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1.
Chemosphere ; 287(Pt 1): 131991, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34461336

RESUMO

Cr contamination is frequently combined with organic pollution. Cr flocculation using flocculants results in difficulty in Cr recovery and increase of salinity. Moreover, the fates of coexisted organic pollutants are rarely attended. In this study, the Fenton-like reaction based on Cr redox reaction (Cr-Fenton-like reaction) coupled with Cr flocculation was established using H2O2 as additives, which gave the opportunity to realize simultaneous removal of Cr and organic matters sustainably. In the coupling system, Cr-Fenton-like reaction generated more OH- for Cr flocculation via the H2O2 decomposition, meanwhile, Cr flocculation provided heterogeneous catalytic regions for Cr-Fenton-like reaction. The formation of Cr flocs was the key to the coupling effect. They created partially alkaline regions, therefore Cr-Fenton-like reaction (reaction condition: pH > 5) and Cr flocculation (reaction condition: pH > 8) occurred in these heterogeneous regions, although the pH of the solutions was below 5. Besides, the Cr flocs in the coupling system tended to adsorb Cr(III) which also contributed to the coupling effect. Although Cr-Fenton-like reaction generated Cr(VI) inevitably, the dissolved Cr(VI) didn't accumulate due to the persistent acidic condition and the heterogeneous catalysis of Cr flocs in the coupling system. When the coupling effect was applied to a stimulated tannery wastewater with Cr and organic co-pollution, the simultaneous removal rates for Cr and total organic carbon were 81.2% and 41.34% respectively after an 8-h running. This study gives deep insights into the coupling effect and provides a sustainable and eco-friendly strategy for the remediation of wastewater with Cr and organic co-pollution.


Assuntos
Peróxido de Hidrogênio , Ferro , Floculação , Oxirredução , Águas Residuárias
2.
Nucleic Acids Res ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34850124

RESUMO

Streptococcus pyogenes Cas9 (SpCas9), a programmable RNA-guided DNA endonuclease, has been widely repurposed for biological and medical applications. Critical interactions between SpCas9 and DNA confer the high specificity of the enzyme in genome engineering. Here, we unveil that an essential SpCas9-DNA interaction located beyond the protospacer adjacent motif (PAM) is realized through electrostatic forces between four positively charged lysines among SpCas9 residues 1151-1156 and the negatively charged DNA backbone. Modulating this interaction by substituting lysines with amino acids that have distinct charges revealed a strong dependence of DNA target binding and cleavage activities of SpCas9 on the charge. Moreover, the SpCas9 mutants show markedly distinguishable DNA interaction sites beyond the PAM compared with wild-type SpCas9. Functionally, this interaction governs DNA sampling and participates in protospacer DNA unwinding during DNA interrogation. Overall, a mechanistic and functional understanding of this vital interaction explains how SpCas9 carries out efficient DNA interrogation.

3.
J Med Chem ; 64(21): 16106-16131, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34723528

RESUMO

Interleukin-17 (IL-17) is a proinflammatory cytokine that plays a dominant role in inflammation, autoimmunity, and host defense. RORγt is a key transcription factor mediating T helper 17 (Th17) cell differentiation and IL-17 production, which is able to activate CD8+ T cells and elicit antitumor efficacy. A series of sulfonamide derivatives as novel RORγt inverse agonists were designed and synthesized. Using GSK2981278 (phase II) as a starting point, we engineered structural modifications that significantly improved the activity and pharmacokinetic profile. In animal studies, oral administration of compound d3 showed a robust and dose-dependent inhibition of the IL-17A cytokine expression in a mouse imiquimod-induced skin inflammation model. Docking analysis of the binding mode revealed that the compound d3 occupied the active pocket suitably. Thus, compound d3 was selected as a clinical compound for the treatment of Th17-driven autoimmune diseases.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34765000

