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The freshness of Atlantic salmon is influenced mainly by tissue metabolism, which in turn is affected by storage time and conditions. The alterations in taste profiles and nutritional values of salmon when packaged using vacuum methods have not been fully understood, and the factors contributing to these changes require further research. In this work, the extraction method for flavor nutrients from salmon was optimized via the Plackett-Burman (PB) test. A sensitive and rapid targeted metabolomics method for the simultaneous determination of 34 nutrients was successfully established via ultra-performance liquid chromatography-triple quadrupole/linear ion trap composite mass spectrometry (UHPLC-QTRAP/MS), and various nutritional compositions during storage at 0 °C under different vacuum conditions (0 kPa or -90 kPa) for 4 and 8 days were analyzed. Results showed that storage time had a significant effect on salmon metabolism. The total amino acids decreased by 62.95% and 65.89% at 0 kPa and -90 kPa, respectively. Notably, a marked reduction in histidine after 8 days at -90 kPa may have diminished bitterness, while decreased levels of umami-tasting amino acids like glutamine and aspartic acid affected the overall flavor profile. Overall, the packaging conditions at 0 °C and 0 kPa were more suitable for the preservation of most nutrients in salmon. Pathway enrichment analysis revealed that the reduction in substances was mainly related to the alanine, aspartate, and glutamate metabolism pathways. Alanine, inosine, and histidine, whose levels changed significantly, can bind to the typical umami taste receptor TIR1/TIR3 and can be biomarkers to monitor and determine the freshness or spoilage of salmon after 4-8 days of storage. This study revealed the changes in small-molecule nutrients in salmon during storage under different packaging conditions, which provides a reference for the packaging preservation technology of fresh salmon and new ideas for the evaluation of salmon quality and determination of freshness.

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Bladder cancer (BCa) stands out as a highly prevalent malignant tumor affecting the urinary system. The Sex determining region Y-box protein family is recognized for its crucial role in BCa progression. However, the effect of Sex determining region Y-box 7 (SOX7) on BCa progression has not been fully elucidated. Herein, RNA-sequencing, western blot (WB), immunohistochemistry (IHC), immunofluorescence (IF) and tissue microarray were utilized to assess SOX7 expression in vitro and in vivo. Additionally, SOX7 expression, prognosis, and SOX7 + cytoglobin (CYGB) score were analyzed using R software. In vitro and vivo experiments were performed with BCa cell lines to validate the effect of SOX7 knockdown and overexpression on the malignant progression of BCa. The results showed that SOX7 exhibits low expression in BCa. It functions in diverse capacities, inhibiting the proliferative, migratory, and invasive capabilities of BCa. In addition, the experimental database demonstrated that SOX7 binds to the promoter of DNA methyltransferase 3 beta (DNMT3B), leading to the transcriptional inhibition of DNMT3B. This subsequently results in a reduced methylation of CYGB promoter, ultimately inhibiting the tumor progression of BCa. SOX7 + CYGB scores were significantly linked to patient prognosis. In conclusion, SOX7 inhibits the malignant progression of BCa via the DNMT3B/CYGB axis. Additionally, the SOX7 + CYGB score is capable of predicting the prognostic outcomes of BCa patients. Therefore, SOX7 and CYGB may play an important role in the progression of bladder cancer, and they can be used as prognostic markers of bladder cancer patients.

Asunto(s)

ADN (Citosina-5-)-Metiltransferasas , ADN Metiltransferasa 3B , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Línea Celular Tumoral , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Animales , Femenino , Ratones , Masculino , Proliferación Celular , Factores de Transcripción SOXF/genética , Factores de Transcripción SOXF/metabolismo , Pronóstico , Regiones Promotoras Genéticas/genética , Metilación de ADN , Ratones Desnudos , Movimiento Celular

