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Increasing nitrogen and phosphorus discharge and decreasing sediment input have made silicon (Si) a limiting element for diatoms in estuaries. Disturbances in nutrient structure and salinity fluctuation can greatly affect metal uptake by estuarine diatoms. However, the combined effects of Si and salinity on metal accumulation in these diatoms have not been evaluated. In this study, we aimed to investigate how salinity and Si availability combine to influence the adsorption of metals by a widely distributed diatom Phaeodactylum tricornutum. Our data indicate that replete Si and low salinity in seawater can enhance cadmium and copper adsorption onto the diatom surface. At the single-cell level, surface potential was a dominant factor determining metal adsorption, while surface roughness also contributed to the higher metal loading capacity at lower salinities. Using a combination of non-invasive micro-test technology, atomic force microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy, we demonstrate that the diversity and abundance of the functional groups embedded in diatom cell walls vary with salinity and Si supply. This results in a change in the cell surface potential and transient metal influx. Our study provides novel mechanisms to explain the highly variable metal adsorption capacity of a model estuarine diatom.
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Diatomeas , Salinidad , Silicio , Contaminantes Químicos del Agua , Adsorción , Silicio/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Estuarios , Agua de Mar/química , Metales/químicaRESUMEN
Across diverse domains of science and technology, electromagnetic (EM) inversion problems benefit from the ability to account for multimodal prior information to regularize their inherent ill-posedness. Indeed, besides priors that are formulated mathematically or learned from quantitative data, valuable prior information may be available in the form of text or images. Besides handling semantic multimodality, it is furthermore important to minimize the cost of adapting to a new physical measurement operator and to limit the requirements for costly labeled data. Here, these challenges are tackled with a frugal and multimodal semantic-EM inversion technique. The key ingredient is a multimodal generator of reconstruction results that can be pretrained, being agnostic to the physical measurement operator. The generator is fed by a multimodal foundation model encoding the multimodal semantic prior and a physical adapter encoding the measured data. For a new physical setting, only the lightweight physical adapter is retrained. The authors' architecture also enables a flexible iterative step-by-step solution to the inverse problem where each step can be semantically controlled. The feasibility and benefits of this methodology are demonstrated for three EM inverse problems: a canonical two-dimensional inverse-scattering problem in numerics, as well as three-dimensional and four-dimensional compressive microwave meta-imaging experiments.
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The indications for bone block augmentation of the glenoid following recurrent anterior shoulder instability are expanding. Arthroscopic anatomic glenoid reconstruction (AAGR) is an evolving technique with similar clinical results to the Latarjet procedure and other open bone block procedures. Multiple types of bone grafts and fixation techniques have been described, with varying results on bony integration, resorption, articular congruity, and recurrence rates. This review focuses on biomechanics, patient workup, indications, current evidence, and the authors' preferred surgical technique for AAGR.
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Artroscopía , Trasplante Óseo , Inestabilidad de la Articulación , Humanos , Artroscopía/métodos , Trasplante Óseo/métodos , Inestabilidad de la Articulación/cirugía , Articulación del Hombro/cirugía , Fenómenos BiomecánicosRESUMEN
This study examined the prevalence and antibiotic resistance pattern of blaCTX-M extended-spectrum ß-lactamase positive Salmonella species isolated from a hospital in Weifang. Salmonella strains were isolated from hospitalized patients from January 2018 to April 2023. Whole-genome sequencing was performed by Illumina platform. CTX-M-producing Salmonella were identified by Comprehensive Antibiotic Research Database (CARD). Strain susceptibility to six antimicrobial agents was assessed by BD Phoenix™ M50 System. MLST analysis confirmed sequence types and additionally, serotypes were determined by SeqSero2. Genetic environments of blaCTX-M genes were analyzed by Isfinder and BLASTn. Single nucleotide polymorphisms were used to construct a phylogenetic tree to analyze homology. A total of 34 CTX-M-producing Salmonella were detected. The most prevalent serotype was Salmonella enterica subsp. enterica 1,4,[5],12:i:- (14/34, 41.18%), belonging to ST34, followed by Salmonella Enteritidis (10/34, 29.41%), belonging to ST11. The highest resistance rate was detected to ampicillin (97.06%), followed by ceftriaxone (94.12%) and ceftazidime (58.83%). In CTX-M-producing Salmonella five types of blaCTX-M genes were identified, the most prevalent was blaCTX-M-55 (47.06%, 16/34), followed by blaCTX-M-14, blaCTX-M-65, blaCTX-M-125, and blaCTX-M-27 at 26.47% (9/34), 11.77% (4/34), 8.82% (3/34), and 5.88% (2/34), respectively. Apart from blaCTX-M, 40 antibiotic resistance genes were also detected, conveying resistance to multiple drugs and the most frequent genes were namely, mcr-1.1, aph(6)-Id, aph(3â³)-Ib, oqxAB, qnrB6, qnrS1. According to genetic environment analysis, the insertion sequence ISEcp1 was prevalent upstream of the blaCTX-M gene. Our study demonstrates that multiple resistance genes are carried by clinical isolates of Salmonella spp. however, the dominant ESBL genotype is CTX-M-55, that is associated with ISEcp1.
