of manipulating metal dissolution-redeposition process for a dynamically stable interface.

Rong Hu,1– 3 Jintao Zhang,1,2,4 Xuemei Liu,1,2 Dong Huang,3 Yu-Qing Cao1,2 1Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA; 2Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; 3Department of Pain Management, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Yu-Qing CaoDepartment of Anesthesiology, Washington University School of Medicine, 660 South Euclid, Box 8054, St. Louis, MO, 63110, USATel +1 314 362 8726Fax +1 314 362 8334Email caoy@anest.wustl.eduPurpose: Nerve injury-induced mechanical hyper-sensitivity, in particular stroking-induced dynamic allodynia, is highly debilitating and difficult to treat. Previous studies indicate that the immunosuppressive regulatory T (Treg) cells modulate the magnitude of punctate mechanical allodynia resulting from sciatic nerve injury. However, whether enhancing Treg-mediated suppression attenuates dynamic allodynia is not known. In the present study, we addressed this knowledge gap by treating mice with low-dose interleukin-2 (ld-IL2) injections or adoptive transfer of Treg cells.Methods: Female Swiss Webster mice received daily injections of ld-IL2 (1 μg/mouse, intraperitoneally) either before or after unilateral spared nerve injury (SNI). Male C57BL/6J mice received adoptive transfer of 1 x 106 Treg cells 3 weeks post-SNI. The responses to punctate and dynamic mechanical stimuli on the hindpaw were monitored before and up to 4– 6 weeks post-SNI. We also compared the distribution of Treg cells and CD3+ total T cells after SNI and/or ld-IL2 treatment.Results: Ld-IL2 pretreatment in female Swiss Webster mice completely blocked the development of SNI-induced dynamic mechanical allodynia and reduced the magnitude of punctate allodynia. Delayed ld-IL2 treatment in female mice significantly attenuated the morphine-resistant punctate and dynamic allodynia at 3– 5 weeks post-SNI. Adoptive transfer of Treg cells to male C57BL/6J mice 3 weeks post-SNI effectively reversed the persistent punctate and dynamic allodynia, supporting that the effect of ld-IL2 is mediated through endogenous Treg cells, and is likely independent of mouse strain and sex. Neither ld-IL2 treatment nor Treg transfer affected the basal responses to punctate or brush stimuli. Ld-IL2 significantly increased the frequency of Treg cells among total CD3+ T cells in the injured sciatic nerves but not in the uninjured nerves or the dorsal root ganglia, suggesting the injured nerve as ld-IL2’s site of action.Conclusion: Collectively, results from the present study supports Treg as a cellular target and ld-IL2 as a potential therapeutic option for nerve injury-induced persistent punctate and dynamic mechanical allodynia.Keywords: spared nerve injury, chronic pain, punctate allodynia, dynamic allodynia, low-dose interleukin-2, regulatory T cell

The effect of laser shock processing (LSP) on the hardness, surface morphology, residual stress, and thermal fatigue properties of a ZCuAl10Fe3Mn2 alloy was investigated to improve the thermal fatigue performance and decrease the surface crack of high-temperature components. The microstructure and crack morphology were analyzed by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The results showed that laser shock could significantly improve the thermal fatigue performance of the alloy at a pulse energy of 4 J. Under the effect of thermal stress and alternating stress, microstructure around the specimen notch was oxidized and became porous, leading to the formation of multiple micro-cracks. The micro-cracks in the vertical direction became the main cracks, which mainly expanded with the conjoining of contiguous voids at the crack tip front. Micro-cracks in other directions grew along the grain boundaries and led to material shedding.

In vitro noncontact cell-based coculture models are frequently employed to study cell-to-cell communication. However, these models cannot accurately represent the complexity of in vivo signaling. d-Lactate is an unusual metabolite produced and released by cancer cells. The characterization of d-lactate is challenging as it shares the same mass but has much lower amounts compared with l-lactate. Herein, d-α-hydroxy acids were specifically recognized and dehydrogenated by d-α-hydroxy acid dehydrogenase. The dehydrogenation products were rapidly quaternized for enhancement of mass signals. An on-probe enzymatic dehydrogenation-derivatization method was proposed for chiral analysis of α-hydroxy acids at the single-cell level. It is a promising amplification methodology and affords over 3 orders of magnitude signal enhancement. Furthermore, direct contact coculture models were used to precisely mimic the tumor microenvironment and explore the communication between cancer and normal cells. Single-cell mass spectrometry (SCMS) was further applied to easily sample cell extracts and study the differences of the aspects of small molecule metabolism in cocultured cells. On the basis of direct contact coculture SCMS, several differential small molecule metabolites and differences of oxidative stress between cocultured and monocultured normal cells were successfully detected. Additionally, d-lactate was discovered as a valuable differential metabolite with application of the two developed methods. It may account for the cancer-associated metabolic behavior of normal cells. These changes could be relieved after d-lactate metabolism-related drug treatment. This discovery may promote the investigation of d-lactate metabolism, which may provide a novel direction for cancer therapy.