RESUMO

Objectives: Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. This study was designed to uncover the healing effect of friedelin, a bioactive compound against UC through bioinformatics of network pharmacology and experimental verification of UC model mice. Materials and Methods: Targets of friedelin and potential mechanism of friedelin on UC were predicted through target searching, PPI network establishing, and enrichment analyzing. We explored effects of friedelin on dextran sulfate sodium (DSS)-induced colitis. Severity of UC was investigated by body weight, disease activity index (DAI), and length of the colon. Inflammation severity was examined by determination of proinflammatory and anti-inflammatory cytokines. The numbers of autophagosome around the epithelial cells were observed by autophagy inhibition via a transmission electron microscope. The expressions of autophagy-related ATG5 protein and AMPK-mTOR signaling pathway were determined by immunofluorescence staining. Results: In this study, 17 potential targets of friedelin and 1111 UC-related targets were identified. 10 therapeutic targets of friedelin against UC were acquired from overlapped targets of UC and friedelin. PPI network construction filtered 14 core targets through target amplification and confidence enhancement. The results of molecular docking showed that the docking scores of the top 5 active targets were higher than the threshold values. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out, showing friedelin alleviates UC through anti-inflammatory pathways and molecular function of autophagy. Subsequently, animal-based experiments revealed the intraperitoneal injection of friedelin ameliorated DSS-induced body weight loss, DAI decrease, colon length shortening and colonic pathological damage with lower myeloperoxidase and proinflammatory cytokines (IL-1ß and IL-6) and higher IL-10 levels, and more autophagosomes in transmission electron microscope results. The AMPK-mTOR signaling pathway plays important role in the friedelin's effect in autophagy as KEGG pathway result and experiment verification. Furthermore, the 3 ma validated the role of autophagy as an improvement in the friedelin's pharmacologic effect to UC model mice. Conclusions: Friedelin ameliorated DSS-induced colitis in mice through of inflammatory inhibition and regulation of autophagy.

5.
Int J Clin Exp Pathol ; 14(10): 1022-1030, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760038

RESUMO

OBJECTIVE: Due to a continued increase in viral pneumonia incidence and resulting high mortality, fast and accurate diagnosis is important for effective management. This investigation examined the significance of blood biomarkers and the CT score in the early diagnosis of viral pneumonia. METHODS: Patients who were hospitalized due to radiologically-confirmed pneumonia and underwent virus antigen rapid test were enrolled. Their clinical information was compared. Blood mononuclear cell count, LDH, and plasma D-dimer were obtained. To evaluate the utility of biomarker levels in differentiating viral pneumonia from other pneumonia, ROC curves were developed to analyze the AUC. The optimal cut-off thresholds, specificity, sensitivity, and predictive values were assessed using the Youden index. The added value of the multi-marker approach was delineated using IDI and Reclassification analyses using NRI; IDI and NRI values were examined with 95% CI. RESULTS: Overall, 1163 inpatients were recruited between January 2017 and January 2021. They were sub-divided into the viral pneumonia (n = 563) and non-viral pneumonia (n = 600) categories. We found that the CT score, blood mononuclear cell count, LDH, and plasma D-dimer were markedly elevated in viral pneumonia patients. At an LDH threshold of 693.595 U/L, an AUC of ROC was 0.805 in differentiating viral pneumonia. The combination of CT score and blood biomarkers had an ROC AUC value of 0.908. CONCLUSIONS: Combining elevated biomarkers with CT assessments outperformed the CT score alone in identifying viral pneumonia. It is crucial to better characterize the significance of biomarkers in combination with CT assessments in the diagnosis of viral pneumonia.

7.
Biosens Bioelectron ; : 113811, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34823963

RESUMO

Numerous efforts have been attempted to mimic human tongue since years. However, they still have limitations because of damages, temperature effects, detection ranges etc. Herein, a self-healable hydrogel-based artificial bioelectronic tongue (E-tongue) containing mucin as a secreted protein, sodium chloride as an ion transporting electrolyte, and chitosan/poly(acrylamide-co-acrylic acid) as the main 3D structure holding hydrogel network is synthesized. This E-tongue is introduced to mimic astringent and bitter mouth feel based on cyclic voltammetry (CV) measurements subjected to target substances, which permits astringent tannic acid (TA) and bitter quinine sulfate (QS) to be detected over wide corresponding ranges of 29.3 mM-0.59 µM and 63.8 mM-6.38 µM with remarkable respective sensitivities of 0.2 and 0.12 wt%-1. Besides, the taste selectivity of this E-tongue is performed in the presence of various mixed-taste chemicals to show its high selective behavior toward bitter and astringent chemicals. The electrical self-healability is shown via CV responses to illustrate electrical recovery within a short time span. In addition, cytotoxicity tests using HeLa cells are performed, where a clear viability of ≥95% verified its biocompatibility. The anti-freezing sensing of E-tongue tastes at -5 °C also makes this work to be useful at sub-zero environments. Real time degrees of tastes are detected using beverages and fruits to confirm future potential applications in food taste detections and humanoid robots.

