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Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.
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Inmunidad Adaptativa , Inmunidad Innata , Activación de Macrófagos , Macrófagos , Psoriasis , Receptor de Adenosina A2A , Psoriasis/inmunología , Animales , Ratones , Inmunidad Innata/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Receptor de Adenosina A2A/metabolismo , Receptor de Adenosina A2A/genética , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Inmunidad Adaptativa/efectos de los fármacos , Ratones Endogámicos C57BL , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/inmunología , Humanos , Ratones Noqueados , Fenetilaminas/farmacología , Adenosina/análogos & derivados , Adenosina/farmacología , Imiquimod/farmacología , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Agonistas del Receptor de Adenosina A2/farmacología , Queratinocitos/inmunología , Queratinocitos/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
OBJECTIVES: To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. METHODS: This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. RESULTS: A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48 mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. CONCLUSION: HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5 mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.
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Agammaglobulinemia , Enfermedades Autoinmunes , Infecciones , Rituximab , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Femenino , Masculino , Agammaglobulinemia/epidemiología , Persona de Mediana Edad , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/complicaciones , Estudios Retrospectivos , Adulto , Infecciones/etiología , Infecciones/epidemiología , Anciano , Glucocorticoides/uso terapéutico , Factores de Riesgo , China/epidemiología , Inmunoglobulina G/sangreRESUMEN
Apurinic/apyrimidinic endonuclease 1 (APE1), as a vital base excision repair enzyme, is essential for maintaining genomic integrity and stability, and its abnormal expression is closely associated with malignant tumors. Herein, we constructed an electrochemiluminescence (ECL) biosensor for detecting APE1 activity by combining nanoconfined ECL silver nanoclusters (Ag NCs) with X-shaped DNA recognizer-triggered cascade amplification. Specifically, the Ag NCs were prepared and confined in the glutaraldehyde-cross-linked chitosan hydrogel network using the one-pot method, resulting in a strong ECL response and exceptional stability in comparison with discrete Ag NCs. Furthermore, the self-assembled X-shaped DNA recognizers were designed for APE1 detection, which not only improved reaction kinetics due to the ordered arrangement of recognition sites but also achieved high sensitivity by utilizing the recognizer-triggered cascade amplification of strand displacement amplification (SDA) and DNAzyme catalysis. As expected, this biosensor achieved sensitive ECL detection of APE1 in the range of 1.0 × 10-3 U·µL-1 to 1.0 × 10-10 U·µL-1 with the detection limit of 2.21 × 10-11 U·µL-1, rendering it a desirable approach for biomarker detection.
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Técnicas Biosensibles , ADN-(Sitio Apurínico o Apirimidínico) Liasa , Técnicas Electroquímicas , Mediciones Luminiscentes , Nanopartículas del Metal , Plata , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , ADN-(Sitio Apurínico o Apirimidínico) Liasa/análisis , Plata/química , Humanos , Nanopartículas del Metal/química , Técnicas Electroquímicas/métodos , Mediciones Luminiscentes/métodos , Técnicas Biosensibles/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , ADN/química , Límite de Detección , ADN Catalítico/química , ADN Catalítico/metabolismoRESUMEN
OBJECTIVE: To analyze the prevalence of burnout among radiology residents. METHOD: Five databases (PubMed, Web of Science, Embase, PsycINFO, and Scopus) were searched for studies reporting burnout in radiology residents for the period up to November 7, 2022. RESULTS: A total of 423 studies were identified, and eventually, 16 studies were selected for the qualitative analysis, of which 11 studies were used in the meta-analysis. There was a total of 2164 radiology residents. Six studies reported the prevalence of burnout but the data could not be pooled due to their inconsistent definitions of burnout. The mean scores of three burnout subscales indicated a moderate to high degree of severity: emotional exhaustion = 25.2 (95% CI, 22.1-28.3; I2 = 94.4%), depersonalization = 10.2 (95% CI, 8.5-11.9; I2 = 93.0%), and low perception of personal accomplishment = 32.9 (95% CI, 30.5-35.4; I2 = 94.4%). The pooled prevalence of high-degree emotional exhaustion was 49.9% (95% CI, 43.6-56.1%; I2 = 55.7%), high-degree depersonalization was 45.1% (95% CI, 38.3-52.0%; I2 = 63.2%), and high-degree diminished personal accomplishment was 58.2% (95% CI, 36.0-77.6%; I2 = 84.9%). The impact of the COVID-19 pandemic on radiology residents was not investigated. In addition, there are inconsistent findings on the effects of female sex, seniority, and social support on burnout. CONCLUSIONS: About half of the radiology residents showed at least one of the three burnout manifestations (emotional exhaustion, depersonalization, and personal accomplishment), with a moderate to high degree of severity. CLINICAL RELEVANCE STATEMENT: Such a high prevalence and severity of burnout among radiology residents warrant the attention of residency program directors. KEY POINTS: ⢠Burnout, not uncommon among radiology residents, has not been effectively analyzed. ⢠Nearly half of the radiology residents experience at least one of the three manifestations of burnout to a moderate to high degree. ⢠The high prevalence and severe degree of burnout among radiology residents warrant the attention of residency program directors.
