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1.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

2.
Artigo em Inglês | MEDLINE | ID: mdl-34510339

RESUMO

N,P-doped carbon quantum dots (N,P-CQDs) are deemed as a promising candidate to environmentally friendly materials owing to the inexpensive, biocompatible nature. TiO2 nanowire is a prospective photocatalyst because of its efficient migration of photoexcited carriers in wastewater treatment. However, the N,P-CQDs-decorated TiO2 nanowire (N,P-CQDs/NW-TiO2) photocatalysts have been rarely reported. In this study, we build N,P-CQDs on the surface of TiO2 nanowires via a simple deposition process. Our investigations demonstrate that N,P-CQDs/NW-TiO2 has a great photocatalytic degradation for methyl blue (MB) under irradiation. The degradation rate of can reach 93.6% within 120 min under proper conditions. The excellent degradation performance of N,P-CQDs/NW-TiO2 is ascribed to the mesoporous structure and high separation rate of photoexcited carriers. In addition, the N,P-CQDs/NW-TiO2 have outstanding recycled photocatalytic capability. After being recycled four times, the N,P-CQDs/NW-TiO2 still maintain 59.9% photocatalytic activity. The fabricated nanosized photocatalyst can be widely utilized in the field of photocatalysis for wastewater treatment.

3.
J Biosci Bioeng ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34479804

RESUMO

Microbial astaxanthin with strong antioxidant activity is greatly demanded for diverse applications. Extractive disruption in aqueous biphasic system (ABS) integrates the cells disruption and biomolecules recovery processes in one-step operation, allowing the direct recovery of intracellular biomolecules with biphasic system upon released from cells. In this study, astaxanthin was recovered from recombinant Kluyveromyces marxianus yeast cells via extractive disruption using alcohol/salt ABS. Recombinant K. marxianus yeast is engineered to produce high concentration of free form astaxanthin. Highest partition coefficient (K = 90.02 ± 2.25) and yield (Y = 96.80% ± 0.05) of astaxanthin were obtained with ABS composed of 20% (w/w) 1-propanol and 20% (w/w) sodium citrate of pH 5, 0.5% (w/w) yeast cells loading and additional of 1% (w/w) 1-butyl-3-methylimidazolium tetrafluoroborate (Bmim)BF4 to improve the migration of astaxanthin to alcohol-rich top phase. The incorporation of 2.5 h of ultrasonication to the biphasic system further enhanced the astaxanthin recovery in ABS. The direct recovery of astaxanthin from recombinant K. marxianus cells was demonstrated with the ultrasonication-assisted alcohol/salt ABS which integrates the extraction and concentration of astaxanthin in a single-step operation.

4.
Nat Prod Res ; : 1-11, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498976

RESUMO

Juncus effusus L. (J. effusus) is a Traditional Chinese Medicine (TCM) that has long been used for dealing with gynaecological disorders, such as relieving insomnia, preventing tinnitus, reducing edema with diuretic effect. In our course of evidence-based medical research focused on this herb, one new phenanthrene, Junfusol B (2), together with seventeen known compounds were isolated and identified. All the structures of these compounds were elucidated by spectroscopic methods. The absolute stereochemistry of compounds 1 and 2 was further determined by comparing their calculated and experimental Electronic Circular Dichroism (ECD) spectra and optical rotation (OR) values. The isolates were evaluated for their estrogenic and anti-inflammatory activities which were considered as relevant etiological factors of insomnia, tinnitus and edema in the ancient TCM theory. The results revealed that most of the obtained phenanthrenes in this work were found exerting agonistic effects on estrogen receptor. This is the first report to declare the exact estrogen-regulating potential among this type of compounds from J. effusus. Moreover, phenanthrenes 3 - 7 exhibited significant inhibitions on superoxide anion generation and elastase release in fMLP/CB-induced human neutrophilic inflammation model. J. effusus may be developed as a complementary agent utilized in menopausal multiple syndromes.