Metal doping for active sites exhibits remarkable potential for improving the hydrogen evolution reaction (HER). Multi-doping and the use of a conductive substrate can further modulate catalytic performance. Herein, Nb-CoSe well dispersed in N-doped carbon nanospheres (NCs, Nb-CoSe@NC) was synthesized to serve as a conductive substrate and facilitated good dispersion of active sites for the HER. Nb doping can also change the electronic structure of CoSe, which facilitates the activity for the HER. In order to further improve the conductivity and intrinsic activity of Nb-CoSe@NC, dual, nonmetal doping was realized through gas sulfurization to prepare hierarchical Nb-CoSeS@NC. The prepared Nb-CoSeS@NC, with a core-shell structure, exhibited a low overpotential of 115 mV at 10 mA cm–2, which is smaller than that of the most doped catalysts. In addition, NCs not only improved the dispersion and conductivity of the catalyst but also prevented metal corrosion in an electrolyte, thus facilitating the long-term stability of Nb-CoSeS@NC. Moreover, the synergistic effect of the multi-doping of Nb, S, and Se was explained. This work provides a promising, multi-doping strategy for the large-scale application of transition-metal-based electrocatalysts for the HER.

IntroductionSpinal cord injury causes permanent neurological deficits, which have devastating physical, social, and vocational consequences for patients and their families. Traditional Chinese medicine uses acupuncture to treat neuropathic pain and improve nerve conduction velocity. This treatment can also reduce peripheral nerve injury joint contracture and muscle atrophy in affected patients. And it's got a remarkable restoration when electrical stimulation therapy on impaired peripheral nerves in animal models and clinical trials.Case descriptionA 48-year-old woman was hit by a heavy object that injured her lower back. The patient had a T12-L1 vertebral flexion and stretch fracture with traumatic spinal stenosis. The patient was transferred to the rehabilitation department after posterior T12-L2-segment pedicle screw system distraction and reduction, internal fixation, decompression, and bone graft fusion. Ultrasound-guided electroacupuncture was used to stimulate the sacral nerve, the spinal nerve, and the head of the patient, accompanied by spinal joint loosening training, respiratory training, lumbar comprehensive sports training, paraplegic limbs comprehensive training, and other manipulative treatment.OutcomesAfter the intervention, the patient showed significant improvements in sensory and motor scores, resulting in functional recovery according to ASIA and FIM. The patient gradually showed reasonable functional remission.DiscussionThe sacral nerve, the spinal cord, and the head were electrically stimulated by ultrasound-guided electroacupuncture in terms of intervention, and various functions of the patient were alleviated to a certain extent. The efficacy of ultrasound-guided electroacupuncture stimulation in treating neurologic symptoms should be validated in future clinical trials.

The bispecific T-cell engager (BiTE) blinatumomab against CD19 and CD3 has emerged as the most successful bispecific antibody (bsAb) to date; however, a significant proportion of patients do not respond to the treatments or eventually experience relapse after an initial response, and the recurrence rate increases significantly due to escape or downregulation of the CD19 antigen. To enhance antitumor efficacy and overcome potential immune escape, we developed a novel approach to design a CD19/CD22/CD3 trispecific antibody (tsAb) by site-specifically fusing anti-CD19 scFv (FMC63) and anti-CD22 nanobody (Nb25) to the defined sites of the CD3 antigen-binding fragment (Fab, SP34). This strategy allows for the optimal formation of immune synapses mediated by CD19/CD22/CD3 between target cells and T cells. Optimized tsAb can be superior for inducing T-cell−specific cytotoxicity and cytokine production against CD19+ and/or CD22+ tumor cells compared to other tsAb formats, and demonstrated significantly enhanced antitumor efficacy and the ability to overcome immune escape compared with the corresponding bsAbs alone or in combination, as well as with blinatumomab. In addition, tsAb treatment can lead to the long-term elimination of primary B-ALL patient samples in the PDX model and significantly prolong survival. This novel approach provides unique insight into the structural optimization of T-cell−redirected multispecific antibodies using site-specific recombination, and may be broadly applicable to heterogeneous and resistant tumor populations as well as solid tumors.

Background The combination of metal-catalyzed reactions and enzyme catalysis has been an essential tool for synthesizing chiral pharmaceutical intermediates in the field of drug synthesis. Metal catalysis commonly enables the highly efficient synthesis of molecular scaffolds under harsh organic conditions, whereas enzymes usually catalyze reactions in mild aqueous medium to obtain high selectivity. Since the incompatibility between metal and enzyme catalysis, there are limitations on the compatibility of reaction conditions that must be overcome. Findings We report a chemoenzymatic cascade reaction involved Palladium (Pd) catalyzed Suzuki–Miyaura coupling and whole-cell catalyzed C = O asymmetric reduction for enantioselective synthesis of value-added chiral alcohol. The cell membrane serves as a natural barrier can protect intracellular enzymes from organic solvents. Conclusions With dual advantages of cascade catalysis and biocompatibility, our work provides a rational strategy to harvest chiral alcohols in high yield and excellent enantioselectivity, as a channel to establish chemoenzymatic catalysis.

