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1.
J Mol Neurosci ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471984

RESUMO

Polo-like kinase 4 (PLK4) is one of the key regulators of centrosomal replication. However, its role and mechanism in spinal cord injury (SCI) are still unclear. The SCI model on rats was constructed and the expression and localization of PLK4 in the spinal cord are analyzed with Western blot and immunofluorescence, respectively. Then the specific siRNAs were encapsulated in nanoparticles for the inhibition of PLK4 expression. Afterward, the role of PLK4 on astrocytes was investigated by knocking down its expression in the primary astrocytes. Moreover, siRNA-loaded nanoparticles were injected into the injured spinal cord of rats, and the motor function recovery of rats after SCI was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale method. Notably, the siRNA-loaded nanoparticles effectively transfect primary astrocytes and significantly inhibit PLK4 expression, together with the expression of PCNA with significance. After treatment, restoration of the motor function following SCI was significantly improved in the PLK4 knockdown group compared with the control group. Therefore, we speculate that inhibition of Plk4 may inhibit the proliferation of astrocytes and decrease the inflammatory response mediated by astrocytes, so as to promote the functional recovery of SCI. In conclusion, inhibition of PLK4 expression via siRNA-loaded nanoparticles may be a potential treatment for SCI.

2.
J Genet Genomics ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509383

RESUMO

Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout. The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used uric acid-lowering treatment, febuxostat on gut microbiota in gout. 16S ribosomal RNA sequencing and metagenomic shotgun sequencing was performed on fecal DNA isolated from 38 untreated gout patients, 38 gout patients treated with febuxostat, and 26 healthy controls (HCs). A restriction of gut microbiota biodiversity was detected in the untreated gout patients, and the alteration was partly restored by febuxostat. Biochemical metabolic indexes involved in liver and kidney metabolism were significantly associated with the gut microbiota composition in gout patients. Functional analysis revealed that the gut microbiome of gout patients had an enriched function on carbohydrate metabolism but a lower potential for purine metabolism, which was comparatively enhanced in the febuxostat treated gout patients. A classification microbial model obtained a high mean area under the curve (AUC) up to 0.973. Therefore, gut dysbiosis characterizings gout could potentially serve as a noninvasive diagnostic tool for gout and may be a promising target of future preventive interventions.

3.
Nanoscale ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523658

RESUMO

Vascular dysfunction and bacterial infection are key factors for the non-healing of diabetic ulcers. Growth factors and antibiotics seem to effectively target both issues. However, the short half-life and high cost of growth factors and the antibiotics resistance of bacteria greatly limit their further widespread applications. Novel strategies or agents with both angiogenic and antibacterial activities are urgently desirable. Copper peroxide (CuO2) nanodots were reported to be decomposed into Cu2+ and H2O2 under mild acid conditions (pH 5.5). Considering that both decomposed products are acknowledged antibacterial agents (Cu2+, H2O2) and angiogenesis activator (Cu2+), we believe that CuO2 nanodots are suitable for diabetic ulcer treatment because the pathological environment of infected chronic wounds is mildly acidic with pH 5.5-5.6. As expected, in vitro experiments showed that CuO2 nanodots possessed excellent bactericidal properties against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and even methicillin-resistant Staphylococcus aureus (MRSA). CuO2 nanodots induced the high expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs), subsequently promoting the cell migration and tube formation for angiogenesis. In particular, CuO2 nanodots exhibited good dispersibility and sprayable behavior in water. In vivo experiments demonstrated that the spayed CuO2 nanodots in the wound area could effectively combat MRSA, reduce inflammation, promote angiogenesis, and consequently accelerate wound healing. Moreover, the sprayed CuO2 nanodots in the wound sites caused negligible system toxicity. This study provides proof-of-principle evidence for applying the sprayed CuO2 nanodots for infected diabetic ulcer treatment.