5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 833-837, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487524

RESUMO

OBJECTIVE: To analyze gene variants in a Chinese pedigree with oculocutaneous albinism (OCA). METHODS: Gene sequencing of the proband and his parents was performed using chip capture high-throughput sequencing and Sanger sequencing techniques, and PolyPhen-2, SIFT, MutationTaster, and FATHMM software were used to predict the function of new variants. At the same time,the pedigree and variant genes of 4 albinism patients from this pedigree were analyzed. RESULTS: Sequencing results showed that the proband's TYR gene (NM_000372) has c.230G>A (p.Arg77Gln) and c.120_121insG (p.Asp42GlyfsTer35) compound heterozygous variants. The proband's father carries c.230G>A heterozygous variant, and the mother carries c.120_121insG heterozygous variant, indicating that the proband's two variants are from his father and mother. The former is a known missense variant, which can cause abnormal or loss of the original function of the protein polypeptide chain. The latter c.120_121insG(p.Asp42GlyfsTer35) is an unreported frameshift variant of the TYR gene subregion (EX1; CDS1). PolyPhen-2, SIFT, MutationTaster and FATHMM predictions are all prompted as "harmful variants". This variant caused the amino acid encoded protein to terminate prematurely, producing a truncated protein, which eventually formed a 76-amino acid short-type TYR protein instead of the 529-amino acid wild-type TYR protein. Through the pedigree analysis, the four patients in the pedigree are all of the same type of compound heterozygous variants, and the disease-causing genes are all from the patient's parents. They belong to a special form of consanguineous marriage within 5 generations. CONCLUSION: The compound heterozygous variants of c.230G>A (p.Arg77Gln) and c.120_121insG (p.Asp42GlyfsTer35) of the TYR gene may underlie the disease in this pedigree. The gene sequencing results enrich the variant spectrum of the TYR gene, and has facilitated molecular diagnosis for the patient.


Assuntos
Albinismo Oculocutâneo , Albinismo Oculocutâneo/genética , Consanguinidade , Heterozigoto , Humanos , Mutação , Linhagem
6.
Bioengineered ; 12(1): 5859-5869, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34477047

RESUMO

Oxaliplatin (OXA) resistance is a great challenge for colon adenocarcinoma (COAD) chemotherapy. The promoting role of RecQ-Like Helicase 4 (RECQL4) in chemoresistance to platinum-based drugs has been identified, whereas the effect and specific mechanism of RECQL4 in regulating OXA resistance within COAD have not been explicated yet. In this work, RECQL4 mRNA expression was detected by RT-qPCR. RECQL4, phosphorylated PI3K (p-PI3K), PI3K, phosphorylated AKT (p-AKT), and AKT protein expression were measured by western blotting. CCK-8, flow cytometry, wound healing, and transwell assays were utilized to analyze OXA resistance, cell proliferation, apoptosis, cell cycle, migration and invasion. Herein, we found RECQL4 was upregulated in COAD, especially in OXA-resistant COAD tissues and cells. RECQL4 overexpression facilitated proliferation and metastasis of OXA-resistant COAD cells; on the contrary, RECQL4 knockdown attenuated proliferative and metastatic capabilities in OXA-resistant COAD cells. Moreover, RECQL4 promoted OXA resistance in OXA-resistant COAD cells via activating the P13 K/AKT signaling. To sum up, the results suggest that RECQL4 depletion may be a crucial mechanism to reverse OXA resistance in COAD via inhibition of the P13 K/AKT pathway in vitro, thereby providing a novel target for overcoming OXA resistance in COAD.

