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1.
Sens Actuators B Chem ; 377: 133006, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36439053

RESUMO

Common reference methods for COVID-19 variant diagnosis include viral sequencing and PCR-based methods. However, sequencing is tedious, expensive, and time-consuming, while PCR-based methods have high risk of insensitive detection in variant-prone regions and are susceptible to potential background signal interference in biological samples. Here, we report a loop-mediated interference reduction isothermal nucleic acid amplification (LM-IR-INA) strategy for highly sensitive single-base mutation detection in viral variants. This strategy exploits the advantages of nicking endonuclease-mediated isothermal amplification, luminescent iridium(III) probes, and time-resolved emission spectroscopy (TRES). Using the LM-IR-INA strategy, we established a luminescence platform for diagnosing COVID-19 D796Y single-base substitution detection with a detection limit of 2.01 × 105 copies/µL in a linear range of 6.01 × 105 to 3.76 × 108 copies/µL and an excellent specificity with a variant/wild-type ratio of significantly less than 0.0625%. The developed TRES-based method was also successfully applied to detect D796Y single-base substitution sequence in complicated biological samples, including throat and blood, and was a superior to steady-state technique. LM-IR-INA was also demonstrated for detecting the single-base substitution D614G as well as the multiple-base mutation H69/V70del without mutual interference, indicating that this approach has the potential to be used as a universal viral variant detection strategy.

2.
Polymers (Basel) ; 14(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36432963

RESUMO

Modified hydrophilic polyurethane is a new and effective material for soil and water conservation, which can form a consolidation layer with soil and has achieved more outstanding results in slope management in Pisha sandstone areas. However, the W-OH-Pisha sandstone system can be destroyed by local natural conditions, which seriously affects its consolidation effect on the soil. This paper focuses on the failure mechanism of the W-OH-Pisha sandstone system under dry-wet cycles; it establishes its failure model and provides theoretical guidance on the use of W-OH materials for slope management. Firstly, mechanical and in-situ morphological observations of W-OH solid consolidation under dry-wet cycles were carried out, and the results showed that W-OH solid consolidation at different concentrations only becomes rougher, and their cohesive failure does not occur under dry-wet cycles. Then, the adhesion model and water damage model of the W-OH-Pisha sandstone system were established based on surface energy theory. It was found that the larger the concentration of W-OH, the better the adhesion and spalling resistance performance. Additionally, we used the water stability constant to express the compatibility of W-OH with Pisha sandstones. The results showed that the greater the concentration of W-OH, the greater the water stability constant and the resistance of the W-OH-Pisha sandstone solid consolidation to the dry-wet cycles. Finally, based on the unconfined compressive strength test of the W-OH-Pisha sandstone solid consolidation, the unconfined strength ratio of the W-OH-Pisha sandstone solid consolidation was established as a function of the water stability constant; the unconfined strength ratio of the solid consolidations increases with an increase in the water stability constant. This also verifies the correctness of the W-OH-Pisha sandstone adhesion model and the water damage model.

3.
Energy Build ; : 112681, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36438077

RESUMO

With the outbreak of infectious diseases such as Corona Virus Disease 2019, medical staff work intensively in isolated plots, medical disposable protective clothing (MDPC) has poor air condition and humidity permeability, which seriously reduces the thermal comfort of medical staff. In this paper, the effect of indoor thermal environment and activity levels on thermal comfort inside MDPC was studied by experiment. Five parts of the body were measured inside MDPC and the appropriate movements were chosen to simulate different levels of labor intensity. Meanwhile, physiological parameters and subjective thermal sensation were statistically analyzed. The results showed the influence range of different indoor temperatures on the temperature and humidity inside MDPC was about 1 °C and 10%, respectively; it indicated that the environment inside MDPC could be improved by reducing indoor temperature, that is, a cross intelligent adjustment mode was proposed. The effect of labor intensity on the temperature inside MDPC was significantly less than that of humidity. Within 20 minutes, the humidity changes under moderate and heavy labor intensity were even more than 10%, and the subjective discomfort threshold of the subjects increased by nearly 50%. Furthermore, the maximum benefit could be obtained by concentrating cooling on back, forehead, chest and upper arm. Theoretical models of working time, labor intensity, and temperature and humidity inside MDPC under different indoor temperatures and different parts were given. In addition, acceptable regions inside MDPC which were approximately parallelogram in the enthalpy-humidity chart. These conclusions could be a reference for future thermal comfort inside MDPC research.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36212967

