Recent progress of MOF-functionalized nanocomposites: From structure to properties.

Metal-organic frameworks (MOFs) are novel crystalline porous materials assembled from metal ions and organic ligands. The adaptability of their design and the fine-tuning of the pore structures make them stand out in porous materials. Furthermore, by integrating MOF guest functional materials with other hosts, the novel composites have synergistic benefits in numerous fields such as batteries, supercapacitors, catalysis, gas storage and separation, sensors, and drug delivery. This article starts by examining the structural relationship between the host and guest materials, providing a comprehensive overview of the research advancements in various types of MOF-functionalized composites reported to date. The review focuses specifically on four types of spatial structures, including MOFs being (1) embedded in nanopores, (2) immobilized on surface, (3) coated as shells and (4) assembled into hybrids. In addition, specific design ideas for these four MOF-based composites are presented. Some of them involve in situ synthesis method, solvothermal method, etc. The specific properties and applications of these materials are also mentioned. Finally, a brief summary of the advantages of these four types of MOF composites is given. Hopefully, this article will help researchers in the design of MOF composite structures.

Mortality risk factors in patients receiving ECPR after cardiac arrest: Development and validation of a clinical prognostic prediction model.

BACKGROUND: Previous studies have shown an increasing trend of extracorporeal cardiopulmonary resuscitation (ECPR) use in patients with cardiac arrest (CA). Although ECPR have been found to reduce mortality in patients with CA compared with conventional cardiopulmonary resuscitation (CCPR), the mortality remains high. This study was designed to identify the potential mortality risk factors for ECPR patients for further optimization of patient management and treatment selection. METHODS: We conducted a prospective, multicentre study collecting 990 CA patients undergoing ECPR in 61 hospitals in China from January 2017 to May 2022 in CSECLS registry database. A clinical prediction model was developed using cox regression and validated with external data. RESULTS: The data of 351 patients meeting the inclusion criteria before October 2021 was used to develop a prediction model and that of 68 patients after October 2021 for validation. Of the 351 patients with CA treated with ECPR, 227 (64.8%) patients died before hospital discharge. Multivariate analysis suggested that a medical history of cerebrovascular diseases, pulseless electrical activity (PEA)/asystole and higher Lactate (Lac) were risk factors for mortality while aged 45-60, higher pH and intra-aortic balloon pump (IABP) during ECPR have protective effects. Internal validation by bootstrap resampling was subsequently used to evaluate the stability of the model, showing moderate discrimination, especially in the early stage following ECPR, with a C statistic of 0.70 and adequate calibration with GOF chi-square = 10.4 (p = 0.50) for the entire cohort. Fair discrimination with c statistic of 0.65 and good calibration (GOF chi-square = 6.1, p = 0.809) in the external validation cohort demonstrating the model's ability to predict in-hospital death across a wide range of probabilities. CONCLUSION: Risk factors have been identified among ECPR patients including a history of cerebrovascular diseases, higher Lac and presence of PEA or asystole. While factor such as age 45-60, higher pH and use of IABP have been found protective against in-hospital mortality. These factors can be used for risk prediction, thereby improving the management and treatment selection of patients for this resource-intensive therapy.

Connecting the Dots: The Cerebral Lymphatic System as a Bridge Between the Central Nervous System and Peripheral System in Health and Disease.

As a recently discovered waste removal system in the brain, cerebral lymphatic system is thought to play an important role in regulating the homeostasis of the central nervous system. Currently, more and more attention is being focused on the cerebral lymphatic system. Further understanding of the structural and functional characteristics of cerebral lymphatic system is essential to better understand the pathogenesis of diseases and to explore therapeutic approaches. In this review, we summarize the structural components and functional characteristics of cerebral lymphatic system. More importantly, it is closely associated with peripheral system diseases in the gastrointestinal tract, liver, and kidney. However, there is still a gap in the study of the cerebral lymphatic system. However, we believe that it is a critical mediator of the interactions between the central nervous system and the peripheral system.