8.
Opt Express ; 29(24): 40397-40405, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809381

RESUMO

In this paper, we investigated the impact of the linewidth of a QCW pulsed sodium laser on the brightness performance of a generating sodium laser guide star by using the numerical simulation tool PRS. We compared the field test results with the simulation results for two TIPC's 30W class sodium guide star lasers and found the results are in good agreement which proves the tool can be used for prediction. Then, we used the tool to study the influence of D2b repumping and different linewidths from 10MHz to 1GHz on the coupling efficiency and the photon return flux. For the TIPC's QCW pulsed solid-state laser, when the on-sky power density is 1 W/m2, the coupling efficiency is 79.6 (photons/s/W/(atoms/m2)) without D2b repumping, however, the value is up to 213.3 (photons/s/W/(atoms/m2)) with 15% D2b enabled and is increased by 168% than the value without D2b; when the power density reaches 10 W/m2, the coupling efficiencies without D2b and with 15% D2b are 66.6 and 233.6 (photons/s/W/(atoms/m2)), respectively. The results show that for the QCW pulsed laser, D2b repumping is necessary. With D2b enabled, if the spectral linewidth is too wide or too narrow, the photon return flux will be adversely affected. The return flux of 60MHz is 52.5% higher than that of 1GHz, while the return flux of 300MHz is 37.8% higher than that of 10 MHz when the laser power is 100W.

9.
Abdom Radiol (NY) ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34820688

RESUMO

OBJECTIVES: To compare the efficacy and safety of percutaneous ethanol injection (PEI) combined with transarterial chemoembolization (TACE + PEI) vs. TACE alone for the treatment of patients with advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). METHODS: A total of 130 HCC patients with PVTT treated from May 2014 to August 2018 were retrospectively evaluated. Among them, 33 patients received TACE + PEI and 97 patients received TACE alone. PVTT was classified according to the Japanese Society of Hepatology; 97 patients had VP3 PVTT. Propensity score matching (PSM) was used to reduce selection bias. RESULTS: Before PSM, the median overall survival (mOS) was 11 months (95% CI: 7.8-14.2) in the TACE + PEI group and 6 months (95% CI: 5.1-6.9) in the TACE group (p < 0.001), and the median progression-free survival (mPFS) was 5 months (95% CI: 3.7-6.3) in the TACE + PEI group and 2.5 months (95% CI: 2.1-2.9) in the TACE group (p < 0.001). Similar results were seen after PSM. Subgroup analysis showed that in patients with tumors > 5 cm in diameter and the VP3 subgroup, TACE + PEI brought a significant survival advantage over TACE alone before and after PSM. In the adverse event analysis, severe abdominal pain and bleeding after operation were seen in more patients in the TACE + PEI group than in the TACE group before PSM (P < 0.05). CONCLUSIONS: For HCC patients with PVTT (especially those with tumor diameters > 5 cm and grade VP3), TACE combined with PEI for HCC patients with PVTT is safe and may provide better survival outcomes.

10.
J Hazard Mater ; 424(Pt B): 127341, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34634702

RESUMO

The need in using reclaimed water increased significantly to address the water shortage and its continuing quality deterioration in sustaining societal development. Degrading micropollutants in wastewater treatment plant effluents is one of the most important tasks in supplying safe drinking water, which is often achieved by full advanced treatment technologies (FATs), including reverse osmosis (RO) and the UV-based advanced oxidation process (AOP). As an emerging AOP, UV/chloramine process shows many noteworthy advantages in the scenario of potable water reuse, including membrane biological fouling control by chloramine, producing highly reactive radicals (e.g., Cl•, HO•, Cl2•-, and reactive nitrogen-containing species) to degrade the RO permeated pollutants, and acting as long-lasting disinfectant in the potable water distribution system. In addition, chloramine is often designedly produced by taking advantage of the ammonia in source. Thus, UV/chloramine processes gather much attention from researcher and published papers on UV/chloramine process have drastically increased since 2016, which were thoroughly reviewed in this paper. The fundamentals of chloramine photolysis, including the photolysis kinetics, the quantum yield, the generation and transformation of radicals and the final products, were scrutinized. Further, the impacts of reaction conditions such as pH, chloramine dosage and water matrix on the degradation of micropollutants by the UV/chloramine process are discussed. Moreover, the formation potential of disinfection by-products is debated. The opportunity of application of the UV/chloramine process in real-world practice is also presented, emphasizing the need for extensive efforts to remove currently prevalent knowledge roadblocks.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34691225