7.
World J Surg Oncol ; 19(1): 274, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517904

RESUMO

BACKGROUND: Dihydropyrimidinase like 2 (DPYSL2) has been linked to tumor metastasis. However, the function of DPSY2L in lung adenocarcinoma (LUAD) is yet to be explored. METHODS: Herein, we assessed DPYSL2 expression in various tumor types via online databases such as Oncomine and Tumor Immune Estimation Resource (TIMER). Further, we verified the low protein and mRNA expressions of DPYSL2 in LUAD via the ULCAN, The TCGA and GEPIA databases. We applied the ROC curve to examine the role of DPYSL2 in diagnosis. The prognostic significance of DPYSL2 was established through the Kaplan-Meier plotter and the Cox analyses (univariate and multivariate). TIMER was used to explore DPYSL2 expression and its connection to immune infiltrated cells. Through Gene Set Enrichment Analysis, the possible mechanism of DPYSL2 in LUAD was investigated. RESULTS: In this study, database analysis revealed lower DPYSL2 expression in LUAD than in normal tissues. The ROC curve suggested that expression of DPYSL2 had high diagnostic efficiency in LUAD. The DPYSL2 expression had an association with the survival time of LUAD patients in the Kaplan-Meier plotter and the Cox analyses. The results from TIMER depicted a markedly positive correlation of DPYSL2 expression with immune cells infiltrated in LUAD, such as macrophages, dendritic cells, CD4+ T cells, and neutrophils. Additionally, many gene markers for the immune system had similar positive correlations in the TIMER analysis. In Gene Set Enrichment Analysis, six immune-related signaling pathways were associated with DPYSL2. CONCLUSIONS: In summary, DPYSL2 is a novel biomarker with diagnostic and prognostic potential for LUAD as well as an immunotherapy target. HIGHLIGHTS: 1. Expression of DPYSL2 was considerably lower in LUAD than in normal tissues. 2. Investigation of multiple databases showed a high diagnostic value of DPYSL2 in LUAD. 3. DPYSL2 can independently predict the LUAD outcomes. 4. Immune-related mechanisms may be potential ways for DPYSL2 to play a role in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Linfócitos do Interstício Tumoral , Prognóstico , Microambiente Tumoral
8.
Sci Total Environ ; 804: 150148, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34520919

RESUMO

Root exudates play essential roles in shaping root-associated microbial communities in plant-soil systems. However, knowledge regarding the influence of root exudates on soil communities, particularly concerning their assembly processes and species coexistence patterns, remains limited. In this study, we performed a 20-month pot experiment using a nitrogen (N) addition gradient (0, 2.5, 5, 7.5, 10, and 15 g N m-2 yr-1), amplicon sequencing, and metabolomics to investigate the effect of short-term N addition on the assembly process and species coexistence of fungal communities, as well as their association with root exudates in the rhizosphere and bulk soils around Bothriochloa ischaemum. The results demonstrated that short-term N addition led to distinct differences in the diversity, composition, assembly process, and co-occurrence networks of fungal communities in the rhizosphere and bulk soils. The diversity of fungal communities in the rhizosphere soil increased with the rate of N input and peaked at N10 treatment; this could be correlated with the increased abundance in long-chain organic acids (LCOAs). However, above the threshold N rate of 10 g N m-2 yr-1, diversity decreased probably because of the high N-induced inhibitory effect on root exudates (i.e., LCOAs). N addition increased the relative abundance of Sordariomycetes in the rhizosphere and decreased the relative abundance of Mortierellomycetes in the bulk soil, while enhancing the abundance of pathotrophs in both bulk and rhizosphere soils. The rhizosphere fungal community was dominated by a stochastic process at a low N input (N0 and N2.5) and by deterministic processes at a high N input (N10 and N15), which is opposite to the trends in the bulk soil. These fungal assembly processes determine the coexistence of fungal species; deterministic processes lead to less interconnected networks in rhizosphere soils that harbor a more complex network than the bulk soil. Associations between the assembly process and species coexistence in the rhizosphere of B. ischaemum were closely related to the changes in root exudates, such as amino acids, short-chain organic acids, and phenols, which were stimulated by N addition. Collectively, our study emphasizes the key roles of root exudates in the establishment of fungal communities in the plant-soil system and furthers our understanding of plant-microbe interactions.

9.
Pediatr Nephrol ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34529137

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common and it is associated with poor clinical outcomes in premature and low birth weight neonates. This systematic review and meta-analysis was performed to summarize the literature and evaluate the prevalence, risk factors, and mortality of premature and low birth weight neonates with AKI. METHODS: A systematic search in PubMed, Embase, and the Cochrane Library was performed. Studies on the prevalence, risk factors, diagnosis, and outcomes of acute kidney injury in preterm neonates and neonates with low birth weight were included and analyzed. RESULTS: Fifty articles of 10,744 patients were included in this study. The overall rate of AKI from the pooled results of all patients was 25% (95% CI 20-30%) with heterogeneity among studies (I2 = 97%; P < 0.01). Patients with AKI had significantly higher rate of mortality than patients without AKI (odds ratio (OR) = 7.13; 95% CI 5.91-8.60; P < 0.01). CONCLUSIONS: AKI was prevalent and was associated with high mortality rate among preterm and low birth weight neonates.

