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Antibiotic resistance genes (ARGs) are an important class of pollutants in the environment. This study investigated the characteristics and ecological effects of ARGs in the Bohai Sea sediments. The results showed that ARGs are widely distributed, and exhibit significant spatial and subtype variations, with absolute abundance following the decreasing order of Liaodong Bay, Laizhou Bay, Bohai Bay, and Bohai Strait. Tetracycline ARGs dominated, comprising 50 % to 62 % of all ARGs, with tetM having the highest abundance at 1.43 × 107 copies/g. Symbiotic network analysis revealed that the phyla Deinococcota, Dadabacteria were serve as the primary likely host of ARGs. The ARGs have a wide range of potential hosts, and bacteria often carry multiple ARGs, enhancing the mobility and ecological niche adaptation of ARGs. This study will provide an important reference for assessing ARGs pollution in semi-enclosed seas.
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Farmacorresistencia Microbiana , Sedimentos Geológicos , Sedimentos Geológicos/microbiología , China , Farmacorresistencia Microbiana/genética , Monitoreo del Ambiente , Genes Bacterianos , Bacterias/genética , Antibacterianos , Contaminantes Químicos del Agua/análisis , Farmacorresistencia Bacteriana/genéticaRESUMEN
The oxygen minimum zone (OMZ) is an important representative of marine hypoxia in the open ocean, and it is developing rapidly under the context of global warming. However, the research on OMZ in the Western Pacific is still deficient. This study focused on its basic characteristics and impact on the degradation of particulate matters in the M4 seamount of Western Pacific. The results showed that the OMZ is located at 290-1100 m, just below the high-salinity area and thermocline. The M4 seamount has a weak impact on the OMZ, and only the bottom waters contacting with the seamount have a weak decrease in dissolved oxygen (DO). With the increase of water depth, particulate nitrogen and phosphorus decrease first above and in the OMZ and then increase below the OMZ, while particulate organic carbon (POC) gradually decreases. The low-DO environment in the OMZ is not conducive to the degradation of particulate matters, which promotes the transport of particulate matters to the deep sea, and most particulate matters have the lowest degradation rate here. The waters above the OMZ have the fastest change rate of particulate matters, in which particulate organic phosphorus (POP) and particulate inorganic phosphorus (PIP) are preferentially degraded, and the degradation rate of them is significantly higher than particulate organic nitrogen (PON) and particulate inorganic nitrogen (PIN). The particulate nitrogen and phosphorus in the waters below the OMZ continue to increase, while PON/total particulate nitrogen (TPN) and POP/total particulate phosphorus (TPP) increase significantly, and the increase rate of PIN and PIP is far lower than PON and POP, indicating that the increase of organic matters in particulate matters is more significant. It is speculated that this phenomenon might be related to the input of Antarctic Bottom Water or the in-situ production by microorganisms. This study revealed the relationship between OMZ and different particulate matters, which may provide a valuable pathway for the biogeochemical effects of OMZ in the Western Pacific.
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Monitoreo del Ambiente , Nitrógeno , Oxígeno , Material Particulado , Fósforo , Agua de Mar , Material Particulado/análisis , Oxígeno/análisis , Oxígeno/metabolismo , Fósforo/análisis , Agua de Mar/química , Nitrógeno/análisis , Océano Pacífico , Contaminantes Químicos del Agua/análisisRESUMEN
Designing selective PARP-1 inhibitors has become a new strategy for anticancer drug development. By sequence comparison of PARP-1 and PARP-2, we identified a possible selective site (S site) consisting of several different amino acid residues of α-5 helix and D-loop. Targeting this S site, 140 compounds were designed, synthesized, and characterized for their anticancer activities and mechanisms. Compound I16 showed the highest PARP-1 enzyme inhibitory activity (IC50 = 12.38 ± 1.33 nM) and optimal selectivity index over PARP-2 (SI = 155.74). Oral administration of I16 (25 mg/kg) showed high inhibition rates of Hela and SK-OV-3 tumor cell xenograft models, both of which were higher than those of the oral positive drug Olaparib (50 mg/kg). In addition, I16 has an excellent safety profile, without significant toxicity at high oral doses. These findings provide a novel design strategy and chemotype for the development of safe, efficient, and highly selective PARP-1 inhibitors.