Background: The dopamine D2 receptor (DRD2) plays an important role in the increased prolactin (PRL) levels associated with the pathogenesis of antipsychotic drugs (ADs). Elevated prolactin levels can affect people’s quality of life. Maiya alkaloids has been used to treat diseases associated with high PRL levels. Maiya, is a processed product of the mature fruits of Hordeum vulgare L. (a gramineous plant) after sprouting and drying and also a common Chinese herbal drug used in the clinic, is traditionally used to treat abnormal lactation, and is currently used clinically for the treatment of abnormal PRL levels.Aims: Epigenetic mechanisms can be related to DRD2 expression. We investigated the role of DRD2 methylation in the induction of PRL expression by ADs and the mechanism underlying the effects of total barley maiya alkaloids (TBMA) on this induction.Methods: The methylation rate of DRD2 in 46 people with schizophrenia who took risperidone was detected by MassARRAY sequencing. Humans were long term users of Ris. Seventy Sprague Dawley female rats were divided into seven groups. A rat model of risperidone-induced PRL was established, and the potential protective effects of TBMA and its components [e.g., hordenine (Hor)] on these increased PRL levels were investigated. The PRL concentration was detected by Enzyme-linked immunosorbent assay. PRL, DRD2, and DNA methyltransferase (DNMT1, DNMT3α, and DNMT3β) protein and mRNA expression were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The positive rate of methylation in the DRD2 promoter region of rats was detected by MassARRAY sequencing.Results: Clinical studies showed that the positive rate of DRD2 methylation associated with increased PRL levels induced by ADs was significantly higher than in the normal prolactinemia (NPRL) group. In vivo and vitro, TBMA and Hor inhibited this induction of PRL expression and increased DRD2 expression by inhibiting the expression of the DNMTs.Conclusions: TBMA and hordenine increased DRD2 expression by inhibiting DNMT-dependent DRD2 methylation.

In this study, cascade membrane technology was applied to classify polysaccharides from the peels of stem lettuce (PPSLs), and three graded polysaccharides (PPSL100, PPSL10, and PPSL1) were obtained using ultrafiltration membranes of 100, 10, and 1 kDa in sequence. The physicochemical properties and immune-modulatory activity of three PPSLs fractions were analyzed and compared. Results showed that all three fractions have characteristic absorption peak of polysaccharides determined by FT-IR, and their monosaccharide composition only consisted of glucose determined by HPLC. PPSL10 had the highest contents of total sugar (88.09 ± 3.52%), uronic acid (2.55 ± 0.10%), and sulfate group (4.15 ± 0.20%). Besides, all three fractions exhibited immune-enhancing activities using RAW264.7 macrophages model, and PPSL10 was the best able to promote phagocytosis of neutral red and nitric oxide generation, which might relate to the high contents of above compositions and medium molecular weight (32 kDa). The findings indicated that PPSL10 could be developed as immune-modulator in the field of functional foods.

In recent years, small intestine as a key target in the treatment of Inflammatory bowel disease caused by NSAIDs has become a hot topic. Sanguinarine (SA) is one of the main alkaloids in the Macleaya cordata extracts with strong pharmacological activity of anti-tumor, anti-inflammation and anti-oxidant. SA is reported to inhibit acetic acid-induced colitis, but it is unknown whether SA can relieve NSAIDs-induced small intestinal inflammation. Herein, we report that SA effectively reversed the inflammatory lesions induced by indomethacin (Indo) in rat small intestine and IEC-6 cells in culture. Our results showed that SA significantly relieved the symptoms and reversed the inflammatory lesions of Indo as shown in alleviation of inflammation and improvement of colon macroscopic damage index (CMDI) and tissue damage index (TDI) scores. SA decreased the levels of TNF-α, IL-6, IL-1β, MDA and LDH in small intestinal tissues and IEC-6 cells, but increased SOD activity and ZO-1 expression. Mechanistically, SA dose-dependently promoted the expression of Nrf2 and HO-1 by decreasing Keap-1 level, but inhibited p65 phosphorylation and nuclear translocation in Indo-treated rat small intestine and IEC-6 cells. Furthermore, in SA treated cells, the colocalization between p-p65 and CBP in the nucleus was decreased, while the colocalization between Nrf2 and CBP was increased, leading to the movement of gene expression in the nucleus to the direction of anti-inflammation and anti-oxidation. Nrf2 silencing blocked the effects of SA. Together our results suggest that SA can significantly prevent intestinal inflammatory lesions induced by Indo in rats and IEC-6 cells through regulation of the Nrf2 pathway and NF-κBp65 pathway.

To date, little attention has been paid to the effects of leaf source reduction on photosynthetic matter production, root function and post-silking N uptake characteristics at different planting densities. In a 2-year field experiment, Xianyu 335, a widely released hybrid in China, was planted at 60 000 plants ha–1 (conventional planting density, CD) and 90 000 plants ha–1 (high planting density, HD), respectively. Until all the filaments protruded from the ear, at which point the plants were subjected to the removal of 1/2 (T1), 1/3 (T2) and 1/4 (T3) each leaf length per plant, no leaf removal served as the control (CK). We evaluated the leaf source reduction on canopy photosynthetic matter production and N accumulation of different planting densities. Under CD, decreasing leaf source markedly decreased photosynthetic rate (Pn), effective quantum yield of photosystem II (ΦPSII) and the maximal efficiency of photosystem II photochemistry (Fv/Fm) at grain filling stage, reduced post-silking dry matter accumulation, harvest index (HI), and the yield. Compared with the CK, the 2-year average yields of T1, T2 and T3 treatments decreased by 35.4, 23.8 and 8.3%, respectively. Meanwhile, decreasing leaf source reduced the root bleeding sap intensity, the content of soluble sugar in the bleeding sap, post-silking N uptake, and N accumulation in grain. The grain N accumulation in T1, T2 and T3 decreased by 26.7, 16.5 and 12.8% compared with CK, respectively. Under HD, compared to other treatments, excising T3 markedly improved the leaf Pn, ΦPSII and Fv/Fm at late-grain filling stage, increased the post-silking dry matter accumulation, HI and the grain yield. The yield of T3 was 9.2, 35.7 and 20.1% higher than that of CK, T1 and T2 on average, respectively. The T3 treatment also increased the root bleeding sap intensity, the content of soluble sugar in the bleeding sap and post-silking N uptake and N accumulation in grain. Compared with CK, T1 and T2 treatments, the grain N accumulation in T3 increased by 13.1, 40.9 and 25.2% on average, respectively. In addition, under the same source reduction treatment, the maize yield of HD was significantly higher than that of CD. Therefore, planting density should be increased in maize production for higher grain yield. Under HD, moderate decreasing leaf source improved photosynthetic performance and increased the post-silking dry matter accumulation and HI, and thus the grain yield. In addition, the improvement of photosynthetic performance improved the root function and promoted post-silking N uptake, which led to the increase of N accumulation in grain.

