Plasma exosomal miR-30a-5p inhibits osteogenic differentiation of bone marrow mesenchymal stem cells from a chronic unpredictable mild stress-induced depression rat model.

With rising society stress, depression-induced osteoporosis is increasing. However, the mechanism involved is unclear. In this study, we explored the effect of plasma exosomal miRNAs on bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation in a chronic unpredictable mild stress (CUMS)-induced depression rat model. After 12 weeks of CUMS-induced depression, the pathological changes in the bone tissue and markers of osteogenic differentiation were tested by micro-computed tomography, hematoxylin-eosin staining, and quantitative real-time reverse transcription PCR (qRT-PCR). Plasma exosomes from rats were isolated and co-incubated with BMSCs for 14 d to detect the effect on osteogenic markers. Next-generation sequencing identified the miRNAs in the plasma exosomes, and the differential miRNAs were analyzed and verified by qRT-PCR. BMSCs were infected with lentivirus to upregulate miRNA-30a-5p and incubated in a medium that induced osteogenic differentiation for 14 d. The effect of miR-30a-5p on osteogenic differentiation was determined by qPCR and alizarin red staining. CUMS-induced depression rat model was established successfully, and exhibited reduced bone mass and damaged bone microstructure compared to that of the controls. The observed pathological changes suggested the occurrence of osteoporosis in the CUMS group, and the mRNA expression of osteogenic markers was also significantly reduced. Incubation of BMSCs with plasma exosomes from the CUMS group for 14 d resulted in a significant decrease in the expression of osteogenic markers. Twenty-five differentially expressed miRNAs in plasma exosomes were identified and upregulation of miR-30a-5p was observed to significantly inhibit the expression of osteogenic markers in BMSCs. Our findings contributed to a comprehensive understanding of the mechanism of osteoporosis caused by depression, and demonstrated the potential of miR-30a-5p as a novel biomarker or therapeutic target for the treatment of osteoporosis.

Site-specific protein conjugates incorporating Para-Azido-L-Phenylalanine for cellular and in vivo imaging.

This work features the use of amber suppression-mediated unnatural amino acid (UAA) incorporation into proteins for various imaging purposes. The site-specific incorporation of the UAA, p-azido-L-phenylalanine (pAzF), provides an azide handle that can be used to complete the strain promoted azide-alkyne click cycloaddition (SPAAC) reaction to introduce an imaging modality such as a fluorophore or a positron emission tomography (PET) tracer on the protein of interest (POI). Such methodology can be pursued directly in mammalian cell lines or on proteins expressed in vitro, thereby conferring a homogeneous pool of protein conjugates. A general procedure for UAA incorporation to use with a site-specific protein labeling method is provided allowing for in vitro and in vivo imaging applications based on the representative proteins PTEN and PD-L1. This approach would help elucidate the cellular or in vivo biological activities of the POI.

ALKBH5-YTHDF2 m6A modification axis inhibits rheumatoid arthritis progression by suppressing NLRP3.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Recently, NLRP3 has been demonstrated to be closely related to RA. The objective of our research was to analyze the specific mechanism of NLRP3 in RA. The m6A levels of NLRP3 was detected with methylated RNA immunoprecipitation (MeRIP) kit. The mRNA and protein levels of related genes were tested with RT-qPCR and Western blot. The inflammatory factors levels were detected with ELISA kits. The cell proliferative ability was measured with CCK-8 and EdU staining assays. NLRP3 levels was prominently in synovial tissues and fibroblast-like synoviocytes (FLS) from RA patients. NLRP3 silencing suppressed FLS proliferation and inflammatory factor levels. Additionally, ALKBH5 was found to bind with NLRP3, and ALKBH5 silencing suppressed FLS proliferation and inflammatory factor levels while NLRP3 overexpressing neutralized the role of ALKBH5 in FLS. Furthermore, m6A modified induced by ALKBH5 suppressed NLRP3 mRNA level through YTHDC2 in RA, and NLRP3 is a hinge factor in RA progression.

Upgrading the genome of an elite japonica rice variety Kongyu 131 for lodging resistance improvement.

