The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease. Understanding the dysregulated ...human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic. In this study, we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia (FOP) patients who underwent lung surgery and served as controls. We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients. In contrast to the FOP patients, Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients. This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients. In summary, our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity. Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.
Silver nanoclusters (AgNCs) have been widely applied in the field of biology, drug therapy and cell imaging in the last decade. In order to study the biosafety of AgNCs, GSH-AgNCs and DHLA-AgNCs were ...synthesized using glutathione (GSH) and dihydrolipoic acid (DHLA) as ligands, and their interactions with calf thymus DNA (ctDNA) from abstraction to visualization were studied. The results of spectroscopy, viscometry and molecular docking demonstrated that GSH-AgNCs mainly bound to ctDNA in a groove mode, while DHLA-AgNCs were both groove and intercalation binding. Fluorescence experiments suggested that the quenching mechanism of both AgNCs to the emission of ctDNA-probe were both in static mode, and thermodynamic parameters demonstrated that the main forces between GSH-AgNCs and ctDNA were hydrogen bonds and van der Waals forces, while hydrogen bonds and hydrophobic forces contributed to the binding of DHLA-AgNCs to ctDNA. The binding strength demonstrated that DHLA-AgNCs bound to ctDNA more strongly than that of GSH-AgNCs. The results of circular dichroism (CD) spectroscopy reflected small effects of both AgNCs on the structure of ctDNA. This study will support the theoretical foundation for the biosafety of AgNCs and have a guiding significance for the preparation and application of AgNCs.
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•The effect of ligand structure on the properties of silver nanoclusters was studied.•The mechanism of the interaction between silver nanoclusters and ctDNA was systematically investigated.•By combining experiments with molecular docking, the experimental results were visualized and credibility was improved.•Providing a new methodology for biosafety studies of ultra-small nanomaterials.•The influence of ligand functional groups on the interaction forces was investigated.
Shot-peened CM400 maraging steel was used to study the mechanism of enhanced notch fatigue properties of ultra-high strength materials. After shot peening, the specimen surface became rougher, but ...the transversal machining traces were reduced. The yield strength was slightly improved while the ultimate tensile strength and hardness maintained constant; as a result, the fatigue limit was promoted by about 1.5 times. The nucleated sites of the fatigue fracture were partly changed from the surface to subsurface/interior of the specimen. To further analyze the influencing factors of fatigue properties, the fatigue damage process may be resolved to two aspects: (a) fatigue damage rate affected by shear deformation and (b) fatigue damage tolerance controlled by the dilatation fracture process. Considering the stress state near the notch tip, the hydrostatic stress and maximum shear stress are considered for better understanding these two aspects. It is observed that the fatigue damage tolerance increased while the fatigue damage rate decreased after shot peening. Therefore, the notch fatigue properties of CM400 maraging steels can effectively be improved.
Ethylene response factors (ERFs) widely exist in plants and have been reported to be an important regulator of plant abiotic stress. Celery, a common economic vegetable of Apiaceae, contains lots of ...ERF transcription factors (TFs) with various functions. AP2/ERF TFs play positive or negative roles in plant growth and stress response. Here,
AgERF8
, a gene encoding EAR-type AP2/ERF TF, was identified. The
AgERF8
mRNA accumulated in response to both abscisic acid (ABA) signaling and salt treatment. AgERF8 was proving to be a nucleus-located protein and could bind to GCC-box. The overexpression of
AgERF8
in
Arabidopsis
repressed the transcription of downstream genes,
AtBGL
and
AtBCH. Arabidopsis
overexpressing
AgERF8
gene showed inhibited root growth under ABA and NaCl treatments.
AgERF8
transgenic lines showed low tolerance to ABA and salt stress than wild-type plants. Low increment in SOD and POD activities, increased accumulation of MDA, and significantly decreased plant fresh weights and chlorophyll levels were detected in
AgERF8
hosting lines after treated with ABA and NaCl. Furthermore, the overexpression of
AgERF8
also inhibited the levels of ascorbic acid and antioxidant-related genes (
AtCAT1
,
AtSOD1
,
AtPOD
,
AtSOS1
,
AtAPX1
, and
AtP5CS1
) expression in transgenic
Arabidopsis
. This finding indicated that
AgERF8
negatively affected the resistance of transgenic
Arabidopsis
to ABA and salt stress through regulating downstream genes expression and relevant physiological changes. It will provide a potential sight to further understand the functions of ERF TFs in celery.
