Effective hemostasis is vital to reduce the pain and mortality of patients, and the research and development of hemostatic materials are prerequisite for effective hemostasis. Chitosan (CS), with ...good biodegradability, biocompatibility and non-toxicity, has been widely applied in bio-medicine, the chemical industry, the food industry and cosmetics. The excellent hemostatic properties of CS have been extensively studied. As a result, chitosan-based composite hemostatic materials have been emerging. In this review, the hemostatic mechanism of chitosan is briefly discussed, and then the progress of research on chitosan-based composite hemostatic materials with multiple forms such as films, sponges, hydrogels, particles and fibers are introduced. Finally, future perspectives of chitosan-based composite hemostatic materials are given. The objective of this review is to provide a reference for further research and development of effective hemostatic materials.
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international ...concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown.
The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records.
The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death.
NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19.
ClinicalTrials, NCT04292964. Registered 03 March 2020.
Background and Purpose
Recent clinical trials report that metformin, an activator of AMP‐activated protein kinase (AMPK) used to treat type 2 diabetes, significantly reduces the risk of stroke by ...actions that are independent of its glucose‐lowering effects. However, the underlying molecular mechanisms are not known. Here, we tested the possibility that acute metformin preconditioning confers neuroprotection by pre‐activation of AMPK‐dependent autophagy in a rat model of permanent middle cerebral artery occlusion (pMCAO).
Experimental Approach
Male Sprague‐Dawley rats were pretreated with either vehicle, an AMPK inhibitor, Compound C, or an autophagy inhibitor, 3‐methyladenine, and were injected with a single dose of metformin (10 mg kg−1, i.p.). Then, AMPK activity and autophagy biomarkers in the brain were assessed. At 24 h after metformin treatment, rats were subjected to pMCAO; infarct volume, neurological deficits and cell apoptosis were evaluated 24 and 96 h later.
Key Results
A single dose of metformin significantly activated AMPK and induced autophagy in the brain. The enhanced autophagic activity was inhibited by Compound C pretreatment. Furthermore, acute metformin preconditioning significantly reduced infarct volume, neurological deficits and cell apoptosis during a subsequent focal cerebral ischaemia. The neuroprotection mediated by metformin preconditioning was fully abolished by Compound C and partially inhibited by 3‐methyladenine.
Conclusions and Implications
These results provide the first evidence that acute metformin preconditioning induces autophagy by activation of brain AMPK, which confers neuroprotection against subsequent cerebral ischaemia. This suggests that metformin, a well‐known hypoglycaemic drug, may have a practical clinical use for stroke prevention.
In humans, tissue injury and depression can both cause pain hypersensitivity, but whether this involves distinct circuits remains unknown. Here, we identify two discrete glutamatergic neuronal ...circuits in male mice: a projection from the posterior thalamic nucleus (PO
) to primary somatosensory cortex glutamatergic neurons (S1
) mediates allodynia from tissue injury, whereas a pathway from the parafascicular thalamic nucleus (PF
) to anterior cingulate cortex GABA-containing neurons to glutamatergic neurons (ACC
) mediates allodynia associated with a depression-like state. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that PO
and PF
populations undergo different adaptations in the two conditions. Artificial manipulation of each circuit affects allodynia resulting from either tissue injury or depression-like states, but not both. Our study demonstrates that the distinct thalamocortical circuits PO
→S1
and PF
→ACC
subserve allodynia associated with tissue injury and depression-like states, respectively, thus providing insights into the circuit basis of pathological pain resulting from different etiologies.
Mussel adhesive proteins (MAPs) have a unique ability to firmly adhere to different surfaces in aqueous environments via the special amino acid, 3,4-dihydroxyphenylalanine (DOPA). The catechol groups ...in DOPA are a key group for adhesive proteins, which is highly informative for the biomedical domain. By simulating MAPs, medical products can be developed for tissue adhesion, drug delivery, and wound healing. Hydrogel is a common formulation that is highly adaptable to numerous medical applications. Based on a discussion of the adhesion mechanism of MAPs, this paper reviews the formation and adhesion mechanism of catechol-functionalized hydrogels, types of hydrogels and main factors affecting adhesion, and medical applications of hydrogels, and future the development of catechol-functionalized hydrogels.