Genetically encoded calcium indicators have proven useful for characterizing dorsal root ganglion neuron excitability in vivo. Challenges persist in achieving high spatial–temporal resolutions in vivo, however, due to deep tissue imaging and motion artifacts that may be limiting technical factors in obtaining measurements. Here we report an ex vivo imaging method, using a peripheral neuron-specific Advillin-GCaMP mouse line and electric field stimulation of dorsal root ganglion tissues, to assess the sensitivity of neurons en bloc. The described method rapidly characterizes Ca(2+) activity in hundreds of dorsal root ganglion neurons (221 ± 64 per dorsal root ganglion) with minimal perturbation to the in situ soma environment. We further validate the method for use as a drug screening platform with the voltage-gated sodium channel inhibitor, tetrodotoxin. Drug treatment led to decreased evoked Ca(2+) activity; half-maximal response voltage (EV(50)) increased from 13.4 V in untreated tissues to 21.2, 23.3, 51.5 (p < 0.05), and 60.6 V (p < 0.05) at 0.01, 0.1, 1, and 10 μM doses, respectively. This technique may help improve an understanding of neural signaling while retaining tissue structural organization and serves as a tool for the rapid ex vivo recording and assessment of neural activity.

Mitochondrial proteins, most of which are encoded in the nucleus and the rest of which are regulated by the mitochondrial genome, play pivotal roles in essential cellular functions. However, fluorescent probes that can be used for monitoring mitochondrial proteins have not yet been widely developed, thereby severely limiting the exploration of the functions of proteins in mitochondria. Towards this end, here we propose a near-infrared (NIR) fluorescence probe MPP to effectively illuminate the dynamic changes in mitochondrial proteins in live cells under oxidative stress, with excellent temporal and spatial resolution. Of particular importance, MPP extends the study of the pharmacology involved in apoptosis induced by anti-cancer drugs (hydroxycamptothecin (HCPT), epirubicin (Epi) and cyclophosphamide (CPA)) for the first time. Furthermore, employing a protein-activatable strategy, this probe could serve as an excellent phototherapeutic agent in photodynamic therapy (PDT). Finally, in vivo experiments suggest that this versatile probe can be used to image tumors in HeLa tumor-bearing mice for 24 h, which demonstrates that our probe could play a dual role as a robust phototherapeutic and imaging agent.

The cube-like TiO2 mesocrystalline hollow boxes (TiO2-MHBs) are fabricated by a topotactic transformation method. TiO2-MHBs consist of one-dimensional nanorod-like rutile TiO2 combined with anatase TiO2. The ordering of TiO2-MHBs is in favor of efficient electron transport. TiO2-MHBs with mesoporous structure show excellent light scattering performance. Dye-sensitized solar cell with TiO2-MHBs light scattering overlayer exhibits an 18.3% increment of cell efficiency (9.51%) compared with the TiO2 nanoparticles film cell (8.04%). The improved photovoltaic performance is attributed to its unique crystallographic property and highly porous structure, which can enhance light scattering capability, quicken electron transport and electrolyte diffusion, and reduce charge recombination.

Five new polycyclic polyprenylated acylphloroglucinols (PPAPs), named mesuaferroic acids H, I, J, K and L (1–5), together with mesuaferroic acid C (6) and laxifloranone (7), were isolated from the petroleum ether extract of Mesua ferrea flower. Their structures were elucidated by comprehensive spectroscopic techniques including 1D, 2D NMR and HRESIMS. Compounds 1 and 7 exhibited excellent antibacterial activity against Staphylococcus aureus ATCC25923 and a series of multi-drug resistant Gram-positive clinic isolates and the MIC values ranged from 1.0 –16.0 μg/mL, which indicated that the PPAPs might be a new leading structure in antibiotic research.

Ecological security is the foundation and guarantee of sustainable development, and its importance is increasingly widely recognized and valued by the world. The Yangtze River Basin is an important ecological security barrier in China and the Wanjiang City Belt (WCB) along the Yangtze River is directly related to the ecological security pattern of the entire basin. Based on the Driver-Pressure-State-Impact-Response (DPSIR) model and a geographical information system (GIS) platform, an ecosystem security evaluation index system was constructed to measure and evaluate the evolution of ecosystem security in the WCB, China. Results showed that: 1) From 2000 to 2018, the overall level of ecological security in the study area was in a state of either early warning or medium warning, but the level of ecological security in each prefecture-level city was significantly different. 2) From the perspective of the evolution of the ecosystem, the value of its comprehensive evaluation index dropped from 4.255 in 2000 to 3.885 in 2018. From the perspective of subsystems, the value of Pressure comprehensive evaluation index is much higher than that of other subsystems, indicating that during the rapid development of the social economy, the pressure on the natural environment tended to rise, and triggered changes in the State and Response subsystems. 3) The coefficient of variation (CV) of the Driver was much higher than other factors influencing the ecological security system. There are large differences in the economic development and ecological evolution of the cities in the WCB. This study has improved the theoretical research on regional ecological security, and has certain practical guiding significance for building a beautiful, green and sustainable China and promoting global ecological security.