The cavity-based X-ray free-electron laser (XFEL) has promise in producing fully coherent pulses with a bandwidth of a few meV and very stable intensity, whereas the currently existing self-amplified ...spontaneous emission (SASE) XFEL is capable of generating ultra-short pulses with chaotic spectra. In general, a cavity-based XFEL can provide a spectral brightness three orders of magnitude higher than that of the SASE mode, thereby opening a new door for cutting-edge scientific research. With the development of superconducting MHz repetition-rate XFEL facilities such as FLASH, European-XFEL, LCLS-II, and SHINE, practical cavity-based XFEL operations are becoming increasingly achievable. In this study, megahertz cavity enhanced X-ray generation (MING) is proposed based on China’s first hard XFEL facility - SHINE, which we refer to as MING@SHINE.
Background
Arterial spin labeling (ASL) has shown potential for the assessment of penumbral tissue in patients with acute ischemic stroke (AIS). The postlabeling delay (PLD) parameter is sensitive to ...arterial transit delays and influences cerebral blood flow measurements.
Purpose
To assess the impact of ASL acquisition at different PLDs for penumbral tissue quantification and to compare their performance regarding assisting patient selection for endovascular treatment with dynamic susceptibility contrast MRI (DSC‐MRI) as the reference method.
Study Type
Retrospective.
Population
A total of 53 patients (59.98 ± 12.60 years, 32% women) with AIS caused by internal carotid or middle cerebral artery occlusion.
Field Strength/Sequence
A 3‐T, three‐dimensional pseudo‐continuous ASL with fast‐spin echo readout.
Assessment
Hypoperfusion volume was measured using DSC‐MRI and ASL with PLDs of 1.500 msec and 2.500 msec, respectively. Eligibility for endovascular treatment was retrospectively determined according to the imaging criteria of the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke trial (DEFUSE 3).
Statistical Tests
Kruskal–Wallis tests, Bland–Altman plots, Cohen's kappa, and receiver operating characteristic analyses were used. The threshold for statistical significance was set at P ˂ 0.05.
Results
Hypoperfusion volume for ASL with a PLD of 1.500 msec was significantly larger than that for DSC‐MRI, while the hypoperfusion volume for a PLD of 2.500 msec was not significantly different from that of DSC‐MRI (P = 0.435). Bland–Altman plots showed that the mean volumetric error between the hypoperfusion volume measured by DSC‐MRI and ASL with PLDs of 1.500/2.500 msec was −107.0 mL vs. 4.49 mL. Cohen's kappa was 0.679 vs. 0.773 for DSC‐MRI and ASL, respectively, with a PLD of 1.500/2.500 msec. The sensitivity and specificity for ASL with a PLD of 1.500/2.500 msec in identifying patients eligible for treatment were 89.74% vs. 97.44% and 92.86% vs. 64.29%, respectively.
Data Conclusion
In AIS, PLDs for ASL acquisition may have a considerable impact on the quantification of the hypoperfusion volume.
Evidence Level
3
Technical Efficacy
Stage 2
Effective antitumor activity of chemotherapy can be counterbalanced by efferocytosis by generating immunosuppressive tumor microenvironment. Targeted blocking efferocytosis at an early stage of cell ...apoptosis exerts promising benefits on achieving improved chemotherapy, but it appears to have considerably limited outcome due to the uncontrolled release of chemotherapeutic and efferocytosis inhibitors. Herein, a mesoporous silica nanoparticle (MSN)-based nanoconfined assembly strategy is created to co-deliver chemotherapeutic drug doxorubicin (DOX) and efferocytosis inhibitor BMS777607 (BMS) for efficient cancer chemo-immunotherapy. DOX and BMS self-assembly forms nanoparticulate crystal confined within the mesopore of tailor-made MSN, and nanocrystal-encapsulated MSN (denoted as SC-MSN@D/B) enables synchronized drug release behaviors, which is beneficial for efferocytosis blockade at the early stage of apoptosis. Consequently, intravenous injection of SC-MSN@D/B leads to a synergistic inhibition of tumor growth in colon and breast cancer models through inducing a stimulatory immune response, from the secretion of pro-inflammatory cytokines to the inhibition of tumor associated macrophages and regulatory T cells infiltration. The combination of SC-MSN@D/B with checkpoint blockade inhibitors further amplifies the therapeutic effect of on tumor growth and pulmonary metastasis of orthotopic 4T1 breast tumors, and establishes long-term immune memory, offering tremendous potential for a combined efferocytosis-blocking strategy in cancer chemo-immunotherapy.