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ortho-Quinone methides (o-QMs) are a class of highly reactive intermediates that serve as important nonisolable building blocks (NBBs) in organic synthesis and small-molecule library construction. Because of their instability and nonisolability, most reported o-QMs are generated through in situ chemical synthesis, and only a few natural o-QMs have been reported due to the lack of directed discovery strategies. Herein, a new natural o-QM precursor (trichophenol A, 2) was identified from the fungal strain of Trichoderma sp. AT0167 through genome mining, which was generated by trilA (nonreducing polyketide synthase) and trilB (2-oxoglutarate dependent dioxygenase). Combinatorial biosynthesis via two other known NRPKS genes with trilA and trilB was performed, leading to the generation of five new trichophenol o-QM oligomers (trichophenols D-H, 5-9). The strategy combining genome mining with combinatorial biosynthesis not only targetedly uncovered a new natural o-QM precursor but also produced various new molecules through oligomerization of the new o-QM and its designated o-QM acceptors without chemical synthesis and isolation of intermediates, which was named NBB genome mining-combinatorial biosynthesis strategy for o-QM molecule library construction. This study provides a new strategy for the targeted discovery of natural o-QMs and small-molecule library construction with natural o-QMs.

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Objectives: Acute aortic dissection (AAD) is an extremely life-threatening medical emergency, often misdiagnosed in its early stages, resulting in prolonged wait times for rescue. This study aims to identify potential serum biomarkers that can assist in the accurate diagnosis of AAD and effectively differentiate it from other conditions causing severe chest pain. Methods: A total of 122 patients with AAD and 129 patients with other severe chest pain disorders were included in the study. Serum samples were analyzed by measuring the peak intensities of Raman spectra. For each measurement, the Raman spectrum was accumulated by two accumulations (3 s per acquisition). Logistic regression and nomogram models were developed using these peak intensities as well as D-dimer levels to predict the occurrence of AAD. The clinical utilities of these models were assessed through receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) in both training and internal test cohorts. Results: The D-dimer levels of AAD patients were significantly increased, as well as higher intensities at specific Raman peaks, including 505 cm-1, 842 cm-1, 947 cm-1, 1254 cm-1, 1448 cm-1, and 1655 cm-1 when compared to non-AAD patients. Conversely, decreased intensities were observed at Raman peaks such as 750 cm-1, 1004 cm-1, 1153 cm-1, 1208 cm-1, and 1514 cm-1 in AAD patients. Least absolute shrinkage and selection operator regression analysis on the training cohort identified eight potential predictors: D-dimer along with intensity measurements at peaks such as 505 cm-1, 750 cm-1, 1153 cm-1, 1208 cm-1, 1254 cm-1, 1448 cm-1, and 1655 cm-1. The combination of these eight potential predictors demonstrated a good discriminatory performance, with an area under the curve (AUC) value of 0.928 in the training cohort and an AUC of 0.936 in the internal test cohort, outperforming the use of D-dimer alone. Furthermore, DCA curve analysis revealed that leveraging this combination of eight potential predictors would provide substantial net benefits for clinical application. Moreover, this combination significantly augmented discrimination power, as evidenced by a continuous NRI of 39.8 % and IDI of 9.95 % in the training cohort, as well as a continuous NRI of 27.1 % and IDI of 9.95 % in the internal test cohort. Conclusions: The employment of this combination of eight potential predictors effectively rules out AAD to a greater extent. This study presents a promising diagnostic strategy for early detection using optical diagnostic techniques such as Raman spectroscopy.

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OBJECTIVES: This study aims to identify risk factors for acute kidney injury (AKI) in patients with ureterolithiasis and to develop a predictive model for early AKI detection in this population. METHODS: A retrospective analysis was conducted on data from 1,016 patients with ureterolithiasis who presented to our outpatient emergency department between January 2021 and December 2022. Using multifactorial logistic regression, we identified independent risk factors for AKI and constructed a nomogram to predict AKI risk. The predictive model's efficacy was assessed through the area under the ROC curve, calibration curves, Hosmer-Lemeshow (HL) test, and decision curve analysis (DCA). RESULTS: AKI was diagnosed in 18.7% of the patients. Independent risk factors identified included age, fever, diabetes, hyperuricemia, bilateral calculi, functional solitary kidney, self-medication, and prehospital delay. The nomogram demonstrated excellent discriminatory capabilities, with AUCs of 0.818 (95% CI, 0.775-0.861) for the modeling set and 0.782 (95% CI, 0.708-0.856) for the validation set. Both calibration curve and HL test results confirmed strong concordance between the model's predictions and actual observations. DCA highlighted the model's significant clinical utility. CONCLUSIONS: The predictive model developed in this study provides clinicians with a valuable tool for early identification and management of patients at high risk for AKI, thereby potentially enhancing patient outcomes.