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Agotamiento Profesional , Internado y Residencia , Radiología , Humanos , Femenino , Pandemias , Encuestas y Cuestionarios , Radiología/educación , Agotamiento Psicológico , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Agotamiento Emocional , PrevalenciaRESUMEN
The self-organization of stem cells (SCs) constitutes the fundamental basis of the development of biological organs and structures. SC-driven patterns are essential for tissue engineering, yet unguided SCs tend to form chaotic patterns, impeding progress in biomedical engineering. Here, we show that simple geometric constraints can be used as an effective mechanical modulation approach that promotes the development of controlled self-organization and pattern formation of SCs. Using the applied SC guidance with geometric constraints, we experimentally uncover a remarkable deviation in cell aggregate orientation from a random direction to a specific orientation. Subsequently, we propose a dynamic mechanical framework, including cells, the extracellular matrix (ECM), and the culture environment, to characterize the specific orientation deflection of guided cell aggregates relative to initial geometric constraints, which agrees well with experimental observation. Based on this framework, we further devise various theoretical strategies to realize complex biological patterns, such as radial and concentric structures. Our study highlights the key role of mechanical factors and geometric constraints in governing SCs' self-organization. These findings yield critical insights into the regulation of SC-driven pattern formation and hold great promise for advancements in tissue engineering and bioactive material design for regenerative application.
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Matriz Extracelular , Ingeniería de Tejidos , Células Madre/citología , Animales , Humanos , Fenómenos Biomecánicos , Fenómenos MecánicosRESUMEN
The incorporation of gem-difluoromethylene units into organic molecules remains a formidable challenge. Conventional methodologies for constructing aryldifluoromethyl derivatives relied on the use of high-functional fluorinating regents under harsh conditions. Herein, we report general and efficient photoredox catalytic systems for defluoroalkylation of readily available trifluoromethylarenes through selective C-F cleavage to deliver gem-difluoromethyl radicals which proceed through reductive addition to both electron-donating and withdrawing alkenes under transition-metal free conditions. Mechanistic studies reveal that thiol serves as both photocatalyst and HAT reagent under visible light irradiation. This synergistic photocatalysis and HAT catalysis protocol exhibits ample and salient features such as high chemo- and regioselectivity, broad substrate scope, amenable gram-scale synthesis and late-stage modification of bioactive molecules.