Developing a new rice variety requires tremendous efforts and years of input. To improve the defect traits of the excellent varieties becomes more cost and time efficient than breeding a completely new variety. Kongyu 131 is a high-performing japonica variety with early maturity, high yield, wide adaptability and cold resistance, but the poor-lodging resistance hinders the industrial production of Kongyu 131 in the Northeastern China. In this study, we attempted to improve the lodging resistance of Kongyu 131 from perspectives of both gene and trait. On the one hand, by QTL analysis and fine mapping we discovered the candidate gene loci. The following CRISPR/Cas9 and transgenic complementation study confirmed that Sd1 dominated the lodging resistance and favourable allele was mined for precise introduction and improvement. On the other hand, the Sd1 allelic variant was identified in Kongyu 131 by sequence alignment, then introduced another excellent allelic variation by backcrossing. Then, the two new resulting Kongyu 131 went through the field evaluation under different environments, planting densities and nitrogen fertilizer conditions. The results showed that the plant height of upgraded Kongyu 131 was 17%-26% lower than Kongyu 131 without penalty in yield. This study demonstrated a precise and targeted way to update the rice genome and upgrade the elite rice varieties by improving only a few gene defects from the perspective of breeding.

Specific detection of Phytophthora parasitica by recombinase polymerase amplification (RPA) assays based on a unique multi-copy genomic sequence.

Phytophthora parasitica is a highly destructive oomycete plant pathogen that is capable of infecting a wide range of hosts including many agricultural cash crops, fruit trees, and ornamental garden plants. One of the most important diseases caused by P. parasitica worldwide is black shank of tobacco. Rapid, sensitive, and specific pathogen detection is crucial for early rapid diagnosis which can facilitate effective disease management. In this study, we used a genomics approach to identify repeated sequences in the genome of P. parasitica by genome sequence alignment, and identified a 203 bp P. parasitica-specific sequence, PpM34, that is present in 31-60 copies in the genome. The P. parasitica genome-specificity of PpM34 was supported by PCR amplification of 24 genetically diverse strains of P. parasitica, 32 strains representing twelve other Phytophthora species, one Pythium specie, six fungal species and three bacterial species, all of which are plant pathogens. Our PCR and real-time PCR assays showed that the PpM34 sequence was highly sensitive in specifically detecting P. parasitica. Finally, we developed a PpM34-based high-efficiency Recombinase Polymerase Amplification (RPA) assay, which allowed us to specifically detect as little as 1 pg of P. parasitica total DNA from both pure cultures and infected Nicotiana benthamiana at 39°C using a fluorometric thermal cycler. The sensitivity, specificity, convenience and rapidity of this assay represents a major improvement for early diagnosis of P. parasitica infection.

LightR-YOLOv5: A compact rotating detector for SARS-CoV-2 antigen-detection rapid diagnostic test results.

Nucleic acid testing is currently the golden reference for coronaviruses (SARS-CoV-2) detection, while the SARS-CoV-2 antigen-detection rapid diagnostic tests (RDT) is an important adjunct. RDT can be widely used in the community or regional screening management as self-test tools and may need to be verified by healthcare authorities. However, manual verification of RDT results is a time-consuming task, and existing object detection algorithms usually suffer from high model complexity and computational effort, making them difficult to deploy. We propose LightR-YOLOv5, a compact rotating SARS-CoV-2 antigen-detection RDT results detector. Firstly, we employ an extremely light-weight L-ShuffleNetV2 network as a feature extraction network with a slight reduction in recognition accuracy. Secondly, we combine semantic and texture features in different layers by judiciously combining and employing GSConv, depth-wise convolution, and other modules, and further employ the NAM attention to locate the RDT result detection region. Furthermore, we propose a new data augmentation approach, Single-Copy-Paste, for increasing data samples for the specific task of RDT result detection while achieving a small improvement in model accuracy. Compared with some mainstream rotating object detection networks, the model size of our LightR-YOLOv5 is only 2.03MB, and it is 12.6%, 6.4%, and 7.3% higher in mAP@.5:.95 metrics compared to RetianNet, FCOS, and R3Det, respectively.

Revealing the Role of Surface Wettability in Ionic Detection Signals of Nanofluidic-Based Chemical Sensors.

The nanofluidic ionic signal is governed by the interactions between ion species and the surface charge, surface wettability, and pore diameter of nanofluidic membranes. However, the effect of surface wettability on the ionic detection signal across the nanofluidic membrane remains poorly explored, limited nanofluidic applications in biochemical sensing. Here, we investigate the effect of surface wettability of the nanofluidic membrane on the ionic signal for the detection of hydrophobic drug molecules using a heterogeneous nanofluidic system. This ionic signal can be tuned by light or the presence of certain ions due to the tailoring of hydrophobic interactions between the ion species and membrane surface. Compared with traditional nanofluidic membranes whose ionic signal is governed by surface charge, the regulation mechanism reported here mainly dependents on specific hydrophobic interactions, which shows a more sensitive ionic signal to environments. By virtue of the mechanism, the selective detection of the three drug molecules was realized owing to their different hydrophobic interactions with membrane surfaces. These findings have implications for understanding mass transport in nanofluidic devices and biological components and porous media involving surface wettability in nanofluidic systems.