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Antineoplásicos , Diseño de Fármacos , Poli(ADP-Ribosa) Polimerasa-1 , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/química , Inhibidores de Poli(ADP-Ribosa) Polimerasas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Animales , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Ratones , Relación Estructura-Actividad , Línea Celular Tumoral , Ratones Desnudos , Femenino , Ensayos Antitumor por Modelo de Xenoinjerto , Células HeLa , Simulación del Acoplamiento Molecular , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Ftalazinas/farmacología , Ftalazinas/química , Ftalazinas/síntesis químicaRESUMEN
Nutrients directly control the level of primary productivity and are crucial for the stability of marine ecosystems. Focusing on the survey results in August 2020 of the Yangtze River Estuary, this study elucidated the distribution characteristics and controlling factors of three nutrients: NO3-N, PO4-P, SiO3-Si. The results showed that the concentrations of NO3-N, PO4-P, SiO3-Si in the study area were generally higher near the shore than far shore, with average concentrations of 11.40, 0.70, and 23.73 µmol/L, respectively. The ocean currents drove the distribution of nutrients, and the transport of CDW and YSCC increased the nutrient levels. The resuspension of sediment caused by factors such as terrain and weather may lead to an abnormal increase in nutrients in the bottom waters. The main controlling factors of the three nutrients were different. NO3-N was significantly affected by human activities, PO4-P and SiO3-Si were mainly affected by natural factors.
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Estuarios , Ríos , Humanos , Ecosistema , Estaciones del Año , Nutrientes , China , Monitoreo del AmbienteRESUMEN
BACKGROUND: SHP2 is highly expressed in a variety of cancer and has emerged as a potential target for cancer therapeutic agents. The identification of uncharged pTyr mimics is an important direction for the development of SHP2 orthosteric inhibitors. METHODS: Surface plasmon resonance analysis and cellular thermal shift assay were employed to verify the direct binding of LXQ-217 to SHP2. The inhibitory effect of LXQ-217 was characterized by linear Weaver-Burke enzyme kinetic analysis and BIOVIA Discovery Studio. The inhibition of tumor cell proliferation by LXQ-217 was characterized by cell viability assay, colony formation assays and hoechst 33258 staining. The inhibition of lung cancer proliferation inâ vivo was studied in nude mice after oral administration of LXQ-217. RESULTS: An electroneutral bromophenol derivative, LXQ-217, was identified as a competitive SHP2 inhibitor. LXQ-217 induced apoptosis and inhibited growth of human pulmonary epithelial cells by affecting the RAS-ERK and PI3â K-AKT signaling pathways. Long-term oral administration of LXQ-217 significantly inhibited the proliferation ability of lung cancer cells in nude mice. Moreover, mice administered LXQ-217 orally at high doses exhibited no mortality or significant changes in vital signs. CONCLUSIONS: Our findings on the uncharged orthosteric inhibitor provide a foundation for further development of a safe and effective anti-lung cancer drug.
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Antineoplásicos , Neoplasias Pulmonares , Animales , Humanos , Ratones , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular , Cinética , Neoplasias Pulmonares/tratamiento farmacológico , Ratones Desnudos , Proteína Tirosina Fosfatasa no Receptora Tipo 11/antagonistas & inhibidores , Fenoles/síntesis química , Fenoles/química , Fenoles/farmacologíaRESUMEN
BACKGROUND: MIRAGE syndrome is a rare autosomal dominant genetic disorder. METHODS: We studied a 15-month-old girl with growth retardation and refractory respiratory infections. RESULTS: The patient had thrombocytopenia and was positive for Epstein-Barr virus, cytomegalovirus IgM and IgG, and herpes simplex virus type I and II IgG. The genomic analysis reported a heterozygous de novo SAMD9 c.2944C > T (p.Arg982Cys) pathogenic variant. She improved after antibiotic treatments, but finally died due to severe recurrent infection. CONCLUSIONS: Patients with MIRAGE syndrome could have various clinical presentations. Infections from mixed pathogens are common, which require adequate coverage for bacteria, viruses, and fungi.
