Background
The impacts of chronic airway diseases on coronavirus disease 2019 (COVID‐19) are far from understood.
Objective
To explore the influence of asthma and chronic obstructive pulmonary ...disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID‐19 patients.
Methods
A total of 961 hospitalized COVID‐19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin‐converting enzyme II (ACE2) expression. BEAS‐2B cell line was stimulated with various cytokines.
Results
In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525‐360.135; P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461‐267.369; P = .025) than asthmatics. COPD patients, particularly those with severe COVID‐19, had lower counts of CD4+ T and CD8+ T cells and B cells and higher levels of TNF‐α, IL‐2 receptor, IL‐10, IL‐8, and IL‐6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL‐4 and IL‐13 downregulated, but TNF‐α, IL‐12, and IL‐17A upregulated ACE2 expression in BEAS‐2B cells.
Conclusion
Patients with asthma and COPD likely have different risk of severe COVID‐19, which may be associated with different ACE2 expression.
After adjusting for confounding factors, COVID‐19 patients with COPD have higher risks of developing severe illness and acute respiratory distress syndrome than COVID‐19 patients with asthma. COPD patients have increased, whereas asthmatics have decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL‐17A, TNF‐α, and IL‐12 promote, while IL‐4 and IL‐13 suppress ACE2 expression in airway BEAS‐2B cells. Abbreviations: ACE2, angiotensin‐converting enzyme II; ARDS, acute respiratory distress syndrome; BEAS‐2B, adenovirus‐12 SV40 hybrid virus transformed bronchial epithelial cells; COPD, chronic obstructive pulmonary disease; COVID‐19, coronavirus disease 2019.
High‐performance perovskite light‐emitting diodes are achieved by an interfacial engineering approach, leading to the most efficient near‐infrared devices produced using solution‐processed emitters ...and efficient green devices at high brightness conditions.
Ziziphi Spinosae Semen (ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin (5-HT), ...glutamic acid (Glu), γ-aminobutyric acid (GABA), noradrenaline (NE) and dopamine (DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESI- MS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring (MRM) and the procedure was completed in less than 10 min. The method showed a good linearity (R2 > 0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower (P < 0.01) in para-chlorophenylalanine (PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group (P < 0.01). Treatment with ZSS aqueous extract (4 or 8 g·kg–1·d–1 for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.
To explore low-pressure-driven nanofiltration (LPDNF) membranes with high permeate flux, a novel preparation route was proposed and investigated. First, an amphiphilic copolymer of poly (methyl ...methacrylate-co-dimethylaminoethyl methacrylate) (P(MMA-co-DMA)) was synthesized via free-radical copolymerization, and then blended with polyvinyl chloride (PVC) to fabricate precursor membranes via non-solvent induced phase separation (NIPS) process. Utilizing the quaternization and cross-linking reaction between p-xylylene dichloride (XDC) and tertiary amine units in PVC/PMMA-co-DMA precursor membranes, positively charged PVC/PMMA-co-DMA LPDNF membranes were obtained. Element alanalysis, X-ray photoelectron spectroscopy and scanning electron microscopy were employed to characterize the composition and morphology of the membranes. Effects of PMMA-co-DMA content and XDC concentration on the LPDNF membranes’ performance were studied and discussed. With the optimized condition, the NF membrane showed the highest salt rejection (R) and water flux (J), e.g., RMgCl2=89.1%, JMgCl2=22.1L/(m2h) and RNaCl=45.1%, JNaCl=27.6L/(m2h) at a pressure of 0.3MPa. Besides, the rejections of the LPDNF membranes for inorganic salts increased in an order of Na2SO4<MgSO4<NaCl<CaCl2<MgCl2. Together with the good stability, PVC/PMMA-co-DMA blend membrane was approved as a promising positively charged LPDNF membranes.
•A novel positively charged nanofiltration membrane was designed.•The membrane was based on PVC/P(DMA-co-MMA) blend precursor.•The membrane was made via quaternization and cross-linking of blend precursor.•The membrane showed good permeation and rejection for salts.
The intracellular NADPH insufficient supply is the main bottleneck to the synthesis of chiral alcohols by asymmetric reduction with whole-cell catalysis. Herein, we provide a novel strategy to ...strengthen intracellular NADPH supply through introducing an NADP
+
-dependent glyceraldehyde 3-phosphate dehydrogenase (
gap
B from
Bacillus subtilis
168) into the Embden-Meyerhof pathway and a NAD kinase (
yfj
B from
E. coli
MG1655) to further enhance the NADP(H) pool. A recombinant
E. coli
(
E. coli
BL21 (DE3)/pETDuet-1-
gap
B-
yue
D&pET28a-
yfj
B) was constructed to co-express
gap
B and
yfj
B with a carbonyl reductase gene
yue
D together. The result showed that the intracellular NADPH amount increased by 134.4% with the strategy. To the model reaction (asymmetric reduction of acetophenone to
S
-phenyl ethanol), the yield was 3.7-fold with this strategy compared to the control. This provides a technological route for strengthening the intracellular NADPH supply in
E. coli
for biocatalysis and biosynthesis.
Graphic Abstract
Morchella species are well known world-round as popular and prized edible fungi due to their unique culinary flavor. Recently, several species have been successfully cultivated in China. However, ...their reproductive modes are still unknown, and their basic biology needs to be elucidated. Here, we use the morel genome information to investigate mating systems and life cycles of fourteen black morel species. Mating type-specific primers were developed to screen and genotype ascospores, hymenia and stipes from 223 ascocarps of the 14 species from Asia and Europe. Our data indicated that they are all heterothallic and their life cycles are predominantly haploid, but sterile haploid fruiting also exists. Ascospores in all species are mostly haploid, homokaryotic, and multinuclear, whereas aborted ascospores without any nuclei were also detected. Interestingly, we monitored divergent spatial distribution of both mating types in natural morel populations and cultivated sites, where the fertile tissue of fruiting bodies usually harbored both mating types, whereas sterile tissue of wild morels constantly had one MAT allele, while the sterile tissue of cultivated strains always exhibited both MAT alleles. Furthermore, MAT1-1-1 was detected significantly more commonly than MAT1-2-1 in natural populations, which strongly suggested a competitive advantage for MAT1-1 strains.