10.
J Virol ; : JVI0088921, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495699

RESUMO

Porcine epidemic diarrhea virus (PEDV) causes a porcine disease associated with swine epidemic diarrhea. Different antagonistic strategies have been identified, and the mechanism by which PEDV infection impairs the production of interferon (IFN) and delays the activation of the IFN response to escape host innate immunity has been determined, but the pathogenic mechanisms of PEDV infection remain enigmatic. Our preliminary results revealed that endogenous F-box and WD repeat domain-containing 7 (FBXW7), the substrate recognition component of the SCF-type E3 ubiquitin ligase, is downregulated in PEDV-infected Vero E6 cells, according to the results from an isobaric tags for relative and absolute quantification (iTRAQ) analysis. Overexpression of FBXW7 in target cells makes them more resistant to PEDV infection, whereas ablation of FBXW7 expression by small interfering RNA (siRNA) significantly promotes PEDV infection. In addition, FBXW7 was verified as an innate antiviral factor capable of enhancing the expression of RIG-I and TBK1, and it was found to induce interferon-stimulated genes (ISGs), which led to an elevated antiviral state of the host cells. Moreover, we revealed that PEDV nonstructural protein 2 (nsp2) interacts with FBXW7 and targets FBXW7 for degradation through the K48-linked ubiquitin-proteasome pathway. Consistent with the results proven in vitro, FBXW7 reduction was also confirmed in different intestinal tissues from PEDV-infected specific-pathogen-free (SPF) pigs. Taken together, the data indicated that PEDV has evolved with a distinct antagonistic strategy to circumvent the host antiviral response by targeting the ubiquitin-proteasome-mediated degradation of FBXW7. Our findings provide novel insights into PEDV infection and pathogenesis. IMPORTANCE To counteract the host antiviral defenses, most viruses, including coronaviruses, have evolved with diverse strategies to dampen host IFN-mediated antiviral response, wither by interfering with or evading specific host regulators at multiple steps of this response. In this study, a novel antagonistic strategy was revealed showing that PEDV infection could circumvent the host innate response by targeted degradation of endogenous FBXW7 in target cells, a process that was verified to be a positive modulator for the host innate immune system. Degradation of FBXW7 hampers host innate antiviral activation and facilitates PEDV replication. Our findings reveal a new mechanism exploited by PEDV to suppress the host antiviral response.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34549024

RESUMO

Background and aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells through the binding of the viral spike protein with human angiotensin-converting enzyme 2 (ACE2), resulting in the development of coronavirus disease 2019 (COVID-19). To date, few antiviral drugs are available that can effectively block viral infection. This study aimed to identify potential natural products from Taiwan Database of Extracts and Compounds (TDEC) that may prevent the binding of viral spike proteins with human ACE2 proteins. Methods: The structure-based virtual screening was performed using the AutoDock Vina program within PyRX software, the binding affinities of compounds were verified using isothermal titration calorimetry (ITC), the inhibitions of SARS-CoV-2 viral infection efficacy were examined by lentivirus particles pseudotyped (Vpp) infection assay, and the cell viability was tested by 293T cell in MTT assay. Results and conclusion: We identified 39 natural products targeting the viral receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in silico. In ITC binding assay, dioscin, celastrol, saikosaponin C, epimedin C, torvoside K, and amentoflavone showed dissociation constant (K d) = 0.468 µM, 1.712 µM, 6.650 µM, 2.86 µM, 3.761 µM and 4.27 µM, respectively. In Vpp infection assay, the compounds have significantly and consistently inhibition with the 50-90% inhibition of viral infection efficacy. In cell viability, torvoside K, epimedin, amentoflavone, and saikosaponin C showed IC50 > 100 µM; dioscin and celastrol showed IC50 = 1.5625 µM and 0.9866 µM, respectively. These natural products may bind to the viral spike protein, preventing SARS-CoV-2 from entering cells. Section 1: Natural Products. Taxonomy classification by evise: SARS-CoV-2, Structure-Based Virtual Screening, Isothermal Titration Calorimetry and Lentivirus Particles Pseudotyped (Vpp) Infection Assay, in silico and in vitro study.

