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1.
BMC Med Res Methodol ; 24(1): 89, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622516

RESUMO

BACKGROUND: Outliers, data points that significantly deviate from the norm, can have a substantial impact on statistical inference and provide valuable insights in data analysis. Multiple methods have been developed for outlier detection, however, almost all available approaches fail to consider the spatial dependence and heterogeneity in spatial data. Spatial data has diverse formats and semantics, requiring specialized outlier detection methodology to handle these unique properties. For now, there is limited research exists on robust spatial outlier detection methods designed specifically under the spatial error model (SEM) structure. METHOD: We propose the Spatial-Θ-Iterative Procedure for Outlier Detection (Spatial-Θ-IPOD), which utilizes a mean-shift vector to identify outliers within the SEM. Our method enables an effective detection of spatial outliers while also providing robust coefficient estimates. To assess the performance of our approach, we conducted extensive simulations and applied it to a real-world empirical study using life expectancy data from multiple countries. RESULTS: Simulation results showed that the masking and JD (Joint Detection) indicators of our Spatial-Θ-IPOD method outperformed several commonly used methods, even in high-dimensional scenarios, demonstrating stable performance. Conversely, the Θ-IPOD method proved to be ineffective in detecting outliers when spatial correlation was present. Moreover, our model successfully provided reliable coefficient estimation alongside outlier detection. The proposed method consistently outperformed other models (both robust and non-robust) in most cases. In the empirical study, our proposed model successfully detected outliers and provided valuable insights in the modeling process. CONCLUSIONS: Our proposed Spatial-Θ-IPOD offers an effective solution for detecting spatial outliers for SEM while providing robust coefficient estimates. Notably, our approach showcases its relative superiority even in the presence of high leverage points. By successfully identifying outliers, our method enhances the overall understanding of the data and provides valuable insights for further analysis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38626353

RESUMO

The massive use of paper has resulted in significant negative impacts on the environment. Fortunately, recent progress has been made in the field of rewritable paper, which has great potential in solving the increasing demand for paper while minimizing its environmental footprint. In this work, we report a green and economic strategy to develop ink-free rewritable paper by introducing hydrochromic covalent organic frameworks (COFs) in paper and using water as the sole trigger. When exposed to water or acidic solvents, two kinds of imino COFs change their colors reversibly from red to black. Additionally, a new visible absorption band appears, indicating that it can be transformed into another structure reversibly. This reversibility may be due to the isomerization from the diiminol to an iminol/cisketoenamine and its inability to doubly tautomerize to a diketoenamine. Specifically, we prepared the rewritable paper by loading these two COFs onto filter paper by using the decompression filtration method. When exposed to water, the paper undergoes a color change from red to black, which shows promising potential for applications in water-jet printing. Additionally, there is no significant performance degradation after 20 uses and 10 days between, further highlighting their potential as rewritable papers. To further improve its uniformity, we take the interface polymerization strategy to yield highly crystalline and more compact membranes, which are then transferred to paper to prepare writable papers. Our research has opened up a way for the application of COFs as a water-based printing material.

3.
Cardiovasc Toxicol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647950

RESUMO

The hearts of subjects with diabetes are vulnerable to ischemia-reperfusion injury (IRI). In contrast, experimentally rodent hearts have been shown to be more resistant to IRI at the very early stages of diabetes induction than the heart of the non-diabetic control mice, and the mechanism is largely unclear. Ferroptosis has recently been shown to play an important role in myocardial IRI including that in diabetes, while the specific mechanisms are still unclear. Non-diabetic control (NC) and streptozotocin-induced diabetic (DM) mice were treated with the antioxidant N-acetylcysteine (NAC) in drinking water for 4 week starting at 1 week after diabetes induction. Mice were subjected to myocardial IRI induced by occluding the coronary artery for 30 min followed by 2 h of reperfusion, subsequently at 1, 2, and 5 week of diabetes induction. The post-ischemic myocardial infarct size in the DM mice was smaller than that in NC mice at 1 week of diabetes but greater than that in the NC mice at 2 and 5 week of diabetes, which were associated with a significant increase of ferroptosis at 2 and 5 week but a significant reduction of ferroptosis at 1 week of diabetes. NAC significantly attenuated post-ischemic ferroptosis as well as oxidative stress and reduced infarct size at 2 and 5 week of diabetes. Application of erastin, a ferroptosis inducer, reversed the cardioprotective effects of NAC. It is concluded that increased oxidative stress and ferroptosis are the major factors attributable to the increased vulnerability to myocardial IRI in diabetes and that attenuation of ferroptosis represents a major mechanism whereby NAC confers cardioprotection against myocardial IRI in diabetes.

