Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating clinical conditions characterized by pulmonary epithelial damage and protein-rich fluid accumulation in the ...alveolar spaces. Statins are a class of HMG-CoA reductase inhibitors, which exert cholesterol-lowering and anti-inflammatory effects.
Rosuvastatin (1 mg/kg) was injected intravenously in rats 12 h before lipopolysaccharide (LPS, 10 mg/kg) administration. Eight hours later after LPS challenge, alveolar fluid clearance (AFC) was detected in rats (n = 6-8). Rosuvastatin (0.3 µmol/mL) and LPS were cultured with primary rat alveolar type II epithelial cells for 8 h.
Rosuvastatin obviously improved AFC and attenuated lung-tissue damage in ALI model. Moreover, it enhanced AFC by increasing sodium channel and Na,K-ATPase protein expression. It also up-regulated P-Akt via reducing Nedd4-2 in vivo and in vitro. Furthermore, LY294002 blocked the increase in AFC in response to rosuvastatin. Rosuvastatin-induced AFC was found to be partly rely on sodium channel and Na,K-ATPase expression via the PI3K/AKT/Nedd4-2 pathway.
In summary, the findings of our study revealed the potential role of rosuvastatin in the management of ALI/ARDS.
•A novel 3D multi-physics field digital twin model for PEMFCs is proposed.•The computational fluid dynamic technique is integrated in the digital twin model.•The model is demonstrated within twenty ...randomly selected working conditions.•The proposed model can predict PEMFC physics field characteristics in 0.913 s.
In times of the commercialization process of proton exchange membrane fuel cells (PEMFCs), a full knowledge of in-situ state in PEMFCs is of critical significance to the in-situ operational process and the evaluation of material stage and potential damage. The conventional experimental observation and in-situ prediction models can only obtain very limited information while the computational fluid dynamics approach takes too long time to get the detailed information. To reach a full knowledge of PEMFC real-time state, a novel 3D multi-physics digital twin model for PEMFCs is proposed based on the proper orthogonal decomposition (POD) method. In the model, firstly, for one kind of PEMFC, 139 ex-situ snapshots are designed and simulated based on the three-dimensional two-phase non-isothermal numerical model with the assumption of liquid pressure continuity in the whole membrane electrode assembly. Then the modes of each field in snapshots are extracted by singular value decomposition method using Jacobi algorithm. Finally, the coefficients in the POD prediction equation are obtained by using the multivariate adaptive regression splines. The digital twin results of voltage, temperature, membrane water content and liquid water saturation fields are exhibited and analyzed. Results suggest that for the studied PEMFC, the digital twin technique can capture the global values and the local distribution characteristics of each above physical fields well in 0.913 s. The mean global deviations of the above four fields of 20 groups of random conditions within wide current density and operational condition ranges are 5.7 %, 1.3 %, 8.9 % and 12.0 % respectively. Even though the practical results can only be applied for the studied PEMFC, the proposed methodology has its general application range.
The relationships among species of
Hygrophorus
sect.
Aurei
were inferred based on morphology, molecular phylogeny, and chemical reactions. It was found that (1) there are at least 14 species within ...the section, seven of which occur in China. Among the Chinese taxa, four are new,
viz.
,
H. alpinus
,
H. esculentus
,
H. pseudohypothejus
, and
H. xiangjun
. They were collected in the subalpine and alpine areas of southwestern China. The occurrence of
H. gliocyclus
,
H. lucorum
, and
H. speciosus
in China was confirmed based on molecular and morphological evidences. (2) Geographic divergences of this section in the Northern Hemisphere were evident. Four taxa were intercontinental,
viz
., two Eurasian species (
H. gliocyclus
and
H. lucorum
), one European-North American species (
H. secretanii
), and one Holarctic species (
H. speciosus
). (3) Most species in this section display relatively high host preferences for their host plants at the generic and even subgeneric level.
•Five Qn+Dy(β-diketonate)4-n precursors were used to prepare five Dy-MOFs.•Qn+Dy(β-diketonate)4-n was first used to control the structure of MOFs.•The change of β-diketone and Qn+ constructed ...different SBUs in MOFs 1–5.•MOFs 1 and 5 exhibit SMMs behavior.
In this study, Qn+Dy(β-diketonate)4-n (β-diketonate = Hfac, Hbtfa, Hdbm; n = 1, Q+ = Et3NH+, Et4N+; n = 2, Q2+= R-H2MPPA2+) was used to regulate the hydrolysis process of DyIII ions to generate different secondary building units (SBUs). The SBUs were further connected with fumaric acid ligands, exhibiting diverse coordination modes. Five dysprosium-based metal–organic frameworks (Dy-MOFs; 1–5) with various structural connections and topologies were synthesized. When cations in Qn+Dy(β-diketonate)4-n were Et3NH+ and the anions changed from Dy(fac)4- to Dy(dbm)4- and Dy(btfa)4-, three SBUs (C2v Dy1O8, D2d Dy2O8 in 1; C2v Dy1O8 in 2; C4v Dy1O9 in 3) were formed. When anions in Qn+Dy(β-diketonate)4-n were Dy(btfa)4- and the cations changed from Et3NH+ to Et4N+ and R-H2MPPA2+, four SBUs (C4v Dy1O9 in 3; Cs Dy1O9, D3h Dy2O9 in 4; D4d Dy1O8 in 5) were formed. Further magnetic characterization indicated that 2, 3, and 4 exhibited antiferromagnetic behavior, while 1 and 5 exhibited ferromagnetic properties. The alternating-current magnetic susceptibilities of 1 and 5 exhibited significant frequency and temperature dependence. The Cole–Cole plot of 1 and 5 displayed a semicircular shape, and the effective energy barrier and relaxation time were 77.54 K and 3.20 × 10–8 s and 6.8 K and 7.50 × 10–5 s for 1 and 5, respectively.