Semi-syntheses and interrogation of indole-substituted Aspidosperma terpenoid alkaloids.

We demonstrated here a series of Aspidosperma terpenoid alkaloids can be quickly prepared using semisynthesis from naturally sourced tabersonine, featuring multiple oxygen-based substituents on the indole ring such as hydroxy and methoxy groups. This panel of complex compounds enabled the exploration of indole modifications to optimize the indole alkaloids' anticancer activity, generating lead compounds (e.g., with C15-hydroxy, C16-methoxy, and/or C17-methoxy derivatizations) that potently inhibit cancer cell line growth in the single-digit micromolar range. These results can help guide the development of Aspidosperma terpenoid alkaloid therapeutics. Furthermore, this synthetic approach features late-stage facile derivatization on complex natural product molecules, providing a versatile path to indole derivatization of this family of alkaloids with diverse chemical functionalities for future medicinal chemistry and chemical biology discoveries.

A tumor-targeted immune checkpoint blocker.

To direct checkpoint inhibition to the tumor microenvironment, while avoiding systemic immune activation, we have synthesized a bispecific antibody [norleucine4, d-Phe7]-melanocyte stimulating hormone (NDP-MSH)-antiprogrammed cell death-ligand 1 antibody (αPD-L1) by conjugating a melanocyte stimulating hormone (α-MSH) analog to the antiprogrammed cell death-ligand 1 to (αPD-L1) antibody avelumab. This bispecific antibody can bind to both the melanocortin-1 receptor (MC1R) and to PD-L1 expressed on melanoma cells and shows enhanced specific antitumor efficacy in a syngeneic B16-SIY melanoma mouse model compared with the parental antibody at a 5 mg/kg dose. Moreover, the bispecific antibody showed increased infiltrated T cells in the tumor microenvironment. These results suggest that a tumor-targeted PD-L1-blocking bispecific antibody could have a therapeutic advantage in vivo, especially when used in combination with other checkpoint inhibitors.

Steric-Free Bioorthogonal Labeling of Acetylation Substrates Based on a Fluorine-Thiol Displacement Reaction.

We have developed a novel bioorthogonal reaction that can selectively displace fluorine substitutions alpha to amide bonds. This fluorine-thiol displacement reaction (FTDR) allows for fluorinated cofactors or precursors to be utilized as chemical reporters, hijacking acetyltransferase-mediated acetylation both in vitro and in live cells, which cannot be achieved with azide- or alkyne-based chemical reporters. The fluoroacetamide labels can be further converted to biotin or fluorophore tags using FTDR, enabling the general detection and imaging of acetyl substrates. This strategy may lead to a steric-free labeling platform for substrate proteins, expanding our chemical toolbox for functional annotation of post-translational modifications in a systematic manner.

Waist-to-height ratio and non-alcoholic fatty liver disease in adults.

BACKGROUND: The waist-to-height ratio (WHtR) has been recognised as a powerful indicator to evaluate non-alcoholic fatty liver disease (NAFLD) in recent years, but few related studies are available. Thus, clarifying the association between the WHtR and NAFLD may be beneficial to the prevention and treatment of NAFLD. METHODS: The cross-sectional study population was from a large-scale health examination programme called 'human dock' in Japan. In this study, 14,125 participants in this health examination programme were included. To understand the association between the WHtR and NAFLD more intuitively, we grouped the WHtR values into quintiles and used a multivariable logistic regression model to assess WHtR and its quintile with NAFLD risk. Moreover, we used the generalised additive model to model the association between WHtR and NAFLD to explore their non-linear relationship. RESULTS: The prevalence of NAFLD among participants in this study was 17.59%, with an average age of 43.53 ± 8.89 years. After adjusting for all non-collinear covariables, we observed a 66% increase in the NAFLD risk per SD increase in WHtR. Furthermore, in the quintile groups of WHtR, the participants in quintile 2, quintile 3, quintile 4, and quintile 5 had 3.62-fold, 5.98-fold, 9.55-fold, and 11.08-fold increased risks of NAFLD, respectively, compared with those in quintile 1 (Ptrend < 0.0001). Non-linear relationship analysis revealed threshold and saturation effects between WHtR and NAFLD in which a WHtR of approximately 0.4 might be the threshold effect of NAFLD risk, 0.6 might be the saturation effect of NAFLD risk. Additionally, subgroup analysis showed that the interaction between WHtR and BMI was significant. CONCLUSIONS: Our results suggest that in adults, the WHtR is associated with NAFLD, and the association is not purely linear but non-linear, with significant threshold and saturation effects.