RESUMO

To further determine how BHE affected the growth of HCC cells, the proportion of each cell cycle phase was explored in HCC cells by flow cytometry. Blue honeysuckle (Lonicera caerulea L.) is a species of bush that grows in eastern Russia. Blue honeysuckle extract (BHE) is rich in bioactive phytochemicals which can inhibit the proliferation of tumor cells. The mechanism underlying the anticancer activity of BHE in primary liver cancer is poorly understood. The purpose of this study was to evaluate the growth inhibition mechanism of bioactive substances from blue honeysuckle on hepatocellular carcinoma (HCC) cells and to explore its protein and gene targets. The compounds in BHE were determined by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Cell counting kit-8 (CCK8) assay was used to evaluate the effects of BHE on HCC cell proliferation, and flow cytometry assay (FCA) was used to determine how BHE arrested the proportion of each cell cycle phase in HCC cells. Western blot (WB) was performed to determine the expression of cell cycle-related proteins in HCC cells treated with different concentrations of BHE. The xenograft tumor animal models were established by HCC cell implantation. The results showed that cyanidin-3-o-glucoside and cyanidin-3-o-sophoroside which are the main biologically active components were detected in BHE. BHE is highly effective in inhibiting the proliferation of HCC cells by arresting the HCC cell cycle in the G2/M phase. BHE also downregulated the expression of conventional or classical dendritic cells-2 (cDC2) and cyclin B1 by promoting the expression of myelin transcription factor 1 (MyT1) in HCC cells. The weight and volume of xenografts were significantly decreased in the BHE treated groups when compared to the control group. BHE increased the expression of MyT1 in xenograft tissues. These findings showed that blue honeysuckle extract inhibits proliferation in vivo and in vitro by downregulating the expression of cDC2 and cyclin B1 and upregulating the expression of MyT1 in HCC cells.

5.
Sci Rep ; 12(1): 16758, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36202900

RESUMO

Since the existing visual question answering model lacks long-term memory modules for answering complex questions, it is easy to cause the loss of effective information. In order to further improve the accuracy of the visual question answering model, this paper applies the multiple attention mechanism combining channel attention and spatial attention to memory networks for the first time and proposes a dynamic memory network model (DMN-MA) based on the multiple attention mechanism. The model uses the multiple attention mechanism in the situational memory module to obtain the most relevant visual vectors for answering questions based on continuous memory updating, storage and iterative inference of the questions, and effectively uses contextual information for answer inference. The experimental results show that the accuracy of the model in this paper reaches 64.57% and 67.18% on the large-scale public datasets COCO-QA and VQA2.0, respectively.


Assuntos
Armazenamento e Recuperação da Informação , Memória de Longo Prazo
6.
Discov Oncol ; 13(1): 99, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36195696

RESUMO

Immune checkpoint inhibitors (ICIs) are changing all aspects of malignant tumour therapy as an immunotherapy subverter in oncology. However, the current ICIs might induce systemic immune activation in other tissues and organs since they are not tumour-specific, causing the immune system to attack some normal tissues and organs of the human body. The toxicity can also amplify greatly although combined immunotherapy for cancer has increased the curative efficacy. The LC4 peptide was modified to improve its tumour-targeting ability and reduce peripheral immune system activation, which was obtained through phage display peptide library screening and could block the CTLA-4/CD80 interaction. The LC4 peptide as a result, like other ICIs, exerts anti-tumour effects by refreshing T cell function, and also activates the peripheral immune system. We used the PLGLAG peptide as a linker at the C-terminal of LC4 to connect with a tumour-targeting peptide RGD to increase the tumour tissue targeting ability, and obtain LC4-PLG-RGD. Further experiments demonstrated that the anti-tumour LC4-PLG-RGD activity was better than LC4 in vivo, and the ability to activate the peripheral immune system was weakened. In conclusion, LC4-PLG-RGD can increase the ICIs tumour-targeting and reduce excessive peripheral tissue immune activation, thereby reducing the side effects of ICIs, while increasing their anti-tumour efficacy. This study confirmed that enhanced ICI tumour targeting can effectively reduce immune-related adverse reaction occurrence.