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Infecciones por Virus de Epstein-Barr , Infecciones del Sistema Respiratorio , Femenino , Humanos , Lactante , Herpesvirus Humano 4 , Inmunoglobulina G , Péptidos y Proteínas de Señalización Intracelular/genéticaRESUMEN
The ability to selectively introduce diverse functionality onto hydrocarbons is of substantial value in the synthesis of both small molecules and pharmaceuticals. In this endeavour, as a photocatalyst- and metal-free process, the electron donor-acceptor (EDA) strategy has not been well explored. Here we report an approach to aliphatic carbon-hydrogen bond diversification through an EDA complex constituted by HCl and SIV=O groups. As an efficient hydrogen atom transfer (HAT) reagent, chlorine radical can be produced via a proton-coupled electron transfer process in this system. Based on this unusual path, a photo-promoted versatile aliphatic C-H functionalization is developed without photo- and metal-catalysts, including thiolation, arylation, alkynylation, and allylation. This conversion has concise and ambient reaction conditions, good functional group tolerance, and substrate diversity, and provides an alternative solution for the high value-added utilization of bulk light alkanes.
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Food service facilities are important sites where foodborne diseases have been reported to occur frequently. This study aims to determine the correlation between self-reported foodborne diseases and food-safety practices followed by food handlers of various food service facilities. A cross-sectional survey was conducted from March 1, 2022 to December 30, 2022 in Wuhu City, Anhui Province, China. Data were collected through face-to-face interviews and having the selected food handlers fill in a self-compiled questionnaire. Of the 1072 food handlers included in the study, 88 (8.2%) reported having experienced symptoms of foodborne diseases in the past 4 weeks. The following food-safety practices correlated with self-reported foodborne diseases: (1) infrequently using 3-compartment sinks to separately clean different types of raw food materials (P < 0.05, OR = 2.312); (2) infrequently removing non-edible parts of aquatic products outside a specific room for food processing (P < 0.001, OR = 3.916); (3) infrequently immediately refrigerating cold dishes prepared in advance to be consumed later (P < 0.001, OR = 4.048); (4) often store perishable foods at 8-60°C in the indoor environment after cooking and before eating (P < 0.05, OR = 2.068); (5) infrequently reheating cooked perishable food stored at 8-60°C for more than 2 h before eating (P < 0.05, OR = 1.934); and (6) often storing raw and cooked food in the same container (P < 0.001, OR = 3.818). Hence, a better supervision of food-safety practices of catering workers may reduce the frequency of foodborne-disease outbreaks in food service facilities.
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Enfermedades Transmitidas por los Alimentos , Humanos , Autoinforme , Estudios Transversales , Enfermedades Transmitidas por los Alimentos/prevención & control , Enfermedades Transmitidas por los Alimentos/epidemiología , Inocuidad de los Alimentos , Manipulación de Alimentos , China/epidemiologíaRESUMEN
Src homology 2 domain-containing phosphatase (SHP2) is a non-receptor protein phosphatase that transduces signals from upstream receptor tyrosine kinases (RTKs)/non-RTKs to Ras/MAPK pathway. Accumulating studies indicated that SHP2 is a critical mediator of resistance to current targeted therapies in multiple cancers. Here, we reported a novel SHP2 allosteric inhibitor JC-010a, which was highly selective to SHP2 and bound at the "tunnel" allosteric site of SHP2. The effect of JC-010a on combating RTK/non-RTK or MAPK inhibitors-induced acquired resistance was explored. Our study demonstrated that JC-010a monotherapy significantly inhibited the proliferation of cancer cells with different oncogenic drivers via inhibiting signaling through SHP2. Importantly, JC-010a abolished acquired resistance induced by targeted therapies: in KRAS-mutant cancers, JC-010a abrogated selumetinib-induced adaptive resistance mediated by RTK/SHP2; in BCR-ABL-driven leukemia cells, we demonstrated JC-010a inhibited BCR-ABL T315I mutation-mediated imatinib resistance and proposed a novel mechanism of JC-010a involving the disrupted co-interaction of SHP2, BCR-ABL, and Hsp90; in non-small cell lung