4.
Front Microbiol ; 15: 1371877, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38591027

RESUMO

The resource recovery and reuse of precious metal-laden wastewater is widely recognized as crucial for sustainable development. Superalloy electrolytes, produced through the electrolysis of superalloy scrap, contain significant quantities of precious metal ions, thereby possessing substantial potential for recovery value. This study first explores the feasibility of utilizing fungi to treat Superalloy electrolytes. Five fungi resistant to high concentrations of heavy metals in electrolytes (mainly containing Co, Cr, Mo, Re, and Ni) were screened from the soil of a mining area to evaluate their adsorption characteristics. All five fungi were identified by ITS sequencing, and among them, Paecilomyces lilacinus showed the best adsorption performance for the five heavy metals; therefore, we conducted further research on its adsorption characteristics. The best adsorption effect of Co, Cr, Mo, Re, and Ni was 37.09, 64.41, 47.87, 41.59, and 25.38%, respectively, under the conditions of pH 5, time 1 h, dosage 26.67 g/L, temperature 25-30°C, and an initial metal concentration that was diluted fivefold in the electrolyte. The biosorption of Co, Mo, Re, and Ni was better matched by the Langmuir model than by the Freundlich model, while Cr displayed the opposite pattern, showing that the adsorption process of P. lilacinus for the five heavy metals is not a single adsorption mechanism, but may involve a multi-step adsorption process. The kinetics study showed that the quasi-second-order model fitted better than the quasi-first-order model, indicating that chemical adsorption was the main adsorption process of the five heavy metals in P. lilacinus. Fourier transform infrared spectroscopy revealed that the relevant active groups, i.e., hydroxyl (-OH), amino (-NH2), amide (- CONH2), carbonyl (-C = O), carboxyl (-COOH), and phosphate (PO43-), participated in the adsorption process. This study emphasized the potential application of P. lilacinus in the treatment of industrial wastewater with extremely complex background values.

5.
Plants (Basel) ; 13(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38475485

RESUMO

Water scarcity constrains the sustainable development of Chinese agriculture, and deficit irrigation as a new irrigation technology can effectively alleviate the problems of water scarcity and water use inefficiency in agriculture. In this study, the drip irrigation cotton field under film in Xinjiang was taken as the research object. Meta-analysis and machine learning were used to quantitatively analyze the effects of different farm management practices, climate, and soil conditions on cotton yield and water use efficiency under deficit irrigation, to investigate the importance of the effects of different factors on cotton yield and water use efficiency, and to formulate appropriate optimization strategies. The results showed that deficit irrigation significantly increased cotton water use efficiency (7.39%) but decreased cotton yield (-15.00%) compared with full irrigation. All three deficit irrigation levels (80~100% FI, 60~80% FI, and 40~60% FI; FI: full irrigation) showed a significant decrease in cotton yield and a significant increase in water use efficiency. Under deficit irrigation, cotton yield reduction was the smallest and cotton water use efficiency increased the most when planted with one film, two tubes, a six-row cropping pattern, an irrigation frequency ≥10 times, a nitrogen application of 300~400 kg·ha-1, and a crop density ≥240,000 per hectare, and planted with the Xinluzhong series of cotton varieties; deficit irrigation in areas with average annual temperature >10 °C, annual evapotranspiration >2000 mm, annual precipitation <60 mm, and with loam, sandy soil had the least inhibition of cotton yield and the greatest increase in cotton water use efficiency. The results of the random forest showed that the irrigation amount and nitrogen application had the greatest influence on cotton yield and water use efficiency. Rational irrigation based on optimal management practices under conditions of irrigation not less than 90% FI is expected to achieve a win-win situation for both cotton yield and water use efficiency. The above results can provide the best strategy for deficit irrigation and efficient water use in drip irrigation cotton under film in arid areas.