7.
Sci Adv ; 8(40): eadd5678, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36206342

RESUMO

Numerous efforts are being made toward constructing artificial nanopockets inside heterogeneous catalysts to implement challenging reactions that are difficult to occur on traditional heterogeneous catalysts. Here, the enzyme-mimetic nanopockets are fabricated inside the typical UiO-66 by coordinating zirconium nodes with terephthalate (BDC) ligands and monocarboxylate modulators including formic acid (FC), acetic acid (AC), or trifluoroacetic acid (TFA). When used in transfer hydrogenation of alkyl levulinates with isopropanol toward γ-valerolactone (GVL), these modulators endow zirconium sites with enhanced activity and selectivity and good stability. The catalytic activity of UiO-66FC is ~30 times that of UiO-66, also outperforming the state-of-the-art heterogeneous catalysts. Distinct from general consensus on electron-withdrawing or electron-donating effect on the altered activity of metal centers, this improvement mainly originates from the conformational change of modulators in the nanopocket to assist forming the rate-determining six-membered ring intermediate at zirconium sites, which are stabilized by van der Waals force interactions.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36193147

RESUMO

The prevalence of allergic rhinitis (AR) has increased tremendously in the recent year in China. Evidence-based medicine to objectively evaluate the prevalence and risk factors for AR in China is urgently required. Toward this, we systematically searched four English and four Chinese databases to identify the literature on the same, from the year of website establishment until November 2021. A total of 51 studies were evaluated, and data were obtained through Stata 16 analysis. Overall pooled risk factors for adult AR were smoking (odds ratio [OR] = 1.89, 95% confidence interval [CI]: 1.25, 2.87), asthma (OR = 3.30, 95% CI: 1.48, 7.39), a family history of AR (OR = 3.17, 95% CI: 2.31, 4.34), a family history of asthma (OR = 3.99, 95% CI: 2.58, 6.16), drug allergy (OR = 1.62, 95% CI: 1.38, 1.89), food allergy (OR = 2.29, 95% CI: 1.39, 3.78), pollen allergy history (OR = 2.41, 95% CI: 1.67, 3.46), antibiotic use (OR = 2.08, 95% CI: 1.28, 3.36), occupational dust exposure (OR = 2.05, 95% CI: 1.70, 2.47), home renovation (OR = 1.73, 95% CI: 0.99, 3.02), and middle school education (OR = 1.99, 95% CI: 1.29, 3.06). Overall pooled risk factors for AR in children were passive smoking (OR = 1.70, 95% CI: 1.02, 2.82), asthma (OR = 3.26, 95% CI: 2.42, 4.39), a family history of AR (OR = 2.59, 95% CI: 2.07, 3.24), a family history of allergy (OR = 4.84, 95% CI: 3.22, 7.26), a history of allergic diseases (OR = 2.11, 95% CI: 1.52, 2.94), eczema(OR = 2.29, 95% CI: 1.36, 3.85), owning pets (OR = 1.56, 95% CI: 1.37, 1.77), eating seafood (OR = 1.30, 95% CI: 1.10, 1.55), boys (OR = 1.58, 95% CI: 1.43, 1.74), and breastfeeding (OR = 0.82, 95% CI: 0.55, 1.22). The results of our meta-analysis showed that the prevalence of allergy rhinitis was 19% (95% CI 14-25) among adults and 22% (95% CI 17-27) among children, with boys showing a higher prevalence than girls. The development of AR in China is associated with several factors, including allergic diseases (eczema, asthma, pollen allergy, and food allergy), a family history of allergy (AR, asthma, and other allergies), and dwelling and working environment (smoking or passive smoking, occupational dust exposure, and owning pets); conversely, breastfeeding can reduce the risk.