The assessment of vehicle dynamic comfort to human body vibration varies from person to person. Even though the dynamic comfort rating can be obtained by placing measurement devices over the cabin, passengers may have dissimilar sensations. For many car manufacturers, both subject and objective measurements are used together at development of new cars. To effectively assess the dynamic comfort of vehicle, this research explores the correlation between the objective measurement of the whole body vibration, hand-transmitted vibration and subjective assessment. The whole body vibration is measured from the backrest, seat surface and vehicle floor, whereas the hand-transmitted vibration is measured from the steering wheel. Four different vehicles are driven at various speeds on five types of pavements. Both simple linear regression and polynomial regression models based on Stevens’s power law from psychophysics are built to correlate the subjective and objective data. The regression results show that (1) the seat surface is more reliable than other positions for assessing the human body vibration; (2) the hand transmitted vibration on rough roads is more trustful for dynamic comfort evaluation than on smooth roads; (3) the overall dynamic comfort value is the most reliable index for dynamic comfort evaluation.

This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies, including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway, anti-oxidative stress effects, enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway, increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway, and reducing the activity of the hypothalamic-pituitary-adrenocortical axis. We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning, shallow depth of stimulation, and difficulty in elucidating the neural circuit mechanism up- and down-stream of the stimulation target brain region.

Epstein-Barr virus (EBV) is a γ-herpesvirus associated with the occurrence of several human malignancies. BBRF2 and BSRF1 are two EBV tegument proteins that have been suggested to form a hetero-complex and mediate viral envelopment, but the molecular basis of their interaction and the functional mechanism of this complex remains unknown. Here, we present crystal structures of BBRF2 alone and in complex with BSRF1. BBRF2 has a compact globular architecture featuring a central β-sheet that is surrounded by 10 helices, it represents a novel fold distinct from other known protein structures. The central portion of BSRF1 folds into two tightly associated antiparallel α-helices, forming a composite four-helix bundle with two α-helices from BBRF2 via a massive hydrophobic network. In vitro, a BSRF1-derived peptide binds to BBRF2 and reduces the number of viral genome copies in EBV-positive cells. Exogenous BBRF2 and BSRF1 co-localize at the Golgi apparatus. Furthermore, BBRF2 binds capsid and capsid-associated proteins, whereas BSRF1 associates with glycoproteins. These findings indicate that the BBRF2-BSRF1 complex tethers EBV nucleocapsids to the glycoprotein-enriched Golgi membrane, facilitating secondary envelopment., Epstein-Barr virus (EBV) tegument proteins BBRF2 and BSRF1 have been suggested to form a hetero-complex. Here, He et al. provide the crystal structures of BBRF2 alone and in complex with BSRF1 and suggest that the complex tethers EBV nucleocapsids to the Golgi membrane, facilitating secondary envelopment.

The rise of the plasmid-encoded colistin resistance gene mcr-1 is a major concern globally. Here, during a routine surveillance, an unexpectedly high prevalence of Escherichia coli with reduced susceptibility to colistin (69.9%) was observed in a Chinese broiler farm. Fifty-three (63.9%) E. coli isolates were positive for mcr-1. All identified mcr-1-positive E. coli (MCREC) were multidrug resistant and carried other clinically significant resistance genes. Furthermore, the mcr-1 genes were mainly located on the IncI2 and IncHI2 plasmids. Conjugation experiments unraveled the co-transfer of mcr-1 with other antibiotic resistance genes (blaCTX-M-55, blaCTX-M-14, floR, and fosA3) via the IncI2 (n=3) and IncHI2 (n=4) plasmids. The stable genetic context mcr-1-pap2 was common in the IncI2 plasmids, whereas ISApl1-mcr-1-pap2-ISApl1 was mainly found in the IncHI2 plasmids. The dominance of mcr-1-bearing IncI2 and IncHI2 plasmids and co-selection of mcr-1 with other antimicrobial resistance genes might contribute to the exceptionally high prevalence of mcr-1 in this broiler farm. Our results emphasized the importance of appropriate antibiotic use in animal production.

The stability and processing of cellular RNA transcripts are efficiently controlled via non-templated addition of single or multiple nucleotides, which is catalyzed by various nucleotidyltransferases including poly(A) polymerases (PAPs). Germline development defective 2 (GLD-2) is among the first reported cytoplasmic non-canonical PAPs that promotes the translation of germline-specific mRNAs by extending their short poly(A) tails in metazoan, such as Caenorhabditis elegans and Xenopus. On the other hand, the function of mammalian GLD-2 seems more diverse, which includes monoadenylation of certain microRNAs. To understand the structural basis that underlies the difference between mammalian and non-mammalian GLD-2 proteins, we determine crystal structures of two rodent GLD-2s. Different from C. elegans GLD-2, mammalian GLD-2 is an intrinsically robust PAP with an extensively positively charged surface. Rodent and C. elegans GLD-2s have a topological difference in the β-sheet region of the central domain. Whereas C. elegans GLD-2 prefers adenosine-rich RNA substrates, mammalian GLD-2 can work on RNA oligos with various sequences. Coincident with its activity on microRNAs, mammalian GLD-2 structurally resembles the mRNA and miRNA processor terminal uridylyltransferase 7 (TUT7). Our study reveals how GLD-2 structurally evolves to a more versatile nucleotidyltransferase, and provides important clues in understanding its biological function in mammals.