6.
Angew Chem Int Ed Engl ; : e202319849, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439625

RESUMO

Glycans on tumor cell surface have significant impacts in the immune-killing process. Here an ultra-galactocation to sialic acid (Sia) strategy is designed to hugely introduce galactose (Gal) to Sia and on tumor cells in vivo by using a penta-functional dendritic probe (Den@5F), which efficiently enhances the immune-killing of tumor cells. The Den@5F contains five different kinds of functional groups, including Gal, Cy5, amino, phenylboronic acid (PBA) and 4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butanoate (mNB), which can be conveniently prepared through a two-step reaction. After injecting into the tumor-bearing mouse, Den@5F can efficiently block Sia through the specific recognition between PBA and Sia on tumor cells and hugely introduce Gal through the subsequent photo-crosslinking between mNB and amino groups to multiply conjugate excessive Den@5Fs. The comprehensively blocked Sia can prevent the immune escape, and the hugely introduced Gal can promote the immune stimulation of the immune cells, which lead to an efficient enhancement of the immune-killing. The proposed strategy provides a significant and promising tool to promote the clinical immunotherapy of tumor.

7.
J Colloid Interface Sci ; 665: 545-553, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38547635

RESUMO

Organic multi-stimulus-responsive materials are widely used in anti-counterfeiting and information encryption due to their unique response characteristics and designability. However, progress in obtaining multi-stimulus-responsive smart materials has been very slow. Herein, a spiropyran derivative is constructed, which shows photochromic, thermochromic and mechanical photochromic properties, and has reversible absorption/luminescence adjustment ability. By introducing non-covalent interactions such as van der Waals force and hydrogen bond, this new molecule is more sensitive to external stimuli and exhibits better photochromic, mechanochromic and thermochromic properties with rapid speed and high contrast. Furthermore, these three stimulus responses can be completely restored to the initial state under white light irradiation. The reversible multiple response characteristics of this molecule make it possible to provide dynamic anti-counterfeiting and advanced information encryption capabilities. To demonstrate its application in advanced information encryption, powders treated with different stimuli are combined with fluorescent dyes to encrypt complex digital information. This work puts forward a new time-resolved encryption strategy, which provides important guidance for the development of time-resolved information security materials.

8.
ACS Appl Mater Interfaces ; 16(12): 15096-15106, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38478831

RESUMO

With the progress of forgery and decryption, the traditional encryption technology is apparent not enough, which strongly requires the development of advanced multidimensional encryption strategies and technologies. Photo-stimuli responsive fluorescent materials are promising as candidate materials for advanced information encryption. Here, we have reported new photo-stimuli responsive materials by encapsulating photochromic molecules spiropyrans (SPs) into naphthalimide-functionalized silica aerogels. By introducing different modification groups (dimethylamino) into 1,8-naphthalimide, we obtained two kinds of silica aerogels that emit blue and green colors. The naphthalimide-functionalized silica aerogels/dye composite exhibits a blue (dimethylamino-modified naphthalimide-functionalized silica aerogel showing green) emission from naphthalimide of silica aerogels at 450 nm (520 nm) and a red emission around 650 nm of SP. Under exposure to ultraviolet light, SP gradually transformed into the merocyanine (MC) form, and a strong absorption band appeared near 540 nm. At that time, the fluorescence resonance energy-transfer (FRET) process occurred between naphthalimide and the MC isomer. As the irradiation time is extended, the fluorescence color changes continuously from blue (green) to red through the FRET process. Using the time dependence of fluorescence, dynamic encryption patterns and multiple codes were successfully developed based on these functionalized silica aerogels. This work has provided important guidance for designing advanced information encryption materials.