cancer (NSCLC) cells, JC-010a inhibited both EGFR T790M/C797S mutation and alternate RTK-driven resistance to gefitinib or osimertinib; importantly, we first proposed a novel potential therapeutic strategy for RET-rearranged cancer, we confirmed that JC-010a monotherapy inhibited cell resistance to BLU-667, and JC-010a/BLU-667 combination prolonged anticancer response both in vivo and in vitro cancer models by inhibiting the alternate MET activation-induced RAS/MAPK reactivation, thereby promoting cancer cell apoptosis. These findings suggested that JC-010a was a novel selective SHP2 allosteric inhibitor, and combing JC-010a with current targeted therapy agents provided a promising therapeutic approach for clinical resistant cancers.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Receptores ErbB/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Inhibidores de Proteínas Quinasas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Oncogenes , Resistencia a Medicamentos , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Línea Celular TumoralRESUMEN
Fluoroquinolone antibiotics (FQs) are one of the most widely used antibiotics, which are new pollutants with 'pseudo persistence' in the environment, causing great ecological risks. FQs could change the structure and function of microbial communities and affect nitrogen cycling mediated by microorganisms. Consequently, FQs would change the composition of various types of nitrogen in the environment and exert a significant impact on the global nitrogen cycling. We encapsulated the distribution of FQs in the environment and its impacts on nitrogen cycling mediated by microorganisms, explained the role of FQs in each key process of nitrogen cycling, aiming to provide an important reference for revealing the ecological effects of FQs. Generally, FQs could be detected in various environmental media, with significant differences in the concentration and types of FQs in different environments. Ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin are the four types of FQs with the highest detection frequency and concentration. The effect of FQs on nitrogen cycling deeply depends on typical characteristics of concentration and species. FQs mainly inhibit nitrification by reducing the abundance of amoA gene related to ammoxidation process and the abundance and composition of ammoxidation bacteria. FQs inhibits nitrification by reducing the abundance and composition of microbial communities. The denitrification process is mainly inhibited due to the reduction of the activity of related enzymes and the abundance of genes such as narG, nirS, norB, and nosZ genes, as well as the abundance and composition of denitrifying functional microorganisms. The process of anammox is restricted due to the reduction of the abundance, composition and hzo gene abundance of anaerobic anammox bacteria. FQs lead to the reduction of active nitrogen removal and the increase of N2O release in the environment, with further environmental problems such as water eutrophication and greenhouse effect. In the future, we should pay attention to the effects of low concentration FQs and complex antibiotics on the nitrogen cycling, and focus on the effects of FQs on the changes of nitrogen cycle-related microbial monomers and communities.
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Fluoroquinolonas , Ciclo del Nitrógeno , Fluoroquinolonas/química , Antibacterianos/farmacología , Antibacterianos/química , Contaminación Ambiental , Nitrógeno , DesnitrificaciónRESUMEN
Metals are crucial to the stability of marine ecosystems, and it is important to analyze their spatial heterogeneity. This study examined the distribution and influencing factors of six metals such as manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu) and cadmium (Cd) in M4 seamount of the Western Pacific. The results showed that the factors affecting the distribution of metals are complex. The concentration ranges of Mn, Fe, Co, Ni, Cu, and Cd in the M4 seamount were 0-0.05, 0-0.44, 0-0.0014, 0-0.082, 0.12-0.16, and 0-0.013 µg/L, respectively, roughly equivalent to those of other open seas, however, there were also some differences. Specifically, the distribution of ferromanganese nodules and Co-rich crusts, resulted in a significant increase in the concentration of metals such as Mn, Fe, and Co in the bottom. This study will significantly contribute to our understanding of the spatial heterogeneity of metals in seamount areas.