RESUMO

Objective: This research aimed at investigating the efficacy of edaravone combined with clopidogrel on acute cerebral infarction (ACI) and its influence on the neurological deficit and life function. Methods: Totally, 154 ACI cases were included and then divided into the control group (CG) (n = 71) and research group (RG) (n = 83) according to the treatment methods. Patients in the CG were treated with clopidogrel alone, and those in the RG were under edaravone-clopidogrel combination therapy. The efficacy, adverse reactions, NIHSS score, cerebral hemodynamic indexes, and Fugl-Meyer scale (FMA) and Barthel index (BI) of activities of daily living (ADL) scores were observed. Results: Compared with before treatment, the symptoms of both groups were improved after treatment: the NIHSS scores decreased, FMA and ADL scores increased, and cerebral hemodynamic indexes were improved. Compared with the CG, the efficacy and cerebral hemodynamic indexes of the RG were better, the adverse reactions were equivalent, the NIHSS score was lower, and the ADL and FMA scores were higher. Conclusion: Edaravone combined with clopidogrel can effectively treat ACI and improve the neurological deficit and life function of patients.

12.
Eur Phys J Plus ; 136(10): 1049, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692366

RESUMO

The patient's breathing and air conditioning system in the enclosed space are the main factors that cause indoor cross-infection. However, the research on the influence and the control mechanism of different air conditioning systems on the transmission path of virus aerosol particles exhaled by patients is still limited. To evaluate the effects of different air conditioning systems on the spread of human exhaled pollutants, computational fluid dynamics (CFD) was used to study the movement and diffusion of exhaled air from two rows of 12 sitting adults in a hospital's closed transfusion room. In this paper, three different air conditioning systems are considered: Ceil-supply and Down-return (Ceil-to-Down), Up-supply and Down-return (Up-to-Down), Down-supply and Up-return (Down-to-Up). The distribution of exhaled air velocity, temperature, and virus particle concentration were studied, and it is found that the horizontal diffusion distance of exhaled pollutants is about 0.75 -1.1 m. When up to down systems are used, the air conditioning system shall be closed in time in case of respiratory infectious diseases, so as to avoid cross-infection in the enclosed space. A relatively clean air area with a height of about 1.1 m will be formed, which can inhibit the transmission of the virus to a certain extent when using the down-to-up system. But for those who are exposed to the enclosed space for a long time, the down-to-up system is not the most suitable air conditioning system.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34699189

RESUMO

MXenes have been used as substrate materials for single-atom catalysts (SACs) due to their unique two-dimensional (2D) structure, high surface area, and high electronic conductivity. Oxygen is the primary terminating group of MXenes; however, all of the reported Pt SACs till now are fabricated with F-terminated MXenes. According to the first-principles calculations of this work, the failure of using O-terminated MXenes as substrates is due to the low charge density around Pt and C, which weakens the catalytic activity of Pt. By adjusting the electronic structure of M2C using a second submetal with a lower work function than M, 18 potential bifunctional Pt SACs are constructed based on O-terminated bimetal MXenes. After further consideration of some important practical application factors such as overpotential, solvation effect, and reaction barriers, only four of them, i.e., Cr2Nb2C3O2-VO-Pt, Cr2Ta2C3O2-VO-Pt, Cr2NbC2O2-VO-Pt, and Cr2TaC2O2-VO-Pt, are screened as bifunctional oxygen reduction reaction/oxygen evolution reaction (ORR/OER) catalysts. All of these screened SACs are originated from Cr-based MXenes, implying the significance of Cr-based MXenes in designing bifunctional Pt SACs.