Asunto(s)

Lesión Renal Aguda , Nomogramas , Ureterolitiasis , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Factores de Riesgo , Adulto , Ureterolitiasis/complicaciones , Anciano , Curva ROC , Modelos Logísticos , Medición de Riesgo/métodos

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While guidelines recommend 150 â€‹min of moderate to vigorous physical activity (MVPA) weekly to enhance health, it remains unclear whether concentrating these activities into 1-2 days of the week, "weekend warrior" (WW) pattern, has the same benefit for neurodegenerative diseases (NDDs). This study aimed to evaluate the associations of WW pattern and the risk of NDDs. This prospective study was conducted using accelerometer-based physical activity data for a full week from June 2013 to December 2015 in the UK Biobank. These individuals were categorized into distinct physical activity patterns, including the WW pattern (i.e., over 50% or 75% of recommended MVPA achieved over 1-2 days), regular pattern, and inactive pattern. Cox proportional hazards model was used to evaluate the association between physical activity patterns and outcomes. Compared to inactive group, WW pattern and regular pattern was similarly linked to a reduced risk of all-cause dementia (WW: Hazard Ratio [HR]: 0.68, 95% Confidence Interval [CI]: 0.56-0.84; regular: HR: 0.86, 95% CI: 0.67-1.1) and all-cause Parkinsonism (WW: HR: 0.47, 95% CI: 0.35-0.63; regular: HR: 0.69, 95% CI: 0.5-0.95). When the exercise threshold was increased to 75% of MVPA, both patterns still were associated with decreased risk of incident all-cause dementia (WW: HR: 0.61, 95% CI: 0.41-0.91; regular: HR: 0.76, 95% CI: 0.63-0.92) and all-cause Parkinsonism (WW: HR: 0.22, 95% CI: 0.10-0.47; regular: HR: 0.59, 95% CI: 0.46-0.75). Concentrating recommended physical activities into 1-2 days per week is associated with a lower incidence of NDDs.

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The activation of PP5 is essential for a variety of cellular processes, as it participates in a variety of biological pathways by dephosphorylating substrates. However, activation of PP5 by small molecules has been a challenge due to its native "self-inhibition" mechanism, which is controlled by the N-terminal TPR domain and the C-terminal αJ helix. Here, we reported the discovery of DDO-3733, a well-identified TPR-independent PP5 allosteric activator, which facilitates the dephosphorylation process of downstream substrates. Considering the negative regulatory effect of PP5 on heat shock transcription factor HSF1, pharmacologic activation of PP5 by DDO-3733 was found to reduce the HSP90 inhibitor-induced heat shock response. These results provide a chemical tool to advance the exploration of PP5 as a potential therapeutic target and highlight the value of pharmacological activation of PP5 to reduce heat shock toxicity of HSP90 inhibitors.