A compact planar directional coupled crossover with a wide fractional bandwidth is proposed in this letter, which is composed of overlapping planar 3-dB couplers based on the substrate integrated waveguide (SIW) and stripline techniques. In the proposed structure, the TE10 mode and TEM mode can be transmitted simultaneously without any interaction, which is helpful to design and integrate the SIW and stripline couplers for realizing a wideband directional coupled crossover with a compact footprint. A prototype with a center frequency of 26 GHz for 5G applications is designed and fabricated. The experimental results show that the measured crossover has high isolation among all ports and good directional coupling performance in orthogonal directions. The proposed crossover has a compact footprint and low loss, which can be a good candidate for developing the miniature feeding networks for multiple beam antennas.

In this work, we developed a rapid and high-sensitivity method for simultaneous analyses of fatty alcohols, fatty aldehydes, and sterols by combining the optimized derivatization reaction with electrospray ionization-ion mobility-mass spectrometry (ESI-IM-MS). Pyridine and thionyl chloride were used as derivatization reagents as they were easily removed after the derivatization reaction and could generate permanently charged tags on different functional groups including hydroxyls and aldehydes. Through this one-step derivatization reaction, the sensitivity of detection for fatty alcohols, fatty aldehydes, and sterols was significantly increased. Moreover, the introduction of ion mobility spectrometry (IMS), offering an additional resolution power, ensured more sensitive and accurate detection of derivative products without increasing analytical time. Being connected with high-performance liquid chromatography, more than 15 kinds of compounds were analyzed within 4 min. Relative quantification using peak intensity ratios between d0-/d5-labeled ions were subsequently applied for analyzing these 15 kinds of compounds in human thyroid carcinoma and para-carcinoma tissues. The results showed significant differences in content of some analytes between these two kinds of tissues (p < 0.05). The correlations between most of the analytes in thyroid carcinoma tissues are better than the correlations in para-carcinoma tissues.

We advocate that innovation carriers proactively grow their own intellectual property, including venture capital investment funds, local governments, industrial clusters, science and technology parks, and peculiarly to China, the High-speed Rail sector. We believe that the timing is right for this novel approach because China's innovation economy is fast becoming world's largest by some measure, and this economy increasingly puts IP at the core, which bridges innovation to value. Via a string of 2019 events and initiatives in China, the public was made much aware of the fact that IP is worth a lot of value: the July opening of the Sci-Tech innovAtion Board (STAR 科创板) of the Shanghai Stock Exchange, which has the explicit purpose of registering companies that are considered high-tech, thus regards highly a listed company's innovation capacity and intellectual property; the July estimate of 24 billion RMB value for the more than 53,000 invention patents granted in the year of 2018 to applicants from Guangdong Province; and the September sale of China's first-of-the-kind securitization of patent license fees. These initiatives show that IP manifests its value in different ways for different innovation carriers, which leads to our proposal that all innovation carriers grow their own IP serving their own purposes, and we consider our proposal an application of Paul Romer's endogenous growth model which encourages the production of knowledge and patents.

Currently in single-cell mass spectrometry, the analysis of low-abundance cell metabolites such as fatty alcohols and sterols remains a challenge. In most research studies, single-cell samples are analyzed directly after sampling. However, this workflow may exclude many effective sample pretreatment methods such as derivatization for the improvement of detection sensitivity for specific cell metabolites in a single-cell sample. Metabolites in low abundance in a cell may not be detected. Herein on-probe derivatization coupled with noncontact nanocarbon fiber ionization is proposed for sensitive fatty alcohol and sterol metabolite analysis at the single-cell level. Fatty alcohol and sterol metabolites were rapidly quaternized by the single-cell on-probe derivatization method. The reaction products were directly ionized with no postreaction processing. Furthermore, a new ionization source for noncontact nanocarbon fiber ionization was developed to show good compatibility with dichloromethane, a low-polarity solvent used in on-probe derivatization. The quaternized fatty alcohols and sterols exhibited evidently enhanced ionization efficiency in mass spectra. In applications of the developed method, seven kinds of even-numbered-carbon fatty alcohols (C12-C22) and five kinds of sterols were detected in single L-02 and HepG2 cells. Then the L-02 and HepG2 cells were readily discriminated through principal component analysis. Additionally, a rough quantitative analysis of the detected fatty alcohols and sterols in single cells was performed. The mass intensities of fatty alcohols show a significant difference between L-02 and HepG2 cells while those of sterols remain stable.