9.
Dalton Trans ; 51(40): 15233-15238, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36190512

RESUMO

A three-dimensional microporous thorium-based metal-organic framework (Th-BPYDC-I) that features a suitable pore size for Xe was prepared. The pore confinement effect enables high Xe uptake (2.15 mmol g-1) and good Xe/Kr selectivity (7.49). This work highlights the critical role of the size-matching rule in noble gas separation and provides an alternative option for Xe/Kr separation.

10.
Nutrients ; 14(19)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36235592

RESUMO

Intrahepatic cholestasis (IC) occurs when the liver and systemic circulation accumulate bile components, which can then lead to lipid metabolism disorders and oxidative damage. Ginsenosides (GS) are pharmacologically active plant products derived from ginseng that possesses lipid-regulation and antioxidation activities. The purpose of this study was to evaluate the possible protective effects of ginsenosides (GS) on lipid homeostasis disorder and oxidative stress in mice with alpha-naphthylisothiocyanate (ANIT)-induced IC and to investigate the underlying mechanisms. A comprehensive strategy via incorporating pharmacodynamics and molecular biology technology was adopted to investigate the therapeutic mechanisms of GS in ANIT-induced mice liver injury. The effects of GS on cholestasis were studied in mice that had been exposed to ANIT-induced cholestasis. The human HepG2 cell line was then used in vitro to investigate the molecular mechanisms by which GS might improve IC. The gene silencing experiment and liver-specific sirtuin-1 (SIRT1) knockout (SIRT1LKO) mice were used to further elucidate the mechanisms. The general physical indicators were assessed, and biological samples were collected for serum biochemical indexes, lipid metabolism, and oxidative stress-related indicators. Quantitative PCR and H&E staining were used for molecular and pathological analysis. The altered expression levels of key pathway proteins (Sirt1, p-AMPK, Nrf2) were validated by Western blotting. By modulating the AMPK protein expression, GS decreased hepatic lipogenesis, and increased fatty acid ß-oxidation and lipoprotein lipolysis, thereby improving lipid homeostasis in IC mice. Furthermore, GS reduced ANIT-triggered oxidative damage by enhancing Nrf2 and its downstream target levels. Notably, the protective results of GS were eliminated by SIRT1 shRNA in vitro and SIRT1LKO mice in vivo. GS can restore the balance of the lipid metabolism and redox in the livers of ANIT-induced IC models via the SIRT1/AMPK signaling pathway, thus exerting a protective effect against ANIT-induced cholestatic liver injury.


Assuntos
Colestase Intra-Hepática , Colestase , Ginsenosídeos , 1-Naftilisotiocianato/toxicidade , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Colestase/patologia , Colestase Intra-Hepática/induzido quimicamente , Colestase Intra-Hepática/tratamento farmacológico , Ácidos Graxos/metabolismo , Ginsenosídeos/farmacologia , Células Hep G2 , Homeostase , Humanos , Lipídeos/farmacologia , Fígado/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , RNA Interferente Pequeno/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo
11.
Front Immunol ; 13: 988303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275690

RESUMO

Background: Colon adenocarcinoma (COAD) is a prevalent malignancy that causes significant mortality. Microsatellite instability plays a pivotal function in COAD development and immunotherapy resistance. However, the detailed underlying mechanism requires further investigation. Consequently, identifying molecular biomarkers with prognostic significance and revealing the role of MSI in COAD is important for addressing key obstacles in the available treatments. Methods: CIBERSORT and ESTIMATE analyses were performed to evaluate immune infiltration in COAD samples, followed by correlation analysis for MSI and immune infiltration. Then, differentially expressed genes (DEGs) in MSI and microsatellite stability (MSS) samples were identified and subjected to weighted gene co-expression network analysis (WGCNA). A prognostic model was established with univariate cox regression and LASSO analyses, then evaluated with Kaplan-Meier analysis. The correlation between the prognostic model and immune checkpoint inhibitor (ICI) response was also analyzed. Results: In total, 701 significant DEGs related to MSI status were identified, and WGCNA revealed two modules associated with the immune score. Then, a seven-gene prognostic model was constructed using LASSO and univariate cox regression analyses to predict survival and ICI response. The high-risk score patients in TCGA and GEO cohorts presented a poor prognosis, as well as a high immune checkpoint expression, so they are more likely to benefit from ICI treatment. Conclusion: The seven-gene prognostic model constructed could predict the survival of COAD and ICI response and serve as a reference for immunotherapy decisions.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Prognóstico , Instabilidade de Microssatélites , Neoplasias do Colo/patologia , Adenocarcinoma/patologia , Inibidores de Checkpoint Imunológico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
12.
Am J Transl Res ; 14(9): 6763-6773, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36247288