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Cadmio , Metales Pesados , Ecosistema , Metales , Cobre , Agua de Mar , Cobalto , NíquelRESUMEN
An organic electrochemical transistor (OECT) with MoS2 nanosheets modified on the gate electrode was proposed for glucose sensing. MoS2 nanosheets, which had excellent electrocatalytic performance, a large specific surface area, and more active sites, were prepared by liquid phase ultrasonic exfoliation to modify the gate electrode of OECT, resulting in a large improvement in the sensitivity of the glucose sensor. The detection limit of the device modified with MoS2 nanosheets is down to 100 nM, which is 1~2 orders of magnitude better than that of the device without nanomaterial modification. This result manifests not only a sensitive and selective method for the detection of glucose based on OECT but also an extended application of MoS2 nanosheets for other biomolecule sensing with high sensitivity.
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Molibdeno , Nanoestructuras , Electrodos , Glucosa , Sistemas de Infusión de InsulinaRESUMEN
Sulfonamides (SAs) are the first broad-spectrum synthetic antimicrobial agents used in human health and veterinary medicine. The majority of SAs entering human body is discharged into aquatic environment in the form of parent material or metabolites. The residues of SAs and their metabolites in the aquatic environment and the development of drug resistance can be serious threats to ecosystems and human health. We summarized recent advances in the research of SAs. The main metabolite types of SAs and the distribution characteristics of metabolites in different aquatic environments were introduced. The ecotoxicology of SAs metabolites, especially the distribution and hazards of sulfonamide resistance genes (sul-ARGs), were discussed with emphasis. Finally, the future research works were proposed. This paper could provide basic information for further research on SAs.
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Ecosistema , Ecotoxicología , Humanos , Sulfanilamida , Sulfonamidas/toxicidadRESUMEN
Synthetic fluoroquinolones (FQs) are the third most commonly used antibiotics in the world and play an extremely important role in antibacterial drugs. The excessive use and discharge will alter ecological environment, with consequence on human health and global sustainable development. It is therefore of great significance for scientific use and management of FQs to systematically understand their biogeochemical behavior and eco-environmental effects. After drug administration in humans and animals, only a small part of FQs are transformed in vivo. The main transformation processes include formylation, acetylation, oxidation and cleavage of piperazine ring, defluorination and decarboxylation of aromatic core ring, etc. About 70% of the original drug and a small amount of transformed products would be migrated to the environment through excretion. After entering the environment, FQs and their transformation products mainly exist in environmental media such as water, soil and sediment, and undergo migration and transformation processes such as adsorption, photolysis and biodegradation. Adsorption facilitates transfer of FQs from medium to another. The photolysis mainly affects the C7-amine substituents of FQs, whereas the core structure of FQs remains intact. Biodegradation mainly refers to the degradation of FQs by microorganisms and microalgae, including piperazine modification of the piperazine ring such as acetylation and formylation, partial or complete ring cleavage, core structure decarboxylation, defluorination and conjugation formation. The migration and transformation processes of FQs cannot completely eliminate them from the environment. Instead, they would become "pseudo-persistent" pollutants, which seriously affect the behavior, growth and reproduction of algae, crustaceans and fish, change biogeochemical cycle, destroy aquatic environment, and stimulate microbial resistance and the generation of resistance genes. In the future, more in-depth studies should be conducted on the environmental behavior of FQs and their impacts on ecological environment, the risk assessment of microbial resistance and resistance genes of FQs, and the mechanism and effect of micro-biodegradation of FQs.