4.
Helicobacter ; : e12849, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34490965

RESUMO

BACKGROUND: Activin A receptor type I (ACVR1) is involved in tumorigenesis. However, the underlying molecular mechanisms of ACVR1 in gastric cancer (GC) and its association with Helicobacter pylori remained unclear. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) database were utilized to explore the ACVR1 expression in GC and normal control and its association with survival. The ACVR1 was knocked out using CRISPR/Cas-9; RNA sequencing analysis was performed in AGS cells with ACVR1 knockout and normal control. Functional experiments (CCK-8, colony-forming, and transwell assays) were conducted to demonstrate the role of ACVR1 in cell proliferation, invasion, and metastasis. H. pylori-infected C57/BL6 models were established. ACVR1, p-Smad1/5, and CDX2 were detected in AGS cells cocultured with H. pylori strains. The CDX2 and key elements of BMP signaling pathway were detected in AGS cells with ACVR1 knockout and normal control. In addition, Immunohistochemistry was performed to detect the ACVR1 and CDX2 expression in gastric samples. RESULTS: ACVR1 expression was higher in GC than normal control from TCGA, GEPIA, and samples collected from our hospital (p < 0.05). ACVR1 promoted cell proliferation, migration, and invasion in vitro. Both cagA+ and cagA- H. pylori could upregulate the expression ACVR1 (p < 0.05). Downregulation of ACVR1 inhibited the H. pylori-induced cell proliferation, migration, and invasion (p < 0.05). H. pylori increased the expression of p-Smad 1/5 and CDX2. The CDX2 and key elements of BMP signaling pathway were downregulated in AGS cells with ACVR1 knockout. ACVR1 and CDX2 were upregulated in the stage of intestinal metaplasia (IM). Moreover, ACVR1 and CDX2 expressions were higher in H. pylori-positive group than H. pylori-negative group (p < 0.05). CONCLUSION: Our data indicate that H. pylori infection increases ACVR1 expression, promoting gastric IM via regulating CDX2, which is an essential step in H. pylori carcinogenesis.

5.
Food Res Int ; 148: 110533, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34507779

RESUMO

Although the microbial diversity and structure in bean-based fermented foods have been widely studied, systematic studies on functional microbiota and mechanism of community forms in multi-microbial fermentation systems were still lacking. In this work, the metabolic pathway and functional potential of microbial community in broad bean paste (BBP) were investigated by metagenomics approach, and Staphylococcus, Bacillus, Weissella, Aspergillus and Zygosaccharomyces were found to be the potential predominant populations responsible for substrate alteration and flavor biosynthesis. Among them, Staphylococcus was the most abundant and widespread functional microbe, and closely related Staphylococcus species were diverse and ubiquitously distributed, with the opportunistic pathogen S. gallinarum being the most abundant Staphylococcus specie isolated from BBP. To explain the dominance status of S. gallinarum and species distributions of Staphylococcus genus, we tested the effects of abiotic and biotic factors on three Staphylococcus species using a tractable BBP model, demonstrating that adaptation to environmental conditions (environmental parameters and other functional microbes) led to the dominant position and species coexistence of Staphylococcus, and congeneric competition among Staphylococcus species further shaped ecological distributions of closely related Staphylococcus species. In general, this work revealed the metabolic potential of microbial community and distribution mechanism of Staphylococcus species during BBP fermentation, which could help traditional factories to more precisely control the safety and quality of bean-based fermented foods.

6.
Math Biosci Eng ; 18(5): 5347-5363, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34517491

RESUMO

With the development of online medical service platform, patients can find more medical information resources and obtain better medical treatment. However, it is difficult for patients to discover the most suitable doctors from the complex information resources. Therefore, the analysis and mining of Electronic Health Record(EHR) is very important for patients' timely and accurate treatment. Discovering the most suitable doctor is actually predicting the exact performance of the doctor for a specific disease. We believe that "a curative/bad treatment is likely to be caused by a good/bad doctor, and a good/bad doctor has a higher/lower evaluation by the patient(s)". In this paper, we propose a novel approach named SeekDoc, which is to seek the most effective doctor for a specific disease. Specifically, we build a doctor-disease heterogeneous information network and collect patients reviews and rating records for doctors. Then, we embed the comprehensive comment data for doctors and the constructed heterogeneous information network. Next, we use the autoencoder mechanism to learn the embedded features, which is an effective learning algorithm for constructing the latent feature representation in an unsupervised manner. After this learning, the latent features are input into the extreme gradient boosting (XGBoost) algorithm to improve their detection capabilities. Finally, extensive experiments show that our method can effectively and efficiently predict the doctor's experience score for specific diseases and has good performance compared with other algorithms.