12.
mSphere ; : e0064121, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550006

RESUMO

The two-component system VraSR responds to the cell wall-active antibiotic stress in Staphylococcus epidermidis. To study its regulatory function in biofilm formation, a vraSR deletion mutant (ΔvraSR) was constructed using S. epidermidis strain 1457 (SE1457) as the parent strain. Compared to SE1457, the ΔvraSR mutant showed impaired biofilm formation both in vitro and in vivo with a higher ratio of dead cells within the biofilm. Consistently, the ΔvraSR mutant produced much less polysaccharide intercellular adhesin (PIA). The ΔvraSR mutant also showed increased susceptibility to the cell wall inhibitor and SDS, and its cell wall observed under a transmission electron microscope (TEM) appeared to be thinner and interrupted, which is in accordance with higher susceptibility to the stress. Complementation of vraSR in the ΔvraSR mutant restored the biofilm formation and the cell wall thickness to wild-type levels. Transcriptome sequencing (RNA-Seq) showed that the vraSR deletion affected the transcription levels of 73 genes, including genes involved in biofilm formation, bacterial programmed cell death (CidA-LrgAB system), glycolysis/gluconeogenesis, the pentose phosphate pathway (PPP), and the tricarboxylic acid (TCA) cycle, etc. The results of RNA-Seq were confirmed by quantitative real-time reverse transcription-PCR (qRT-PCR). In the ΔvraSR mutant, the expression of icaA and lrgAB was downregulated and the expression of icaR and cidA was upregulated, in comparison to that of SE1457. The transcriptional levels of antibiotic-resistant genes (pbp2, serp1412, murAA, etc.) had no significant changes. An electrophoretic mobility shift assay further revealed that phosphorylated VraR bound to the promoter regions of the ica operon, as well as its own promoter region. This study demonstrates that in S. epidermidis, VraSR is an autoregulator and directly regulates biofilm formation in an ica-dependent manner. Upon cell wall stress, it indirectly regulates cell death and drug resistance in association with alterations to multiple metabolism pathways. IMPORTANCE S. epidermidis is a leading cause of hospital-acquired catheter-related infections, and its pathogenicity depends mostly on its ability to form biofilms on implants. The biofilm formation is a complex procedure that involves multiple regulating factors. Here, we show that a vancomycin resistance-associated two-component regulatory system, VraSR, plays an important role in modulating S. epidermidis biofilm formation and tolerance to stress. We demonstrate that S. epidermidis VraSR is an autoregulated system that selectively responds to stress targeting cell wall synthesis. Besides, phosphorylated VraR can bind to the promoter region of the ica operon and directly regulates polysaccharide intercellular adhesin production and biofilm formation in S. epidermidis. Furthermore, VraSR may indirectly modulate bacterial cell death and extracellular DNA (eDNA) release in biofilms through the CidA-LrgAB system. This work provides a new molecular insight into the mechanisms of VraSR-mediated modulation of the biofilm formation and cell death of S. epidermidis.

13.
PLoS One ; 16(8): e0255732, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34352018

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common gynecological disease that is often accompanied by some metabolic abnormality such as insulin resistance and dyslipidemia. As a non-pharmacological therapy, acupuncture is widely used for the treatment of PCOS, but the effectiveness for insulin resistance and lipid metabolic disorder remains controversial. OBJECTIVES: To assess the effectiveness and safety of acupuncture for insulin resistance and lipid metabolic disorder of women with PCOS. SEARCH METHODS: Eight databases will be searched from inception to June 2021, three clinical trial registration platforms will be searched for relevant trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) of acupuncture therapy for insulin resistance and lipid metabolic of PCOS will be included. DATA COLLECTION AND ANALYSIS: Study screening, data collection, and analysis will be performed by two or more reviewers independently. We will calculate mean difference (MD), standard mean difference (SMD) with 95% confidence intervals (CIs). Data synthesis will be performed with RevMan V.5.3 software and with Stata V.15.0 software when necessary. PROSPERO REGISTRATION NUMBER: CRD42020177846.