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•The combination of BMS and DOX elicited a synergistic antitumor effect.•Confined assembly of DOX and BMS was observed in the nanopores of a tailored-made mesoporous silica nanoparticle (MSN).•SC-MSN@D/B effectively blocked the efferocytosis and improved cancer chemo-immunotherapy.
Gibberellin (GA) is a phytohormone of a biguanide compound that plays an important role throughout the life cycle of a plant. Lignin, a phenylalanine-derived aromatic polymer, can enhance the water ...transport function and structural resistance of cell walls. This function is also the core on biology of higher terrestrial plants. An appropriate lignin level is important to the quality of leafy vegetables, such as celery. The relationship between gibberellin levels and the occurrence of lignification has not been reported in celery. In this study, the leaf blades and petioles of celery cultivars ‘Liuhe Huangxinqin’ and ‘Jinnan Shiqin’ were used as materials, and different concentrations of exogenous gibberellin were applied to analyze the growth and lignin distribution of leaf blades and petioles. It was found that gibberellin treatment could influence the lignin content in celery leaves. Autofluorescence analysis under ultraviolet (UV) excitation showed that gibberellin treatment caused lignification of celery leaf tissue. The expression profiles of 12 genes related to lignin synthesis changed with the increase of gibberellin concentration. Our results showed that gibberellin played a significant role in the accumulation of lignin in the development of celery leaves. This provides a basis for further study on the regulation of lignin metabolism in plants and exerts a vital part in the application of plant growth regulators to production.
Aqueous zinc-ion batteries have attracted much attention due to their high theoretical capacity, low cost, high safety, and eco-friendly. However, challenges such as dendrite growth and side ...reactions severely hinder the electrochemical performance of the Zn anode, leading to low Coulombic efficiency (CE) or even short circuits. Herein, phenolic resin (PF) is used as a protective coating on the surface of the zinc metal electrode. The PF layer can greatly improve the corrosion resistance of the Zn electrode in the electrolyte. Importantly, this artificial electrode/electrolyte interphase also elevates the nucleation barrier and restrains Zn
2+
2D diffusion, regulating the zinc deposition/dissolution behavior. As a result, PF@Zn symmetric cells exhibit superior performance than that of bare Zn symmetric cells, achieving a stable and dendrite-free cycle of 1400 h. Furthermore, the carbon nanotube/MnO
2
||PF@Zn (CNT/MnO
2
||PF@Zn) full cell also delivers a long cycle life with a high-capacity retention of about 180.0 mAh·g
−1
after 1400 cycles, far exceeding that of bare Zn anode. This work provides a facile strategy for achieving a dendrite-free and rechargeable zinc anode.
Graphical abstract
Gibberellins (GAs), as one of the important hormones in regulating the growth and development of higher plants, can significantly promote cell elongation and expansion. Celery is a widely grown leafy ...vegetable crop with rich nutritional value. However, the effect of gibberellins on celery leaves is unclear. In this paper, the celery variety “Jinnan Shiqin” plants were treated with gibberellic acid (GA
3
) and paclobutrazol (PBZ, a gibberellin inhibitor). Our results showed that GA
3
treatment promoted the growth of celery leaves and caused lignification of celery leaf tissue. In addition, the transcript levels of genes associated with gibberellins, auxin, cytokinins, ethylene, jasmonic acid, abscisic acid, and brassinolide were altered in response to increased or decreased exogenous gibberellins or inhibitor. GA
3
may regulate celery growth by interacting with other hormones through crosstalk mechanisms. This study provided a reference for further study of the regulation mechanism of gibberellins metabolism, and exerted effects on understanding the role of gibberellins in the growth and development of celery.
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