9.
Chem Sci ; 15(11): 3901-3906, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38487245

RESUMO

Glycan oxidation on the cell surface occurs in many specific life processes including pathogen-cell interactions. This work develops a surface-enhanced Raman scattering (SERS) imaging strategy for in situ quantitative monitoring of protein-specific glycan oxidation mediated pathogen-cell interactions by utilizing Raman reporter DTNB and aptamer co-assembled platinum shelled gold nanoparticles (Au@Pt-DTNB/Apt). Using Fusarium graminearum (FG) and MCF-7 cells as models, Au@Pt-DTNB/Apt can specifically bind to MUC1 protein on the cell surface containing heavy galactose (Gal) and N-acetylgalactosamine (GalNAc) modification. When FG interacts with cells, the secreted galactose oxidase (GO) can oxidize Gal/GalNAc, and the generated reactive oxygen species (ROS) further oxidizes DTNB to produce TNB for greatly enhancing the SERS signal. This strategy can quantitatively visualize for the first time both the protein-specific glycan oxidation and the mediated pathogen-cell interactions, thus providing key quantitative information to distinguish and explore the pathogen-resistance and pharmacological mechanisms of different drugs.

10.
Microbiol Spectr ; 12(4): e0379723, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38483478

RESUMO

Hospital-acquired infections (HAIs) represent one of the significant causes of morbidity and mortality worldwide, and controlling pathogens in the hospital environment is of great importance. Currently, the standard disinfection method in the hospital environment is chemical disinfection. However, disinfectants are usually not used strictly according to the label, making them less effective in disinfection. Therefore, there is an emergent need to find a better approach that can be used in hospitals to control pathogenic bacteria in the clinical environment. Bacteriophages (phages) are effective in killing bacteria and have been applied in the treatment of bacterial infections but have not received enough attention regarding the control of contamination in the clinical environment. In this study, we found that various phages remain active in the presence of chemical disinfectants. Moreover, the combined use of specific phages and chemical disinfectants is more effective in removing bacterial biofilms and eliminating bacteria on hard surfaces. Thus, this proof-of-concept study indicates that adding phages directly to chemical disinfectants might be an effective and economical approach to enhance clinical environment disinfection. IMPORTANCE: In this study, we investigated whether the combination of bacteriophages and chemical disinfectants can enhance the efficacy of reducing bacterial contamination on hard surfaces in the clinical setting. We found that specific phages are active in chemical disinfectants and that the combined use of phages and chemical disinfectants was highly effective in reducing bacterial presence on hard surfaces. As a proof-of-concept, we demonstrated that adding specific phages directly to chemical disinfectants is an effective and cost-efficient strategy for clinical environment disinfection.


Assuntos
Bacteriófagos , Infecção Hospitalar , Desinfetantes , Humanos , Desinfetantes/farmacologia , Desinfecção/métodos , Bactérias
11.
J Agric Food Chem ; 72(6): 3025-3035, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38300990

RESUMO

Zearalenone (ZEN) is a widespread mycotoxin that causes serious damage to animal husbandry and poses a threat to human health. A screen of ZEN-degrading soil bacteria yielded Bacillus subtilis YT-4, which yielded 80% ZEN degradation after 6 h and 95% after 36 h. The gene sequence encoding the degradative enzyme ZENY was mined from the genome of YT-4 and expressed in yeast. ZENY is an α/ß-hydrolase with an optimal enzyme activity at 37 °C and pH 8. By breaking the lactone ring of ZEN, it produces ZENY-C18H24O5 with a molecular weight of 320.16 g/mol. Sequence comparison and molecular docking analyses identified the catalytic ZENY triad 99S-245H-123E and the primary ZEN-binding mode within the hydrophobic pocket of the enzyme. To improve the thermal stability of the enzyme for industrial applications, we introduced a mutation at the N-terminus, specifically replacing the fifth residue N with V, and achieved a 25% improvement in stability at 45 °C. These findings aim to achieve ZEN biodegradation and provide insight into the structure and function of ZEN hydrolases.