14.
Chemosphere ; 286(Pt 2): 131722, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34352547

RESUMO

The rapid development of global logistics has led to the overuse of packaging cartons, causing problems for municipal solid waste disposal. Diverse methods of exploiting the potential value of waste cartons are needed. Herein, we fabricated a magnetic composite (MC) from waste cartons via a one-step hydrothermal treatment and characterized. Using methylene blue (MB) as a model organic pollutant, tests of the activation of persulfate (PS) via the MC for the removal of MB were performed. Meanwhile, a comparison with activation with pre-magnetized zero-valent iron (Pre-ZVI/PS) was made. The comparative results show that the removal of MB was successfully accomplished with both Pre-ZVI/PS and MC/PS. Specifically, MC/PS could remove almost 100 % of MB, with the COD removal efficiency reaching over 70 % when the MB concentration was 50 mg/L at 80 min under different pH conditions. Even when reused twice, the MC still displayed robust activation performance. Additionally, we evaluated the lifetime of magnetic memory for Pre-ZVI, and first found its consecutive loss of pre-magnetization over 30 days, corresponding to the incremental attenuation of reaction rate constants in the Pre-ZVI-activated PS process. Overall, activating PS using the MC is a promising advanced oxidation technology and also provides a valuable reference on the valorization of lignocellulosic biomass.

15.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 240-246, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374234

RESUMO

Objective: To investigate the effects of novel BimunoGalactooligosaccharides (B-GOS) on cognitive behavior and depression of APP/PS1/tau Alzheimer's disease transgenic mice. Methods: Five-month-old male APP/PS1/tau AD transgenic mice and C57BL/6J control mice were divide into C57+Vehicle group, C57+B-GOS group, APP/PS1/tau+Vehicle group and APP/PS1/tau+B-GOS group, with 10 mice in each group. After continuous administration of B-GOS for 5 months, the cognitive behavior and depressive mood changes of mice in each group were detected by open field experiment, new object recognition experiment, Y maze experiment, Morris water maze experiment, tail suspension test, forced swimming test and conditioned fear experiment, respectively. Results: ①Open field experiment: the percentage of activity time in the central area of open field in APP/PS1/tau+Vehicle group mice was significantly lower than that in C57+Vehicle group mice (P<0.01), and was remarkably increased after B-GOS intervention (P<0.05). ② New object recognition experiment: the new object recognition index (NOI) of APP/PS1/tau+Vehicle group mice was significantly lower than that of C57+Vehicle group mice (P<0.01), and was observably increased after B-GOS intervention (P<0.05). ③ Y maze experiment: the spontaneous alternation correct rate of APP/PS1/tau+Vehicle group mice was notably lower than that in C57+Vehicle group (P<0.01), and was distinctly increased after B-GOS intervention (P<0.01). ④ Classical water maze experiment: the escape latency of APP/PS1/tau+Vehicle group mice on the 4th and 5th days was significantly longer than that of C57+Vehicle group mice (P<0.01), which was markedly shortened after B-GOS intervention (P<0.05). During the space exploration phase, the percentage of swimming time in the target quadrant and the times of crossing the platform in APP/PS1/tau+Vehicle group mice were significantly lower than those in C57+Vehicle group mice (P<0.01), which were notably increased after B-GOS intervention (P<0.01). ⑤ Tail suspension test and forced swimming test: the percentage of immobility time in APP/PS1/tau+Vehicle group mice was dramatically higher than that in C57+Vehicle group mice (P<0.01), and was obviously reduced after B-GOS intervention (P< 0.01). ⑥ Conditioned fear experiment: before conditioned stimulus (CS), the freezing ratio of mice in each group had no statistical difference (P>0.05). After CS, the freezing ratio of APP/PS1/tau+Vehicle group mice was significantly lower than that of C57+Vehicle group mice (P<0.01), and was notably increased after B-GOS intervention (P<0.01). Conclusion: B-GOS could reverse the cognitive behavioral impairment of APP/PS1/tau mice and alleviate their depression to a large extent.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide/genética , Animais , Cognição , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-1/genética
16.
J Virol ; : JVI0124621, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379449