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In the past decade, metal halide materials have been favored by many researchers because of their excellent physical and chemical properties under thermal, electrical, and light stimuli, such as ferroelectricity, dielectric, nonlinearity, fluorescence, and semiconductors, greatly promoting their application in optoelectronic devices. In this study, we successfully constructed an unleaded organic-inorganic hybrid perovskite crystal: [Cl-C6H4-(CH2)2NH3]3SbBr6 (1), which underwent a high-temperature reversible phase transition near Tp = 368 K. The phase transition behavior of 1 was characterized by differential scanning calorimetry, accompanied by a thermal hysteresis of 6 K. In addition, variable-temperature Raman spectroscopy analysis and PXRD further verified the sensitivity of 1 to temperature and the phase transition from low symmetry to high symmetry. Temperature-dependent dielectric testing shows that 1 can be a sensitive switching dielectric constant switching material. Remarkably, 1 exhibits strong photoluminescence emission with a wavelength of 478 nm and a narrow band gap of 2.7 eV in semiconductors. As the temperature increases and decreases, fluorescence undergoes significant changes, especially near Tc, which further confirms the reversible phase transition of 1. All of these findings provide new avenues for designing and assembling new phase change materials with high Tp and photoluminescence properties.
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BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).
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Anestésicos por Inhalación , Anestésicos Intravenosos , Procedimientos Quirúrgicos Cardíacos , Desflurano , Complicaciones Posoperatorias , Propofol , Humanos , Propofol/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/mortalidad , Anestésicos Intravenosos/efectos adversos , Anestésicos por Inhalación/efectos adversos , Anciano , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/prevención & control , Adulto , Sevoflurano/efectos adversos , Anestesia Intravenosa/métodos , China/epidemiología , Tiempo de Internación/estadística & datos numéricos , Anestesia por Inhalación/métodos , Anestesia por Inhalación/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the role of TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 in the mechanism of asthma combined with obstructive sleep apnea (OSA) in mice. METHOD: C57BL/6 mice were randomly divided into four groups: control group (NS-RA), asthma group (OVA-RA), OSA group (NS-IH), and asthma combined with OSA group (OVA-IH). After monitoring lung function in each group, the expression levels of TASK-1 and TASK-3 mRNA and protein in lung tissues were measured, and the correlation between the changes of both and lung function was analyzed. RESULTS: A total of 64 male mice were studied. Penh, serum IgE concentrations, and the percentage of eosinophils in bronchoalveolar lavage fluid (BALF) were higher in OVA-RA and OVA-IH mice compared with NS-RA (P < 0.05),while the above indexes were slightly elevated in NS-IH mice compared with NS-RA (P > 0.05), where the Penh and the percentage of eosinophils in BALF was higher in OVA-IH mice than NS-IH (P < 0.05).Increased TASK-3 mRNA expression (P < 0.05) as well as TASK-1 and TASK-3 protein expression (P > 0.05) in lung tissues of OVA-RA and NS-IH mice compared with NS-RA, and TASK-3 mRNA expression was slightly more in the OVA-IH group compared with NS-RA (P > 0.05), but less compared with OVA-RA (P < 0.05) or NS-IH (P > 0.05), while TASK-1 and TASK-3 protein expression was increased in the OVA-IH group compared with the remaining three groups, and TASK-3 protein expression was associated with lung function impairment was positively correlated with the degree of lung function impairment (P < 0.05). CONCLUSION: Task-1 and Task-3 may be involved in the pathogenesis of asthma with OSA by affecting lung function.
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Asma , Animales , Masculino , Ratones , Líquido del Lavado Bronquioalveolar , Modelos Animales de Enfermedad , Pulmón/metabolismo , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , ARN MensajeroRESUMEN
Objective To demonstrate the feasibility of oblique lumbar interbody fusion (OLIF) combined with 4-screw fixation for treating two-level lumbar degenerative diseases.Methods An intact finite element model of L3-S1 (M0) was constructed and validated.Then,we constructed the M1 model by simulating OLIF surgery at L3/4 and L4/5 segments on the M0 model.By attachment of posterior 4-screw or 6-screw fixation to the M1 model,three 4-screw fixation models (M2-M4) and one 6-screw fixation model (M5) were established.The segmental and overall range of motion (ROM) and the peak von Mises stresses of superior endplate,cage,and posterior screw-rod were investigated under each implanted condition.Results Under the motion modes of forward flexion,backward extension,bilateral (left and right) flexion,and left and right rotation,the L3/4 ROM of M2 model and L4/5 ROM of M3 model increased,while the L3/4 and L4/5 ROM of M4 and M5 models significantly decreased compared with those of M1 model.Under all motion modes,the L4 superior endplate in M2 model and the L5 superior endplate in M3 model showed the maximum peak von Mises stress,and the peak von Mises stresses of L4 and L5 superior endplates in M4 and M5 models were close.The L3/4 cage in M2 model and the L4/5 cage in M3 model showcased the largest peak von Mises stress,and the peak von Mises stresses of cages in M4 and M5 models were close.The peak stresses of internal fixation in M2-M5 models were close.Conclusion Four-screw fixation can replace 6-screw fixation in the OLIF surgery for treating two-level degenerative lumbar diseases.