Asunto(s)

Proteínas HSP90 de Choque Térmico , Fosfoproteínas Fosfatasas , Regulación Alostérica/efectos de los fármacos , Humanos , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/química , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Fosfoproteínas Fosfatasas/metabolismo , Fosfoproteínas Fosfatasas/química , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Factores de Transcripción del Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico/química , Fosforilación/efectos de los fármacos , Respuesta al Choque Térmico/efectos de los fármacos , Relación Estructura-Actividad , Proteínas Nucleares

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Hydrogels have excellent swelling properties and have been widely applied in tissue engineering because of their similarity to the extracellular matrix (ECM). Sodium alginate (SA) and carboxymethyl chitosan (CMCS) were prepared into hydrogel microspheres with Ca2+crosslinking in our study. The morphology, inner structure, mechanical properties, water content, swelling rate and BMP-2 loading and releasing properties were characterized. Our results showed that the composite SA /CMCS hydrogel microspheres were translucent and spherical in shape with uniform particle size. The incorporation of CMCS further increased the diameters of the microspheres, internal pore structure, water content, and mechanical properties of the SA/CMCS hydrogel microspheres. At the same SA concentration, with the increase of CMSC concentration, the diameter of microspheres could be increased by about 0.4 mm, the water content can be increased about 1%-2%. As for the mechanical properties, the compressive strength can be increased by 0.04-0.1 MPa, and the modulus of elasticity can be increased by 0.1-0.15 MPa. BMP-2 was chosen as a model agent and it could be loaded into SA/CMCS microspheres, and the incorporation of CMCS increased BMP-2 loading. The encapsulated BMP-2 was sustainably releasedin vitro. The leaching solutions of the SA/CMCS hydrogel microspheres exhibited good cytocompatibility and could increase ALP activity, ALP expression, and biomineralization on MC3T3-E1 cells. After 7 d of co-culture, ALP activities in S2.5C2 and S2.5C3 groups was increased by 50% and 45% compared with that of the control group. When embedded in the SA/CMCS microspheres, the MC3T3-E1 cells were evenly distributed inside the hydrogel microspheres and remained viable. Transcriptomic studies showed that incorporation of CMCS induced upregulation of 1141 differentially expressed genes (DEGs) and downregulation of 1614 DEGs compared with SA microspheres. The most significantly enriched pathways were the Wnt and MAPK signaling pathways induced by the incorporation of CMCS and BMP-2. In conclusion, our results indicated that the physiochemical characteristics of the SA hydrogel microspheres could be greatly modulated by CMCS to better mimic the ECM microenvironment and induce osteo-inductive activities of MC3T3-E1 cells.

Asunto(s)

Alginatos , Proteína Morfogenética Ósea 2 , Proliferación Celular , Quitosano , Hidrogeles , Microesferas , Ingeniería de Tejidos , Quitosano/química , Quitosano/análogos & derivados , Animales , Ratones , Hidrogeles/química , Proliferación Celular/efectos de los fármacos , Alginatos/química , Proteína Morfogenética Ósea 2/metabolismo , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Fuerza Compresiva , Tamaño de la Partícula , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoblastos/citología , Ensayo de Materiales , Matriz Extracelular/metabolismo , Línea Celular , Osteogénesis/efectos de los fármacos , Agua/química

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Perylene diimides (PDIs) have garnered considerable attention due to its immense potential in photocatalysis. However, manipulating the molecular packing within their aggregates and enhancing the efficiency of photogenerated carrier recombination remain significant challenges. In this study, we demonstrate the incorporation of a PDI unit into a covalent organic framework (COF), named PDI-PDA, by linking an ortho-substituted PDI with p-phenylenediamine (PDA) to control its intermolecular aggregation. The incorporation enables precise modulation of electron transfer dynamics, leading to a ten-fold increase in the efficiency of photocatalytic oxidation of thioether to sulfoxide with PDI-PDA compared to the PDI molecular counterpart, achieving yields exceeding 90%. Electron property studies and density functional theory calculations show that the PDI-PDA with its well-defined crystal structure, enhances π-π stacking and lowers the electron transition barrier. Moreover, the strong electron-withdrawing ability of the PDI unit promotes the spatial separation of the valency band maximum and conduction band minimum of PDI-PDA suppressing the rapid recombination of photogenerated electron-hole pairs and improving charge separation efficiency to give high photocatalytic efficiency. This study provides a brief yet effective way for the improvement of the photocatalytic efficiency of commonly used PDI-based dyes by integrating them into a framework skeleton.