14.
J Hazard Mater ; 424(Pt B): 127444, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34655880

RESUMO

Metal-free carbonaceous catalysts are receiving increasing attention in wastewater treatment. Here, nitrogen and sulfur co-doped carbon sphere catalysts (N,S-CSs900-OH) were synthesized using glucose and L-cysteine via a hydrothermal method and high temperature alkali activation. The N,S-CSs900-10%-OH exhibited excellent catalytic performance for the degradation of oxytetracycline (OTC). The degradation rate was 95.9% in 60 min, and the reaction equilibrium rate constant was 0.0735 min-1 (k0-15 min). The synergistic effect of adsorption-promoting degradation was demonstrated in the removal process of OTC. The excellent adsorption capacity of N,S-CSs900-10%-OH ensured the efficient oxidation of OTC. N,S-CSs900-10%-OH reduced the activation energy of the OTC degradation reaction (Ea=18.23 kJ/mol). Moreover, the pyrrolic N, thiophene S and carbon skeleton played an important role in the degradation of OTC based on density function theory, and the catalytic mechanism was expounded through radical and nonradical pathways. The active species involved in the reaction were O2•-, 1O2, SO4•- and •OH, of which O2•- was the primary reactive species. This study provides a new insight into the reaction mechanism for efficient treatment of organic pollutants using metal-free doped porous carbon materials.

15.
Front Physiol ; 12: 676096, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594232

RESUMO

The Amur ide (Leuciscus waleckii) is a fish in the Cyprinidae family. Compared with other Amur ide living in freshwater ecosystems, the Amur ide population in Lake Dali Nor of China is famous for its high tolerance to the alkaline conditions of 54 mM (pH 9.6). Yet, surprisingly, the ionoregulatory mechanism responsible for this remarkable alkaline adaptation remains unclear. Therefore, this study sought to investigate how bicarbonate affects the acid-base balancing and ionoregulatory responses of this animal. Here, using a comparative approach, the alkali form of Amur ide and its ancestral freshwater form living in other freshwater basins were each exposed to 50 mM (pH 9.59 ± 0.09), a level close to the alkalinity of Lake Dali Nor, and their physiological (AE1) adjustment of ions and acid-base regulation were investigated. This study highlighted differences in blood pH and serum ions (e.g., Na+, K+, Cl-, and Ca2+), Na+/K+ ATPase (NKA) activity and its mRNA level, and mRNA expression of gill transporters (Na+/H+ exchanger member 2 and/or 3, Na+/ HCO 3 - cotransporter (NBC1), Cl-/ HCO 3 - exchanger, Na+/Cl- cotransporter (NCC), Na+/K+/2Cl- (NKCC1), SLC26A5, and SLC26A6) for alkalinity adaptation between the two forms of Amur ide differing in alkalinity tolerance. Specifically, close relationships among the serum Na+ and mRNA levels of NCC, NKCC1, and NHE, and also NKA and NBC1, in addition to serum Cl- and bicarbonate transporters (e.g., SLC26A5 and SLC26A6), characterized the alkali form of Amur ide. We propose that this ecotype can ensure its transepithelial Cl- and Na+ uptake/base secretions are highly functional, by its basolateral NKA with NBC1 and apical ionic transporters, and especially NCC incorporated with other transporters (e.g., SLC26). This suggests an evolved strong ability to maintain an ion osmotic and acid-base balance for more effectively facilitating its adaptability to the high alkaline environment. This study provides new insights into the physiological responses of the alkaline form of the Amur ide fish for adapting to extreme alkaline conditions. This information could be used as a reference to cultivating alkaline-tolerant fish species in abandoned alkaline waters.

16.
Front Oncol ; 11: 683256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650909

RESUMO

Objective: Recently, long noncoding RNA SLCO4A1 antisense RNA 1 (SLCO4A1-AS1) has been shown to act as an oncogene in several cancer types; however, its role in gastric cancer (GC) and its underlying molecular mechanisms are yet to be elucidated. Methods: Using the ENCORI database, we identified SLCO4A1-AS1, miR-149-5p (miR-149), and the X-linked inhibitor of apoptosis (XIAP) whose expressions were obviously changed in GC samples, and analyzed the correlation between their expressions in GC samples. Moreover, we explored the expression of SLCO4A1-AS1, miR-149, and XIAP in clinical samples and GC cell lines using RT-qPCR and western blotting assay; the correlation between them was analyzed using RNA immunoprecipitation and dual-luciferase reporter. CCK-8, colony formation, and Transwell assays were conducted to determine the effects of SLCO4A1-AS1, miR-149, and XIAP expression on cell proliferation, migration, and invasion, respectively. A nude mouse xenograft model was used to explore their function in xenograft growth. Results: SLCO4A1-AS1 was significantly upregulated in the GC samples and cell lines, and a high level of SLCO4A1-AS1 was associated with an advanced tumor stage and shortened patient survival. Mechanistically, SLCO4A1-AS1 post-transcriptionally regulated XIAP by functioning as competing endogenous RNA in GC to sponge miR-149. Further functional assays revealed that the overexpression of miR-149 and knockdown of XIAP considerably inhibited GC cell viability and its migratory and invasive characteristics in vitro. SLCO4A1-AS1 knockdown also determined the function of GC cells but was diminished by the miR-149 inhibitor in vitro. Finally, we demonstrated that the deletion of SLCO4A1-AS1 suppressed tumor growth and metastasis in vivo. Conclusions: Altogether, these findings suggest that SLCO4A1-AS1 functions as a crucial oncogenic lncRNA in GC and it can facilitate GC tumor growth and metastasis by interacting with miR-149 and enhancing XIAP expression. Therefore, SLCO4A1-AS1 is a potential novel therapeutic target in GC treatment.