RESUMO

Rotaviruses are the causative agents of severe and dehydrating gastroenteritis in children, piglets, and many other young animals. They replicate their genomes and assemble double-layered particles in cytoplasmic electron-dense inclusion bodies called 'viroplasms'. The formation of viroplasms is reportedly associated with the stability of microtubules. Although material transport is an important function of microtubules, whether and how microtubule-based transport influences the formation of viroplasms is still unclear. Here, we demonstrate that the small viroplasms move and fuse in living cells. We show that microtubule-based dynein transport affects rotavirus infection, viroplasm formation, and the assembly of transient enveloped particles (TEPs) and triple-layered particles (TLPs). The dynein intermediate chain (DIC) is shown to localize in the viroplasm and to interact directly with non-structural protein 2 (NSP2), indicating that DIC is responsible for connecting the viroplasm to dynein. The WD40 repeat domain of DIC regulates the interaction between DIC and NSP2, and the knockdown of DIC inhibited rotaviral infection, viroplasm formation, and the assembly of TEPs and TLPs. Our findings show that rotavirus viroplasms hijack dynein transport for fusion events, required for maximal assembly of infectious viral progeny. This study provides novel insights into the intracellular transport of viroplasms, which is involved in their biogenesis. Importance Because the viroplasm is the viral factory for rotavirus replication, viroplasm formation undoubtedly determines the effective production of progeny rotavirus. Therefore, understanding the virus-host interactions involved in the biogenesis of the viroplasm is critical for the future development of prophylactic and therapeutic strategies. Previous studies have reported that the formation of viroplasms is associated with the stability of microtubules, whereas little is known about its specific mechanism. Here, we demonstrate that rotavirus viroplasm formation takes advantage of microtubule-based dynein transport mediated by an interaction between NSP2 and DIC. These findings provide new insight into the intracellular transport of viroplasms.

17.
Sensors (Basel) ; 21(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34451017

RESUMO

With the improvement of the quality and resolution of remote sensing (RS) images, scene recognition tasks have played an important role in the RS community. However, due to the special bird's eye view image acquisition mode of imaging sensors, it is still challenging to construct a discriminate representation of diverse and complex scenes to improve RS image recognition performance. Capsule networks that can learn the spatial relationship between the features in an image has a good image classification performance. However, the original capsule network is not suitable for images with a complex background. To address the above issues, this paper proposes a novel end-to-end capsule network termed DS-CapsNet, in which a new multi-scale feature enhancement module and a new Caps-SoftPool method are advanced by aggregating the advantageous attributes of the residual convolution architecture, Diverse Branch Block (DBB), Squeeze and Excitation (SE) block, and the Caps-SoftPool method. By using the residual DBB, multiscale features can be extracted and fused to recover a semantic strong feature representation. By adopting SE, the informative features are emphasized, and the less salient features are weakened. The new Caps-SoftPool method can reduce the number of parameters that are needed in order to prevent an over-fitting problem. The novel DS-CapsNet achieves a competitive and promising performance for RS image recognition by using high-quality and robust capsule representation. The extensive experiments on two challenging datasets, AID and NWPU-RESISC45, demonstrate the robustness and superiority of the proposed DS-CapsNet in scene recognition tasks.


Assuntos
Diagnóstico por Imagem , Pesquisa , Progressão da Doença , Humanos
18.
Drug Des Devel Ther ; 15: 3543-3560, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34429584