RESUMEN

Aims: Aortic root motion is suspected to contribute to proximal aortic dissection. While motion of the aorta in four dimensions can be traced with real-time imaging, displacement and rotation in quantitative terms remain unknown. The hypothesis was to show feasibility of quantification of three-dimensional aortic root motion from dynamic CT imaging. Methods and results: Dynamic CT images of 40 patients for coronary assessment were acquired using a dynamic protocol. Scans were ECG-triggered and segmented in 10 time-stepped phases (0-90%) per cardiac cycle. With identification of the sinotubular junction (STJ), a patient-specific co-ordinate system was created with the z-axis (out-of-plane) parallel to longitudinal direction. The left and right coronary ostia were traced at each time-step to quantify downward motion in reference to the STJ plane, motion within the STJ plane (in-plane), and the degree of rotation. Enrolled individuals had an age of 65 ± 12, and 14 were male (35%). The out-of-plane motion was recorded with the largest displacement of 10.26 ± 2.20 and 8.67 ± 1.69 mm referenced by left and right coronary ostia, respectively. The mean downward movement of aortic root was 9.13 ± 1.86 mm. The largest in-plane motion was recorded at 9.17 ± 2.33 mm and 6.51 ± 1.75 mm referenced by left and right coronary ostia, respectively. The largest STJ in-plane motion was 7.37 ± 1.96 mm, and rotation of the aortic root was 11.8 ± 4.60°. Conclusion: In vivo spatial and temporal displacement of the aortic root can be identified and quantified from multiphase ECG-gated contrast-enhanced CT images. Knowledge of normal 4D motion of the aortic root may help understand its biomechanical impact in patients with aortopathy and pre- and post-surgical or transcatheter aortic valve replacement.

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As emerging environmental contaminants, nanoplastics (NPs) are progressively accumulating in terrestrial and aquatic ecosystems worldwide, posing a potential threat to human health. The liver is considered as one of the primary organs targeted by NPs accumulation in living organisms. However, there remains a large knowledge gap concerning NPs-induced hepatotoxicity. In this study, we examined the impact of chronic exposure to environmentally relevant doses of polystyrene (PS) NPs on hepatic pyroptosis in mice. The results demonstrated that both particle sizes of PS-NPs (100 nm and 500 nm) significantly triggered pyroptosis in the mouse liver, as evidenced by the upregulation of GSDMD-N protein levels; moreover, this pyroptotic effect induced by 100 nm PS-NPs was more pronounced compared to that of 500 nm PS-NPs. Mechanistically, exposure to 100 nm and 500 nm PS-NPs resulted in an upregulation of TXNIP protein expression, thereby activating NLRP3 inflammasome and subsequently inducing inflammatory responses and pyroptosis. Notably, following the termination of PS-NPs exposure and a subsequent recovery period of 50 days, PS-NPs-mediated inflammation and pyroptosis via TXNIP/NLRP3 pathway were effectively ameliorated, even returning to levels close to the baseline. Collectively, our findings provide novel evidence for the size-dependence and reversibility of NPs-induced hepatic pyroptosis through TXNIP/NLRP3/GSDMD pathway in vivo.

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CD8 + T cells exert a critical role in eliminating cancers and chronic infections, and can provide long-term protective immunity. However, under the exposure of persistent antigen, CD8 + T cells can differentiate into terminally exhausted CD8 + T cells and lose the ability of immune surveillance and disease clearance. New insights into the molecular mechanisms of T-cell exhaustion suggest that it is a potential way to improve the efficacy of immunotherapy by restoring the function of exhausted CD8 + T cells. Transforming growth factor-ß (TGF-ß) is an important executor of immune homeostasis and tolerance, inhibiting the expansion and function of many components of the immune system. Recent studies have shown that TGF-ß is one of the drivers for the development of exhausted CD8 + T cells. In this review, we summarized the role and mechanisms of TGF-ß in the formation of exhausted CD8 + T cells and discussed ways to target those to ultimately enhance the efficacy of immunotherapy.