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Tornillos Óseos , Análisis de Elementos Finitos , Vértebras Lumbares , Fusión Vertebral , Fusión Vertebral/métodos , Fusión Vertebral/instrumentación , Humanos , Vértebras Lumbares/cirugíaRESUMEN
Diabetic nephropathy(DN), a progressive chronic kidney disease(CKD) induced by diabetes mellitus, is the main cause of end-stage renal disease. Renal interstitial fibrosis(RIF) is an irreversible factor in the progression and deterioration of the renal function in DN. Chronic inflammation has become a key link in the pathogenesis of DN-RIF. The NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome is an important inflammatory regulator regulated by a variety of signals. It promotes the production of pro-inflammatory cytokines and induces renal inflammatory cell infiltration to participate in the process of renal fibrosis, demonstrating a complex mechanism of action. In view of the important role of NLRP3 inflammasomes in the prevention and treatment of DN-RIF, a large number of experimental studies have demonstrated that traditional Chinese medicine(TCM) can reduce the inflammation by regulating the pathways involving NLRP3 inflammasome, thereby slowing down the progression of DN-RIF and improving the renal function. This paper reviews the relationship between NLRP3 inflammasomes and DN-RIF, and the research progress in the mechanism of TCM intervention in NLRP3 inflammasomes to alleviate DN-RIF, aiming to provide new ideas for the targeted treatment of DN-RIF.
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Diabetes Mellitus , Nefropatías Diabéticas , Humanos , Inflamasomas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Medicina Tradicional China , Inflamación/metabolismo , FibrosisRESUMEN
The combination of chirality and phase-transition materials has broad application prospects. Therefore, based on the quasi-spherical theory and the thought strategy of introducing chirality, we have successfully synthesized a pair of chiral enantiomeric ligands (R/S)-triethyl-(2-hydroxypropyl)ammonium iodide, which can be combined with a tin hexachloride anion to obtain a pair of new organic-inorganic hybrid enantiomeric high-temperature plastic phase-transition materials: (R/S)-[CH3 CH(OH)CH2 N(CH2 CH3 )3 ]2 SnCl6 (1-R/1-S), which have a high temperature phase transition of Tc =384â K, crystallize in the P21 chiral space group at room temperature, and have obvious CD signals. In addition, compounds 1-R and 1-S have a good low-loss dielectric switch and broadband gap. This work is conducive to the research into chiral high-temperature reversible plastic phase-transition materials, and promotes the development of multi-functional phase-transition materials.
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Ultraviolet (UV) filters are emerging contaminants that have been found in high concentrations in human tissues. Food intake is generally considered to be the primary route of human exposure to contaminants. In this study, 184 composite food samples, prepared from 4268 individual samples in eight categories collected from 23 Chinese provinces for the sixth Chinese total diet study, were analyzed. The total and median UV filter concentrations in food samples were 1.5-68.3 and 7.9 ng/g wet weight, respectively. The highest median concentrations were found in decreasing order in meat, cereals, and legumes. In total, 15 UV filters were analyzed. 2-Ethylhexyl salicylate, homosalate, and 2-ethylhexyl-4-methoxycinnamate were dominant and made median contributions of 34.1%, 22.6%, and 14.5%, respectively, and 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol contributed the median of 0.03%, of the total UV filter concentrations. The estimated total daily UV filter intake in animal-origin foods and total UV filter concentration in human milk from the same province were significantly correlated (r = 0.44, p < 0.05). Predicted absorption, distribution, metabolism, and elimination properties led to 10 UV filters being prioritized as most likely to be retained in human tissues. The prioritization results and toxicity assessments indicated that octocrylene and 2-ethylhexyl-4-methoxycinnamate have stronger effects in vivo and therefore require more attention than others.