Arbutin attenuates ethanol-induced acute hepatic injury by the modulation of oxidative stress and Nrf-2/HO-1 signaling pathway.

Alcoholic liver disease (ALD) is a pervasive ailment due to the excessive consumption of alcohol and there is no operative drug for its treatment. The current exploration was intended to examine the hepatoprotective efficacy of arbutin against ethanol-provoked liver injury in rats via the modulation of the Nrf-2/HO-1 signaling cascade. Wistar rats were challenged with the 3 g/kg/day (40% v/v) of ethanol for 4 weeks to provoke the ALD and concomitantly supplemented with 40 mg/kg of arbutin. The liver function markers enzymes, inflammatory cytokines, and oxidative stress markers levels were scrutinized by using the respective assay kits. The mRNA expression of Nrf-2/HO-1 signaling proteins was studied by reverse-transcription polymerase chain reaction. The histological alterations of liver tissues were examined. HepG2 cells were used for the in vitro studies. The levels of oxidative stress markers and liver marker enzymes were examined by using kits. Reactive oxygen species (ROS) and apoptotic cell death was detected by using fluorescent staining. There were no major differences in the body weight and liver weight of experimental animals. Arbutin treatment appreciably reduced the liver marker enzymes, upregulated superoxide dismutase, glutathione peroxidase, total antioxidant capacity, and the hydroxyl scavenging ability, and diminished the tumor necrosis factor-α and interleukin-6 levels in the serum of ethanol provoked animals. Arbutin triggered Nrf-2/HO-1 signaling cascade liver tissues of ethanol-provoked animals. Histological findings proved the preventing effects of arbutin. Arbutin did not demonstrate toxicity to the HepG2 cells. It reduced the aspartate aminotransferase and alanine aminotransferase, ROS, apoptotic cell death, lipid peroxidation and improved the antioxidants' levels in the ethanol-challenged HepG2 cells. In conclusion, our findings unveiled the hepatoprotective efficacy of arbutin against ethanol-provoked liver injury in rats. It could be a promising agent to treat alcoholic liver disease in the future.

Usefulness of the triglyceride glucose-body mass index in evaluating nonalcoholic fatty liver disease: insights from a general population.

BACKGROUND: Triglyceride glucose-body mass index (TyG-BMI) is a recently developed alternative indicator to identify insulin resistance. However, few studies have investigated the association between the TyG-BMI and nonalcoholic fatty liver disease (NAFLD). Therefore, this study aimed to study the relationship between NAFLD and the TyG-BMI in the general population and its predictive value. METHODS: A cross-sectional study was conducted on 14,251 general subjects who took part in a comprehensive health examination. The anthropological characteristics and many risk factors for NAFLD were measured. RESULTS: After fully adjusting for confounding variables, a stable positive correlation was found between NAFLD and the TyG-BMI (OR: 3.90 per SD increase; 95% CI: 3.54 to 4.29; P-trend< 0.00001). This positive correlation was not simply linear but a stable non-linear correlation. Additionally, obvious threshold effects and saturation effects were found, in which a threshold effect occurred when the TyG-BMI was between 100 and 150; when the TyG-BMI was between 300 and 400, the corresponding NAFLD risk appeared saturated. Furthermore, receiver operating characteristic analysis showed that the TyG-BMI could better predict the risk of NAFLD than other traditional indicators [TyG-BMI (AUC): 0.886; 95% CI: 0.8797-0.8927; P < 0.0001], particularly among young and middle-aged and non-obese people. CONCLUSIONS: This epidemiological study is the first on the association between the TyG-BMI and NAFLD risk in the general population. In this large data set from the general population, the TyG-BMI showed an independent positive correlation with NAFLD. The discovery of the threshold effect and saturation effect between them provides a new idea to prevent and treat NAFLD.

Comparison of Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) in Evaluating Anxiety and Depression in Patients with Psoriatic Arthritis.