Asunto(s)

Linfocitos T CD8-positivos , Factor de Crecimiento Transformador beta , Humanos , Factor de Crecimiento Transformador beta/metabolismo , Linfocitos T CD8-positivos/inmunología , Inmunoterapia/métodos , Neoplasias/inmunología , Neoplasias/terapia , Animales

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Hydrological variations affect habitat characteristics and fish distribution in floodplain lakes. Assessing the contributions of the local community (i.e., LCBD, community uniqueness) and species to overall ß diversity (i.e., SCBD, species uniqueness) of fish assemblages is valuable for habitat and species conservation planning, particularly from functional and phylogenetic perspectives. We examined the changes in multifaceted LCBD and SCBD of fish across different hydrological periods in the Poyang Lake, China, and analyzed their responsive mechanisms using regression models, based on which the conservation priorities of habitats and species were evaluated. The findings revealed that taxonomic, functional, and phylogenetic LCBD and SCBD were lowest during the wet season compared to the normal and dry seasons, emphasizing the regulatory effects of hydrological regimes on fish assemblages. Taxonomic and functional LCBD were significantly impacted by the mean abundance of migratory fish, highlighting the importance of specific species combinations on community uniqueness. Taxonomic and functional SCBD exhibited positive correlations primarily with mean abundance, suggesting the potential uniqueness of certain common species. Additionally, we identified the river-lake junction (Hukou station) and natural reserve (Xingzi and Nanjishan stations) with high overall community uniqueness as critical habitats. We also emphasized the necessity for increased conservation efforts for species having high overall species uniqueness during different hydrological periods, including Coilia brachygnathus, Ctenopharyngodon idella, Coilia nasus, Saurogobio dabryi, Hypophthalmichthys molitrix, Megalobrama amblycephala, and Parabramis pekinensis. This research underscores the significance of integrating multiple ecological perspectives to manage biodiversity changes and maintain ecological conservation values effectively.

Asunto(s)

Biodiversidad , Conservación de los Recursos Naturales , Ecosistema , Peces , Lagos , Animales , China , Ríos , Filogenia

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The Ti6Al4V (TC4) alloy, a prevalent biomedical material in orthopedics, still faces limitation of the insufficient osseointegration. To improve the bioactivity of TC4, introducing the electric environment onto the TC4 surface may be an effective way in the view of the necessity of endogenous electric microenvironment in bone regeneration. Herein, a Volta potential pattern was engendered on the TC4 surface via parallel laser patterning, so as to promote the osteogenic differentiation of cells. A 15 W laser successfully transformed the original α + ß dual phase towards radially distributed lath-like martensite phase in the laser treated region. The atomic lattice distortion between the heterogeneous microstructures of the laser treated and untreated regions leads to a significant Volta potential fluctuation on the TC4 surface. The Volta potential pattern as well as the laser-engraved microgrooves respectively induced mutually orthogonal cell alignments. The hBMSCs osteogenic differentiation was significantly enhanced on the laser treated TC4 surfaces in comparison to the surface without the laser treatment. Moreover, a drastic Volta potential gradient on the TC4 surface (treated with 15 W power and 400 µm interval) resulted in the most pronounced osteogenic differentiation tendency compared to other groups. Modulating the electric environment on the TC4 surface by manipulating the phase transformation may provide an effective way in evoking favorable cell response of bone regeneration, thereby improving the bioactivity of TC4 implant.

Asunto(s)

Aleaciones , Diferenciación Celular , Rayos Láser , Células Madre Mesenquimatosas , Osteogénesis , Propiedades de Superficie , Titanio , Osteogénesis/efectos de la radiación , Osteogénesis/fisiología , Aleaciones/química , Titanio/química , Humanos , Células Madre Mesenquimatosas/citología , Células Cultivadas