Assuntos
Zearalenona , Animais , Humanos , Zearalenona/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Simulação de Acoplamento Molecular , Hidrolases/genética , Mutação
13.
Open Forum Infect Dis ; 11(2): ofad647, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38328500

RESUMO

Background: Pseudomonas aeruginosa is one of the most common pathogens in surgical site infections (SSIs). However, comprehensive epidemiological and antibiotic resistance details for P aeruginosa in Chinese SSIs are lacking. We evaluated the proportions and antimicrobial resistance of P aeruginosa among patients with SSIs in China. Methods: Relevant papers from January 2010 to August 2022 were searched in databases including PubMed, Embase, Web of Science, China Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang, and Weipu. A meta-analysis was performed to analyze the proportions and 95% confidence interval (CIs) of P aeruginosa among patients with SSIs. Meta-regression analysis was used to investigate the proportion difference among different subgroups and antimicrobial resistance. Results: A total of 72 studies met inclusion criteria, involving 33 050 isolated strains. The overall proportion of P aeruginosa among patients with SSIs was 16.0% (95% CI, 13.9%-18.2%). Subgroup analysis showed higher proportions in orthopedic (18.3% [95% CI, 15.6%-21.0%]) and abdominal surgery (17.3% [95% CI, 9.9%-26.2%]). The proportion in the central region (18.6% [95% CI, 15.3%-22.1%]) was slightly higher than that in other regions. Antibiotic resistance rates significantly increased after 2015: cefoperazone (36.2%), ceftriaxone (38.9%), levofloxacin (20.5%), and aztreonam (24.0%). Notably, P aeruginosa resistance to ampicillin and cefazolin exceeded 90.0%. Conclusions: The proportion of P aeruginosa infection among patients with SSIs was higher than the data reported by the Chinese Antimicrobial Resistance Surveillance System, indicating rising antimicrobial resistance. The existing antimicrobial drug management plan should be strengthened to prevent a hospital epidemic of drug-resistant P aeruginosa strains.

14.
J Chem Phys ; 160(6)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38345116

RESUMO

The dynamics of polymer nanocomposites varies depending on the physics and chemistry at the polymer-nanoparticle interface. The physical aging of the nanocomposites is accelerated or retarded based on interfacial interactions and the state of polymer adsorption at the interfaces. In this study, we investigated the aging kinetics of silica-polystyrene nanocomposites using differential scanning calorimetry, focusing on the effect of local conformations of chains adsorbed on the nanofiller surface. The results show that the temperature dependence of the aging rate follows a Vogel-Fulcher-Tammann relationship at high temperatures, whereas it exhibits an Arrhenius-like behavior below a characteristic temperature (Tc). Notably, at T < Tc, the aging rate decreases with increasing loop height of the chains adsorbed on the filler surface, but the activation energy remains unchanged. We proposed that the suppression of the aging rate at T < Tc is likely related to an increase in the length scale over which the slow interfacial dynamics can propagate due to the increased topological interactions between the chain loops of a larger size and the free chains in the matrix. The increased packing frustration occurring at the filler surface occupied by the larger loops might also contribute to the decreased aging rate.