Display omitted
In this study, we investigated the neuroprotective effect of sevoflurane against ischemic brain injury and its underlying molecular mechanisms. Transient global brain ischemia was induced by 4-vessel ...occlusion in adult male Sprague-Dawley rats. The rats were pretreated with sevoflurane alone or sevoflurane combined with LY294002/wortmannin (selective inhibitor of PI3K) before ischemia. Cresyl violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. Immunoblotting and immunoprecipitation were performed to measure the phosphorylation of Akt1, PRAS40, ASK1, and JNK3 and the expression of cleaved-caspase-3. The results demonstrated that a moderate dose of sevoflurane inhalation of 2 % for 2 h had significant neuroprotective effects against ischemia/reperfusion induced hippocampal neuron death. Sevoflurane significantly increased Akt and PRAS40 phosphorylation and decreased the phosphorylation of ASK1 at 6 h after reperfusion and the phosphorylation of JNK3 at 3 days after reperfusion following 15 min of transient global brain ischemia. Conversely, LY294002 and wortmannin significantly inhibited the effects of sevoflurane. Taken together, the results suggest that sevoflurane could suppress ischemic brain injury by downregulating the activation of the ASK1/JNK3 cascade via increasing the phosphorylation of Akt1 during ischemia/reperfusion.
Methylmercury (MeHg) is a notorious neurotoxin, and its production and degradation in the environment are mainly driven by microorganisms. A variety of microbial MeHg producers carrying the gene pair
...and degraders carrying the
gene have been separately reported in recent studies. However, surprisingly little attention has been paid to the simultaneous investigation of the diversities of microbial MeHg producers and degraders in a given habitat, and no studies have been performed to explore to what extent these two contrasting microbial groups correlate with MeHg accumulation in the habitat of interest. Here, we collected 86 acid mine drainage (AMD) sediments from an area spanning approximately 500,000 km
in southern China and profiled the sediment-borne putative MeHg producers and degraders using genome-resolved metagenomics. 46 metagenome-assembled genomes (MAGs) containing
and 93 MAGs containing
were obtained, including those from various taxa without previously known MeHg-metabolizing microorganisms. These diverse MeHg-metabolizing MAGs were formed largely via multiple independent horizontal gene transfer (HGT) events. The putative MeHg producers from Deltaproteobacteria and
as well as MeHg degraders from
were closely correlated with MeHg accumulation in the sediments. Furthermore, these three taxa, in combination with two abiotic factors, explained over 60% of the variance in MeHg accumulation. Most of the members of these taxa were characterized by their metabolic potential for nitrogen fixation and copper tolerance. Overall, these findings improve our understanding of the ecology of MeHg-metabolizing microorganisms and likely have implications for the development of management strategies for the reduction of MeHg accumulation in the AMD sediments.
Microorganisms are the main drivers of MeHg production and degradation in the environment. However, little attention has been paid to the simultaneous investigation of the diversities of microbial MeHg producers and degraders in a given habitat. We used genome-resolved metagenomics to reveal the vast phylogenetic and metabolic diversities of putative MeHg producers and degraders in AMD sediments. Our results show that the diversity of MeHg-metabolizing microorganisms (particularly MeHg degraders) in AMD sediments is much higher than was previously recognized. Via multiple linear regression analysis, we identified both microbial and abiotic factors affecting MeHg accumulation in AMD sediments. Despite their great diversity, only a few taxa of MeHg-metabolizing microorganisms were closely correlated with MeHg accumulation. This work underscores the importance of using genome-resolved metagenomics to survey MeHg-metabolizing microorganisms and provides a framework for the illumination of the microbial basis of MeHg accumulation via the characterization of physicochemical properties, MeHg-metabolizing microorganisms, and the correlations between them.
A novel diarylethene derivative with hydrazinopyridine as functional group was synthesized and its multi-controllable photoswitchable behaviors with light, Al3+ and OH− were investigated ...systematically. The diarylethene derivative could serve as a highly selective “turn-on” fluorescence chemosenor to recognize Al3+ and “naked-eye” chemosensor to detect OH−.
Display omitted
•A diarylethene derivative 1o with hydrazinopyridine as a functional group was designed and synthesized.•Its multi-controllable photoswitchable behaviors with light, Al3+ and OH− were investigated systematically.•The mechanisms of coordination with Al3+ and deprotonation with OH− have been discussed.