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OBJECTIVE: To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA). METHODS: Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12-week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL-BREF) and the treatment-emergent adverse events (TEAEs) for all the participants in the study. RESULTS: At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed (p > .05). CONCLUSION: In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
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Antirreumáticos , Artritis Reumatoide , Quimioterapia Combinada , Hidroxicloroquina , Metotrexato , Calidad de Vida , Humanos , Metotrexato/efectos adversos , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/sangre , Femenino , Antirreumáticos/efectos adversos , Antirreumáticos/administración & dosificación , Antirreumáticos/uso terapéutico , Masculino , Resultado del Tratamiento , Persona de Mediana Edad , Adulto , Factores de Tiempo , Dimensión del Dolor , Biomarcadores/sangre , Anciano , Mediadores de Inflamación/sangreRESUMEN
Doping narrow-gap semiconductors is a well-established approach for designing efficient thermoelectric materials. Semiconducting half-Heusler (HH) and full-Heusler (FH) compounds have garnered significant interest within the thermoelectric field, yet the number of exceptional candidates remains relatively small. It is recently shown that the vacancy-filling approach is a viable strategy for expanding the Heusler family. Here, a range of near-semiconducting Heuslers, TiFexCuySb, creating a composition continuum that adheres to the Slater-Pauling electron counting rule are theoretically designed and experimentally synthesized. The stochastic and incomplete occupation of vacancy sites within these materials imparts continuously changing electrical conductivities, ranging from a good semiconductor with low carrier concentration in the endpoint TiFe0.67Cu0.33Sb to a heavily doped p-type semiconductor with a stoichiometry of TiFe1.00Cu0.20Sb. The optimal thermoelectric performance is experimentally observed in the intermediate compound TiFe0.80Cu0.28Sb, achieving a peak figure of merit of 0.87 at 923 K. These findings demonstrate that vacancy-filling Heusler compounds offer substantial opportunities for developing advanced thermoelectric materials.
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Familial exudative vitreoretinopathy (FEVR) is a severe genetic disorder characterized by incomplete vascularization of the peripheral retina and associated symptoms that can lead to vision loss. However, the underlying genetic causes of approximately 50% of FEVR cases remain unknown. Here, we report two heterozygous variants in calcyphosine-like gene (CAPSL) that is associated with FEVR. Both variants exhibited compromised CAPSL protein expression. Vascular endothelial cell (EC)-specific inactivation of Capsl resulted in delayed radial/vertical vascular progression, compromised endothelial proliferation/migration, recapitulating the human FEVR phenotypes. CAPSL-depleted human retinal microvascular endothelial cells (HRECs) exhibited impaired tube formation, decreased cell proliferation, disrupted cell polarity establishment, and filopodia/lamellipodia formation, as well as disrupted collective cell migration. Transcriptomic and proteomic profiling revealed that CAPSL abolition inhibited the MYC signaling axis, in which the expression of core MYC targeted genes were profoundly decreased. Furthermore, a combined analysis of CAPSL-depleted HRECs and c-MYC-depleted human umbilical vein endothelial cells uncovered similar transcription patterns. Collectively, this study reports a novel FEVR-associated candidate gene, CAPSL, which provides valuable information for genetic counseling of FEVR. This study also reveals that compromised CAPSL function may cause FEVR through MYC axis, shedding light on the potential involvement of MYC signaling in the pathogenesis of FEVR.