RESUMO

OBJECTIVES: Intrahepatic cholestasis of pregnancy (IHCP) causes itching, preterm birth, and stillbirth. However, there is no accurate diagnostic method for IHCP. Currently, circulating microRNAs (miRNAs) have become candidate biomarkers for the diagnosis of multiple diseases. Here, we investigated the diagnostic value of miRNAs in IHCP and aimed to predict the molecular mechanism of IHCP pathogenesis. METHODS: We analyzed differentially expressed miRNAs in both women with IHCP and normal pregnant women. The selected candidate miRNAs were validated in 46 IHCP cases and 46 normal pregnant subjects, and we constructed receiver operator characteristic curves of miRNAs. Pearson correlations between levels of total bile acid (TBA) and differentially expressed miRNAs were also calculated. In addition, we clustered functionally significant biological pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. RESULTS: The expression levels of 13 miRNAs were remarkably upregulated while the other 35 miRNAs were significantly downregulated, in women with IHCP (P≤0.05) when compared with healthy pregnant women. The areas under the curves of miRNA-7706, miRNA-877-3p, and miRNA-128-3p were higher than 0.90, indicating more reliable diagnosis of IHCP. The Pearson analysis showed that the levels of these miRNAs were positively correlated to TBA level. Additionally, the results of bioinformatics analysis revealed that the differentially expressed miRNAs mainly influenced fatty acid biosynthesis, the endoplasmic reticulum ubiquitin ligase complex, and the p53, and mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways. CONCLUSION: The panel of three-miRNAs (miRNA-7706, miRNA-877-3p, and miRNA-128-3p) may be a useful noninvasive diagnostic biomarker of IHCP.

13.
Front Nutr ; 9: 967902, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091250

RESUMO

Backgrounds: The patient-generated subjective global assessment (PG-SGA) is one of the screening criteria for malnutrition, the skeletal muscle radiodensity (SMD) and skeletal muscle mass index (SMI) are associated with survival in colorectal cancer patients. Body composition parameters can be easily assessed; however, few studies have examined the association between total muscle wasting scores in PG-SGA and body composition parameters and two muscle abnormalities. Methods: This cohort study included 1,637 stage I-III CRC patients from 2 clinical centers in China, who were enrolled in the training cohort (n = 1,005) and validation cohort (n = 632). Baseline data were collected prospectively from patients including age, BMI, staging, gait speed, hand grip strength (HGS), peak expiratory flow (PEF), neutrophil-lymphocyte ratio (NLR), intermuscular adipose tissue (IMAT), visceral fat area (VFA) and total muscle wasting score in PG-SGA. Relevant risk factors were subjected to logistic regression analysis and Cox regression analysis to identify characteristics associated with muscle abnormalities and survival. Based on the logistic model results, normograms were established to predict muscle abnormalities, and its discrimination and calibration were assessed using the receiver operating characteristic (ROC) curve and calibration curve. The Kaplan-Meier curves were used to assess the survival of colorectal cancer patients with malnutrition or sarcopenia in an inflammatory state (assessed by NLR). Results: The mean age of all participants was 57.7 ± 10.6 years (56.9% males) and the prevalence of low SMD and low SMI was 32.2 and 39.5%, respectively. Low SMD rate was significantly associated with age, TNM stage, BMI, IMAT, walking speed, total muscle wasting score and NRS2002 score by logistic regression analysis (p < 0.05). Low SMI rate was significantly correlated with age, NLR, BMI, PEF, handgrip strength, calf circumference, walking speed, total muscle wasting score and NRS2002 score (p < 0.05). The AUCs of the diagnostic nomograms were 0.859 (95% CI, 0.831-0.886) for low SMD and 0.843 (95% CI, 0.813-0.871) for low SMI in the validation cohort. We also found that patients with colorectal cancer with malnutrition or sarcopenia had a worse prognosis when NLR ≥3.5. Conclusion: Muscle abnormalities and malnutrition are strongly associated with mortality in patients with non-metastatic colorectal cancer. Early identification and intervention of the associated risk factors may offer new ways to improve patient prognosis.