17.
Theranostics ; 11(19): 9358-9375, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646375

RESUMO

Rationale: Atherosclerosis plaque rupture (PR) is the pathological basis and chief culprit of most acute cardiovascular events and death. Given the complex and important role of macrophage apoptosis and autophagy in affecting plaque stability, an important unanswered question include is whether, and how, immunity-related GTPase family M protein (IRGM) and its mouse orthologue IRGM1 affect macrophage survival and atherosclerotic plaque stability. Methods: To investigate whether serum IRGM of ST-segment elevation myocardial infarction (STEMI) patients is related to plaque morphology, we divided 85 STEMI patients into those with and without plaque rupture (PR and non-PR, respectively) based on OCT image analysis, and quantified the patients' serum IRGM levels. Next, we engineered Irgm1 deficient mice (Irgm1 +/-) and chimera mice with Irgm1 deficiency in the bone marrow on an ApoE -/- background, which were then fed a high-fat diet for 16 weeks. Pathological staining was used to detect necrotic plaque cores, ratios of neutral lipids and cholesterol crystal, as well as collagen fiber contents in these mice to characterize plaque stability. In addition, immunofluorescence, immunohistochemical staining and western blot were used to detect the apoptosis of macrophages in the plaques. In vitro, THP-1 and RAW264.7 cells were stimulated with ox-LDL to mimic the in vivo environment, and IRGM/IRGM1 expression were modified by specific siRNA (knockdown) or IRGM plasmid (knocked-in). The effect of IRGM/Irgm1 on autophagy and apoptosis of macrophages induced by ox-LDL was then evaluated. In addition, we introduced inhibitors of the JNK/p38/ERK signaling pathway to verify the specific mechanism by which Irgm1 regulates RAW264.7 cell apoptosis. Results: The serum IRGM levels of PR patients is significantly higher than that of non-PR patients and healthy volunteers, which may be an effective predictor of PR. On a high-fat diet, Irgm1-deficient mice exhibit reduced necrotic plaque cores, as well as neutral lipid and cholesterol crystal ratios, with increased collagen fiber content. Additionally, macrophage apoptosis is inhibited in the plaques of Irgm1-deficient mice. In vitro, IRGM/Irgm1 deficiency rapidly inhibits ox-LDL-induced macrophage autophagy while inhibiting ox-LDL-induced macrophage apoptosis in late stages. Additionally, IRGM/Irgm1 deficiency suppresses reactive oxygen species (ROS) production in macrophages, while removal of ROS effectively inhibits macrophage apoptosis induced by IRGM overexpression. We further show that Irgm1 can affect macrophage apoptosis by regulating JNK/p38/ERK phosphorylation in the MAPK signaling pathway. Conclusions: Serum IRGM may be related to the process of PR in STEMI patients, and IRGM/Irgm1 deficiency increases plaque stability. In addition, IRGM/Irgm1 deficiency suppresses macrophage apoptosis by inhibiting ROS generation and MAPK signaling transduction. Cumulatively, these results suggest that targeting IRGM may represent a new treatment strategy for the prevention and treatment of acute cardiovascular deaths caused by PR.