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Vitreorretinopatías Exudativas Familiares , Humanos , Vitreorretinopatías Exudativas Familiares/genética , Células Endoteliales/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Animales , Neovascularización Retiniana/genética , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Movimiento Celular/genética , Proliferación Celular/genética , Ratones , Vasos Retinianos/metabolismo , Vasos Retinianos/patología , Masculino , Neovascularización Patológica/genética , Transducción de Señal , Femenino , AngiogénesisRESUMEN
Background: Targeted therapy with neoadjuvant chemotherapy for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer has increased the rates of pathological complete response (pCR) and breast preservation surgery and improved the overall disease-free survival rate. This study aimed to determine whether tumor enhancement and shrinkage patterns in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can predict the efficacy of targeted therapy in patients with HER2-positive breast cancer and differentiate pCR from non-pCR. Methods: The data of 64 patients with HER2-positive breast cancer who received targeted therapy prior to surgery were retrospectively collected. All patients had complete postoperative pathological data. The pretreatment evaluation of the tumor enhancement pattern and the shrinkage pattern after two treatment cycles were assessed. The difference in the enhancement and shrinkage patterns between the pCR and non-pCR groups was evaluated via the χ2 test. Logistic regression analysis was used to assess the value of enhancement and shrinkage patterns for predicting pCR in patients with HER2-positive breast cancer. Results: There were statistically significant differences in tumor size, estrogen receptor (ER) status, lymph node metastasis, enhancement pattern, and shrinkage pattern between the pCR and non-pCR cases. Patients with a tumor size ≤20 mm were likely to achieve pCR. ER status, lymph node metastasis, and enhancement and shrinkage patterns each had good precision for predicting pCR, and the combination of enhancement and shrinkage patterns had the highest prediction accuracy. Multivariate logistic regression analysis indicated that only enhancement pattern had a significant predictive value. Conclusions: Among patients with HER2-positive breast cancer, those with tumor size ≤20 mm, ER-negative status, no lymph node metastases, and mass enhancement and concentric shrinkage patterns are more likely to achieve pCR. Mass enhancement combined with concentric shrinkage had the highest accuracy in predicting pCR, indicating that preoperative imaging may be useful for guiding clinical decisions regarding targeted treatments.
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This study investigated the impact of processing temperatures (190 °C, 210 °C, and 230 °C) and durations (7 min, 10 min, and 14 min) on the formation of Maillard reaction products (MRPs) and antioxidant activities in pan baked buns. Key Maillard reaction indicators, including glyoxal (GO), methylglyoxal (MGO), 5-hydroxymethylfurfural (5-HMF), melanoidins, and fluorescent advanced glycation end products (AGEs) were quantified. The results demonstrated significant increases in GO, MGO, 5-HMF contents (p < 0.05), and antioxidant activities (p < 0.05) when the buns were baked at 210 °C for 14 min, 230 °C for 10 min and 14 min. However, the interior MRPs of baked buns were minimally affected by the baking temperature and duration. Prolonged heating temperatures and durations exacerbated MRPs production (43.8 %-1038 %) in the bottom crust. Nonetheless, this process promoted the release of bound phenolic compounds and enhanced the antioxidant activity. Heating induces the thermal degradation of macromolecules in food, such as proteins and polysaccharides, which releases bound phenolic compounds by disrupting their chemical bonds within the food matrix. Appropriate selections of baking parameters can effectively reduce the formation of MRPs while simultaneously improve sensory quality and health benefit of the pan baked buns. Considering the balance between higher antioxidant properties and lower MRPs, the optimal thermal parameters for pan baked buns were 210 °C for 10 min. Furthermore, a normalized analysis revealed a consistent trend for GO, MGO, 5-HMF, fluorescent AGEs, and melanoidins. Moreover, MRPs were positively correlated with total contents of phenolic compounds, ferric-reducing antioxidant power (FRAP), and color, but negatively correlated with moisture contents and reducing sugars. Additionally, the interaction between baking conditions and Maillard reactions probably contributed to enhanced primary flavors in the final product. This study highlights the importance of optimizing baking parameters to achieve desirable MRPs levels, higher antioxidant activity, and optimal sensory attributes in baked buns.