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Fabaceae , Alimentos , Animales , Humanos , Cinamatos , DietaRESUMEN
Chlorinated paraffins (CPs) are used in many products, including soft poly(vinyl chloride) curtains, which are used in many indoor environments. Health hazards posed by CPs in curtains are poorly understood. Here, chamber tests and an indoor fugacity model were used to predict CP emissions from soft poly(vinyl chloride) curtains, and dermal uptake through direct contact was assessed using surface wipes. Short-chain and medium-chain CPs accounted for 30% by weight of the curtains. Evaporation drives CP migration, like for other semivolatile organic plasticizers, at room temperature. The CP emission rate to air was 7.09 ng/(cm2 h), and the estimated short-chain and medium-chain CP concentrations were 583 and 95.3 ng/m3 in indoor air 21.2 and 172 µg/g in dust, respectively. Curtains could be important indoor sources of CPs to dust and air. The calculated total daily CP intakes from air and dust were 165 ng/(kg day) for an adult and 514 ng/(kg day) for a toddler, and an assessment of dermal intake through direct contact indicated that touching just once could increase intake by 274 µg. The results indicated that curtains, which are common in houses, could pose considerable health risks through inhalation of and dermal contact with CPs.
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Contaminación del Aire Interior , Hidrocarburos Clorados , Cloruro de Vinilo , Exposición por Inhalación/análisis , Parafina/análisis , Contaminación del Aire Interior/análisis , Monitoreo del Ambiente/métodos , Hidrocarburos Clorados/análisis , Polvo/análisis , ChinaRESUMEN
Enterococcus faecium (E. faecium) is widely used in foods and is known as a probiotic to treat or prevent diarrhea in pets and livestock. However, the poor resistance of E. faecium to high temperature processing procedures limits its use. Strain domestication is a low-cost and effective method to obtain high-temperature-resistant strains. In this study, heat treatment was performed from 45 °C to 70 °C and the temperature was gradually increased by 5 °C every 3 days. After domestication, the survival rates of the high temperature adaptation strain RS047-wl under 65 °C water bath for 40 min was 11.5 times higher than WT RS047. Moreover, the saturated fatty acid (SFA) contents in cell membrane and the cell volume significantly increased in the RS047-wl. The combined transcriptomic, metabolomic, and proteomics analysis results showed a significant enhancement of cell wall and membrane synthesis ability in the RS047-wl. In conclusion, one of the main factors contributing to the improved high temperature resistance of RS047-wl was its enhanced ability to synthesize cell wall and membrane, which helped maintain normal cell morphology. Developing a high-temperature-resistant strain and understanding its mechanism enables it to adapt to high temperatures. This lays the groundwork for its future development and application.