7.
MedComm (Beijing) ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34541573

RESUMO

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants has posed a serious global public health emergency. Therapeutic interventions or vaccines are urgently needed to treat and prevent the further dissemination of this contagious virus. This study described the identification of neutralizing receptor-binding domain (RBD)-specific antibodies from mice through vaccination with a recombinant SARS-CoV-2 RBD. RBD-targeted monoclonal antibodies (mAbs) with distinct function and epitope recognition were selected to understand SARS-CoV-2 neutralization. High-affinity RBD-specific antibodies exhibited high potency in neutralizing both live and pseudotype SARS-CoV-2 viruses and the SARS-CoV-2 pseudovirus particle containing the spike protein S-RBDV367F mutant (SARS-CoV-2(V367F)). These results demonstrated that these antibodies recognize four distinct groups (I-IV) of epitopes on the RBD and that mAbs targeting group I epitope can be used in combination with mAbs recognizing groups II and/or IV epitope to make mAb cocktails against SARS-CoV-2 and its mutants. Moreover, structural characterization reveals that groups I, III, and IV epitopes are closely located to an RBD hotspot. The identification of RBD-specific antibodies and cocktails may provide an effective therapeutic and prophylactic intervention against SARS-CoV-2 and its isolates.

8.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34481128

RESUMO

BACKGROUND: Out-of-pocket (OOP) health care costs can cause financial burden and deferred care for many Americans. Little is known about OOP spending for asthma-related care among the commercially insured. OBJECTIVES: To analyze OOP spending for asthma-related care overall, across types of care, and by income. METHODS: Using enrollment, claims, and geocoded census tract data on income from a large US commercial health plan from 2004 to 2016, we measured inflation-adjusted OOP spending for individuals with asthma ages 4 to 64 years (n = 1,986,769). We estimated annual asthma-related OOP spending over time, and average total, asthma-related, asthma type of care, and asthma medication spending by income. We measured trends in median OOP cost per medication. Linear regression models were adjusted for patient covariates and deductible level. RESULTS: Asthma-related OOP spending decreased over time both for patients enrolled in high-deductible health plans and for those in traditional plans. High-deductible plan enrollment increased from 7% to 54%. Compared with patients living in high-income areas, patients in the lowest-income areas had similar annual total and asthma-related OOP spending, but spent 30% less on controller medications and a higher proportion of their asthma-related OOP spending on inpatient and emergency care (10% vs 3%; P < .001). Asthma-related OOP spending represented a higher proportion of household income for patients in lower-income areas. CONCLUSIONS: Patients with asthma living in the lowest-income areas have greater cost burden, lower spending on controller medications, and greater spending on high-acuity care than higher-income counterparts.

11.
Org Biomol Chem ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34476428

RESUMO

An exquisite metal-free cascade cyclization reaction of 2-acylbenzoic acids with amines was developed, which provided a powerful method for the one-pot synthesis of diverse isoindoloisoquinoline and benzoindolizinoindole derivatives. This protocol avoided the use of metal catalysts, proceeded with high efficiency and had broad substrate scope. These resulting products could be transformed into tertiary amines under the reduction of LiAlH4/AlCl3, followed by the Hofmann elimination offering lots of nitrogen-containing nine-membered ring compounds in excellent yields. All synthesized products containing fused N-polycyclic skeletons were difficult to be constructed using traditional methods and they have a wide range of applications in the pharmaceutical area.

12.
Immunogenetics ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477936

RESUMO

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose principal pathological change is aggressive chronic synovial inflammation; however, the specific etiology and pathogenesis have not been fully elucidated. We downloaded the synovial tissue gene expression profiles of four human knees from the Gene Expression Omnibus database, analyzed the differentially expressed genes in the normal and RA groups, and assessed their enrichment in functions and pathways using bioinformatics methods and the STRING online database to establish protein-protein interaction networks. Cytoscape software was used to obtain 10 hub genes; receiver operating characteristic (ROC) curves were calculated for each hub gene and differential expression analysis of the two groups of hub genes. The CIBERSORT algorithm was used to impute immune infiltration. We identified the signaling pathways that play important roles in RA and 10 hub genes: Ccr1, Ccr2, Ccr5, Ccr7, Cxcl5, Cxcl6, Cxcl13, Ccl13, Adcy2, and Pnoc. The diagnostic value of these 10 hub genes for RA was confirmed using ROC curves and expression analysis. Adcy2, Cxcl13, and Ccr5 are strongly associated with RA development. The study also revealed that the differential infiltration profile of different inflammatory immune cells in the synovial tissue of RA is an extremely critical factor in RA progression. This study may contribute to the understanding of signaling pathways and biological processes associated with RA and the role of inflammatory immune infiltration in the pathogenesis of RA. In addition, this study shows that Adcy2, Cxcl13, and Ccr5 have the potential to be biomarkers for RA treatment.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34501650