Advances of mesenchymal stem cells and their derived extracellular vesicles as a promising therapy for acute respiratory distress syndrome: from bench to clinic.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury characterized by diffuse alveolar damage. The period prevalence of ARDS was 10.4% of ICU admissions in 50 countries. Although great progress has been made in supportive care, the hospital mortality rate of severe ARDS is still up to 46.1%. Moreover, up to now, there is no effective pharmacotherapy for ARDS and most clinical trials focusing on consistently effective drugs have met disappointing results. Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have spawned intense interest of a wide range of researchers and clinicians due to their robust anti-inflammatory, anti-apoptotic and tissue regeneration properties. A growing body of evidence from preclinical studies confirmed the promising therapeutic potential of MSCs and their EVs in the treatment of ARDS. Based on the inspiring experimental results, clinical trials have been designed to evaluate safety and efficacy of MSCs and their EVs in ARDS patients. Moreover, trials exploring their optimal time window and regimen of drug administration are ongoing. Therefore, this review aims to present an overview of the characteristics of mesenchymal stem cells and their derived EVs, therapeutic mechanisms for ARDS and research progress that has been made over the past 5 years.

Molecular hydrogen attenuates sepsis-induced cognitive dysfunction through regulation of tau phosphorylation.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a cognitive dysfunction caused by sepsis. Hyperphosphorylated tau is considered to play a significant role in the progression of neurodegenerative disease and also contributes to cognitive dysfunction in septic mice. Molecular hydrogen (H2) plays an antioxidant and anti-inflammatory role, and plays a protective role in septic mice. This study explored the possible effects of H2 on cognition and tau phosphorylation in a mouse model of SAE. METHODS: The model of sepsis was established in C57BL/6J male mice by cecal ligation and puncture surgery. Mice treated with 2 % H2 inhalation for 60 min at 1 h and 6 h after surgery, respectively. HY-15769, the inhibitor of Tau Tubulin Kinase 1 (TTBK1), was injected 1 h before the surgery. The 7-day survival rates of the mice were recorded. Cognitive behavior was tested with both novel object recognition and the Y-maze novelty arm recognition on day 7 after surgery. Hematoxylin-eosin staining was used to observe the histological damage in CA1 region of hippocampus. The expression of inflammatory factors in hippocampus was assessed by Elisa. Western blotting was adopted to determine the tau phosphorylation levels at AT8 epitopes (pSer202 and pThr205) and T22 epitopes (neurofibrillary tangle protein oligomer), and the GSK3ß phosphorylation levels (Tyr216), as well as p-Ser422 and TTBK1 levels in the hippocampus. The number of dendritic spine and mushroom type of dendritic spines in the hippocampus were assessed by Golgi staining. RESULTS: The survival rate, visual and spatial learning ability, and memory ability were improved in septic mice treated with H2. After H2 treatment, the density of dendritic spine, mushroom type of dendritic spine, and the number of normal hippocampal neurons were progressively elevated. H2 decreased the levels of phosphorylated tau protein, tau oligomer and TTBK1, as well as the phosphorylation of tau key kinase. Furthermore, the injection of HY-15769 (a TTBK1 inhibitor) protected SAE through the similar way. CONCLUSION: The protective effect of H2 on cognitive dysfunction induced by SAE may be achieved by inhibiting tau phosphorylation, which is perhaps related with the inhibition of TTBK1.

Tandem mass tag-based quantitative proteomic analysis of effects of multiple sevoflurane exposures on the cerebral cortex of neonatal and adult mice.

Introduction: Sevoflurane is the most commonly used general anesthetic in pediatric surgery, but it has the potential to be neurotoxic. Previous research found that long-term or multiple sevoflurane exposures could cause cognitive deficits in newborn mice but not adult mice, whereas short-term or single inhalations had little effect on cognitive function at both ages. The mechanisms behind these effects, however, are unclear. Methods: In the current study, 6- and 60-day-old C57bl mice in the sevoflurane groups were given 3% sevoflurane plus 60% oxygen for three consecutive days, each lasting 2 hours, while those in the control group only got 60% oxygen. The cortex tissues were harvested on the 8th or 62nd day. The tandem mass tags (TMT)pro-based quantitative proteomics combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, Golgi staining, and western blotting analysis were applied to analyze the influences of multiple sevoflurane anesthesia on the cerebral cortex in mice with various ages. The Morris water maze (MWM) test was performed from postnatal day (P)30 to P36 or P84 to P90 after control or multiple sevoflurane treatment. Sevoflurane anesthesia affected spatial learning and memory and diminished dendritic spines primarily in newborn mice, whereas mature animals exhibited no significant alterations. Results: A total of 6247 proteins were measured using the combined quantitative proteomics methods of TMTpro-labeled and LC-MS/MS, 443 of which were associated to the age-dependent neurotoxic mechanism of repeated sevoflurane anesthesia. Furthermore, western blotting research revealed that sevoflurane-induced brain damage in newborn mice may be mediated by increasing the levels of protein expression of CHGB, PTEN, MAP2c, or decreasing the level of SOD2 protein expression. Conclusion: Our findings would help to further the mechanistic study of age-dependent anesthetic neurotoxicity and contribute to seek for effective protection in the developing brain under general anesthesia.