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Rosacea is a chronic inflammatory skin disease that affects a patient's appearance and quality of life. It mainly affects the midface region and presents as erythema, flushing, telangiectasia, papules, pustules, and rhinophyma. Despite its prevalence, the precise pathophysiology of rosacea remains unknown, and novel pharmacological therapies are currently under investigation. Tranexamic acid (TA) is a synthetic, lysine-like compound that competitively inhibits fibrinogen production by synthesizing fibrinolytic enzymes. In addition to its popular application in hemorrhage treatment, TA has been used to manage a number of skin conditions, including melasma, chronic urticaria, and angioedema. TA is a better option for melasma treatment. However, the role of TA in treating rosacea has not yet been systematically elucidated. In this study, we reviewed all available literature on the use of TA for rosacea treatment. The included articles examined the therapeutic effects of TA in patients with rosacea, including traditional methods such as oral and topical administration and more novel approaches such as intradermal injections, microneedling, and laser-assisted delivery. Several recent clinical studies demonstrated that TA alleviates rosacea symptoms by restoring the permeability barrier, ameliorating the immune reaction, and inhibiting angiogenesis. In this review, we summarized the function and potential application of TA in rosacea treatment, aiming to facilitate the implementation of clinical applications.

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OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.

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Background: The right anterior mini-thoracotomy (RAMT) approach has become a popular technique in cardiac surgery and applied in valve surgery. However, there is very limited evidence on the application of RAMT in the Bentall surgery. In the present study, we aimed to evaluate the safety and feasibility of the RAMT approach in Bentall surgery. Methods: A retrospective analysis was performed on 27 patients who underwent Bentall surgery between September 2020 and April 2022 in the First Affiliated Hospital of Xi'an Jiaotong University. Follow-ups were undertaken 1 and 6 months after their operations. The baseline, perioperative, and follow-up results were retrospectively analyzed. Results: A total of 27 male patients aged 48-61 years were included in the study. The operation time ranged from 4.0 to 5.0 hours, with a median of 4.5 hours. The median aortic cross-clamping time was 122 minutes [interquartile range (IQR): 109-145 minutes], and the median cardiopulmonary bypass (CPB) time was 156 minutes (IQR: 143-183 minutes). The median intensive care unit stay was 3 days (IQR: 1.75-4.25 days). The ventilation time ranged from 6.5 to 22.0 hours, with a median of 13.0 hours. The median drainage volume in the first 24 hours was 210 mL. In the following-up data, no deaths or severe complications were observed. Conclusions: The mini-Bentall procedure through an RAMT approach is a feasible and safe approach with few wounds and good clinical results in patients undergoing aortic root replacement.

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With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become a hot topic of research. However, investigations into their endocrine-disrupting toxicity under combined binary exposure, especially the molecular mechanism of combined effects, have rarely been documented. In this study, two typical EDCs, perfluorooctanoic acid (PFOA) and 4-hydroxybenzophenone (4-HBP), were selected to examine their combined effects and molecular mechanism on MCF-7 cell proliferation at environmentally relevant exposure concentrations. We have successfully established a model to evaluate the binary combined toxic effects of endocrine disruptors, presenting combined effects in a simple and direct way. Results indicated that the combined effect changed from additive to synergistic from 1.25 × 10-8 M to 4 × 10-7 M. Metabolomics analyses suggested that exposure to PFOA and 4-HBP caused significant alterations in purine metabolism, arginine, and proline metabolism and had superimposed influences on metabolism. Enhanced combined effects were observed in glycine, serine, and threonine metabolic pathways compared to exposure to PFOS and 4-HBP alone. Additionally, the differentially expressed genes (DEGs) are primarily involved in Biological Processes, especially protein targeting the endoplasmic reticulum, and significantly impact the oxidative phosphorylation and thermogenesis-related KEGG pathway. By integrating metabolome and transcriptome analyses, PFOA and 4-HBP regulate purine metabolism, the TCA cycle, and endoplasmic reticulum protein synthesis in MCF-7 cells via mTORC1, which provides genetic material, protein, and energy for cell proliferation. Furthermore, molecular docking confirmed the ability of PFOA and 4-HBP to stably bind the estrogen receptor, indicating that they have different binding pockets. Collectively, these findings will offer new insights into understanding the mechanisms by which EDCs produce combined toxicity.

