Incorporating biomolecules into metal‐organic frameworks (MOFs) as exoskeletons to form biomolecules‐MOFs biohybrids has attracted great attention as an emerging class of advanced materials. Organic ...devices have been shown as powerful platforms for next‐generation bioelectronics, such as wearable biosensors, tissue engineering constructs, and neural interfaces. Herein, biomolecules‐incorporated MOFs as innovative gating module is realized for the first time, which is exemplified by biocatalytic precipitation (BCP)‐oriented horseradish peroxidase (HRP)‐embedded zeolitic imidazolate framework‐90 (HRP@ZIF‐90)/CdIn2S4 gated organic photoelectrochemical transistor under light illumination. In connection to a sandwich immunocomplexing targeting the model analyte human IgG, the IgG‐dependent generation of H2O2 and the tandem HRP‐triggered BCP reaction can cause the in situ blocking of the pore network of ZIF‐90, leading to variant gating effect with corresponding responses of the device. This representative biodetection achieved good analytical performance with a wide linear range and a low detection limit of 100 fg mL−1. In the view of the plentiful biomolecule‐MOF complexes and their potential interactions with organic systems, this study provides a proof‐of‐concept study for the generic development of biomolecules‐MOFs‐gated electronics and beyond.
Herein, biomolecules‐incorporated MOFs as innovative gating module is realized for the first time, which is exemplified by biocatalytic precipitation‐oriented horseradish peroxidase (HRP)‐embedded zeolitic imidazolate framework‐90 (HRP@ZIF‐90)/CdIn2S4 gated organic photoelectrochemical transistor under light illumination. By linking with a sandwich immunoassay, the proposed biosensor achieved good analytical performance at zero gate bias.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of ...aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19.
The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 10
nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging.
Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 10
/L vs. 1.78 × 10
/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients.
Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 10
nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population.
MEXCOVID, NCT04276987.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The Mg-3.0Zn-0.2Ca (wt.%) alloy has been extruded at temperature range of 25–300 °C and the resulting microstructure, texture and mechanical properties are systematically investigated. The results ...show that the grain size monotonically increases with the increasing of the extrusion temperature and the texture intensity increases firstly and decreases subsequently. In addition, a large number of nano-scale precipitates are formed in alloys extruded above 250 °C. The weakest basal texture developed in the cold extrusion alloy is related to the deformation twinning, while, the combining effects of activation of multiple deformation mechanisms and dynamic precipitates contribute to developing the weaker basal texture in alloys extruded above 250 °C. A sharp basal texture enhances the yield strength of alloy extruded at 150 °C greatly at the cost of work hardening rate. The highest elongation is achieved in the alloy extruded at 300 °C. The enhanced formability is considered to be associated with the dependence of the weaker basal texture and dynamic precipitates on the strain hardening behavior. Among the multiple strengthening mechanisms, the fine grain strengthening and the solid solution strengthening play a dominant role in the increment of strength for the as-extruded alloys.
•The Mg-3.0Zn-0.2Ca alloy was extruded at temperature range of 25–300 °C.•The excellent comprehensive mechanical properties were obtained.•The multiple strengthening mechanisms of the Mg alloy were analyzed.•The fine grain strengthening and solid solution strengthening dominate strength.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
As the largest substantive organ of animals, the liver plays an essential role in the physiological processes of digestive metabolism and immune defense. However, the cellular composition of the pig ...liver remains poorly understood. This investigation used single-nucleus RNA sequencing technology to identify cell types from liver tissues of pigs, providing a theoretical basis for further investigating liver cell types in pigs.
The analysis revealed 13 cells clusters which were further identified 7 cell types including endothelial cells, T cells, hepatocytes, Kupffer cells, stellate cells, B cells, and cholangiocytes. The dominant cell types were endothelial cells, T cells and hepatocytes in the liver tissue of Dahe pigs and Dahe black pigs, which accounts for about 85.76% and 82.74%, respectively. The number of endothelial cells was higher in the liver tissue of Dahe pigs compared to Dahe black pigs, while the opposite tendency was observed for T cells. Moreover, functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic endothelial cells were significantly enriched in the protein processing in endoplasmic reticulum, MAPK signaling pathway, and FoxO signaling pathway. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic T cells were significantly enriched in the thyroid hormone signaling pathway, B cell receptor signaling pathway, and focal adhesion. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic hepatocytes were significantly enriched in the metabolic pathways.
In summary, this study provides a comprehensive cell atlas of porcine hepatic tissue. The number, gene expression level and functional characteristics of each cell type in pig liver tissue varied between breeds.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Xyloglucan endotransglycosylase/hydrolase (XTH) genes play an important role in plant resistance to abiotic stress. However, systematic studies of the response of
(ramie)
genes (
) to cadmium (Cd) ...stress are lacking. We sought to identify the
-family genes in ramie through bioinformatics analyses and to investigate their responses to Cd stress. We identified 19 members of the
gene family from the ramie genome, referred to as
, among which
and
were located on no chromosomes and the remaining genes were unevenly distributed across 11 chromosomes. The 19 members were divided into four groups, Groups I/II/IIIA/IIIB, according to their phylogenetic relationships, and these groups were supported by analyses of intron-exon structure and conserved motif composition. A highly conserved catalytic site (HDEIDFEFLG) was observed in all BnXTH proteins. Additionally, three gene pairs (
-
,
-
, and
-
) were obtained with a fragment and tandem-repeat event analysis of the ramie genome. An analysis of cisregulatory elements revealed that
expression might be regulated by multiple hormones and abiotic and biotic stress responses. In particular, 17 cisregulatory elements related to abiotic and biotic stress responses and 11 cisregulatory elements related to hormone responses were identified. We also found that most
genes responded to Cd stress, and
,
,
, and
were most likely to contribute to the Cd tolerance of ramie, as evidenced by the substantial increases in expression under Cd treatment. Heterologous expression of
,
, and
significantly enhanced the Cd tolerance of transgenic yeast cells. These results suggest that the
gene family is involved in Cd stress responses, laying a theoretical foundation for functional studies of
genes and the innovative breeding of Cd-tolerant ramie.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In this letter, the voltage sensitivity-based coherent reactive power control is proposed to perform the online voltage security enhancement for insecure buses in the multi-area wind power generation ...systems. The proposed approach is realized in the two-level optimization problem, containing a master problem and two subproblems. The master problem is responsible for the equal reactive power adjustments in multiple regional clustering wind farms regarding to the voltage security enhancement while the subproblems proceed the further improvement of the voltage security based on the analysed result of the master problem. Case studies on IEEE 57-bus test system are presented to validate the cost-effectiveness of the proposed method. Also, the time-domain simulation is conducted to illustrate the validity of the proposed control scheme.