BACKGROUND: This study aimed to compare the Hospital Anxiety and Depression Scale (HADS) and the Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) in evaluating anxiety and depression in psoriatic arthritis (PsA) patients. METHODS: A total of 70 PsA patients were enrolled. Demographic and clinical characteristics were collected after enrollment. HADS-A and SAS were used to evaluate the anxiety of PsA patients, while HADS-D and SDS were used to evaluate the depression of PsA patients. RESULTS: Similar results were observed in detecting the rate of anxiety by HADS-A and SAS (27.1 vs. 21.4%, p = 0.424), and there was no difference in classifying the severity of anxiety by HADS-A and SAS (p = 0.347). The Spearman test also disclosed that HADS-A score was positively associated with SAS score (p <0.001). The rates of depression were similar by HADS-D and SDS (27.1 vs. 40.0%; p = 0.108). However, different results were observed in grading the severity of anxiety by HADS-D and SDS (p = 0.009), and no correlation was observed between HADS-D and SDS scores (p = 0.138). The consumption of time for HADS assessment was shorter than that for SAS/SDS assessment (p < 0.001). In addition, a positive correlation of HADS-A score with patients' global assessment (PGA) (p = 0.022) and fatigue scores (p = 0.028) was discovered, and HADS-D score was positively associated with PGA score (p = 0.019). SAS or SDS score presented less correlation with clinical features of PsA patients, which illuminated that only SAS score was positively associated with duration of psoriasis (p = 0.030). CONCLUSION: HADS seems to be a better option for anxiety and depression assessment than SAS/SDS in PsA patients.

Improving the blast resistance of the elite rice variety Kongyu-131 by updating the pi21 locus.

BACKGROUND: As an elite japonica rice variety, Kongyu-131 has been cultivated for over 20 years in the third accumulated temperature zone of Heilongjiang Province, China. However, the cultivated area of Kongyu-131 has decreased each year due to extensive outbreaks of rice blast. To achieve the goals of improving blast resistance and preserving other desirable traits in Kongyu-131, a genome-updating method similar to repairing a bug in a computer program was adopted in this study. A new allele of the broad-spectrum blast resistance gene pi21 in the upland rice variety GKGH was mined by genetic analysis and introgressed into the genome of Kongyu-131 to upgrade its blast resistance. RESULT: QTL analysis was performed with an F2 population derived from a cross between Kongyu-131 and GKGH, and a blast resistance QTL was detected near the pi21 locus. Parental Pi21 sequence alignment showed that the pi21 of the donor (GKGH) was a new allele. By 5 InDel or SNP markers designed based on the sequence within and around pi21, the introgressed chromosome segment was shortened to less than 634 kb to minimize linkage drag by screening recombinants in the target region. The RRPG was 99.92%, calculated according to 201 SNP markers evenly distributed on 12 chromosomes. Artificial inoculation at the seedling stage showed that the blast resistance of the new Kongyu-131 was improved significantly. Field experiments also indicated that the improved Kongyu-131 had enhanced field resistance to rice blast and grain-quality traits similar to those of the original Kongyu-131. CONCLUSIONS: It is feasible to improve resistance to rice blast and preserve other desirable traits by precisely improving the Pi21 locus of Kongyu-131. Linkage drag can be eliminated effectively via recombinant selection on both sides of the target gene.

Genetically encoding phosphotyrosine and its nonhydrolyzable analog in bacteria.

Tyrosine phosphorylation is a common protein post-translational modification that plays a critical role in signal transduction and the regulation of many cellular processes. Using a propeptide strategy to increase cellular uptake of O-phosphotyrosine (pTyr) and its nonhydrolyzable analog 4-phosphomethyl-L-phenylalanine (Pmp), we identified an orthogonal aminoacyl-tRNA synthetase-tRNA pair that allows site-specific incorporation of both pTyr and Pmp into recombinant proteins in response to the amber stop codon in Escherichia coli in good yields. The X-ray structure of the synthetase reveals a reconfigured substrate-binding site, formed by nonconservative mutations and substantial local structural perturbations. We demonstrate the utility of this method by introducing Pmp into a putative phosphorylation site and determining the affinities of the individual variants for the substrate 3BP2. In summary, this work provides a useful recombinant tool to dissect the biological functions of tyrosine phosphorylation at specific sites in the proteome.

Site-Specific Immuno-PET Tracer to Image PD-L1.