The anticancerous effects of PCHPs (HBSS, CHSS, DASS, and CASS) were investigated on Human cervical cancer Hela cells proliferation inhibition, cytotoxicity, caspase-3 activity, cell cycle, and apoptosis. The inhibition rate was expressed as CASS > HBSS > CHSS > DASS, with the maximum inhibition of 74.453 ± 3.399%. Cell cytotoxicity was observed (CASS > CHSS > HBSS > DASS) with the maximum cell death rate of 82.472 ± 3.488%. The caspase-3 activity was induced by CASS > HBSS > DASS > CHSS, with the maximum multiple of 2.954 ± 0.103. CASS induced cell cycle block at the G2/M phase by elevating mRNA expression of CyclinD1, p21, p53 and Wee1, and lowering the expression of Survivin, CHK2, Wee1, CyclinB1, and CDK-1. CASS enhanced the mRNA expression of DR3, DR5, FasL, FADD, PARP, TNF- α, TNF- R1, TRDAA, caspases-8, caspases-10 and the protein expression of FasL and caspases-8, -10 in the death receptor pathway; while, lowered the mRNA expression of antiapoptotic genes (Bcl - 2 and Bcl-xL) and the protein expression of Bcl - 2. The mRNA expression of apoptosis genes (Bak, Cytc, Puma, and caspases-3, -7, -9) and the protein expression of caspases-3, -9 of mitochondria pathway was up regulated which led to cell apoptosis.

Fms-like tyrosine kinase 3 (FLT3) mutation has been strongly associated with increased risk of relapse, and the irreversible covalent FLT3 inhibitors had the potential to overcome the drug-resistance. In this study, a series of simplified 4-(4-aminophenyl)-6-methylisoxazolo[3,4-b] pyridin-3-amine derivatives containing two types of Michael acceptors (vinyl sulfonamide, acrylamide) were conveniently synthesized to target FLT3 and its internal tandem duplications (ITD) mutants irreversibly. The kinase inhibitory activities showed that compound C14 displayed potent inhibition activities against FLT3 (IC

In this study, we explored a novel approach to enhancing the production and bioactivities of Ganoderma exopolysaccharides. The homologous phosphomannomutase gene (PMM1) was cloned and overexpressed in Ganoderma for the first time. As a result, the maximum production of exopolysaccharides by the PMM1 transformant was 1.53 g/L, which was 1.41-fold higher than of a wild-type (WT) strain in a 5-L bioreactor. The transcription levels of PMM1 and PMM2 increased 40.5- and 2.4-fold, respectively, whereas the value of the GDP-D-mannose pyrophosphorylase gene did not change significantly in this transgenic strain. Furthermore, the major exopolysaccharide fractions from PMM1 transformants contained higher amounts of mannose (56.5 % and 21.1 %) than those from a WT strain (26.7 % and 9.3 %). Moreover, the major fractions from PMM1 transformants exhibited stronger regulation effects on macrophage. In conclusion, this study is helpful for the efficient production and application of Ganoderma exopolysaccharides and facilitates an understanding of polysaccharide biosynthesis regulation.

Low-dose interleukin-2 (LD-IL-2) treatment has been shown to effectively reverse chronic migraine-related behaviors and the sensitization of trigeminal ganglion (TG) neurons through expansion and activation of peripheral regulatory T cells (Tregs) in mice. In this study, we investigated the molecular mechanisms underlying the effects of LD-IL-2 and Treg cells. LD-IL-2 treatment increases the production of cytokines interleukin-10 (IL-10) and transforming growth factor beta-1 (TGFβ1) in T cells, especially Treg cells, suggesting that they may mediate the therapeutic effect of LD-IL-2. Indeed, neutralizing antibodies against either IL-10 or TGFβ completely blocked the effects of LD-IL-2 on the facial mechanical hypersensitivity as well as the sensitization of TG neurons resulting from repeated nitroglycerin (NTG, a reliable trigger of migraine in patients) administration in mice, indicating that LD-IL-2 and Treg cells engage both peripheral IL-10 and TGFβ signaling pathways to reverse chronic-migraine related sensitizations. In an

Glioblastoma is the most common primary tumor in the central nervous system, and thrombosis-associated genes are related to its occurrence and progression. Univariate Cox and LASSO regression analysis were utilized to develop a new prognostic signature based on thrombosis-associated genes. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and HALLMARK were used for functional annotation of risk signature. ESTIMATE, MCP-counter, xCell, and TIMER algorithms were used to quantify immune infiltration in the tumor microenvironment. Genomics of Drug Sensitivity in Cancer (GDSC) was used for selecting potential drug compounds. Risk signature based on thrombosis-associated genes shows moderate performance in prognosis prediction. The functional annotation of the risk signature indicates that the signaling pathways related to the cell cycle, apoptosis, tumorigenesis, and immune suppression are rich in the high-risk group. Somatic mutation analysis shows that tumor-suppressive gene TP53 and oncogene PTEN have higher expression in low-risk and high-risk groups, respectively. Potential drug compounds are explored in risk score groups and show higher AUC values in the low-risk score group. A nomogram with valuable prognostic factors exhibits high sensitivity in predicting the survival outcome of GBM patients. Our research screens out multiple thromboses-associated genes with remarkable clinical significance in GBM and further develops a meaningful prognostic risk signature predicting drug sensitivity and survival outcome.

The solar flare is a sudden eruptive solar phenomenon with significant enhancements in solar X-ray and Extreme Ultraviolet radiations, resulting in large amounts of energy being injected into the planetary atmosphere. Case studies have been extensively presented to analyze the effect of extremely large flares on the Martian upper atmosphere, but the general features of the Martian thermospheric response to flares are still poorly understood. In this work, we select 12 intense solar flares that occurred between 2015 and 2017 and investigate the densities and compositional variations of the dayside Martian thermosphere to these flares with the aid of the measurements made by the Mars Atmosphere and Volatile EvolutioN. The statistical studies indicate that the responses of the Martian thermosphere to flares are complicated that both the class of the flare and the wavelength of the enhanced radiation may have prominent influences on the thermal expansion of the atmosphere and the atmospheric photochemical reactions.