Abstract
Study Objectives
Mounting evidence indicated the correlation between sleep and cerebral small vessel disease (CSVD). However, little is known about the exact causality between poor sleep and ...white matter injury, a typical signature of CSVD, as well as the underlying mechanisms.
Methods
Spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats were subjected to sleep fragmentation (SF) for 16 weeks. The effects of chronic sleep disruption on the deep white matter and cognitive performance were observed.
Results
SHR were validated as a rat model for CSVD. Fragmented sleep induced strain-dependent white matter abnormalities, characterized by reduced myelin integrity, impaired oligodendrocytes precursor cells (OPC) maturation and pro-inflammatory microglial polarization. Partially reversible phenotypes of OPC and microglia were observed in parallel following sleep recovery.
Conclusions
Long-term SF-induced pathological effects on the deep white matter in a rat model of CSVD. The pro-inflammatory microglial activation and the block of OPC maturation may be involved in the mechanisms linking sleep to white matter injury.
Graphical Abstract
Iron metabolism dysregulation is tightly associated with cancer development. But the underlying mechanisms remain poorly understood. Increasing evidence has shown that long noncoding RNAs (lncRNAs) ...participate in various metabolic processes via integrating signaling pathway. In this study, we revealed one iron-triggered lncRNA, one target of YAP, LncRIM (LncRNA Related to Iron Metabolism, also named ZBED5-AS1 and Loc729013), which effectively links the Hippo pathway to iron metabolism and is largely independent on IRP2. Mechanically, LncRIM directly binds NF2 to inhibit NF2-LATS1 interaction, which causes YAP activation and increases intracellular iron level via DMT1 and TFR1. Additionally, LncRIM-NF2 axis mediates cellular iron metabolism dependent on the Hippo pathway. Clinically, high expression of LncRIM correlates with poor patient survival, suggesting its potential use as a biomarker and therapeutic target. Taken together, our study demonstrated a novel mechanism in which LncRIM-NF2 axis facilitates iron-mediated feedback loop to hyperactivate YAP and promote breast cancer development.
In the current study, the effects of extrusion temperatures on the extrudability, microstructure, recrystallization behavior and mechanical properties of the Mg–3.0Zn–0.2Ca–0.5Y alloy have been ...systematically investigated. The results show that the magnesium alloy bars with excellent mechanical properties are obtained at the extrusion temperature above 523K. Both the dynamic recrystallized grain size and fraction increase with an increase in the deformation temperature. The MgY phase particles (>1μm) contribute to increasing DRX fraction, while the finer I-phase precipitates exert a pinning effect on the movement of grain boundaries and thus suppress the grain growth. The competitive mechanism between the particle-stimulated nucleation and grain boundary pinning determines the final microstructure that strongly affects the mechanical properties of the extruded alloys. The yield strength is improved with the decrease of the DRX grain size by grain boundary strengthening, and the ductility is increased by the enhanced work hardening ability with the increase of the DRX fraction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Angiopoietin‐like protein (ANGPTL) 4 is a key factor in the regulation of lipid and glucose metabolism in metabolic diseases. ANGPTL4 is highly expressed in various cancers, but the regulation of ...energy metabolism in tumours remains to be determined. This study explored the role of ANGPTL4 in aerobic glycolysis, glutamine consumption and fatty acid oxidation in nonsmall cell lung cancer (NSCLC) cells. Two NSCLC cell lines (A549 and H1299) were used to investigate the role of ANGPTL4 in energy metabolism by tracer techniques and with Seahorse XF technology in ANGPTLs4 knockdown cells. RNA microarrays and specific inhibitors were used to identify targets in ANGPTLs4‐overexpressing cells. The results showed that knockdown of ANGPTLs4 could inhibit energy metabolism and proliferation in NSCLC. ANGPTLs4 had no significant effect on glycolysis but affected glutamine consumption and fatty acid oxidation. Knockdown of ANGPTLs4 also significantly inhibited tumour metastasis and energy metabolism in mice and had a weak effect on glycolysis. RNA microarray analysis showed that ANGPTLs4 significantly affected glutaminase (GLS) and carnitine palmitoyl transferase 1 (CPT1). ANGPTLs4‐overexpressing cells were exposed to a glutamine deprivation environment, and cell proliferation and energy metabolism were significantly decreased but still differed from normal NSCLC cells. Treatment of ANGPTLs4‐overexpressing cells with GLS and CPT1 inhibitors simultaneously prevented the regulatory effects on cell proliferation and energy metabolism. ANGPTLs4 could promote glutamine consumption and fatty acid oxidation but not glycolysis or accelerate energy metabolism in NSCLC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