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Enterococcus faecium , Termotolerancia , Membrana Celular , Pared Celular , CalorRESUMEN
Four new germacrane sesquiterpene dilactones, 2ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (1), 3ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (2), 1α,3ß-dihydroxy-4,9-germacradiene-12,8:15,6-diolide (3), and (11ß,13-dihydrodeoxymikanolide-13-yl)-adenine (4), together with five known ones (5-9) were isolated from the aerial parts of Mikania micrantha. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compound 4 is featured with an adenine moiety in the molecule, which is the first nitrogen-containing sesquiterpenoid so far isolated from this plant species. These compounds were evaluated for their in vitro antibacterial activity against four Gram-(+) bacteria of Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC) and Curtobacterium. flaccumfaciens (CF), and three Gram-(-) bacteria of Escherichia coli (EC), Salmonella. typhimurium (SA), and Pseudomonas Solanacearum (PS). Compounds 4 and 7-9 were found to show strong in vitro antibacterial activity toward all the tested bacteria with the MIC values ranging from 1.56 to 12.5 µg/mL. Notably, compounds 4 and 9 showed significant antibacterial activity against the drug-resistant bacterium of MRSA with MIC value 6.25 µg/mL, which was close to reference compound vancomycin (MIC 3.125 µg/mL). Compounds 4 and 7-9 were further revealed to show in vitro cytotoxic activity toward human tumor A549, HepG2, MCF-7, and HeLa cell lines, with IC50 values ranging from 8.97 to 27.39 µM. No antibacterial and cytotoxic activity were displayed for the other compounds. The present research provided new data to support that M. micrantha is rich in structurally diverse bioactive compounds worthy of further development for pharmaceutical applications and for crop protection in agricultural fields.
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Antineoplásicos , Staphylococcus aureus Resistente a Meticilina , Mikania , Humanos , Mikania/química , Sesquiterpenos de Germacrano , Células HeLa , Antibacterianos/química , Bacterias , Pruebas de Sensibilidad MicrobianaRESUMEN
This study analyzes the impact of circulation types (CTs) on ozone (O3) pollution in Beijing. The easterly high-pressure (SWW) circulation occurred most frequently (30%; 276 day), followed by northwesterly high-pressure (AN) circulation (24.3%; 224 day). The SWW type had the highest O3 anomaly of +17.28 µg/m3, which was caused by excellent photochemical reactions, poor diffusion ability and regional transport. Due to the higher humidity and precipitation in the low-pressure type (C), the O3 increase (+8.02 µg/m3) was less than that in the SWW type. Good diffusion/wet deposition and weak formation ability contributed to O3 decrease in AN (-12.54 µg/m3) and northerly high-pressure (ESN) CTs (-12.26 µg/m3). The intra-area transport of O3 was significant in polluted circulations (SWW- and C-CTs). In addition, higher temperature, radiation and less rainfall also contributed to higher O3 in northern Beijing under the SWW type. For the clean CTs (AN and ESN CTs), precursor amount and intra-area transport played a dominant role in O3 distribution. Under the northeasterly low-pressure CT, better formation conditions and higher precursor amount combined with the intra-area southerly transport to cause higher O3 values in the south than in the north. The higher O3 in the northwestern area under the northeasterly high-pressure type was influenced by weaker titration loss and high O3 concentration in previous day. Annual variation in the CTs contributed up to 86.1% of the annual variation in O3. About 78%-83% of the diurnal variation in O3 resulted from local meteorological factors.
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Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Ozono/análisis , Beijing , Contaminantes Atmosféricos/análisis , Estaciones del Año , Monitoreo del Ambiente , China , Contaminación del Aire/análisisRESUMEN
Objective: To evaluate the efficacy of applying mecapegfilgrastim for peripheral blood hematopoietic stem cell (PBSC) mobilization in patients with hematologic neoplasms, and to investigate the influencing factors of PBSC collection. Methods: Patients who underwent PBSC mobilization in the Department of Hematology, Mianyang Central Hospital between April 2016 and May 2022 were retrospectively analyzed. The CD34 + cell collection results of two groups, the mecapegfilgrastim group ( n=28), or the PEG group, and the recombinant human granulocyte colony-stimulating factor (rhG-CSF) group ( n=30), were compared, and the influencing factors of collection failure were analyzed. Results: The success rates of CD34 + cells collection in the PEG group and the rhG-CSF group were 75.0% and 63.3%, respectively ( P>0.05). The median CD34 + cell counts were 3.37×10 6/kg and 2.68×10 6/kg, respectively, showing no significant difference. After combined mobilization with plerixafor, the median counts of CD34 + cells collected in the PEG group and rhG-CSF group were 4.23×10 6/kg and 3.26×10 6/kg, respectively, showing no significant difference ( P>0.05). There was no significant difference in hematopoietic system reconstruction and infections between the two groups ( P>0.05). Multivariate analysis found non-plasma cell disease (odds ratio [ OR]=19.697, 95% confidence interval [ CI] : 1.501-258.537, P=0.023), anemia before collection ( OR=18.571, 95% CI: 1.354-254.775, P=0.029) and white blood cell count before collection under 32×10 9 L -1 ( OR=85.903, 95% CI: 4.947-1491.807, P=0.002) to be independent risk factors for PBSC collection failure. Conclusion: The effect of PBSC mobilization with mecapegfilgrastim was comparable to that of rhG-CSF in patients with hematologic neoplasms. Furthermore, combined mobilization with plerixafor was feasible and effective. Patients with leukemia or lymphoma, anemia, and WBC<32×10 9 L -1 before stem cell collection have a high probability of PBSC collection failure.
Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Humanos , Movilización de Célula Madre Hematopoyética/métodos , Estudios Retrospectivos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Hematológicas/terapia , Antígenos CD34RESUMEN
Ozone is a potent environmental oxidant with high chemical reactivity and is present in the ambient environment at a low level of a few tens of ppb. However, only limited information is known about low-level ozone's influence on the respiratory system. In the present study, we systematically investigated the degradation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), which is one of the major components of the pulmonary surfactant (PS), enabling breath function of the lung exposed to low ambient-level ozone (40 ± 10 ppb). Using the liquid chromatography-mass spectrometry technique combined with the Langmuir-Blodgett approach, we first tracked the degradation process of POPC molecules by determining the degradation products during exposure to the ambient environment. As a result, we found that the POPC molecules can be readily degraded from the CâC moiety in 45 min, yielding an aldehyde-type product of 1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3-phosphocholine (POnPC) and a trace amount of an acid-type one of 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PAzPC), as well as a pair of secondary ozonide (SOZ) isomers. Furthermore, with prolonged exposure, the SOZ stayed constant but the yield of PAzPC significantly increased with the decrease in POnPC. The low-level ozone-induced oxidation mechanisms for unsaturated lipids are discussed based on the quantitative analyses of these experimental observations. The present results demonstrate that the ground-level ozone is strong enough to induce dramatic oxidation damage to the unsaturated lipids of the PS. These oxidized species may trigger the lung's inflammatory response and be used as biomarkers for oxidative stress and inflammation.
Asunto(s)
Ozono , Surfactantes Pulmonares , Pulmón/metabolismo , Espectrometría de Masas , Oxidación-Reducción , Ozono/química , Fosfatidilcolinas/química , Surfactantes Pulmonares/metabolismoRESUMEN
The distributions of organic pollutants in the gas phase and size-fractionated particle phases can largely affect human health risks posed by them. Gas-particle partitioning and particle-size distributions of some known pollutants have been investigated. However, the pollutants which are more likely to enter the human body and cause strong adverse effects may be neglected. In this study, a nontargeted screening approach combining comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry and chemometrics was developed. Eighty-eight compounds with markedly different proportions in the gas phase and PM1, as well as 50 contaminants with significant differences in PM1 and particles with diameters of 1-2.5 µm, were identified. Of these compounds, 18 were found in the air for the first time. There were obvious discrepancies between the measured and predicted gas-particle partitioning coefficients for some pollutants, suggesting unexpected environmental fates and health risks. The human daily intakes through inhalation and dermal exposure to these pollutants were estimated with the International Commission on Radiological Protection deposition model and transdermal permeability model. A risk-based prioritization was performed. The results indicated that adverse effects posed by 9H-fluoren-9-one, 2-ethylhexyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate, p-cumenol, 2,4-diisocyanato-1-methyl-benzene, bis(2-ethylhexyl) phthalate, perylene, (E)-cinnamaldehyde, 4-methyl-2-nitro-phenol, benzoic acid, and bis(2-methylpropyl) ester hexanedioic acid in ambient air may be more severe than those posed by conventionally monitored pollutants. The findings would facilitate raising concerns about these pollutants before they cause further severe and widespread impacts.