An efficient aminofluorosulfonylation strategy was developed for the synthesis of various pyrazoline-functionalized aliphatic sulfonyl fluorides using β,γ-unsaturated hydrazones with sulfur dioxide ...and NFSI as the starting materials under mild conditions. The sulfonyl fluoride products could be successfully transformed into the corresponding sulfonate esters and amides via the sulfur(VI) fluoride exchange (SuFEx) click reactions. Preliminary mechanistic investigations demonstrate that the reaction operates through a radical cyclization/SO2 insertion/fluorination cascade process.
In this report, we present a photocatalytic ring-opening fluorosulfonylation of strained cycloalkanols with sulfur dioxide and NFSI under mild conditions for the synthesis of carbonyl-containing ...aliphatic sulfonyl fluorides. The synthetic potential of the carbonyl-containing aliphatic sulfonyl fluoride products has been examined by diverse transformations, including SuFEx reactions and Baeyer–Villiger oxidation reactions. Mechanistic studies demonstrate that the reaction operates through a radical C–C bond cleavage/SO2 insertion/fluorination cascade process.
Background The over-activation of adenosine A.sub.2A receptors (A.sub.2AR) is closely implicated in cognitive impairments of Alzheimer's disease (AD). Growing evidence shows that A.sub.2AR blockade ...possesses neuroprotective effects on AD. Spatial navigation impairment is an early manifestation of cognitive deficits in AD. However, whether A.sub.2AR blockade can prevent early impairments in spatial cognitive function and the underlying mechanism is still unclear. Methods A transgenic APP/PS1 mouse model of AD amyloidosis was used in this study. Behavioral tests were conducted to observe the protective effects of A.sub.2AR blockade on early spatial memory deficits in 4-month old APP/PS1 mice. To investigate the underlying synaptic mechanism of the protective effects of A.sub.2AR blockade, we further examined long-term potentiation (LTP) and network excitation/inhibition balance of dentate gyrus (DG) region, which is relevant to unique synaptic functions of immature adult-born granule cells (abGCs). Subsequently, the protective effects of A.sub.2AR blockade on dendritic morphology and synaptic plasticity of 6-week-old abGCs was investigated using retrovirus infection and electrophysiological recordings. The molecular mechanisms underlying neuroprotective properties of A.sub.2AR blockade on the synaptic plasticity of abGCs were further explored using molecular biology methods. Results APP/PS1 mice displayed DG-dependent spatial memory deficits at an early stage. Additionally, impaired LTP and an imbalance in network excitation/inhibition were observed in the DG region of APP/PS1 mice, indicating synaptic structural and functional abnormalities of abGCs. A.sub.2AR was found to be upregulated in the hippocampus of the APP/PS1 mouse model of AD. Treatment with the selective A.sub.2AR antagonist SCH58261 for three weeks significantly ameliorated spatial memory deficits in APP/PS1 mice and markedly restored LTP and network excitation/inhibition balance in the DG region. Moreover, SCH58261 treatment restored dendritic morphology complexity and enhanced synaptic plasticity of abGCs in APP/PS1 mice. Furthermore, SCH58261 treatment alleviated the impairment of synaptic plasticity in abGCs. It achieved this by remodeling the subunit composition of NMDA receptors and increasing the proportion of NR2B receptors in abGCs of APP/PS1 mice. Conclusions Blockade of A.sub.2AR improves early spatial memory deficits in APP/PS1 mice, possibly by reversing synaptic defects of abGCs. This finding suggests that A.sub.2AR blockade could be a potential therapy for AD. Keywords: Alzheimer's disease, Spatial memory, Adenosine A.sub.2A receptors, LTP, Adult born granule cells
Aging is characterized with a progressive decline in many cognitive functions, including behavioral flexibility, an important ability to respond appropriately to changing environmental contingencies. ...However, the underlying mechanisms of impaired behavioral flexibility in aging are not clear. In this study, we reported that necroptosis-induced reduction of neuronal activity in the basolateral amygdala (BLA) plays an important role in behavioral inflexibility in 5-month-old mice of the senescence-accelerated mice prone-8 (SAMP8) line, a well-established model with age-related phenotypes. Application of Nec-1s, a specific inhibitor of necroptosis, reversed the impairment of behavioral flexibility in SAMP8 mice. We further observed that the loss of glycogen synthase kinase 3α (GSK-3α) was strongly correlated with necroptosis in the BLA of aged mice and the amygdala of aged cynomolgus monkeys (Macaca fascicularis). Moreover, genetic deletion or knockdown of GSK-3α led to the activation of necroptosis and impaired behavioral flexibility in wild-type mice, while the restoration of GSK-3α expression in the BLA arrested necroptosis and behavioral inflexibility in aged mice. We further observed that GSK-3α loss resulted in the activation of mTORC1 signaling to promote RIPK3-dependent necroptosis. Importantly, we discovered that social isolation, a prevalent phenomenon in aged people, facilitated necroptosis and behavioral inflexibility in 4-month-old SAMP8 mice. Overall, our study not only revealed the molecular mechanisms of the dysfunction of behavioral flexibility in aged people but also identified a critical lifestyle risk factor and a possible intervention strategy.
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