Asunto(s)

Caprilatos , Disruptores Endocrinos , Fluorocarburos , Humanos , Caprilatos/toxicidad , Células MCF-7 , Disruptores Endocrinos/toxicidad , Fluorocarburos/toxicidad , Proliferación Celular/efectos de los fármacos , Parabenos/toxicidad , Metabolómica , Multiómica

RESUMEN

Chronic non-communicable diseases (CNCDs) pose a significant public health challenge. Addressing this issue, there has been a notable breakthrough in the prevention and mitigation of NCDs through the use of antioxidants and anti-inflammatory agents. In this study, we aim to explore the effectiveness of Eupatorium adenophora Spreng leaves (EASL) as an antioxidant and anti-inflammatory agent, and its potential applications. To construct a cellular model of oxidative damage and inflammation, Caco-2 cells were treated with tert-butyl hydroperoxide (t-BHP). The biocompatibility of EASL-AE with Caco-2 cells was assessed using the MTT assay, while compatibility was further verified by measuring LDH release and the protective effect against oxidative damage was also assessed using the MTT assay. Additionally, we measured intracellular oxidative stress indicators such as ROS and 8-OHdG, as well as inflammatory pathway signalling protein NFκB and inflammatory factors TNF-α and IL-1ß using ELISA, to evaluate the antioxidant and anti-inflammatory capacity of EASL-AE. The scavenging capacity of EASL-AE against free radicals was determined through the DPPH Assay and ABTS Assay. Furthermore, we measured the total phenolic, total flavonoid, and total polysaccharide contents using common chemical methods. The chemical composition of EASL-AE was analyzed using the LC-MS/MS technique. Our findings demonstrate that EASL-AE is biocompatible with Caco-2 cells and non-toxic at experimental levels. Moreover, EASL-AE exhibits a significant protective effect on Caco-2 cells subjected to oxidative damage. The antioxidant effect of EASL-AE involves the scavenging of intracellular ROS, while its anti-inflammatory effect is achieved by down-regulation of the NFκB pathway. Which in turn reduces the release of inflammatory factors TNF-α and IL-1ß. Through LC-MS/MS analysis, we identified 222 compounds in EASL-AE, among which gentianic acid, procaine and L-tyrosine were the compounds with high antioxidant capacity and may be the effective constituent for EASL-AE with antioxidant activity. These results suggest that EASL-AE is a natural and high-quality antioxidant and anti-inflammatory biomaterial that warrants further investigation. It holds great potential for applications in healthcare and other related fields.

Asunto(s)

Antiinflamatorios , Antioxidantes , Estrés Oxidativo , Extractos Vegetales , Hojas de la Planta , terc-Butilhidroperóxido , Humanos , Células CACO-2 , terc-Butilhidroperóxido/farmacología , Hojas de la Planta/química , Antioxidantes/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Estrés Oxidativo/efectos de los fármacos , Eupatorium/química , Especies Reactivas de Oxígeno/metabolismo , FN-kappa B/metabolismo

RESUMEN

Temperature is one of the seven fundamental physical quantities. The ability to measure temperatures approaching absolute zero has driven numerous advances in low-temperature physics and quantum physics. Currently, millikelvin temperatures and below are measured through the characterization of a certain thermal state of the system as there is no traditional thermometer capable of measuring temperatures at such low levels. In this study, we develop a kind of diamond with sp2-sp3 composite phase to tackle this problem. The synthesized composite phase diamond (CPD) exhibits a negative temperature coefficient, providing an excellent fit across a broad temperature range, and reaching a temperature measurement limit of 1 mK. Additionally, the CPD demonstrates low magnetic field sensitivity and excellent thermal stability, and can be fabricated into probes down to 1 micron in diameter, making it a promising candidate for the manufacture of next-generation cryogenic temperature sensors. This development is significant for the low-temperature physics researches, and can help facilitate the transition of quantum computing, quantum simulation, and other related technologies from research to practical applications.