RESUMO

Purpose: We aimed to investigate potential synergistic antiplatelet effects of Ginkgo biloba extract (GBE50) in combination with aspirin using in vitro models. Methods: Arachidonic acid (AA), platelet activating factor (PAF), adenosine 5'-diphosphate (ADP) and collagen were used as inducers. The antiplatelet effects of GBE50, aspirin and 1:1 combination of GBE50 and aspirin were detected by microplate method using rabbit platelets. Synergy finder 2.0 was used to analyze the synergistic antiplatelet effect. The compounds in GBE50 were identified by UPLC-Q/TOF-MS analysis and the candidate compounds were screened by TCMSP database. The targets of candidate compounds and aspirin were obtained in TCMSP, CCGs, Swiss target prediction database and drugbank. Targets involving platelet aggregation were obtained from GenCLiP database. Compound-target network was constructed and GO and KEGG enrichment analyses were performed to identify the critical biological processes and signaling pathways. The levels of thromboxane B2 (TXB2), cyclic adenosine monophosphate (cAMP) and PAF receptor (PAFR) were detected by ELISA to determine the effects of GBE50, aspirin and their combination on these pathways. Results: GBE50 combined with aspirin inhibited platelet aggregation more effectively. The combination displayed synergistic antiplatelet effects in AA-induced platelet aggregation, and additive antiplatelet effects occurred in PAF, ADP and collagen induced platelet aggregation. Seven compounds were identified as candidate compounds in GBE50. Enrichment analyses revealed that GBE50 could interfere with platelet aggregation via cAMP pathway, AA metabolism and calcium signaling pathway, and aspirin could regulate platelet aggregation through AA metabolism and platelet activation. ELISA experiments showed that GBE50 combined with aspirin could increase cAMP levels in resting platelets, and decreased the levels of TXB2 and PAFR. Conclusion: Our study indicated that GBE50 combined with aspirin could enhance the antiplatelet effects. They exerted both synergistic and additive effects in restraining platelet aggregation. The study highlighted the potential application of GBE50 as a supplementary therapy to treat thrombosis-related diseases.

19.
Bioresour Technol ; 341: 125771, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34411945

RESUMO

This study mainly investigated the feasibility of utilizing cellulase to enhance waste activated sludge (WAS) and paper waste (PW) co-fermentation for the generation of volatile fatty acids (VFAs). The introduction of cellulase effectively enhanced the co-fermentation efficiency, and the maximum VFAs generation reached 3014 mg COD/L with 60 mg cellulase/g TSS while it was 1512 mg COD/L in the control reactor. The presence of cellulase evidently improved the concentration of soluble bioavailable substrates (e.g., carbohydrates and proteins) via inducing the EPS disintegration and PW disruption. More importantly, the functional anaerobes (i.e., Macellibacteroides and Bacteroides) and the microbial activities (i.e., ATP, key acid-forming enzymes, and genetic expressions) that related with the VFAs biosynthesis were enriched and enhanced due to the stimulation of cellulase, contributing to the ultimate VFAs promotion. This study provided a novel strategy to recover valuable products from waste biomass with constructive mechanistic exploration.

20.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361033

RESUMO

Apolipoprotein E (ApoE), an essential plasma apolipoprotein, has three isoforms (E2, E3, and E4) in humans. E2 is associated with type III hyperlipoproteinemia. E4 is the major susceptibility gene to Alzheimer's disease (AD) and coronary heart disease (CHD). We investigated lipid metabolism and atherosclerotic lesions of novel humanized ApoE knockin (hApoE KI) rats in comparison to wide-type (WT) and ApoE knockout (ApoE KO) rats. The hApoE2 rats showed the lowest bodyweight and white fat mass. hApoE2 rats developed higher serum total cholesterol (TC), total triglyceride (TG), and low- and very low density lipoprotein (LDL-C&VLDL-C). ApoE KO rats also exhibited elevated TC and LDL-C&VLDL-C. Only mild atherosclerotic lesions were detected in hApoE2 and ApoE KO aortic roots. Half of the hApoE2 rats developed hepatic nodular cirrhosis. A short period of the Paigen diet (PD) treatment led to the premature death of the hApoE2 and ApoE KO rats. Severe vascular wall thickening of the coronary and pulmonary arteries was observed in 4-month PD-treated hApoE4 rats. In conclusion, hApoE2 rats develop spontaneous hyperlipidemia and might be suitable for studies of lipid metabolism-related diseases. With the PD challenge, hApoE4 KI rats could be a novel model for the analysis of vascular remodeling.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/genética , Hiperlipidemias/genética , Metabolismo dos Lipídeos , Cirrose Hepática/genética , Animais , Apolipoproteínas E/metabolismo , Colesterol/sangue , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Técnicas de Introdução de Genes , Humanos , Lipoproteínas LDL/sangue , Masculino , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue , Remodelação Vascular
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