Effects of toxic apolipoprotein E fragments on Tau phosphorylation and cognitive impairment in neonatal mice under sevoflurane anesthesia.

BACKGROUND: Anesthesia induces Tau phosphorylation and cognitive impairment in young, but not adult, mice. Apolipoprotein E (ApoE) may play a protective role in neuronal activity and injury repair, whereas its toxic fragments are reported to induce neurodegeneration and neurocognitive impairment in patients with Alzheimer's disease (AD). Therefore, we set out to test the hypothesis that the difference in ApoE fragments, but not the full-length ApoE, contributes to the difference in Tau phosphorylation and neurocognitive functions following sevoflurane anesthesia in young mice. METHODS: Sevoflurane was administered to wild-type (WT), ApoE-knockout (ApoE-KO), ApoE3-targeted replacement (ApoE3 expresses both full-length and fragmented ApoE), and ApoE2-targeted replacement (ApoE2 only expresses full-length ApoE) mice. The mRNA and protein levels of ApoE, phosphorylated Tau (pTau), and cognitive function were tested in the mice. RESULTS: Sevoflurane anesthesia enhanced ApoE mRNA, total ApoE, full-length ApoE, ApoE fragments, Tau phosphorylation (AT8 and PHF1), and cognitive impairment in young mice, but not in adult mice. ApoE2, but not ApoE3 or ApoE-KO, mice showed reduced sevoflurane-induced pTau elevation and cognitive impairment. CONCLUSION: These data suggest that elevated ApoE fragments rather than full-length ApoE might be one of the underlying mechanisms of age-dependent Tau phosphorylation and cognitive impairment in young mice following sevoflurane anesthesia.

Brain-derived extracellular vesicles mediated coagulopathy, inflammation and apoptosis after sepsis.

INTRODUCTION: The activation of coagulation, inflammation and other pathways is the basic response of the host to infection in sepsis, but this response also causes damage to the host. Brain-derived extracellular vesicles (BDEVs) have been reported to cause a hypercoagulable state that can rapidly develop into consumptive coagulopathy, which is consistent with the pathophysiological process of sepsis-induced coagulopathy. However, the role of BDEVs in sepsis-induced coagulopathy remains unclear. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were used for sepsis modeling using cecal ligation puncture (CLP). Flow cytometry was used to measure the levels of circulating BDEVs. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of plasminogen activator inhibitor type 1 (PAI-1), thrombin-antithrombin (TAT), D-dimer, fibrinogen(Fib), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß and IL-6. Nanoparticle tracking analysis (NTA) and Transmission electron microscopy (TEM) were used to identify BDEVs. Western blot (WB) was used to determine the expression of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), bax, bcl-2 and cleaved caspase-3. Hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining were performed to detect tissue injury. Survival was monitored over the course of 168 h. RESULTS: We found that a large number of BDEVs were released into the circulating blood in septic rats. Moreover, we observed that BDEVs injection activated the systemic coagulation reaction and induced lung, liver and kidney inflammation and apoptosis(P < .05). Compared with BDEVs from sham-operated rats, BDEVs from septic rats exacerbated this process(P < .05). CONCLUSIONS: This finding suggests that inhibiting BDEVs may yield therapeutic benefits in the treatment of sepsis-induced coagulopathy.

More Stable Ties or Better Structure? An Examination of the Impact of Co-author Network on Team Knowledge Creation.

This study aims to explore the influence of co-author network on team knowledge creation. Integrating the two traditional perspectives of network relationship and network structure, we examine the direct and interactive effects of tie stability and structural holes on team knowledge creation. Tracking scientific articles published by 111 scholars in the research field of human resource management from the top 8 American universities, we analyze scholars' scientific co-author networks. The result indicates that tie stability changes the teams' information processing modes and, when graphed, results in an inverted U-shape relationship between tie stability and team knowledge creation. Moreover, structural holes in co-author network are proved to be harmful to team knowledge sharing and diffusion, thereby impeding team knowledge creation. Also, tie stability and structural hole interactively influence team knowledge creation. When the number of structural hole is low in the co-author network, the graphical representation of the relationship between tie stability and team knowledge creation tends to be a more distinct U-shape.