RESUMO

COVID-19 has caused nearly 4.3 million deaths all around the world. People who have experienced loss during this special period may find it difficult to adapt to life after loss, and may even suffer from prolonged grief disorder or other mental health problems. However, there is a huge gap of grief research in China, with almost no comprehensive grief intervention training system or very few professional grief consultants. Considering the large number of bereaved individuals who are suffering from grief and other mental health problems, it is significant to develop a suitable and effective intervention protocol immediately. This article illustrates a study protocol initiated by a Chinese university to investigate the mental health of bereaved individuals during the COVID-19 pandemic and train grief counselors to provide grief counseling to the bereaved, as well as to evaluate the effectiveness of the grief counseling. The method is as follows: (1) 300 psychological counselors will be recruited to attend the grief counseling training. Assessments will be conducted at three time points: baseline (T0), after the basic training (T1), and after the advanced training (T2); (2) 500 bereaved Chinese will be recruit to join the online survey and will be assessed at two time points with a six-month interval; and (3) a two-armed (grief counseling versus wait-list controls) RCT (random control trials) will be conducted with 160 bereaved individuals. Assessments will be conducted at three time points: before randomization (baseline, T0), at the post-counseling (T1), and three months after the post-counseling (T2). Primary outcomes will be assessed by the Prolonged Grief Questionnaire (PG-13), the 20-item PTSD Checklist for DSM-5 (PCL-5), the Depression Anxiety and Stress Scale (DASS-21), and the Posttraumatic Growth Inventory (PTGI). This research will help develop grief research and grief counseling in China, as well as provide professional mental health services for individuals who may suffer from grief-related disorders in the future.


Assuntos
Luto , COVID-19 , China , Aconselhamento , Pesar , Humanos , Estudos Longitudinais , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
14.
Artigo em Inglês | MEDLINE | ID: mdl-34500403

RESUMO

Lead compound is an important concept for modern drug discovery. In this study, a new concept of lead chemome and an efficient strategy to discover lead chemome were proposed. Compared with the concept of lead compound, lead chemome can provide not only the starting point for drug development, but also the direction for structure optimization. Two traditional Chinese medicines of Mahonia bealei and Mahonia fortunei were used as examples to illustrate the strategy. Based on natural chromatogram-effect correlation (NCEC), berberine, palmatine and jatrorrhizine were discovered as acetylcholinesterase (AchE) inhibitors. Taking the three compounds as template molecules, a lead chemome consisting of 10 structurally related natural compounds were generated through natural structure-effect correlation (NSEC). In the lead chemome, the IC50 values of jatrorrhizine, berberine, coptisine, palmatine and epiberberine are at nanomolar level, which are comparable to a widely used drug of galantamine. Pharmacophore modeling shows that the positive ionizable group and aromatic rings are important substructures for AchE inhibition. Molecular docking further shows that pi-cation interaction and pi-pi stacking are critical for compounds to maintain nanomolar IC50 values. The structure-activity information is helpful for drug design and structure optimization. This work also expanded the traditional understanding of "stem is the medicinal part of Mahonia bealei and Mahonia fortunei". Actually, all parts except the leaf of Mahonia bealei exhibited potent AchE-inhibitory activity. This study provides not only a strategy to discover lead chemome for modern drug development, but also a reference for the application of different parts of medicinal plants.

15.
BMC Pediatr ; 21(1): 384, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479510

RESUMO

BACKGROUND: The Raynaud-Claes type of X-linked syndromic mental retardation (MRXSRC) is a very rare condition, by intellectual disability ranged from borderline to profound, impaired language development, brain abnormalities, facial dysmorphisms and seizures. MRXSRC is caused by variants in CLCN4 which encodes the 2Cl-/H+ exchanger ClC-4 prominently expressed in brain. CASE PRESENTATION: We present a 3-year-old Chinese girl with intellectual disability, dysmorphic features, brain abnormalities, significant language impairment and autistic features. Brain magnetic resonance imaging (MRI) showed a thin corpus callosum, a mega cisterna magna and ventriculomegaly. Whole exome sequencing (WES) was performed to detect the molecular basis of the disease. It was confirmed that this girl carried a novel heterozygous missense variant (c.1343C > T, p.Ala448Val) of CLCN4 gene, inherited from her mother. This variant has not been registered in public databases and was predicted to be pathogenic by multiple in silico prediction tools. CONCLUSION: Our investigation expands the phenotype spectrum for CLCN4 variants with syndromic X-linked intellectual disability, which help to improve the understanding of CLCN4-related intellectual disability and will help in genetic counselling for this family.