A novel photochromic diarylethene derivative 1o with hydrazinopyridine as a functional group was designed and synthesized. It had multi-responsively photoswitchable properties under various stimulations (UV/vis lights and chemical substances). Compound 1o could be served as a potential fluorescent probe to selectively and sensitively detect Al3+. When Al3+ was added to 1o, complex 1o′ (1o-Al3+) exhibited an obviously strong fluorescence with a significant fluorescence color change from dark to bright green. Moreover, compound 1o could be used as a selective ‘naked-eye’ colorimetric sensor for OH−, in which OH− made the ring-closed absorption band of 1c to display an obvious red-shift from 554nm to 662nm with a notable color change from violet to blue. In addition, two logic circuits were constructed based on the multi-responsive properties of 1o induced by light and chemical stimulations (one contained four input signals (In1: 297nm light, In2:>500nm light, In3: Al3+, In4: EDTA) and an output signal (O1: fluorescence intensity at 534nm), another contained three input signals (In1: 297nm light, In5: NaOH, and In6: HCl) and an output signal (O2: absorbance at 662nm).
Recent evidence indicates that small noncoding RNA molecules, known as microRNAs (miRNAs), are involved in cancer initiation and progression. We hypothesized that genetic variations in miRNAs and ...miRNA target sites could be associated with the efficacy of androgen-deprivation therapy (ADT) in men with prostate cancer.
We systematically evaluated 61 common single nucleotide polymorphisms (SNPs) inside miRNAs and miRNA target sites in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT were assessed by Kaplan-Meier analysis and Cox regression model.
Four, seven, and four SNPs were significantly associated with disease progression, PCSM, and ACM, respectively, after ADT in univariate analysis. KIF3C rs6728684, CDON rs3737336, and IFI30 rs1045747 genotypes remained as significant predictors for disease progression; KIF3C rs6728684, PALLD rs1071738, GABRA1 rs998754, and SYT9 rs4351800 remained as significant predictors for PCSM; and SYT9 rs4351800 remained as a significant predictor for ACM in multivariate models that included clinicopathologic predictors. Moreover, strong combined genotype effects on disease progression and PCSM were also observed. Patients with a greater number of unfavorable genotypes had a shorter time to progression and worse prostate cancer-specific survival during ADT (P for trend < 0.001).
SNPs inside miRNAs and miRNA target sites have a potential value to improve outcome prediction in prostate cancer patients receiving ADT.
Inflammasomes are large multimolecular complexes best recognized because of their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-18 (IL-18) and ...interleukin-1 β (IL-1β). IL-1β was originally identified as a pro-inflammatory cytokine, capable of inducing local and systemic inflammation as well as a fever response reaction in response to infection or injury. Excessive production of IL-1β is related to inflammatory and autoimmune diseases. Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are characterized by excessive inflammatory response. For SARS, there is no correlation between viral load and worsening symptoms. However, there is no specific medicine which is available to treat the disease. As an important part of medical practice, TCM showed an obvious therapeutic effect in SARS-CoV-infected patients. In this article, we summarize the current applications of TCM in the treatment of COVID-19 patients. Herein, we also offer an insight into the underlying mechanisms of the therapeutic effects of TCM, as well as introduce new naturally occurring compounds with anti-coronavirus activity, in order to provide a new and potential drug development strategy for the treatment of COVID-19.
Abnormal regulation of long non-coding RNAs (lncRNAs) appears to be a primary feature of numerous types of human cancer. However, the association between the dysregulation of lncRNAs and functional ...alterations in gastric cancer (GC) remains unclear. In previous studies, we applied microarray and bioinformatics analyses to screen for key lncRNAs from the tumor tissues and matched adjacent non-tumor tissues of 10 patients with GC. There were seven key lncRNAs demonstrated to be significantly different between carcinoma tissues and adjacent non-tumor tissues. In the present study, the expression of these seven selected lncRNAs were validated in 82 patients with GC to further investigate the association between lncRNAs and GC clinical characterization. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results demonstrated that
, MCPH1 antisense RNA 1 (
) and urothelial carcinoma-associated 1 (
) exhibited consistent upregulation in cancer compared with adjacent non-tumor tissues, whereas
, tumor suppressor candidate 8 (
) and maternally expressed 3 (
) showed consistent downregulation. The results from the microarray and RT-qPCR experiments achieved 100% agreement. A correlation analysis indicated that
and
were significantly associated with tumor differentiation degree,
and
were significantly associated with lymph node metastasis, and
and
were significantly associated with tumor-node-metastasis stage (P<0.05). In addition, it was identified that the differential expression of
and
significantly correlated with the age and gender of the GC patients, respectively (P<0.05). The results suggest that the lncRNAs
and
are closely associated with the invasion and metastasis of GC, which reveals these indicators as potential specificity biomarkers for the diagnosis, prognosis and classification of GC. Thus, these lncRNAs merit further study as novel candidate biomarkers for the clinical diagnosis of GC and as potential targets for therapy.
PDF