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Clima , Fluoroquinolonas , Animales , Humanos , Antibacterianos , Biodegradación Ambiental , PiperazinasRESUMEN
Background: Noninvasive positive-pressure ventilation (NPPV) can be effective in children with acute asthma. However, clinical evidence remains limited. The objective of the meta-analysis was to systematically assess NPPV's effectiveness and safety in treating children with acute asthma. Methods: Relevant randomized controlled trials were obtained from electronic resources, including PubMed, Embase, Cochrane's Library, Wanfang, and CNKI databases. The influence of potential heterogeneity was taken into account before using a random-effect model to pool the results. Results: A total of 10 RCTs involving 558 children with acute asthma were included in the meta-analysis. Compared to conventional treatment alone, additional use of NPPV significantly improved early blood gas parameters such as the oxygen saturation (mean difference [MD]: 4.28%, 95% confidence interval [CI]: 1.51 to 7.04, p = 0.002; I2 = 80%), partial pressure of oxygen (MD: 10.61â mmHg, 95% CI: 6.06 to 15.16, p < 0.001; I2 = 89%), and partial pressure of carbon dioxide (MD: -6.29â mmHg, 95% CI: -9.81 to -2.77, p < 0.001; I2 = 85%) in the arterial blood. Moreover, NPPV was also associated with early reduced respiratory rate (MD: -12.90, 95% CI: -22.21 to -3.60, p = 0.007; I2 = 71%), improved symptom score (SMD: -1.85, 95% CI: -3.65 to -0.07, p = 0.04; I2 = 92%), and shortened hospital stay (MD: -1.82 days, 95% CI: -2.32 to -1.31, p < 0.001; I2 = 0%). No severe adverse events related to NPPV were reported. Conclusions: NPPV in children with acute asthma is associated with improved gas exchange, decreased respiratory rates, a lower symptom score, and a shorter hospital stay. These results suggest that NPPV may be as effective and safe as conventional treatment for pediatric patients with acute asthma.
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The continuous expansion of the oxygen minimum zone (OMZ) is a microcosm of marine hypoxia problem. Based on a survey in M4 seamount area of Tropical Western Pacific Ocean, the effects of thermodynamic parameters on OMZ were discussed. The study showed thermodynamic parameters mainly affect the upper oxycline of OMZ. The increase in temperature aggravates seawater stratification, which not only shallows oxycline but also increases the strength of DO stratification, promoting the expansion of OMZ. Based on relationships between thermodynamic parameters, water mass and DO, OMZ in this area is defined as follows: the water layer with low DO between the lower boundary of high-salt area and 1000 m. Moreover, the study showed that though there is no "seamount effect" on a scale of 3000 m, low-value areas of DO form at the bottom of seamount. This study will provide an evidence for expansion of OMZ exacerbated by global warming.
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Oxígeno , Agua de Mar , Océano Pacífico , Oxígeno/análisis , Temperatura , AguaRESUMEN
Cell surface engineering technologies can regulate cell function and behavior by modifying the cell surface. Previous studies have mainly focused on investigating the effects of cell surface engineering reactions and materials on cell activity. However, they do not comprehensively analyze other cellular processes. This study exploits covalent bonding, hydrophobic interactions, and electrostatic interactions to modify the macromolecules succinimide ester-methoxy polyethylene glycol (NHS-mPEG), distearoyl phosphoethanolamine-methoxy polyethylene glycol (DSPE-mPEG), and poly-L-lysine (PLL), respectively, on the cell surface. This work systematically investigates the effects of the three surface engineering reactions on the behavior of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts, including viability, growth, proliferation, cell cycle, adhesion, and migration. The results reveals that the PLL modification method notably affects cell viability and G2/M arrest and has a short modification duration. However, the DSPE-mPEG and NHS-mPEG modification methods have little effect on cell viability and proliferation but have a prolonged modification duration. Moreover, the DSPE-mPEG modification method highly affects cell adherence. Further, the NHS-mPEG modification method can significantly improve the migration ability of HUVECs by reducing the area of focal adhesions. The findings of this study will contribute to the application of cell surface engineering technology in the biomedical field.