Assuntos
Deficiência Intelectual , Retardo Mental Ligado ao Cromossomo X , Pré-Escolar , China , Canais de Cloreto/genética , Feminino , Genes Ligados ao Cromossomo X , Humanos , Deficiência Intelectual/genética , Retardo Mental Ligado ao Cromossomo X/genética , Mutação , Linhagem , Fenótipo , Sequenciamento Completo do Exoma
16.
Microbiol Spectr ; : e0059021, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550000

RESUMO

To assess the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies produced by natural infection and describe the serological characteristics over 7 months after symptom onset among coronavirus disease 2019 (COVID-19) patients by age and severity group, we followed up COVID-19 convalescent patients confirmed from 1 January to 20 March 2020 in Jiangsu, China and collected serum samples for testing IgM/IgG and neutralizing antibodies against SARS-CoV-2 between 26 August and 28 October 2020. In total, 284 recovered participants with COVID-19 were enrolled in our study. Patients had a mean age of 46.72 years (standard deviation [SD], 17.09), and 138 (48.59%) were male. The median follow-up time after symptom onset was 225.5 (interquartile range [IQR], 219 to 232) days. During the follow-up period (162 to 282 days after symptom onset), the seropositive rate of IgM fluctuated around 25.70% (95% confidence interval [CI], 20.72% to 31.20%) and that of IgG fluctuated around 79.93% (95% CI, 74.79% to 84.43%). Of the 284 patients, 64 participants were tested when discharged from hospital. Compared with that at the acute phase, the IgM/IgG antibody levels and IgM seropositivity have decreased; however, the seropositivity of IgG was not significantly lower at this follow-up (78.13% versus 82.81%). Fifty percent inhibitory dilution (ID50) titers of neutralizing antibody for samples when discharged from hospital (geometric mean titer [GMT], 82; 95% CI, 56 to 121) were significantly higher than those at 6 to 7 months after discharge (GMT, 47; 95% CI, 35 to 63) (P < 0.001). After 7 months from symptom onset, the convalescent COVID-19 patients continued to have high IgG seropositive; however, many plasma samples decreased neutralizing activity. IMPORTANCE The long-term characteristics of anti-SARS-CoV-2 antibodies among COVID-19 patients remain largely unclear. Tracking the longevity of these antibodies can provide a forward-looking reference for monitoring COVID-19. We conducted a comprehensive assessment combining the kinetics of specific and neutralizing antibodies over 7 months with age and disease severity and revealed influencing factors of the protection period of convalescent patients. By observing the long-term antibody levels against SARS-CoV-2 and comparing antibody levels at two time points after symptom onset, we found that the convalescent COVID-19 patients continued to have a high IgG seropositive rate; however, their plasma samples decreased neutralizing activity. These findings provide evidence supporting that the neutralizing activity of SARS-CoV-2-infected persons should be monitored and the administration of vaccine may be needed.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34375531

RESUMO

Thin-film composite (TFC) membranes are attracting wide attention because their ultrathin selective layer usually corresponds to the higher membrane flux for pervaporation. However, the direct preparation of the TFC membranes on ceramic substrates confronted with the great difficulties because the larger pores on ceramic substrate surfaces are detrimental to the formation of an intact polyamide (PA) selective layer produced by interfacial polymerization (IP) reaction. Here, the integrated ZIF-L nanosheets were proposed to be used as an assistance interlayer for the first time to eliminate the existence of the pores of the ceramic support, and provides a better basis for the formation of an intact PA selective layer by IP reaction between TMC and ethylenediamine (EDA). The experimental data obtained in pervaporation (PV) show that the increased flux from 1.1 to 2.9 kg/m2h corresponds to the decreased separation factor from 396 to 110 when the feed concentration of ethanol decreases from 95 wt % to 80 wt % at 50 °C. In addition, the membrane flux increases from 0.8 to 2.5 kg/m2h with a change of the separation factor from 683 to 111 when the operational temperature varies from 30 to 60 °C. These results demonstrate the great potential of the fabricated TFC membranes in practical application for PV dehydration of organic solutions.