Caddisworms (Trichoptera) spin adhesive silks to construct a variety of underwater composite structures. Many studies have focused on the fibroin heavy chain of caddisworm silk and found that it ...contains heavy phosphorylation to maintain a stable secondary structure. Besides fibroins, recent studies have also identified some new silk proteins within caddisworm silk. To better understand the silk composition and its secretion process, this study reports the silk gland proteome of a retreat-building caddisworm, Stenopsyche angustata Martynov (Trichoptera, Stenopsychidae). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), 2389 proteins were identified in the silk gland of S. angustata, among which 192 were predicted as secreted silk proteins. Twenty-nine proteins were found to be enriched in the front silk gland, whereas 109 proteins were enriched in the caudal silk gland. The fibroin heavy chain and nine uncharacterized silk proteins were identified as phosphorylated proteins. By analysing the sequence of the fibroin heavy chain, we found that it contains 13 Gly/Thr/Pro-rich regions, 12 Val/Ser/Arg-rich regions and a Gly/Arg/Thr-rich region. Three uncharacterized proteins were identified as sericin-like proteins due to their larger molecular weights, signal peptides and repetitive motifs rich in serine. This study provides valuable information for further clarifying the secretion and adhesion of underwater caddisworm silk.
As a novel risk gene for Alzheimer's disease (AD), triggering receptor expressed on myeloid cells 2 (TREM2) gene encodes a type I transmembrane receptor that is uniquely expressed by the microglia in ...the brain. Emerging evidence indicates a strong association between TREM2 and tau pathology in the cerebral spinal fluid or brain tissue of AD patients. In line with these clinical findings, we found that TREM2 was upregulated in the brain of P301S mice, an animal model of tau pathology, during disease progression. However, despite this information, the precise role of TREM2 in tau pathology remains largely unknown. In our recent studies, we revealed that silencing microglial TREM2 expression in P301S mice exacerbated spatial cognitive deficits and tau pathology. Based on this evidence, we hypothesized that TREM2 might exert a protective effect in tau-related neurodegenerative diseases. In the present study, to test this hypothesis, a lentiviral-mediated strategy was employed to selectively overexpress TREM2 on microglia in the brain of P301S mice. For the first time, we showed that TREM2 overexpression rescued spatial cognitive impairments and ameliorated neuropathologies including neuronal and synaptic loss as well as tau hyperphosphorylation. Meanwhile, this protective effect was likely attributed to the suppression of neuroinflammation and subsequent attenuation of tau kinase activity, since the expression of pro-inflammatory cytokines including Tnf, Il1b and Il6 as well as the activity of tau kinase including glycogen synthase kinase 3β and cyclin-dependent kinase 5 was significantly reduced following TREM2 overexpression. Additionally, the suppressed neuroinflammation might be ascribed to the M2 activation of microglia induced by TREM2, as the expression of M2 phenotype makers including Arg1, Retnla, Il4 and Il10 was markedly increased. Taken together, these findings support the concept of TREM2 as a valuable target against AD as well as other tau-related neurodegenerative diseases.
•TREM2 overexpression rescues spatial cognitive impairments in P301S mice.•TREM2 overexpression prevents neuronal and synaptic loss and attenuates tau pathology.•This protection may be achieved by reducing inflammation and inactivating tau kinase.•The reduced inflammation is likely ascribed to the M2 activation of microglia.
ABSTRACT
Abiotic stress is one of the most important factors reducing soybean yield. It is essential to identify regulatory factors contributing to stress responses. A previous study found that the ...tandem CCCH zinc‐finger protein GmZF351 is an oil level regulator. In this study, we discovered that the GmZF351 gene is induced by stress and that the overexpression of GmZF351 confers stress tolerance to transgenic soybean. GmZF351 directly regulates the expression of GmCIPK9 and GmSnRK, leading to stomata closing, by binding to their promoter regions, which carry two CT(G/C)(T/A)AA elements. Stress induction of GmZF351 is mediated through reduction in the H3K27me3 level at the GmZF351 locus. Two JMJ30‐demethylase‐like genes, GmJMJ30‐1 and GmJMJ30‐2, are involved in this demethylation process. Overexpression of GmJMJ30‐1/2 in transgenic hairy roots enhances GmZF351 expression mediated by histone demethylation and confers stress tolerance to soybean. Yield‐related agronomic traits were evaluated in stable GmZF351‐transgenic plants under mild drought stress conditions. Our study reveals a new mode of GmJMJ30‐GmZF351 action in stress tolerance, in addition to that of GmZF351 in oil accumulation. Manipulation of the components in this pathway is expected to improve soybean traits and adaptation under unfavorable environments.