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Antioxidantes , Culinaria , Furaldehído , Productos Finales de Glicación Avanzada , Calor , Reacción de Maillard , Piruvaldehído , Antioxidantes/análisis , Antioxidantes/química , Furaldehído/análogos & derivados , Furaldehído/análisis , Furaldehído/química , Piruvaldehído/química , Culinaria/métodos , Humanos , Glioxal/química , Gusto , Polímeros/química , Pan/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese herbal medicines (TCHM) have been extensively used in China and other East and Southeast Asian countries. Due to the low content of bioactive components in most TCHM and the potential toxicity of some herbal ingredients to humans, researchers have turned to probiotic fermentation to enhance the efficacy, mitigate the toxic or side effects and improve the taste of TCHM. Both probiotics and certain TCHM benefit the intestinal microbiota and intestinal barrier of human body, demonstrating synergistic effects on in intestinal microecology. AIM OF THE STUDY: This review aims to provide an overview of the development of fermentation technology, commonly used probiotic strains for TCHM fermentation, the advantages of probiotic fermentation and the challenges and limitations of probiotic- fermented TCHM. Additionally, it summarises and discusses the impact of probiotic-fermented TCHM on the intestinal barrier and microbiota, as well as the possible mechanisms involved. MATERIALS AND METHODS: An extensive search of primary literature was conducted using various databases including PubMed, Google Scholar, Web of Science, Elsevier, SpringerLink, ScienceDirect, CNKI, and others. All the plant names have been checked with World Flora Online (http://www.worldfloraonline.org) on August 7, 2024. RESULTS: The literature mentioned above was analyzed and summarized comprehensively. Probiotic-fermented TCHM can improve the intestinal barrier, modulate gut microbiota, and maintain homeostasis of the intestinal microecology. Modulating intestinal microecology by probiotic-fermented TCHM may be a crucial mechanism for its beneficial effects. CONCLUSIONS: This article establishes a theoretical basis for further research on the relationship between probiotic-fermented TCHM and the intestinal microecology, with the hope of inspiring innovative concepts for the development of TCHM and exploring the potential of probiotic-fermented TCHM as a promising strategy for maintaining intestinal microecological balance.
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The dramatical increase of sulfur concentration in eutrophic lakes, especially sulfate (SO42-), has brought attention to the impact on the lake ecosystem; however, the mechanisms driving the intensification of eutrophication and the role of SO42- concentrations remain poorly understood. To assess the impact of eutrophication on SO42- dynamics in lakes, this study monitored SO42- concentrations in water and sediments across seven lakes with varying trophic statuses on a spatial scale, and in the eutrophic Lake Taihu over one year on a temporal scale, as well as a series of microcosms with different initial SO42- concentrations. Exogenous sulfur input is the primary driver of increased SO42- concentrations in lakes, the highest SO42- concentration in overlying water was 100 mg/L, as well as which reached 310.9 mg/L in sediment. The concurrent input of nutrients such as nitrogen and phosphorus exacerbated eutrophication, resulting in the destabilization of the sulfur cycle. Eutrophication promoted the SO42- concentration on the spatio-temporal scale, especially in sediment, and trophic lake index (TLI) showed a positive correlation with the SO42- in sediments (R2 = 0.99; 0.88). The SO42- concentration in water and TLI showed a nonlinear correlation on the temporal scale (R2 = 0.44), and showed a positive correlation on the spatial scale (R2 = 0.49). Microscopic experiments demonstrate that the anaerobic environment created by cyanobacteria decomposition induced sulfate reduction and significantly reduces SO42- concentrations. Concurrently, the anaerobic environment facilitates the coupling of iron reduction with sulfate reduction, leading to a substantial increase in Acid Volatile Sulfides (AVS) in the sediment. These findings reveal that eutrophication has a dual effect on the dynamic change of SO42- concentrations in overlying water, which is helpful to accurately evaluate and predict the change of SO42- concentrations in lakes.
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Receptor-interacting serine/threonine protein kinase 1 (RIPK1) has emerged as an important regulator of pathologic cell death and inflammation and is implicated in the pathologies of various central nervous system diseases. In this study, we reported the development of three potent dihydropyrazole-cored RIPK1 positron emission tomography (PET) ligands [18F]WL1-3. Among these, [18F]WL1 showed specific binding to RIPK1 in mouse brain sections in vitro through autoradiography and exhibited favorable brain kinetics in mice, characterized by a high initial uptake (brain2â¯min = 4.89% ID/g) and rapid washout (brain60â¯min = 0.21% ID/g). PET studies in rat brains revealed that [18F]WL1 could readily penetrate the brain with specific binding confirmed by inhibition effects of unlabeled WL1 and GSK'547. Notably, [18F]WL1 showed significant potential in imaging the alterations of RIPK1 in a rat brain of tumor necrosis factor α-induced systemic inflammatory response syndrome model. These findings may pave the way for the future design of potent RIPK1 PET ligands.
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A novel electron donor-acceptor (EDA) complex/copper catalysis model has been proposed for the construction of 2,3-diarylpropionitriles under visible light conditions. The developed protocol proceeds via intermolecular charge transfer between the photoactive EDA complex of dibutamine (DBA), aryl thianthrenium salts, and trimethylsilyl cyanide (TMSCN), followed by a copper catalytic cycle. UV-vis absorption measurements confirm the participation of EDA complexes as reactive intermediates. This three-component process proceeds smoothly in the presence of pharmaceutically relevant core structures and sensitive functional groups, which offers the possibility of the precise editing of drug molecules with important scaffolds.