[Quality analysis of olive oil and quantification detection of adulteration in olive oil by near-infrared spectrometry and chemometrics].

Discriminant analysis was used to classify 20 olive oil samples based on their near-infrared (NIR) spectra. The samples were successfully classified into two categories which are consistent with extra virgin olive oil and ordinary olive oil defined in the products. The NIR spectra of olive-oil mixtures containing colza oil, corn oil, peanut oil, camellia oil, sunflower oil, and poppy seed oil were collected, respectively. The volume percent of adulterants ranged from 0 to 100%. The best spectrum bands for analysis were selected before developing partial least-squares (PLS) calibration models. The relative errors of prediction ranged from -5.67% to 5.61%. Results showed that the method combined with chemometrics methods and near-infrared spectrometry is simple, fast and credible for qualitative and quantitative analyses of olive oil samples.

Transforming growth factor beta regulates the expression of the M2 muscarinic receptor in atrial myocytes via an effect on RhoA and p190RhoGAP.

Transforming growth factor beta (TGFbeta) signaling is involved in the development and regulation of multiple organ systems and cellular signaling pathways. We recently demonstrated that TGFbeta regulates the response of atrial myocytes to parasympathetic stimulation. Here, TGFbeta(1) is shown to inhibit expression of the M(2) muscarinic receptor (M(2)), which plays a critical role in the parasympathetic response of the heart. This effect is mimicked by overexpression of a dominant negative mutant of RhoA and by the RhoA kinase inhibitor Y27632, whereas adenoviral expression of a dominant activating-RhoA reverses TGFbeta inhibition of M(2) expression. TGFbeta(1) also mediates a decrease in GTP-bound RhoA and a reciprocal increase in the expression of the RhoA GTPase-activating protein, p190RhoGAP, whereas total RhoA is unchanged. Inhibition of M(2) promoter activity by TGFbeta(1) is mimicked by overexpression of p190RhoGAP, whereas a dominant negative mutant of p190RhoGAP reverses this effect of TGFbeta(1). In contrast to atrial myocytes, in mink lung epithelial cells, in which TGFbeta signaling through activation of RhoA has been previously identified, TGFbeta(1) stimulated an increase in GTP-bound RhoA in association with a reciprocal decrease in the expression of p190RhoGAP. Both effects demonstrated a similar dose dependence on TGFbeta(1). Thus TGFbeta regulation of M(2) muscarinic receptor expression is dependent on RhoA, and TGFbeta regulation of p190RhoGAP expression may be a cell type-specific mechanism for TGFbeta signaling through RhoA.

Transforming growth factor beta (TGFbeta ) signaling via differential activation of activin receptor-like kinases 2 and 5 during cardiac development. Role in regulating parasympathetic responsiveness.

Little is known regarding factors that induce parasympathetic responsiveness during cardiac development. We demonstrated previously that in atrial cells cultured from chicks 14 days in ovo, transforming growth factor beta (TGFbeta) decreased parasympathetic inhibition of beat rate by the muscarinic agonist, carbamylcholine, by 5-fold and decreased expression of Galpha(i2). Here in atrial cells 5 days in ovo, TGFbeta increased carbamylcholine inhibition of beat rate 2.5-fold and increased expression of Galpha(i2). TGFbeta also stimulated Galpha(i2) mRNA expression and promoter activity at day 5 while inhibiting them at day 14 in ovo. Over the same time course expression of type I TGFbeta receptors, chick activin receptor-like kinase 2 and 5 increased with a 2.3-fold higher increase in activin receptor-like kinase 2. Constitutively active activin receptor-like kinase 2 inhibited Galpha(i2) promoter activity, whereas constitutively active activin receptor-like kinase 5 stimulated Galpha(i2) promoter activity independent of embryonic age. In 5-day atrial cells, TGFbeta stimulated the p3TP-lux reporter, which is downstream of activin receptor-like kinase 5 and had no effect on the activity of the pVent reporter, which is downstream of activin receptor-like kinase 2. In 14-day cells, TGFbeta stimulated both pVent and p3TP-lux. Thus TGFbeta exerts opposing effects on parasympathetic response and Galpha(i2) expression by activating different type I TGFbeta receptors at distinct stages during cardiac development.