The soybean zinc finger protein GmZF351 regulates oil levels and mainly works in seeds. However, the histone demethylase GmJMJ30‐1/2 activates GmZF351 in leaves and roots to improve stress tolerance by mechanisms that differ from the mechanisms acting in seeds.
The incorporation of large π-conjugated ligands into metal–organic frameworks (MOFs) can introduce intriguing photophysical and electrochemical properties into the framework. However, these effects ...are often hindered by the strong π–π interaction and the low solubility of the arylated ligands. Herein, we report the synthesis of a porous zirconium-based MOF, Zr6(μ3-O)4(μ3-OH)4(OH)6(H2O)6(HCHC) (PCN-136, HCHC = hexakis(4-carboxyphenyl)hexabenzocoronene), which is composed of a hexacarboxylate linker with a π-conjugated hexabenzocoronene moiety. Direct assembly of the Zr4+ metal centers and the HCHC ligands was unsuccessful due to the low solubility and the unfavorable conformation of the arylated HCHC ligand. Therefore, PCN-136 was obtained from aromatization-driven postsynthetic annulation of the hexaphenylbenzene fragment in a preformed framework (pbz-MOF-1) to avoid π–π stacking. This postsynthetic modification was done through a single-crystal-to-single-crystal transformation and was clearly observable utilizing single -crystal X-ray crystallography. The formation of large π-conjugated systems on the organic linker dramatically enhanced the photoresponsive properties of PCN-136. With isolated hexabenzocoronene moieties as photosensitizers and Zr–oxo clusters as catalytic sites, PCN-136 was employed as an inherent photocatalytic system for CO2 reduction under visible-light irradiation, which showed increased activity compared with pbz-MOF-1.
Recent study has demonstrated that electron cyclotron harmonic (ECH) waves can be excited by a low energy electron beam. Such waves propagate at moderately oblique wave normal angles (∼70°). The ...potential effects of beam‐driven ECH waves on electron dynamics in Earth's plasma sheet is not known. Using two‐dimensional Darwin particle‐in‐cell simulations with initial electron distributions that represent typical plasma conditions in the plasma sheet, we explore the excitation and saturation of such beam‐driven ECH waves. Both ECH and electron acoustic waves are excited in the simulation and propagate at oblique wave normal angles. Compared with the electron acoustic waves, ECH waves grow much faster and have more intense saturation amplitudes. Cold, stationary electrons are first accelerated by ECH waves through cyclotron resonance and then accelerated in the parallel direction by both the ECH and electron acoustic waves through Landau resonance. Beam electrons, on the other hand, are decelerated in the parallel direction and scattered to larger pitch angles. The relaxation of the electron beam and the continuous heating of the cold electrons contribute to ECH wave saturation and suppress the excitation of electron acoustic waves. When the ratio of plasma to electron cyclotron frequency ωpe/ωce increases, the ECH wave amplitude increases while the electron acoustic wave amplitude decreases. Our work reveals the importance of ECH and electron acoustic waves in reshaping sub‐thermal electron distributions and improves our understanding on the potential effects of wave‐particle interactions in trapping ionospheric electron outflows and forming anisotropic (field‐aligned) electron distributions in the plasma sheet.
Plain Language Summary
Recent study has demonstrated that electron cyclotron harmonic (ECH) waves can be excited by a low energy electron beam. The potential role of beam‐driven ECH waves in affecting electron dynamics is not known. Using numerical simulations, we explore the interactions between electrons and such beam‐driven ECH waves. Both ECH and electron acoustic waves are excited in the simulation and propagate at oblique wave normal angles. Compared with the electron acoustic waves, ECH waves grow much faster. Cold, stationary electrons are first accelerated in the perpendicular direction then accelerated in the parallel direction. Beam electrons, on the other hand, are decelerated in the parallel direction and scattered to larger pitch angles. The relaxation of the electron beam and the continuous heating of the cold electrons contribute to the saturation of ECH waves. When the ratio of plasma to electron cyclotron frequency increases, the ECH wave amplitude increases while the electron acoustic wave amplitude decreases. Our work reveals the importance of ECH and electron acoustic waves in modifying electron distributions in Earth's plasma sheet.
Key Points
Electron cyclotron harmonic (ECH) and electron acoustic waves are excited by an electron beam in a 2‐D particle‐in‐cell simulation
Beam electrons are thermalized and cold electrons are accelerated through resonant interactions with ECH and electron acoustic waves
When ωpe/ωce increases, ECH wave intensity increases while electron acoustic wave intensity decreases
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