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BACKGROUND: B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide is the only blood biomarker in established risk calculators for pulmonary arterial hypertension (PAH). Profiling systemic-originated plasma immunoglobulin G (IgG) N-glycans, which reflect different components of the pathophysiology of PAH including immune dysregulation and inflammation, may improve PAH risk assessment. OBJECTIVES: This study sought to identify plasma IgG N-glycan biomarkers that predict survival in PAH to improve risk assessment. METHODS: This cohort study examined 622 PAH patients from 2 national centers (Beijing [discovery] cohort: n = 273; Shanghai [validation] cohort: n = 349). Plasma IgG N-glycomes were profiled by a robust mass spectrometry-based method. Prognostic IgG N-glycan traits were identified and validated in the 2 cohorts using Cox regression and Kaplan-Meier survival analyses. The added value of IgG N-glycan traits to previously established risk models was assessed using Harrell C-indexes and survival analysis. RESULTS: Plasma IgG fucosylation was found to predict survival independent of age and sex in the discovery cohort (HR: 0.377; 95% CI: 0.168-0.845; P = 0.018) with confirmation in the validation cohort (HR: 0.445; 95% CI: 0.264-0.751; P = 0.005). IgG fucosylation remained a robust predictor of mortality in combined cohorts after full adjustment and in subgroup analyses. Integrating IgG fucosylation into previously established risk models improved their predictive capacity, marked by an overall elevation in Harrell C-indexes. IgG fucosylation was useful in further stratifying the intermediate-risk patients classified by a previously established model. CONCLUSIONS: Plasma IgG fucosylation informs PAH prognosis independent of established factors, offering additional value for predicting PAH outcomes.
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Biomarcadores , Inmunoglobulina G , Humanos , Femenino , Masculino , Inmunoglobulina G/sangre , Persona de Mediana Edad , Pronóstico , Biomarcadores/sangre , Adulto , Hipertensión Arterial Pulmonar/sangre , Hipertensión Arterial Pulmonar/mortalidad , Estudios de Cohortes , Polisacáridos/sangre , Anciano , Medición de Riesgo/métodos , China/epidemiologíaRESUMEN
Simultaneously improving the activity and stability of catalysts for anodic oxygen evolution reaction (OER) in proton exchange membrane water electrolysis (PEMWE) remains a notable challenge. Here, we report a chromium-doped ruthenium dioxide with oxygen vacancies, termed Cr0.2Ru0.8O2-x, that drives OER with an overpotential of 170 mV at 10 mA cm-2 and operates stably over 2000 h in acidic media. Experimental and theoretical studies show that the synergy of Cr dopant and oxygen vacancy induces an unconventional dopant-mediated hydroxyl spillover mechanism. Such dynamic hydroxyl spillover from Cr dopant to Ru active site changes the rate-determining step from OOH* formation to O2 formation and thus greatly improves the OER performance. Moreover, the Cr dopant and oxygen vacancy also play a crucial role in stabilizing surface Ru and lattice oxygen in the Ru-O-Cr structural motif. When assembled into the anode of a practical PEMWE device, Cr0.2Ru0.8O2-x enables long-term durability of over 200 h at an ampere-level current density and 60 degrees centigrade.
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Human noroviruses (HuNoVs) are a leading cause of acute viral gastroenteritis worldwide. Infectious outbreaks due to recombinant NoV genotype called GII.P16-GII.2 have been frequently reported since 2016. In this study, we expressed the major capsid protein VP1 from three GII.2 NoV strains using the recombinant baculovirus expression system. The assembly, histo-blood group antigen (HBGA)-binding patterns, and cross-blocking abilities of VP1 proteins were investigated. All the three NoV VP1 proteins successfully assembled into virus-like particles (VLPs). The HBGA-binding assay demonstrated a temporal binding pattern. The latest isolate bound to saliva samples of all blood types. Sequence alignment suggested that the observed gain in HBGA-binding ability was attributed to a limited number of amino acid mutations. Using chimeric VP1 proteins, we demonstrated that synergistic effects resulted in enhanced binding ability. Bile salts increased GII.2 VLP avidity for HBGAs except GII.2-2011/M1. In vitro blockade assay of salivary HBGA-VLP binding demonstrated the presence of cross-blocking effects among different strains. This study provides insight into the evolutionary binding characteristics and cross-blocking effects of GII.2 NoVs to facilitate the development of measures to control this type of viruses.