14.
Updates Surg ; 74(6): 1861-1870, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36161396

RESUMO

Transvaginal (TV) repair, featuring its feasibility, effectiveness, safety, and technically less demandingness, is one of the surgical approaches for management of rectovaginal fistula (RVF). However, there are limited numbers of publications available on the transvaginal approach for RVF repair. To this end, the purpose of this study is to evaluate the preliminary outcomes of the transvaginal approach performed by the team, and to further assess its feasibility, safety and effectiveness in the management of RVF. A retrospective analysis was conducted at a single institution. Patients with RVF who had undergone three transvaginal surgical techniques, i.e. transvaginal fistulectomy and stratified suture, transvaginal flip and ligation fistula tract and transvaginal fistula stapled closure were included. Besides, the demographics, operative data, postoperative complications and follow-up outcomes of the patients were collected prospectively. A total of 49 female patients (mean age, 35.76 ± 13.97 years) underwent transvaginal approach, 42 of which were followed up with a median follow-up of 26 months (range 3-82 months), and 29 had closure of the fistula (successful closure rate of 59.1%). The successful closure rates were only significantly different between previous repair times (p = 0.031), and several minor complications including postoperative pain (n = 3), constipation (n = 1), and lower urinary tract infection (n = 1) were observed. Symptomatic improvement was reported in all patients with failed closure. Transvaginal approach for RVF repair is effective, safe, and feasible, and is therefore considered an alternative to transrectal advancement flap for low and mid-level traumatic RVF with normal sphincter function. With the advantage of better surgical access, transvaginal approach is recognized as the initial choice for the surgical repair of RVF.


Assuntos
Fístula Retovaginal , Retalhos Cirúrgicos , Humanos , Feminino , Lactente , Pré-Escolar , Criança , Fístula Retovaginal/cirurgia , Fístula Retovaginal/etiologia , Estudos Retrospectivos , Suturas/efeitos adversos , Complicações Pós-Operatórias , Resultado do Tratamento
15.
Laryngoscope ; 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36102297

RESUMO

OBJECTIVE: To assess the role and possible mechanism of surfactant protein A (SPA) in the pathogenesis of otitis media with effusion (OME). METHODS: This was a multi-part study with both an in vivo mouse model study as well as an in vitro study. The control and study groups (OME group) received phosphate-buffered saline and inactivated Streptococcus pneumoniae, respectively, via external auditory meatus injections. Changes in the surface tension of secretions from the eustachian tube (ET) and SPA expression were measured in both groups. A transwell assay was performed to observe the effect of different concentrations of SPA on the migration ability of macrophages. We examined the differentially expressed genes related to SPA-treated macrophages using RNA-seq analysis. RESULTS: On Day 3, the surface tension of the OME group was higher than that of the control group (p = 0.014). The variation intensity of SPA in the ET of the OME group was significantly lower than that of the control group (p < 0.001). Surface tension was correlated with SPA (r = -0.525, p = 0.037). The expression of SPA and macrophages in the ET was different between the two groups. In vitro experiments revealed that macrophages showed different migration abilities with SPA concentration changes (p < 0.05). RNA-seq and western blotting were performed after macrophages were treated with SPA. The results showed that RhoA and Rac1/2/3 were differentially expressed. CONCLUSIONS: SPA can change the surface tension of secretions from the ET and affect macrophage migration to alter the function of the ET. Although research in this field of OME is nascent, initial work suggests that SPA likely plays an important role in OME progression. LEVEL OF EVIDENCE: NA Laryngoscope, 2022.