18.
J Ethnopharmacol ; : 114532, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34416296

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qufeng Zhitong capsule (QFZTC) is a traditional Chinese medicine (TCM) clinically used for treating pain. However, the active ingredients of QFZTC and its pharmacological mechanism in the treatment of neuropathic pain (NP) remain unclear. AIM OF THE STUDY: We aimed to identify the active ingredients of QFZTC and reveal its target genes and underlying mechanism of action in NP. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used to identify the active ingredients of QFZTC. Network pharmacology analysis was conducted to determine the core targets and pathway enrichment of QFZTC. An NP mice model was established through chronic compression injury (CCI) surgery of the sciatic nerve, while von Frey instrumentation and a thermal stimulator were employed to measure the sensitivity of mice to mechanical and thermal stimuli. Immunofluorescence was used to observe the expression of TLR4 and p-P65 in microglia. Western blotting was used to detect the levels of protein expression of Iba-1, TLR4, MyD88, P65, p-P65, and c-Fos, while ELISA kits were used to detect the release of TNF-α, IL-6, and IL-1ß. RESULTS: Seven active ingredients were identified in QFZTC: gallic acid, loganylic acid, syringin, corilagin, loganin, ellagic acid, and osthole. Network analysis identified TLR4, TNF, IL6, IL1ß, and c-Fos as core targets, and Toll-like receptors and NF-κB as core signaling pathways. Treatment with QFZTC significantly relieved mechanical allodynia and thermal hyperalgesia in CCI mice models. CCI induced an increase in the expression of TLR4 and p-P65 in microglia, whereas QFZTC dose-dependently reduced the expression of Iba-1, TLR4, MyD88, and p-P65 in the spinal cord. QFZTC inhibited the expression of the c-Fos pain marker and reduced the expression of the TNF-α, IL-6, and IL-1ß inflammatory factors. CONCLUSION: We combined the active ingredients of QFZTC with network pharmacology research to clarify its biological mechanism in the treatment of NP. We demonstrated that QFZTC reduced NP in mice probably through regulating the spinal microglia via the TLR4/MyD88/NF-κB signaling pathway. Hence, QFZTC could be regarded as a potential drug for relieving NP.

19.
Environ Sci Technol ; 55(17): 11501-11510, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34370449

RESUMO

We implemented a context-sensitive and prospective framework to assess the global warming potential (GWP) impacts of cool pavement strategies on specific roads for different cities. The approach incorporates several interconnections among different elements of the built environment, such as buildings and urban road segments, as well as the transportation fleet, using specific building and pavement information from an urban area. We show that increasing pavement albedo lowers urban air temperatures but can adversely affect the building energy demand in the areas with high incident radiation exposure. The heating energy savings and the radiative forcing effect improve the GWP savings in cold and humid climate conditions. The total GWP savings intensity is sensitive to the city morphology and road traffic. The probabilistic results show that cool pavement strategies can offset 1.0-3.0% and 0.7-6.0% of the total GHG emissions of the U.S. cities Boston and Phoenix, respectively, for a 50-year analysis period. The worldwide range of savings can be as large as 5.0-44.7 Gt of CO2 eq. A paradigm shift in pavement strategy selection is required in most neighborhoods.

20.
Nucleic Acids Res ; 49(16): 9246-9263, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34370013

RESUMO

To reconstruct systematically hyperactive transcription factor (TF)-dependent transcription networks in squamous cell carcinomas (SCCs), a computational method (ELMER) was applied to 1293 pan-SCC patient samples, and 44 hyperactive SCC TFs were identified. As a top candidate, DLX5 exhibits a notable bifurcate re-configuration of its bivalent promoter in cancer. Specifically, DLX5 maintains a bivalent state in normal tissues; its promoter is hypermethylation, leading to DLX5 transcriptional silencing in esophageal adenocarcinoma (EAC). In stark contrast, DLX5 promoter gains active histone marks and becomes transcriptionally activated in ESCC, which is directly mediated by SOX2. Functionally, silencing of DLX5 substantially inhibits SCC viability both in vitro and in vivo. Mechanistically, DLX5 cooperates with TP63 in regulating ∼2000 enhancers and promoters, which converge on activating cancer-promoting pathways. Together, our data establish a novel and strong SCC-promoting factor and elucidate a new epigenomic mechanism - bifurcate chromatin re-configuration - during cancer development.

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