15.
Heliyon ; 10(2): e24612, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38293396

RESUMO

Vaccination is the most feasible way of preventing rabies, an ancient zoonosis that remains a major public health concern globally. However, administration of inactivated rabies vaccination without adjuvants is always inefficient and necessitates four to five injections. In the current study, we explored the adjuvant characteristics of cordycepin, a major bioactive component of Cordyceps militaris, to boost immune responses against a commercially available rabies vaccine. We found that cordycepin could stimulate stronger phenotypic and functional maturation of dendritic cells (DCs). For animal experiments, mice were immunized 3 times with rabies vaccine in the presence or absence of cordycepin at 1-week interval. Analysis of T cell differentiation and serum antibody isotypes showed that humoral immunity was dominant with a Th2 biased immune response. These results were also supported by the raised ratio of follicular helper T cells (TFH) and germinal center B cells (GCB). Thus, titer of rabies virus neutralizing antibody (RVNAb) and rabies virus-specific memory B cells were both raised as a result. Furthermore, administration of cordycepin did not cause pathological phenomena or body weight loss. The findings indicate that cordycepin could be used as a promising adjuvant for rabies vaccines to get a higher range of protection without any side effects.

16.
Int Immunopharmacol ; 128: 111429, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38171057

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) has recently risen to the top spot among chronic liver diseases in the world. However, there are no recognized treatments for it. Magnesium isoglycyrrhizate (MgIG) has potential as a NAFLD/NASH therapy. AIMS: To investigate the efficacy of MgIG in improving NAFLD/NASH and the possible pathways and mechanisms. METHODS: C57bl/6 mice were fed a high-fat diet (HFD) and 1 % dextran sulfate sodium (DSS) for 12 weeks to establish the NAFLD/NASH model. MgIG was administered by gavage during the last 7 weeks. First, the therapeutic effects of MgIG on hepatic steatosis and fibrosis, liver injury, and inflammation in the NAFLD/NASH mice were evaluated. Second, liver oxidative stress and hepatocyte apoptosis were detected. Finally, the effect of MgIG on intestinal permeability and short-chain fatty acid (SCFA) levels in mice's intestinal contents were examined. RESULTS: MgIG administration attenuated HFD-induced hepatic steatosis and fibrosis, improved serum biochemical and NAFLD/NASH mice, reduced liver oxidative stress and hepatocyte apoptosis, improved intestinal permeability, and increased fecal SCFA levels in NAFLD/NASH mice. CONCLUSION: MgIG protects against HFD-induced NAFLD/NASH through multiple pathways as well as mechanisms and holds promise as a potentially effective treatment for NAFLD/NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Saponinas , Triterpenos , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/patologia , Fígado/patologia , Inflamação/metabolismo , Dieta Hiperlipídica , Cirrose Hepática/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
17.
Toxicon ; 239: 107615, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38219915

RESUMO

Dielectric barrier discharge plasma (DBDP) displays strong against fungal spores, while its precise mechanism of spore inactivation remains inadequately understood. In this study, we applied morphological, in vivo and in vitro experiments, transcriptomics, and physicochemical detection to unveil the potential molecular pathways underlying the inactivation of Aspergillus flavus spores by DBDP. Our findings suggested that mycelium growth was inhibited as observed by SEM after 30 s treatment at 70 kV, meanwhile spore germination ceased and clustering occurred. It led to the release of cellular contents and subsequent spore demise by disrupting the integrity of spore membrane. Additionally, based on the transcriptomic data, we hypothesized that the induction of spore inactivation by DBDP might be associated with downregulation of genes related to cell membranes, organelles (mitochondria), oxidative phosphorylation, and the tricarboxylic acid cycle. Subsequently, we validated our transcriptomic findings by measuring the levels of relevant enzymes in metabolic pathways, such as superoxide dismutase, acetyl-CoA, total dehydrogenase, and ATP. These physicochemical indicators revealed that DBDP treatment resulted in mitochondrial dysfunction, redox imbalance, and inhibited energy metabolism pathways. These findings were consistent with the transcriptomic results. Hence, we concluded that DBDP accelerated spore rupture and death via ROS-mediated mitochondrial dysfunction, which does not depend on cell membranes.