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Apoptosis , Polietilenglicoles , Animales , Humanos , Línea Celular Tumoral , Puntos de Control de la Fase G2 del Ciclo Celular , Polietilenglicoles/farmacología , Polietilenglicoles/química , Lisina , Células Endoteliales de la Vena Umbilical Humana , MamíferosRESUMEN
Preparing sponge dressings with stable wet adhesion remains difficult in wound repair, especially in burn wounds with bleeding and large amounts of exudate. In this work, a multifunctional hybrid sponge dressing (DHGT+PHMB+TiO2NPs) with good wet adhesion was developed by combining biomimetic and enzymatic cross-linking reactions. The sponge dressing matrix (DHGT) was prepared by tyrosinase-catalyzed cross-linking of dopamine-modified hyaluronic acid (DOPA-HA) and gelatin. The multifunctional hybrid sponge dressing was obtained by loading polyhexamethylene biguanide (PHMB) and titanium dioxide nanoparticles (TiO2NPs) onto the DHGT matrix. The newly developed sponge dressing exhibited high mechanical properties, good wet adhesion, antibacterial activity, reactive oxygen species (ROS) scavenging, biocompatibility, and excellent hemostasis ability. In vivo studies showed that the multifunctional hybrid sponge dressing could significantly accelerate the healing of infected full-thickness burn wounds by inhibiting bacterial growth, accelerating skin tissue reepithelialization, collagen deposition, and angiogenesis, as well as regulating the expression of inflammatory factors and cytokines.
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Biomimética , Quemaduras , Humanos , Cicatrización de Heridas , Piel , Vendajes , Quemaduras/tratamiento farmacológico , Antibacterianos/farmacologíaRESUMEN
Arctigenin (AR), extracted from Arctium lappa L. (Burdock), is a folk herbal medicine used to treat diabetes. However, its mechanism of action has remained elusive. In this study, type 2 diabetes mellitus (T2DM) mice received AR orally for 10 weeks to evaluate its therapeutic effect based on changes in glucose and lipid metabolism, histological examination of target tissues, and liver immunohistochemistry. Furthermore, HepG2 insulin-resistant cells were established to verify the mechanism of AR against diabetes. The results showed that AR treatment reduced blood glucose and lipid levels, reversing liver as well as pancreas tissue damage in T2DM mice. AR reduced the levels of pro-inflammatory cytokines in the serum of T2DM mice, as well as those in insulin-resistant HepG2 cell supernatants, while increasing interleukin-10 (IL-10) levels. The levels of p-p65, phospho-c-Jun N-terminal kinase (p-JNK), induced nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were reduced in the liver tissue of T2DM mice, accompanied by an upregulation of glucose transporter 4 (GLUT4) and insulin receptor substrate 2 (IRS-2). In vitro studies further showed that AR downregulated toll-like receptor 4-mediated inflammation, while upregulating insulin pathway-related proteins and ultimately improving glucose uptake in insulin-resistant HepG2 cells. In conclusion, AR protected mice from insulin resistance, and its therapeutic effect was likely associated with inhibition of toll-like receptor 4 inflammatory signaling to reactivate IRS-2/GLUT4.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Ratones , Animales , Diabetes Mellitus Tipo 2/metabolismo , Receptor Toll-Like 4/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , InsulinaRESUMEN
We aimed to investigate the life events, life satisfaction, and coping style of college students, and to assess the relationship between them by performing mediating effect analysis. Our findings may provide a scientific basis for promoting the mental health of college students. Students in a medical college were selected using grade-stratified cluster sampling, and administered a standardized questionnaire survey. Out of 2,000 participants, 1827 participants provided valid questionnaires (response rate: 91.4%). The mean scores of life satisfaction and life events were 181.39 ± 30.28 and 19.32 ± 15.62, respectively. The mean score of coping style was 14.34 ± 7.54, which reflected positive coping style. Analysis of life satisfaction, life events, and factor scores showed that different grades, sibling status (whether the respondent was the only child in the family or not), family location, and life events had a significant association with life satisfaction (p < 0.001). There were significant differences in coping style between male and female students, and between students in different grades (p < 0.001). Positive coping style was found to play a partial mediating role between life events and life satisfaction, and the mediating effect accounted for 33.2% of the total effect. These results suggest that both life events and coping styles are related to college students' life satisfaction. The impact of life events on life satisfaction can be adjusted by psychological interventions to develop coping styles that can help promote the mental health of college students.