16.
Environ Pollut ; 313: 120101, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36064059

RESUMO

Antibiotic resistance genes (ARGs) are abundantly shed in feces. Thus, it is crucial to identify their host sources so that ARG pollution can be effectively mitigated and aquatic ecosystems can be properly conserved. Here, spatiotemporal variations and sources of ARGs in the Longjiang watershed of South China were investigated by linking them with microbial source tracker (MST) indicators. The most frequently detected ARGs (>90%) were sulI, sulII, blaTEM, tetW, ermF, and the mobile element intI1. Spatial distribution analyses showed that tributaries contributed significantly more sulI, sulII, and ermF contamination to the Longjiang watershed than the main channel. MST indicator analysis revealed that the Longjiang watershed was contaminated mainly by human fecal pollution. Livestock- and poultry-associated fecal pollution significantly declined after the swine fever outbreak. The occurrence of most ARGs is largely explained by human fecal pollution. In contrast, pig fecal pollution might account for the prevalence of tetO. Moreover, combined human-pig fecal pollution contributed to the observed blaNDM-1 distribution in the Longjiang watershed. Subsequent analysis of the characteristics of MST markers disclosed that the relatively lower specificities of BacHum and Rum-2-Bac may lead to inaccurate results of tracking ARG pollution source. The present study determined spatiotemporal variations and ARG origins in the Longjiang watershed by combining MST markers. It also underscored the necessity of using multiple MST markers simultaneously to identify and characterize ARG pollution sources accurately.


Assuntos
Antibacterianos , Peste Suína Clássica , Animais , Peste Suína Clássica/genética , Resistência Microbiana a Medicamentos/genética , Ecossistema , Monitoramento Ambiental , Fezes , Genes Bacterianos , Humanos , Suínos
17.
Life Sci ; 307: 120848, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35940221

RESUMO

AIMS: In this study, we will examine if RSL1D1 influences PPARγ expression and explore the underlying mechanism that RSL1D1 regulates PPARγ expression. Moreover, the significance of RSL1D1-PPARγ pathway in cell senescence and proliferation will also be determined. MAIN METHODS: Our main methods include western blotting, immunoprecipitation (IP), real-time PCR, RNA Immunoprecipitation (RIP), biotin-labeled RNA pull down assay, dual luciferase reporter gene assay, senescence-associated ß-galactosidase staining, cell proliferation assay, colony formation assay, wound healing assay, blood biochemistry test and Oil red O staining. KEY FINDINGS: By analyzing gene chip results we find that the expression of RSL1D1 and PPARγ might be correlated. Then we show that RSL1D1 is a posttranscriptional regulator of PPARγ. RSL1D1 overexpression elevates, while RSL1D1 knockdown inhibits, PPARγ mRNA and protein expression levels. Mechanistically, we find that RSL1D1 directly interacts with the 3'-untranslated region of PPARγ mRNA, and then promotes its stability and increases PPARγ protein expression level. We further demonstrate that RSL1D1 modulates cellular senescence and cell proliferation partially via PPARγ-regulated downstream target genes such as PTEN/p27, NF-κB, GLUT4, and ACL. Moreover, we find that RSL1D1 regulates PPARγ expression and function in a HuR-dependent manner. Last, we show that RSL1D1 knockout in mouse adipose tissue shortens mouse lifespan and leads to hepatic damage which may impair liver damage repair function. SIGNIFICANCE: Collectively, our findings unveil a novel posttranscriptional regulation of PPARγ by RSL1D1 and uncover a critical role of RSL1D1-PPARγ-PPARγ downstream target genes in regulating cellular senescence and cell proliferation.


Assuntos
NF-kappa B , PPAR gama , Proteínas da Gravidez/metabolismo , Proteínas Ribossômicas/metabolismo , Regiões 3' não Traduzidas , Animais , Biotina , Proliferação de Células , Senescência Celular/genética , Camundongos , NF-kappa B/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , beta-Galactosidase/metabolismo
18.
ACS Omega ; 7(31): 27714-27721, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35967043