18.
J Breast Cancer ; 24(5): 428-442, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34652079

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) is a subtype of breast cancer. Increasing evidence supports that dysregulation of long noncoding RNAs (lncRNAs) plays a vital role in cancer progression. RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a lncRNA, is characterized as a tumor-propeller in some cancers, but its mechanism in TNBC remains poorly understood. This study aimed to determine whether and how RMRP functions in TNBC. METHODS: Cell proliferation was determined by cell counting kit-8 (CCK-8) and colony formation assays and cell apoptosis by flow cytometry analysis and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Cell migration and invasion were determined by transwell assays. RNA-binding protein immunoprecipitation (RIP), luciferase reporter, and RNA pulldown assays were implemented to assess the interaction of RMRP with other molecules in TNBC cells. RESULTS: RMRP expression was elevated in TNBC cells. RMRP knockdown repressed cell proliferation, migration, and invasion, but induced apoptosis in TNBC. In addition, RMRP was found to target microRNA-766-5p (miR-766-5p) in TNBC cells. Silencing miR-766-5p enhanced cell viability and decreased apoptosis, whereas miR-766-5p overexpression had opposite effects. Furthermore, miR-766-5p was found to bind to yes-associated protein 1 (YAP1). Moreover, miR-766-5p inhibition reversed the repressive effect of RMRP knockdown on the malignant progression of TNBC. CONCLUSION: The present study manifested that RMRP promotes the growth, migration, and invasion of TNBC cells via the miR-766-5p/YAP1 axis. These findings provide novel perspectives for TNBC treatment.

19.
Sci Rep ; 11(1): 20434, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650167

RESUMO

Cell shape is linked to cell function. The significance of cell morphodynamics, namely the temporal fluctuation of cell shape, is much less understood. Here we study the morphodynamics of MDA-MB-231 cells in type I collagen extracellular matrix (ECM). We systematically vary ECM physical properties by tuning collagen concentrations, alignment, and gelation temperatures. We find that morphodynamics of 3D migrating cells are externally controlled by ECM mechanics and internally modulated by Rho/ROCK-signaling. We employ machine learning to classify cell shape into four different morphological phenotypes, each corresponding to a distinct migration mode. As a result, we map cell morphodynamics at mesoscale into the temporal evolution of morphological phenotypes. We characterize the mesoscale dynamics including occurrence probability, dwell time and transition matrix at varying ECM conditions, which demonstrate the complex phenotype landscape and optimal pathways for phenotype transitions. In light of the mesoscale dynamics, we show that 3D cancer cell motility is a hidden Markov process whereby the step size distributions of cell migration are coupled with simultaneous cell morphodynamics. Morphological phenotype transitions also facilitate cancer cells to navigate non-uniform ECM such as traversing the interface between matrices of two distinct microstructures. In conclusion, we demonstrate that 3D migrating cancer cells exhibit rich morphodynamics that is controlled by ECM mechanics, Rho/ROCK-signaling, and regulate cell motility. Our results pave the way to the functional understanding and mechanical programming of cell morphodynamics as a route to predict and control 3D cell motility.

20.
Huan Jing Ke Xue ; 42(11): 5554-5562, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708995

RESUMO

Aerobic composting is an important approach to treat livestock manure; however, traditional composting has some problems, such as low efficiency, or odorous pollution. In order to speed up the composting process and reduce malodorous gas emissions, this study explored the mechanism of nano-membrane for improving the efficiency of livestock manure composting. A trough aerobic composting experiment was set up to evaluate the physicochemical properties, enzyme activities, and emission of odorous gases. The results showed that covering with nano-membrane could accelerate the temperature rise; reduce the pH, organic matter(OM), and ammonia nitrogen(NH4+-N); increase electrical conductivity(EC); enhance the activities of urease, protease, cellulase, xylanase, and peroxidase; while the total cumulative emissions of NH3, H2S, and TVOC were reduced by 58%, 100%, and 61%, respectively. The correlation analysis showed that most enzyme activities were easily affected by temperature(T), EC, OM, and C/N. The emission rate of NH3 was positively correlated with T and negatively correlated with pH, and TVOC was significantly correlated with various physicochemical properties. This experiment showed that covering nano-membrane could accelerate the compost maturity and reduce the emission of odorous gases. This approach has no health risks and produces low malodorous gas, which may effectively solve the problem of pollutant emission caused by livestock manure compost fermentation, promoting the green and sustainable development of the breeding industry. In addition, it facilitates livestock manure fertilizer application, and provides technical support for the development of resource utilization of biomass waste.


Assuntos
Compostagem , Esterco , Amônia , Animais , Gado , Nitrogênio/análise , Odorantes , Solo
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