The rapid ascension of immune checkpoint blockade treatments has placed an emphasis on the need for viable, robust, and noninvasive imaging methods for immune checkpoint proteins, which could be of diagnostic value. Immunoconjugate-based positron emission tomography (immuno-PET) allows for sensitive and quantitative imaging of target levels and has promising potential for the noninvasive evaluation of immune checkpoint proteins. However, the advancement of immuno-PET is currently limited by available imaging tools, which heavily rely on full-length IgGs with Fc-mediated effects and are heterogeneous mixtures upon random conjugation with chelators for imaging. Herein, we have developed a site-specific αPD-L1 Fab conjugate with the chelator 1,4,7-triazacyclononane- N, N', N″-triacetic acid (NOTA), enabling radiolabeling for PET imaging, using the amber suppression-mediated genetic incorporation of unnatural amino acid (UAA), p-azidophenylalanine. This Fab conjugate is homogeneous and demonstrated tight binding toward the PD-L1 antigen in vitro. The radiolabeled version, 64Cu-NOTA-αPD-L1, has been employed in PET imaging to allow for effective visualization and mapping of the biodistribution of PD-L1 in two normal mouse models, including the capturing of different PD-L1 expression levels in the spleens of the different mouse types. Follow-up in vivo blocking studies and ex vivo fluorescent staining further validated specific tissue uptakes of the imaging agent. This approach illustrates the utility of UAA-based site-specific Fab conjugation as a general strategy for making sensitive PET imaging probes, which could facilitate the elucidation of the roles of a wide variety of immune checkpoint proteins in immunotherapy.

Recombinant thiopeptides containing noncanonical amino acids.

Thiopeptides are a subclass of ribosomally synthesized and posttranslationally modified peptides (RiPPs) with complex molecular architectures and an array of biological activities, including potent antimicrobial activity. Here we report the generation of thiopeptides containing noncanonical amino acids (ncAAs) by introducing orthogonal amber suppressor aminoacyl-tRNA synthetase/tRNA pairs into a thiocillin producer strain of Bacillus cereus .We demonstrate that thiopeptide variants containing ncAAs with bioorthogonal chemical reactivity can be further postbiosynthetically modified with biophysical probes, including fluorophores and photo-cross-linkers. This work allows the site-specific incorporation of ncAAs into thiopeptides to increase their structural diversity and probe their biological activity; similar approaches can likely be applied to other classes of RiPPs.

Rational design of a Kv1.3 channel-blocking antibody as a selective immunosuppressant.

A variable region fusion strategy was used to generate an immunosuppressive antibody based on a novel "stalk-knob" structural motif in the ultralong complementary-determining region (CDR) of a bovine antibody. The potent Kv1.3 channel inhibitory peptides Moka1-toxin and Vm24-toxin were grafted into different CDRs of the humanized antibodies BVK and Synagis (Syn) using both ß-sheet and coiled-coil linkers. Structure-activity relationship efforts led to generation of the fusion protein Syn-Vm24-CDR3L, which demonstrated excellent selectivity and potency against effector human memory T cells (subnanomolar to picomolar EC50 values). This fusion antibody also had significantly improved plasma half-life and serum stability in rodents compared with the parent Vm24 peptide. Finally, this fusion protein showed potent in vivo efficacy in the delayed type hypersensitivity in rats. These results illustrate the utility of antibody CDR fusions as a general and effective strategy to generate long-acting functional antibodies, and may lead to a selective immunosuppressive antibody for the treatment of autoimmune diseases.

Electron-Scale Quadrants of the Hall Magnetic Field Observed by the Magnetospheric Multiscale spacecraft during Asymmetric Reconnection.

An in situ measurement at the magnetopause shows that the quadrupole pattern of the Hall magnetic field, which is commonly observed in a symmetric reconnection, is still evident in an asymmetric component reconnection, but the two quadrants adjacent to the magnetosphere are strongly compressed into the electron scale and the widths of the remaining two quadrants are still ion scale. The bipolar Hall electric field pattern generally created in a symmetric reconnection is replaced by a unipolar electric field within the electron-scale quadrants. Furthermore, it is concluded that the spacecraft directly passed through the inner electron diffusion region based on the violation of the electron frozen-in condition, the energy dissipation, and the slippage between the electron flow and the magnetic field. Within the inner electron diffusion region, magnetic energy was released and accumulated simultaneously, and it was accumulated in the perpendicular directions while dissipated in the parallel direction. The localized thinning of the current sheet accounts for the energy accumulation in a reconnection.