RESUMO

Hyperglycemia is one of the common symptoms of diabetes, and it produces excessive reactive oxygen species (ROS). This study investigated whether the long noncoding RNA (lncRNA) UC.360+ is involved in diabetic cardiac autonomic neuropathy (DCAN) mediated by NLRP3 inflammasome-induced pyroptosis in the stellate ganglion (SG). Using a rat type 2 diabetes model, we found that lncRNA UC.360+ short hairpin RNA (shRNA) ameliorated the dyslipidaemia of type 2 diabetic rats and reduced serum adrenaline and ROS production in SG under hyperglycemia. In addition, UC.360+ shRNA also reduced the expression of nuclear factor kappa-B (NF-κB), NLRP3, ASC, caspase-1, interleukin-1ß (IL-1ß), and IL-18 in the SG of diabetic rats and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Therefore, lncRNA-UC.360+ shRNA may modulate the NLRP3 inflammasome/inflammatory pathway in the SG, which in turn alleviates diabetic heart sympathetic nerve damage.

19.
Med Phys ; 49(10): 6384-6394, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35938604

RESUMO

PURPOSE: To develop a novel multimodal data fusion model by incorporating computed tomography (CT) images and clinical variables based on deep learning for predicting the invasiveness risk of stage I lung adenocarcinoma that manifests as ground-glass nodules (GGNs) and compare the diagnostic performance of it with that of radiologists. METHODS: A total of 1946 patients with solitary and histopathologically confirmed GGNs with maximum diameter less than 3 cm were retrospectively enrolled. The training dataset containing 1704 GGNs was augmented by resampling, scaling, random cropping, and so forth, to generate new training data. A multimodal data fusion model based on residual learning architecture and two multilayer perceptron with attention mechanism combining CT images with patient general data and serum tumor markers was built. The distance-based confidence scores (DCS) were calculated and compared among multimodal data models with different combinations. An observer study was conducted and the prediction performance of the fusion algorithms was compared with that of the two radiologists by an independent testing dataset with 242 GGNs. RESULTS: Among the whole GGNs, 606 GGNs are confirmed as invasive adenocarcinoma (IA) and 1340 are non-IA. The proposed novel multimodal data fusion model combining CT images, patient general data, and serum tumor markers achieved the highest accuracy (88.5%), area under a ROC curve (0.957), F1 (81.5%), F1weighted (81.9%), and Matthews correlation coefficient (73.2%) for classifying between IA and non-IA GGNs, which was even better than the senior radiologist's performance (accuracy, 86.1%). In addition, the DCSs for multimodal data suggested that CT image had a stronger influence (0.9540) quantitatively than general data (0.6726) or tumor marker (0.6971). CONCLUSION: This study demonstrated that the feasibility of integrating different types of data including CT images and clinical variables, and the multimodal data fusion model yielded higher performance for distinguishing IA from non-IA GGNs.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Aprendizado Profundo , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
20.
J Am Chem Soc ; 144(30): 13634-13642, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35867972

RESUMO

Radon (Rn), a ubiquitous radioactive noble gas, is the main source of natural radiation to human and one of the major culprits for lung cancer. Reducing ambient Rn concentration by porous materials is considered as the most feasible and energy-saving option to lower this risk, but the in-depth Rn removal under ambient conditions remains an unresolved challenge, mainly due to the weak van der Waals (vdW) interaction between inert Rn and adsorbents and the extremely low partial pressure (<1.8 × 10-14 bar, <106 Bq/m3) of Rn in air. Adsorbents having either favorable adsorption thermodynamics or feasible diffusion kinetics perform poorly in in-depth Rn removal. Herein, we report the discovery of a metal-organic framework (ZIF-7-Im) for efficient Rn capture guided by computational screening and modeling. The size-matched pores in ZIF-7-Im abide by the thermodynamically favorable principle and the exquisitely engineered quasi-open apertures allow for feasible kinetics with little sacrifice of sorption thermodynamics. The as-prepared material can reduce the Rn concentration from hazardous levels to that below the detection limit of the Rn detector under ambient conditions, with an improvement of at least two orders of amplitude on the removal depth compared to the currently best-performing and only commercialized material activated charcoal.


Assuntos
Poluentes Radioativos do Ar , Estruturas Metalorgânicas , Monitoramento de Radiação , Radônio , Poluentes Radioativos do Ar/análise , Gases , Humanos , Cinética , Radônio/análise , Termodinâmica
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