Assuntos
Aspergillus flavus , Doenças Mitocondriais , Esporos Fúngicos/metabolismo , Membrana Celular , Perfilação da Expressão Gênica , Doenças Mitocondriais/metabolismo
19.
Adv Sci (Weinh) ; 11(2): e2304971, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37870206

RESUMO

The enhancement of immunotherapy is an emerging direction to develop highly effective and practical cancer therapeutic methods. Here a triply enhanced immunotherapy drug (TEID) is designed for ingeniously integrating in situ dual glycan reforming with perforation on cell membrane. The TEID is composed of galactose and neuraminidase conjugated streptolysin O (SLO-Gal and SLO-NEU), which are encapsulated in a hyaluronic acid (HA) shell for targeted recognition to tumor tissue via cell surface CD44. After targeted delivery and HAase-mediated degradation in the tumor region, the TEID releases SLO-Gal and SLO-NEU, which can easily anchor Gal and NEU on the tumor cell membrane via the perforation of SLO to perform dual glycan reforming for the introduction of Gal and the cleavage of sialic acid. The former can activate immune cells to secret cytokines for immune-killing, and the latter can weaken the immune inhibition to improve the immunotherapeutic efficacy. Meanwhile, the perforation of SLO can promote the delivery of cytokines into the tumor cells to further enhance the efficacy. The designed triply enhanced immunotherapy strategy opens a significant and promising route to promote clinical immunotherapy of cancer.


Assuntos
Neoplasias , Humanos , Membrana Celular , Citocinas , Imunoterapia
20.
J Periodontal Res ; 59(1): 174-186, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37957805

RESUMO

BACKGROUND: Periodontal ligament cells (PDLCs) are key mechanosensory cells involved in extracellular matrix (ECM) remodeling during orthodontic tooth movement (OTM). Mechanical force changes the ECM components, such as collagens and matrix metalloproteinases. However, the associations between the changes in ECM molecules and cellular dynamics during OTM remain largely uncharacterized. OBJECTIVES: To investigate the influence of mechanical force on the morphology and migration of PDLCs and explore the interaction between ECM remodeling and cellular dynamics, including the detailed mechanisms involved. METHODS: Human PDLCs (hPDLCs) were subjected to a static mechanical compression to mimic the compression state of OTM in vitro. A mouse OTM model was used to mimic the OTM procedure in vivo. The migration of hPDLCs was compared by wound healing and transwell migration assays. Moreover, expression levels of ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) and fibronectin (FN) in hPDLCs were determined via western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assays. Expression levels of ADAMTS9 and FN in mice were assessed via immunohistochemical staining. Additionally, the relative expression of long non-coding RNA (lncRNA) ADAMTS9-antisense RNA 2 (ADAMTS9-AS2) was assessed via quantitative real-time polymerase chain reaction. ADAMTS9-AS2 knockdown was performed to confirm its function in hPDLCs. RESULTS: Mechanical compression induced changes in the morphology of hPDLCs. It also promoted migration and simultaneous upregulation of FN and downregulation of ADAMTS9, a fibronectinase. The mouse OTM model showed the same expression patterns of the two proteins on the compression side of the periodontium of the moved teeth. RNA sequencing revealed that lncRNA ADAMTS9-AS2 expression was significantly upregulated in hPDLCs under mechanical compression. After knocking down ADAMTS9-AS2, hPDLCs migration was significantly inhibited. ADAMTS9 expression was increased as FN expression decreased compared to that in the control group. Moreover, knockdown of ADAMTS9-AS2 reduced the effect of mechanical compression on hPDLCs migration and reversed the expression change of ADAMTS9 and FN. RNA immunoprecipitation revealed direct binding between ADAMTS9-AS2 and ADAMTS9 protein. CONCLUSION: Our study suggests that mechanical compression induces the expression of ADAMTS9-AS2, which directly binds to ADAMTS9 and inhibits its function, leading to the promotion of downstream FN expression and ECM remodeling to facilitate hPDLCs migration and maintain the stability of the periodontium.


Assuntos
RNA Longo não Codificante , Humanos , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ligamento Periodontal/metabolismo , Proteína ADAMTS9/genética , Proteína ADAMTS9/metabolismo , Fibronectinas , Movimento Celular , Proliferação de Células/genética
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