Zinc oxide nanoparticles (ZnO-NPs) have gained significant interest in the agricultural and food industry as a means of killing or reducing the activity of microorganisms. The antibacterial properties of ZnO-NPs may improve food quality, which has a direct impact on human health. ZnO-NPs are one of the most investigated inorganic nanoparticles and have been used in various related sectors, with the potential to rapidly gain attention and increase interest in the agriculture and food industries. In this review, we describe various methods for preparing ZnO-NPs, their characterizations, modifications, applications, antimicrobial activity, testing procedures, and effects, including bactericidal and bacteriostatic mechanisms. It is hoped that this review could provide a better understanding of the preparation and application of ZnO nanoparticles in the field of food and agriculture, and promote their development to advance the field of food and agriculture.

Excessive manganese (Mn) exposure produces neurotoxicity with mitochondrial damage. Mitophagy is a protective mechanism to eliminate damaged mitochondria to protect cells. The aim of this study was to determine the dose-response of Mn-induced mitochondria damage, the expression of mitophagy-mediated protein PINK1/Parkin and mitophagy in dopamine-producing SK-N-SH cells. Cells were exposed to 0, 300, 900, and 1500 μM Mn2+ for 24 h, and ROS production, mitochondrial damage and mitophagy were examined. The levels of dopamine were detected by ELISA and neurotoxicity and mitophagy-related proteins (α-synuclein, PINK1, Parkin, Optineurin, and LC3II/I) were detected by western blot. Mn increased intracellular ROS and apoptosis and decreased mitochondrial membrane potential in a concentration-dependent manner. However, at the low dose of 300 μM Mn, autophagosome was increased 11-fold, but at the high dose of 1500 μM, autophagosome was attenuated to 4-fold, together with decreased mitophagy-mediated protein PINK1/Parkin and LC3II/I ratio and increased Optineurin expression, resulting in increased α-synuclein accumulation and decreased dopamine production. Thus, Mn-induced mitophagy exhibited a novel biphasic regulation: at the low dose, mitophagy is activated to eliminate damaged mitochondria, however, at the high dose, cells gradually loss the adaptive machinery, the PINK1/Parkin-mediated mitophagy weakened, resulting in neurotoxicity.

The first complete mitochondrial genome of Euroleon coreanus (Okamoto, 1926) was 15,797 bp in length, and contained 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and the control region. Compared to the classic insect mitochondrial genome, E. coreanus showed a gene rearrangement of ND2-C-W-Y-COX1. The overall AT content of the mitochondrial genome was 75.5%. The monophyly of Ascalaphidae, Myrmeleontidae, Nemopteridae, Nymphidae, and Psychopsidae was supported in both BI and ML trees. And E. coreanus was a sister clade to the clade of genus Myrmeleon.

Deep partial-thickness and full-thickness burn wounds often undergo tangential excision or escharectomy to expose healthy tissue, combined with skin grafting to promote wound healing. However, conventional tangential excision with the humby knife leads to inevitable damage to the dermis while excising burn tissue due to the lack of precision. Indeed, the preservation of dermal tissue is a key factor in determining wound healing and scar quality. The precision and tissue selectivity of the Versajet Hydrosurgical System has been established for excising burn tissue while preserving dermal tissue. In this study, we retrospectively compared the efficacy of "Hydrosurgical excision combined with skin grafting" and "Conventional tangential excision combined with skin grafting" in treating deep partial-thickness and full-thickness burn wounds to demonstrate that hydrosurgery improved the treatment of deep partial-thickness and full-thickness burns.A total of 86 patients with deep partial-thickness and/or full-thickness burns with a total burn surface area (TBSA) ≤ 25% from July 2018 to July 2020 were included in this study and were divided into experimental (hydrosurgical excision combined with skin grafting, n = 43) and control (conventional tangential excision combined with skin grafting, n = 43) groups. Parameters were analyzed, including the intraoperative blood loss volume per unit area of grafted skin, surgery duration, wound healing time, skin graft survival, and the treatment costs per unit of burned area. Scar assessment was performed at 1 year with the modified Vancouver Scar Scale linked with TBSA (mVSS-TBSA).No significant difference was found in male to female ratio, age, weight, TBSA, burn depth, skin grafting area (SKA), skin grafting methods, cases treated with carbon dioxide fractional laser or incidence of inhalation injury, and the incidence of hypovolemic shock between two groups(p 0.05). Compared with the control group, patients treated with hydrosurgical excision combined with skin grafting experienced less intraoperative blood loss volume per unit area of grafted skin (p 0.05). The mVSS-TBSA of patients that underwent hydrosurgical excision combined with skin grafting was significantly improved in comparison to the control group (p 0.01). No significant difference was found in surgery duration, wound healing time, skin graft survival and treatment costs per unit of burned area between the two groups (p 0.05).Hydrosurgical excision combined with skin grafting reduced intraoperative blood loss volume per unit area of grafted skin, improved scarring 1-year after injury, and did not increase the treatment costs per unit of burned area. This technique provides a novel alternative for managing deep partial-thickness and full-thickness burn wounds.